Laboratory Introduction: Tohoku University Graduate School of Medicine

Tohoku University
Graduate School of Medicine
Laboratory Introduction
2016
Medical Sciences Course Health Sciences Course Other
Laboratory Index Disability Sciences Course School of Public Health Course
Graduate School of Medicine

Radiation Biology HOSOI, Yoshio 1
Organ Anatomy OWADA, Yuji 2
Stem Cell Biology and Histology DEZAWA, Mari 3
Molecular Biology and Applied Physiology IGARASHI, Kazuhiko 4
Biochemistry IGARASHI, Kazuhiko 5
Medical Biochemistry YAMAMOTO, Masayuki 6
Neurophysiology MUSHIAKE, Hajime 7
Cell Physiology MUSHIAKE, Hajime 8
Systems Neuroscience MUSHIAKE, Hajime 9
Molecular Pharmacology YANAI, Kazuhiko 10
Pharmacology YANAI, Kazuhiko 11
Molecular Pathology HORII, Akira 187
Histopathology SASANO, Hironobu 187
Anatomic Pathology SASANO, Hironobu 12
Virology OSHITANI, Hitoshi 13
Microbiology and Immunology ISHII, Naoto 14
Nephrology Endocrinology and Vascular Medicine ITO, Sadayoshi 15
Hematology and Rheumatology HARIGAE, Hideo 16
Infection Control and Laboratory Diagnostics KAKU, Mitsuo 17
Diagnostic Radiology TAKASE, Kei 18
Radiation Oncology JINGU, Keiichi 19
Metabolism and Diabetes KATAGIRI, Hideki 20
Gastroenterology SHIMOSEGAWA, Toru 21
Cardiovascular Medicine SHIMOKAWA, Hiroaki 22
Infectious Diseases KAKU, Mitsuo 23
Respiratory Medicine ICHINOSE, Masakazu 24
Pediatrics KURE, Shigeo 25
Pediatric Surgery NIO, Masaki 26
Gynecology YAEGASHI, Nobuo 27
Obstetrics YAEGASHI, Nobuo 28
Advanced Surgical Science and Technology OHUCHI, Noriaki 29
Surgical Oncology OHUCHI, Noriaki 30
Orthopaedic Surgery ITOI, Eiji 31
Gastrointestinal Surgery UNNO, Michiaki 32
Hepato-Biliary Pancreatic Surgery UNNO, Michiaki 33
Cardiovascular Surgery SAIKI, Yoshikatsu 34
Urology ARAI, Yoichi 35
Anesthesiology and Perioperative Medicine YAMAUCHI, Masanori 36
Palliative Medicine INOUE, Akira 37
Emergency and Critical Care Medicine KUSHIMOTO, Shigeki 38
Plastic and Reconstructive Surgery TACHI, Masahiro 39
Neurology AOKI, Masashi 40
Neurosurgery TOMINAGA, Teiji 41
Neuroendovascular Therapy TOMINAGA, Teiji 42
Psychiatry MATSUOKA, Hiroo 43
Dermatology AIBA, Setsuya 44
Ophthalmology NAKAZAWA, Toru 45
Otolaryngology-Head and Neck Surgery KATORI, Yukio 46
Medicine and Science in Sports and Exercise NAGATOMI, Ryoichi 47
Behavioral Medicine FUKUDO, Shin 48
Physical Medicine and Rehabilitation IZUMI, Shin-ichi 49
Laboratory Index i
Laboratory Index Medical Sciences Course Health Sciences Course
Disability Sciences Course School of Public Health Course
Other
Epileptology NAKASATO, Nobukazu 50

Internal Medicine and Rehabilitation Science KOHZUKI, Masahiro 51
Behavioral Neurology and Cognitive Neuroscience MORI, Etsuro 52
Music and Acoustical Medicine ICHIE, Masayoshi 53
Advanced Interdisciplinary Biomedical Engineering KIMURA, Yoshitaka 54
Science of Nursing Practice MARUYAMA, Ryoko 55
Nursing Education and Administration ASAKURA, Kyoko 56
Gerontological and Home Healthcare Nursing OZAKI, Akiko 57
Nursing Science of Community Health Care System OMORI, Junko 58
Community Health MIYASHITA, Mitsunori 59
Public Health Nursing OMORI, Junko 60
Adult Health Nursing IMATANI, Akira 61
Oncology Nursing SATO,Fumiko 62
Palliative Nursing MIYASHITA, Mitsunori 63
Child Health Nursing SHIWAKU, Hitoshi 64
Psychiatric Nursing SAITO, Hidemitsu 65
Maternal Nursing SATO, Kineko 66
Women's Health Nursing YOSHIZAWA, Toyoko 67
Medical Physics GONDA, Kohsuke 68
Medical Imaging and Applied Radiology MACHIDA, Yoshio 69
Radiological Imaging and Informatics HOMMA, Noriyasu 70
Clinical Imaging ISHIBASHI, Tadashi 71
Diagnostic Image Analysis SAITO, Haruo 72
Radiological Examination and Technology CHIDA, Koichi 73
Therapeutic Radiology TAKEDA, Ken 74
Molecular and Functional Dynamics HAYASHI, Shin-ichi 75
Medical Microbiology, Mycology and Immunology KAWAKAMI, Kazuyoshi 76
Endocrinology and Applied Medical Science TAKAHASHI, Kazuhiro 77
Pathology and Histotechnology SUZUKI, Takashi 78
Clinical Physiology SHINDOH, Chiyohiko 79
Molecular Hematology SHIMIZU, Ritsuko 80
Molecular Endocrinology SUGAWARA, Akira 187
Epidemiology TSUJI, Ichiro 81
Biostatistics YAMAGUCHI, Takuhiro 82
Medical Informatics TSUJI, Ichiro 83
Medical Genetics AOKI, Yoko 84
Health Administration and Policy FUJIMORI, Kenji 85
Environmental Health Sciences and Molecular Toxicology AKAIKE, Takaaki 86
Forensic Medicine FUNAYAMA, Masato 87
Medical Ethics ASAI, Atsushi 88
Cell Proliferation NAKAYAMA, Keiko 89
Developmental Neuroscience OSUMI, Noriko 90
Molecular Medicine and Therapy MIYATA, Toshio 91
Clinical Cell Therapy ABE, Toshiaki 92
Advanced Therapeutics for Metabolic Diseases KATAGIRI, Hideki 187
Gene Therapy MATSUBARA, Mitsunobu 93
Transplantation and Regenerative Medicine GOTO, Masafumi 94
Neurochemistry DOH-URA, Katsumi 95
Neurological Science KITAMOTO, Tetsuyuki 96
Interdisciplinary Medical Science(Center for Oxygen Medicine) SUZUKI, Norio 188
Interdisciplinary Medical Science (Center for Neuroscience) MATSUI, Ko 97
Regional Innovation KATO, Yukinari 98
ii Laboratory Index
Laboratory Animal Medicine MIYOSHI, Ichiro 99

Office of Medical Education KAGAYA, Yutaka 100
Radioisotope Laboratory YAMAMOTO, Masayuki 188
Informative Genetics ARIMA, Takahiro 101
Molecular Epidemiology KURIYAMA, Shinichi 102
Development and Environmental Medicine NAKAI, Kunihiko 103
Pediatric Endocrinology and Environmental Medicine FUJIWARA, Ikuma 104
Autopsy Imaging Center ISHIBASHI, Tadashi 105
Center for Community Health TSUJI, Ichiro 188
Comprehensive Education Center for Community Medicine HARIGAE, Hideo 106
Tohoku Community Cancer Services Program MORI, Takahiro 107
Tohoku University Hospital

Education and Support for Community Medicine ISHII, Tadashi 108
Psychosomatic Medicine FUKUDO, Shin 109
Clinical Pharmaceutical Science MANO, Nariyasu 110
Occupational Health KUROSAWA, Hajime 188
Central Operation Division SAIKI, Yoshikatsu 188
Intensive Care Unit UNNO, Michiaki 189
Pathology SASANO, Hironobu 189
Blood Transfusion HARIGAE, Hideo 189
Institute of Development, Aging and Cancer

Gene Expression Regulation MOTOHASHI, Hozumi 111
Experimental Immunology TAKAI, Toshiyuki 112
Immunobiology OGASAWARA, Koetsu 113
Molecular and Cellular Biology HORIUCHI, Hisanori 114
Metabolism YAMAMOTO, Tokuo 115
Medical Engineering and Cardiology YAMBE, Tomoyuki 116
Pathology TBD 189
Vascular Biology SATO, Yasufumi 117
Molecular Oncology TANAKA, Kozo 118
Cancer Biology CHIBA, Natsuko 119
Clinical Oncology ISHIOKA, Chikashi 120
Thoracic Surgery OKADA, Yoshinori 121
Developmental Neurobiology OGURA, Toshihiko 122
Functional Brain Imaging SUGIURA, Motoaki 123
Nuclear Medicine and Radiology TAKI, Yasuyuki 124
Geriatrics and Gerontology ARAI, Hiroyuki 125
Cell Resource Center for Biomedical Research MATSUI, Yasuhisa 126
Smart Ageing International Research Center KAWASHIMA, Ryuta 127
Graduate School of Biomedical Engineering

Audiology KAWASE, Tetsuaki 128
Surgical and Molecular Pathophysiology FUKUSHIMA, Kouhei 129
Clinical Biology and Hormonal Regulation ABE, Takaaki 130
Biomedical Imaging SAIJO, Yoshifumi 131
International Research Institute of Disaster Science

International Cooperation for Disaster Medicine EGAWA, Shinichi 132
Disaster-related Infecious Disease TBD 133
Disaster Medical Radiology CHIDA, Koichi 134
Laboratory Index iii

Laboratory Index Medical Sciences Course Health Sciences Course
Disability Sciences Course School of Public Health Course
Other
Disaster Psychiatry TOMITA, Hiroaki 135

Disaster Obstetrics and Gynecology ITO, Kiyoshi 136
Disaster Public Health KURIYAMA, Shinichi 137
Disaster Medical Informatics NAKAYAMA, Masaharu 138
Other Cooperative Departments in Tohoku University

Cyclotron Nuclear Medicine TASHIRO, Manabu 139
Clinical Pharmacology and Therapeutics SATO, Hiroshi 190
Molecular and Cellular Neuroscience YAWO, Hiromu 140
Neuroendocrinology ITOI, Keiichi 141
Informatics on Pathophysiology KINOUCHI, Yoshitaka 142
Mental Health Science ITO, Chihiro 143
Oncology, Pharmacy Practice and Sciences TOMIOKA, Yoshihisa 144
Pharmacotherapy HIRASAWA, Noriyasu 145
Tohoku Medical Megabank Organization

Integrated Nephrology and Telemedicine KIYOMOTO, Hideyasu 146
Feto-Maternal Medical Science SUGAWARA, Junichi 147
Medical Neuroimaging Analysis TAKI, Yasuyuki 190
Community Oral Health Science TSUBOI, Akito 148
Personalized Prevention and Epidemiology HOZAWA, Atsushi 149
Biobank Life Science MINEGISHI, Naoko 150
Biomarker Investigation FUSE, Nobuo 190
Molecular Network Analysis YASUDA, Jun 151
Functional Evaluation of Genomic Polymorphisms TANABE, Osamu 190
Biomedical Information Analysis NAGASAKI, Masao 152
Statistical Genomics and Genetics TAMIYA, Gen 153
Biomedical Informatics TBD 191
Genomic Medicine Support and Genetic Counseling KAWAME, Hiroshi 154
Genetic Epidemiology Research Support SUZUKI, Yoichi 155
Extramural Collaborative Departments

Molecular Neuroimaging (National Institute of Radiological Sciences) SUHARA,Tetsuya 156
Cancer Molecular Biology (Miyagi Cancer Center) SHIMA,Hiroshi 157
Cancer Pathology (Miyagi Cancer Center) TANAKA,Nobuyuki 191
Cancer Stem Cell Research (Miyagi Cancer Center) SATOH, Kennichi 158
Gynecologic Oncology (Miyagi Cancer Center) YAMADA, Hidekazu 159
Urologic Oncology (Miyagi Cancer Center) KAWAMURA, Sadafumi 160
Respiratory Oncology (Miyagi Cancer Center) MAEMONDO, Makoto 191
Cancer Pathology (Miyagi Cancer Center) SATO, Ikuro 191
Head and Neck Oncology (Miyagi Cancer Center) MATSUURA, Kazuto 161
Pediatric Hematology and Oncology (Miyagi Children's Hospital) IMAIZUMI, Masue 162
Pediatric Neurosurgery (Miyagi Children's Hospital) SHIRANE, Reizo 192
Fetal Medicine (Miyagi Children's Hospital) MUROTSUKI, Jun 192
Cellular and Molecular Imaging of Cancer (Japanese Foundation for Cancer Research) HIROTA, Toru 192
Screening for Molecular Target of Cancer (Japanese Foundation for Cancer Research) NODA, Tetsuo 192
Oncotherapeutic Medicine (Japanese Foundation for Cancer Research) TAKAHASHI, Shunji 163
Oncotherapeutic Surgery (Japanese Foundation for Cancer Research) SANO, Takeshi 193
Community Psychiatry (Miyagi Psychiatric Center) TBD 164
Innovative Cardiovascular Medicine (National Cerebral and Cardiovascular Center) YASUDA, Satoshi 165
Innovative Cardiovascular Surgery (National Cerebral and Cardiovascular Center) KOBAYASHI, Junjiro 166
Preventive Cardiology and Epidemiology (National Cerebral and Cardiovascular Center) MIYAMOTO, Yoshihiro 167
iv Laboratory Index
Gastrointestinal and Community Medicine (Internal Medicine) (Iwaki Kyouritsu General Hospital) TAKAHASHI, Seiichi 168
Gastrointestinal and Community Medicine (Surgery) (Iwaki Kyouritsu General Hospital) YOSHIDA, Hiroshi 193
Gastrointestinal and Community Medicine (Preventive Medicine) (Iwaki Kyouritsu General Hospital) TBD 193
Infection and Epidemiology (National Institute of Infectious Diseases) OISHI, Kazunori 169
Infection and Pathology (National Institute of Infectious Diseases) HASEGAWA, Hideki 193
Infection and Microbiology (National Institute of Infectious Diseases) OHNISHI, Makoto 194
Disease for Mycobacterium Tuberculosis Infection (Miyagi Cardiovascular & Respiratory Center) TBD 194
Manegement of Infectious Diseases (Miyagi Cardiovascular & Respiratory Center) HIRAKATA, Yoichi 170
Pharmaceutical and Medical Device Regulatory Science (Pharmaceuticals and Medical Devices Agency) TBD 194
Preemptive Medicine in the Community of the North Miyagi (Osaki Citizen Hospital) NAMIKI, Kenji 171
Advanced Pediatric Medicine (National Center for Child Health and Development)
UMEZAWA, Akihiro; SAGO, Haruhiko; SAITO, Hirohisa
172
Emerging and Reemerging Infectious Diseases (National Center for Global Health and Medicine) OHMAGARI, Norio 173
Intramural Endowed Departments

Innovative Cardiovascular Medicine SHIMOKAWA, Hiroaki 174
Evidence-based Cardiovascular Medicine SHIMOKAWA, Hiroaki 175
Multiple Sclerosis Therapeutics FUJIHARA, Kazuo 195
Advanced Preventive Medicine for Infectious Disease YAMAYA, Mutsuo 176
Nano-Medical Science OHUCHI, Noriaki 177
Advanced Ophthalmic Medicine NAKAZAWA, Toru 178
Research Division of Sciences for Aortic Disease SAIKI, Yoshikatsu 179
Upper Extremity Musculoskeletal Medicine ITOI, Eiji 180
Preventive Psychiatry MATSUMOTO, Kazunori 195
Retinal Disease Control, Ophthalmology NAKAZAWA, Toru 181
Integrative Renal Replacement Therapy ITO, Sadayoshi 182
Kampo and Integrative Medicine
Ophthalmic Imaging and Information Analytics
Advanced Respiratory Management
Clinical Hypertension, Endocrinology and Metabolism
Research Division for Development of Anti-Infectve Agents WATANABE, Akira 183
Developmental Cognitive Neuroscience KAWASHIMA, Ryuta 184
Geriatric Pharmacotherapy OHRUI, Takashi 185
Neuro-Imaging KUDO, Yukitsuka 195
Geriatric Behavioral Neurology MEGURO, Kenichi 186
Laboratory Index v
Keyword Index
Number anti-tuberculosis drug 168
1-methyladenosine 129 antibody-engineering 98
3D printing 75 antimicrobial resistance 18, 183
7T-MRI for small animals 122 aortic disease 175
arrhythmia 23, 80
A arterial graft 164
AAV virus 174 arteriosclerotic disease 173
abdominal fetal ECG device 55 artificial organ support 39
absorbable plate 40 artificial ventilation 37
academic-industry partnership 42 aspiration pneumonia 185
acquired von Willebrand syndrome 114 assisted reproductive technology (ART) 101
acute brain slice 97 asthma model mice 154
acute kidney injury (AKI) 146 atherosclerosis 115
adaptive radiotherapy 20, 75 ATM 1
adherence 185 ATP binding cassette (ABC) transporters 33
adjuvant analgesics 38 attachment to the local community 61
adrenal cortex 13 audio-visual speech perception 127
adrenal venous sampling 16 autism 123
advanced life support in obstetrics 67 autism spectrum disorder 91, 102
advanced medical technology 28, 29 autistic spectrum disorder 65
adverse drug event 185 autoimmunity 15
advocacy 59 automated computer diagnosis 72
aging 82, 95, 115 autonomic nervous activity 56
airway epithelial cell culture 172 autonomy 57
allergic dermatitis 144 autopsy 28
allergic disease 154
allergy/inflammation/autoantibody 112 B
Alzheimer's disease 12, 53, 186 B lymphocyte 112
Alzheimers disease and dementia 124 B lymphoid cell 5
anaerobic culture 147 barostat 109
analyses of brain function 21 basal ganglia 71
analyses of systemic energy metabolism 21 beating heart surgery 164
analyses of systemic glucose metabolism 21 behavioral medicine 49
anastomotic stenosis 35 behavioral neurology 53
anesthesia 37 behavioral teratology 103
angiogenesis 116 big data 86, 165
animal disease model 155 big data analysis 123
animal experiment 3, 4, 6, 40, 42, 56, 62, 77, 79, 91, big data in genomics 152
93, 95, 118, 135, 157, 174, 176, 179 big data with high dimension and low sample size 152
animal experimentation 29, 99 bile acid 110
animal metastasis models 162 biliary atresia 27
animal model 22, 26, 134 binaural hearing 127
animal research 52 bio-monitoring 39
animal study 49 bioanalytical chemistry 110
anthropologic measurement 105 bioartificial pancreatic islets 145
anti-allergic drugs 144 biobank 136, 149
anti-biofilm drug 183 biochemical analysis 115
anti-fibrosis 129 biochemistry 76, 114, 116, 155
anti-influenza agent 183 biofilm 40
Keyword Index vii

bioinformatics 5, 90, 151 cancer screening 135
biomarker 25, 119, 134, 157, 170 cancer stem cell marker 160
biomarkers of cancer 162 cancer stem cells 157
biomechanical analysis 32 cancer therapy 117, 169
biomechanics 130 cancer treatment 119
biomolecules 110 cancer-specific monoclonal antibody 98
biospecimen 149 candidate gene marker 142
biostatistics 60, 83 capsule endoscopy 166
birth cohort study 103 carbonyl stress 92
birth defects 153 cardiac rehabilitation 180
bladder cancer 159 cardiac surgery 164
blind source separation 55 cardiorenal syndrome 16
blind source separation with reference signal 55 cardiovascular disease 82, 165
blindness prevention 93 cardiovascular endocrinology 78
blood and immune disorders 26 cardiovascular MDCT 73
blood cell transplantation 161 cardiovascular medicine 137
blood flow imaging 130 cardiovascular MRI 73
blood flow sensor 35 care management 163
blood pressure 94 career choice 100
blood purification 146 case-control study 60, 169
body fluid 94 CasMab 98
body schema 50 catecholamines 140
bone marrow failure 176 catheter ablation 23, 170
bone metabolism 32 cause of death 105
bone metastases of cancer 162 CBPR (community based participatory research) 61
bone mineral density 104 CD271 160
brain 123 cell biology 90, 114, 116, 118, 143
brain aging 126 cell culture 1, 2, 3, 4, 6, 7, 15, 22, 26, 62, 76, 78, 79, 81,
brain development 91 85, 91, 95, 117, 125, 135, 145, 157, 174, 176
brain histamine 142 cell culture and gene manipulation 93
brain imaging 49, 184 cell cycle 90
brain ischemia 97 cell differentiation 125
brain surgery 140 cell imaging 9
brain training 126 cell islolation enzymes 145
brain-gut interaction 49, 109 cell isolation 157
breast cancer 31, 76, 79 cell kinetics 3, 6
bronchial asthma 172 cell sorting 134
bronchoscopy 25 cell transplantation 93, 145
cell-based research 149
C cell-based therapy 39
2+
Ca imaging 139 cell-surface glycoconjugates 99
caddisfly watch 103 cell-surface receptor protein 112
calcium 71 cellular and animal model 41
calcium imaging 71 cellular biology 11
cancer 60, 69, 82, 173 centrosome regulation 118
cancer chemotherapy 119 cerebellar slices 8
cancer development 157 cerebral cortex 2
cancer genomics 150 cerebral aneurysm 43
cancer imaging 19 cerebrovascular diseases 42
cancer immunotherapy 107 CGH array technique 26
cancer microenvironment 34 channelrhodopsin 139
cancer pain 38 chemical biology 87, 95
cancer registry 60 chemical exposure 103
viii Keyword Index

chemosensitivity 34 community based cohort study 148
chemotherapy 159 community health 58, 169
child 65 community health activity at the disaster area 59
child and adolescent psychiatry 44 community medicine 106
childhood cancer 161 community mental health activities 163
childhood leukemia 161 community psychiatry 163
childhood thrombocyotopenia 161 comparative and experimental medicine 99
cholesterol 115 comprehensive analyses of clinical samples 178
chromatin 5 comprehensive expression analysis 119
chromatography 143 comprehensive gene expression analysis 46, 135
chromosomal instability 117 comprehensive medicine 108
chromosome segregation 117 comprehensive rehabilitation 52
chronic disease 102 compressed sensing 70
chronic heart failure 23, 171 computational fluid dynamics 42, 43
chronic kidney disease (CKD) 146 computational intelligence 71
chronic obstructive pulmonary disease 172 computational neuroscience 10
circulating tumor cells 162 computed assisted detection 72
circulating tumor DNA 162 computed tomography 19, 88, 105
clarification of pathological characteristics of computer-aided diagnosis 71
immune cells in autoimmune diseases 17 congenital imprinting diseases(BWS,AS,PWS,SRS) 101
CLEC-2 98 consensus building 59
clinical ethics 89 contact dermatitis 45
clinical genetics 29 contemporary ethics issues 89
clinical imaging 19 control of infectious diseases 18
clinical judgment 57 controlled drug delivery 93
clinical microbiology 18 convection enhanced delivery 42
clinical observational study 142 conversion 96
clinical pharmacology 138 coparenting 68
clinical research 52, 163, 175 coronary vasospasm 23
clinical research methodology 83 corticotropin-releasing hormone (CRH) 49
clinical research support system 83 counseling 67
clinical specimens 179 couple communications 68
clinical statistics 169 crisis management 18
clinical studies of hematological and critical care 39
autoimmune diseases 17 Crohn's disease 128
clinical study 12, 92, 108 cryopreservation of biospecimen 149
clinical trial 119, 171 culture 61
cluster approach 131 curriculum development 100
co-culture 13 cutting-edge medical technology 106
coagulo-fibrinolytic abnormalities 39 CYP variants 144
cochlear implant 47, 127 cytogenetic analysis 161
cognition 122
cognitive behavior therapy 109 D
cognitive behavioral task 10 daily habit 184
cognitive behavioral therapy 44 daily home hemodialysis 146
cognitive function 10, 44 damage-associated molecular patterns 39
cognitive neuroscience 53 data analysis 86
cohort 165 data archiving 134
cohort study 48, 60, 82, 102, 134, 148 data collection/management 171
coil 43 data management 83
colony assay 81 data management and statistical analyses 14
comfort 68 data-driven science 151
common cold syndrome 172 database 86, 123, 131, 137
Keyword Index ix
decision making 65 drug development 12, 46, 174
deformable image registration 20 drug discovery 81, 95, 176
dementia 53, 123, 155, 186 drug discovery and development 92
dementia with Lewy bodies 53 drug screening 46
dengue fever 24, 132 duodenojejunal bypass (DJB) 33
descriptive ethics methods 89 dynamic homeostasis of systemic metabolism 21
deterministic and stochastic effects 74, 133 dysphagia and voice disorders 47
development 184
development and aging 123 E
development of ICT-based pill-box for frail elderly 124 early diagnosis 69
development of imaging probes 124 early intervention in psychiatry 44
development of medical staff resources 180 early psychosis 44
development of surgical device 30 earthquake 163
development of therapeutic devices 98 eating disorders 109
developmental changes in synapses 8 education 58
developmental disorder 65, 184 education and learning 126
developmental engineering 99, 113 education for perinatal women 67
diabetes 21 education of disaster medicine 131
diabetes mellitus 104 education program 108
diagnostic radiology 19, 105 educational program development 66
diaphragm muscle contractility 80 effective dose and equivalent dose 74, 133
differentiation 3, 6, 62 EKG on QR code 137
diffusion tensor imaging 50 electrical cortical stimulation 51
diffusive lung disease 25 electrical stimulation 70, 80
digital mammography 72 electrocorticography 51
digital radiography 72 electroencephalogram 97
disaster 136, 137 electroencephalography 51
disaster geriatric medicine 124 electromicroscopy 8
disaster medical and public health coordinator 131 electron microscopy 128
disaster medicine 39, 106, 108 electronmicroscopy 2
disaster nursing 67 electronic medical (health) record 137
disaster psychiatry 134 electrophysiology 10, 47, 97, 139
disaster related diseases 180 ELISA 78
disaster stress 135 elispot 24, 132
disclosure of cancer 38 embolization 43
disease model mouse 154 emergency 106
disease modelling 9 emergency medical transportation 182
disease modifying drugs 124 emotion 49
disease susceptibility gene 22 empowerment 59
disease-associated gene 99 end of life care 65
diseases 136 endocrinology 28
dissected diaphragm muscle 80 endometrial cancer 135
DNA array 45 endoplasmic reticulum membrane 9
DNA damage response 118 endoscopic laryngo-pharyngeal surgery 160
DNA methylation 101 endoscopic surgery 27, 47
DNA methylation analysis 119 endoscopy 166
DNA microarray analysis 177 endotoxin 80
DNA-PK 1 endovascular therapy 30, 43
dose calculation algorithm 75 energy and beam quality 74, 133
DPC/PDPS 86 energy metabolism in cancer cells 33
dressed NK cells 113 environmental response 7
drug delivery 93 epidemiological study in earthquake-hit areas 124
drug delivery system 35 epidemiology 60, 82, 83, 136, 148, 158, 165
x Keyword Index
epidemiological analysis 18 fluorescent dye loading 80
epigenetics 90, 91, 101, 125 flux analyzser 129
epigenome 141 follow-up study 171
epigenome wide association study 141 foot care 180
epilepsy 42, 97 force-sensing proteins 121
epilepsy monitoring unit 51 forensic autopsy 105
epithelial to mesenchymal transition (EMT) 22 forensic imaging 72
erythroid cell 5 forensic medicine 105
erythroid differentiation and iron metabolism 17 forensic pathology 88
esophageal cancer 20 forensic radiology 88
estimation of pharmacokinetics 144 forensic toxicology 88
estrogen 76 frozen shoulder 177
ethics committee activities 89 functional brain imaging 73
ethics consultation interventions 89 functional brain mapping 51
ethnography 61 functional gastroenterological disorders 109
evaluation of drug efficacy 69 functional imaging 138
evaluation study 64 functional neuroimaging 109
evaluation systems for retinal function and functional preservation 158
pharmaceutical effectiveness 178 functional preservation treatment 160
evidence-based medicine 171 fundamental family program 68
exercise medicine 138 fungus 77
exercise pill (exercise mimetics) 121
exercise therapy 52 G
exercising test 52 galectin 9 24, 132
exome analysis 26 gastric acid secretion 22
experiment with microbial infection 77 gastric cancer 62
experimental animal model 18 gastrointestinal endoscopy 22
experimental hematological analysis; gastrointestinal manometry 109
e.g. transplantation 81 gastrointestinal motility 49
experimental pathology 116 GATA 7
exploratory clinical trial 92 GATA factors 81
extracellular matrix 34 gender analysis 57
extraction algorithm of fetal electrocardiogram 55 gene 140, 148
gene analysis 25, 94, 115, 120, 142
F gene editing in mice 81
facility care/ residential care/ long-term care 58 gene engineering mouse 90
family 65, 66 gene expression 121
family support 38 gene expression analysis 3, 6, 17
family support program 38 gene expression analysis of fetal dysfunction 55
fatty acid binding protein 2 gene expression analysis/protein analysis 55
female chinese medicine 28 gene knock-out 121
fertility preservation 158 gene knockout mouse 2
field epidemiology 14 gene manipulation 15, 125
field epidemiology training program-japan (FETP-J) 167 gene polymorphism 62
field research in the environment 103 gene targeting 2
finite element analysis 175 gene technology 4
finite element method 32 gene therapy 46, 174
flow cytometric fine sorting of gene transfer 91
human peripheral blood cells 112 gene-by-environment interaction 152
flow cytometry 7, 15, 24, 111, 113, 132 gene-engineered mice 112
fluid dynamics 130 gene-environment interaction 148
fluorescence nano-imaging 31 general radiology 19
fluorescent activated cell sorter 81 generation of model mouse 17
Keyword Index xi
genetic analysis 42, 85, 104, 119, 123, 154, 174 heme 4
genetic analysis of tuberculosis 180 hemorragic fever 24, 132
genetic and genomic literacy 153 hepatic virus 22
genetic counseling 153 hepatocyte transplantation 145
genetic counseling program 153 hereditary cancer 118
genetic epidemiology 154 Helicobacter 62
genetic instability 156 high accuracy 69
genetic polymorphism 184 high frequency oscillation 51
genetic polymorphism and cellular characteristics 149 high frequency ultrasound 130
genetic research 49 high performance computing 151
genetic skeletal disorders 104 high performance sequence 151
genetical analysis 18 high-precision radiotherapy 75
genetically engineered animal 99 high-throughput screening 81
genetically engineered mouse 12, 140, 156 higher the quality of life 59
genetically modified mouse 117, 125 histamine 12
genom 37 histochemical analysis 91
genome analysis 46, 161 histochemistry 47
genome cohort 136 histological analysis 3, 6, 32
genome editing 99 histological assessment 179
genome structures 150 histone modification 101
genome wide association study 141, 151 histopathological analysis 96
genomic analysis 146 histopathology 145
genomic cohort 152 history of midwifery education 67
genomic imprinting 101 history of nursing education 67
genomic medicine 152, 154 home care 179
genotyping 62 hormonal therapy 76
geographic information system 182 hormone 79
germ cells 125 human development 85
GI cancer 166 human genome 149, 151
glaucoma 46, 174 human immunodeficiency virus 24, 132
glia 97 humanized knock-in mouse 96
glial cell differentiation 91 hydration therapy 38
glucocorticoids 140 hyperinsulinemic euglycemic clamp 21
glycobiology 36, 98 hypothalamus 140
gut microbiota 129 hypoxic pathway 48
gynecologic malignancies 158
gynecological disease 135 I
gynecological oncology 28 IBD 166
ICT 131, 165
H ictal tachycardia 51
health belief 61 identification and characterization of autoantibody 17
health impact of the Great Eastern Japan Earthquake 148 IDH1/2 98
health monitoring 136 image analysis 123, 173
health promotion 59, 61 image display 72
health sciences 138 image processing 69
healthcare policy 86 image quality 70
healthy life expectancy 82 image reconstruction 70
hearing aid 127 image-cytometry 113
hearing loss 127 image-guide radiotherapy 20
heart disease 175 image-guided radiation therapy 71, 75
heart rate variability 54, 56 imaging 69, 122
hematopoietic cell sorting 17 immune mechanism 25
hematopoietic differentiation 7 immune memory 77
xii Keyword Index

immune regulation 112 intracellular ionic composition 97
immunity isolating 34 intractable and rare disease 85
immunofluorescence 140 intrathecal baclofen therapy 50
immunofluorescence staining 117 invasion 79
immunohistochemistry 2, 13, 33, 62, 78, 79, 128, 140 invasion and metastasis 34
immunological analysis 77 ion channel function 9
immunological memory 112 ion channel structure 9
immunological tolerance 112 ionizing radiation 1
immunology 56 iPS cells 46
immunotoxicity 45 iPSC technology and regenerative medicine 41
in silico drug design 92 irritable bowel syndrome (IBS) 49
in vitro B cell development 112 ischemia-reperfusion lung injury 120
in vitro hematopoietic cell differentiation 17 ischemic heart disease 23, 164
in vitro molecular evolution technique 112 ischemic-reperfusion injury 35
in vivo / in vitro imaging 145 islet transplantation 34, 145
in vivo imaging 155 isolating individual cellular components from
in vivo imaging of ATP 45 adult human lungs 172
in vivo molecular imaging with high accuracy 173 IVR 73
in-home care 58
individual identification 105 J
inducible tissue-specific knockout mice 21 J-START 31, 181
infection 56
infection and immunity 77 K
infection control network 18 kampo drugs 108
infection crisis management 18 kampo medicine 108
infectious disease epidemiology 167 Keap1-Nrf2 7
infectious diseases 14 knockout mouse 7, 80, 111
inflammation 15
inflammatory bowel disease 141 L
information and communication technology 108, 146 laboratory information management system 149
information network among different fields 182 LAMP 24, 132
information security 84 laparoscopic surgery 36
infrared spectroscopy (NIRS) 138 large animal model 35
inherited bone marrow failure 161 large p small n problem 152
inner ear dysfunction 47 large randomized controlled trial 31
innovative medical devices 170 large-scale clinical study 16
integrated analysis 102 large-scale cohort study 23
integrative medicine 138 laser-doppler method 16
intelligence measurement 103 LC/MS/MS 143
intensity modulated radiotherapy 20 LCM 13
intensity-modulated radiation therapy 75 leukemia 81, 176
intensive care medicine 37 lifestyle 60, 148
inter-organ metabolic communication 21 lifestyle disease 171
international health regulations (IHR) 167 lifestyle related disease 141, 147, 169, 180
international medicine and public health 131 lipid 2
internet questionnaire survey 66 liquid chromatography-tandem mass spectrometry 88
intervention study 63, 82 liquid media 168
interventional radiology 19, 74, 133 live cell imaging 2, 117
interview 58 live imaging 156
intestinal adaptation 128 local cortical circuits 10
intestinal flora 128 long-read sequencers 150
intracellular calcium 80 low dose radiation 1
intracellular dynamics of GPCR 11 lower limb edema 68
Keyword Index xiii

lower urinary tract symptoms 36 mental health 66, 126
lucife assay 45 mental health care 67, 142
lumbar spinal canal stenosis 177 mesenchymal stem cell 34
luminex 24, 132 meta-analysis 165
lung allograft rejection 120 metabolic analysis 156
lung cancer 25 metabolic regulation 111
lung repair and regeneration 172 metabolic syndrome 87
lymphocyte 2 metabolome 87
LYMQOL 68 metabolomic analysis 111
metabolomics 110, 143
M metagenomic analysis 48, 147
machine learning 71, 151 metagenomics 151
macrophage 5 metal allergy 144
magnetic resonance image 123 metastasis 79, 173
magnetic resonance imaging 19, 105, 122, 126, 184 methodology of collaboration 59
magnetoencephalography 51, 122, 127 methylmercury 103
malignant brain tumors 42 micro fabrication 93
mammography 31, 181 microarray 79, 128
management 59 microbiome 48
mass screening 159 microdissection 45
mass spectrometry 143 microdose test 92
mass spectrometry analysis 5 microperfusion of renal tuble 16
massively parallel sequencing 85 MICS 164
mathematical analysis of single-cell gene expression 55 minimally invasive surgery 36
MDCT 73 minimally invasive surgery for
measurement 64 upper gastrointestinal tract 30
measurement of cough reflex 185 misfolded protein 95
measurement of swallowing latency 185 mitf 4
mechanical manipulation 121 mitochondria 129
medical and public health needs 131 mitochondrial disease 11, 129
medical check-up for musculoskeletal disease 177 mitophagy 11
medical check-up for survivors of mitosis 117, 118
the Great East Japan Earthquake 177 mixed method 61
medical cooperation system 180 MND/ALS 41
medical device development 42 mobile assessment 137
medical devices 23 molecular and behavioral pharmacology 12
medical e-claim data 86 molecular and cellular biology 14, 113
medical engineering 35 molecular and functional imaging 41
medical evacuation in disasters 182 molecular biological analysis 32, 77
medical humanities approach 89 molecular biological approaches 52
medical informatics 84 molecular biology 5, 11, 23, 26, 47, 62, 76, 78, 91,
medical information network 84 95, 110, 114, 116, 118, 121,
medical oncology 119 139, 143, 157, 174, 176
medical professionalism 89 molecular biology of cancer 107
medical safety control 84 molecular biology techniques 34
medical semantics 84 molecular epidemiology 14, 102, 136
medical simulation 100 molecular genetics 154
medical system 67 molecular imaging 12, 138
medical therapy 104 molecular neuroimaging 124, 155
medication management in elderly people 124 molecular target drug 119
melanin 4 molecular target therapy 76
melanogenesis 45 molecular toxicology 87
mental development measurement 103 monoclonal antibody 98
xiv Keyword Index

Monte Carlo method 75 neuromodulation 70
mood disorder 134, 155 neuromyelitis optica 41
motion analysis 48 neuronal cell death 95
mouse 5, 140 neuropathology 155
mouse biology 114 neuropeptide 78
mouse handling 15 neuroprotection 46, 93, 174, 178
mouse model for diseases 55 neuroprotective therapies 178
mouse modeling 85 neuropsychology 53, 186
MR fast imaging 70 neuroradiology 19
MRI 70, 71, 73 neutral theory 152
MRSA 183 neutrophil NETs 114
mTOR 1, 114 new antineoplastic drugs 162
mucosal immunology 62 new retinal drug therapies 178
multi dimensional omics analysis 151 newborn disorders 26
multi-channel recording 10 newborn errors of metabolism 26
multi-organ connection 52 next generation EHR 84
multicellular cardiac muscle preparation 80 next generation sequencer 22, 41, 90, 150
multidrug resistance (MDR) 33 next generation sequences 113
multimer analysis of von Willebrand factor 114 next generation sequencing 5, 33, 162
multiple sclerosis 41 next-generation cell therapy 145
multiplex gene mutation analysis 162 nicorandil (the N-K hybrid) 11
muscular diseases 41 NK cells 113
musculoskeletal disorder 50 NKT cell 40
Muse cell 45 non-invasive molecular imaging 12
music 54 non-invasive therapy 72, 170
MyD88KO mice 80 non-invasiveness 170
normal polymorphism and mutations 96
N normal pressure hydrocephalus 53
nano medicine 31, 69 normalization of heterogeneous
nano-sheet 93 information resources 182
nanoparticle 77 normative analysis 89
NASH 166 notification 65
nasopharyngeal cancer 20 nuclear medicine 19
national database 86 nuclear medicine (PET/SPECT) 69
national epidemiological surveillance of nuclear receptor 76
infectious diseases (NESID) 167 numerical experiment 70
natural history 153 nurses 66
near-infrared spectroscopy (NIRS) 54, 126 nursing 64
neonatal surgery 27 nursing care 56
nerve block 37, 38 nutritional therapy 160
nerve-sparing surgery 36
network medicine 18 O
network reorganization 139 obesity 21, 115
networking between University hospitals and obesity as a disease 33
community cancer center hospitals 107 observational study 171
neural decoding 126 obstetrics and gynecology 28, 29
neurochemistry 12 obstructive pulmonary disease 25
neurodevelopmental disorders 44 occupational mobility 57
neuroendocrine tumor 13 older subjects 185
neuroendocrinology 78 omics study 134
neuroepidemiology 186 oncogenesis 117
neurogenesis 91 oncology nursing 63
neuroimaging 44, 53 ontology 84
Keyword Index xv
optimization of radiation dose and image quality 74, 133 peer review 100
optogenetics 10, 97, 139 PEM (positron emission mammography) 181
oral care 172 perception 122
oral health 147 perinatal medicine 29
oral metagenomics 147 perinatal nursing 67
organ and cell transplantation 30 peripheral artery disease 69
organ damage and protection 52 peritoneal dialysis 179
organ fibrosis 22 personalized medicine 33, 143, 144, 146, 153
organ pathophysiology relating to ion channels 9 personalized medicine and health care 149
organ preserving treatment for resectable esophageal persons with mental disorders 66
cancer definitive chemoradiotherapy followed by PET 73, 155
salvage treatment 30 phantom and image performance 74, 133
organ protection 35 phantom limb pain 50
osteogenesis imperfecta 104 pharmaceutical effectiveness 178
osteoporosis 32 pharmacogenomics 33, 144
outcome evaluation 100 pharmacokinetic analysis 69
outreach 163 pharmacokinetics 110
ovarian cancer 158 phase I trial 162
oxidative stress 87 photoacoustic effect 130
photoacoustic imaging 130
P photoacoustic imaging system 177
PA tag 98 physical activity 48
PAI-1 92 physical forces 121
pain clinic 37 physiological analysis 94, 120
palliative care 64 physiological function 78
palliative sedation 38 physiological measurements 126
pancreatic beta cell regeneration 21 physiological models 8
pancreatobiliary malignancies 34 physiology 29
Parkinson's disease 53, 71 pigment cell 4
Parkinsons disease and related disorders 41 PK-PD 183
patch-clamp 8, 139, 140 placenta 101
patch-clamping 9 plasma irradiation 183
pathogen detection and isolation 14 plasticity 122
pathogenesis 14 play therapy 44
pathogenesis of head and neck cancer 47 pluripotent stem cells 3, 6
pathologic analysis 52 pluripotential stem cells 125
pathological analysis 22, 77, 120, 161 pneumococcal vaccine 183
pathology 28, 29, 40, 79, 95, 106, 157 podoplanin 98
pathology and biochemistry techniques 41 population genetics 150, 152
pathology elucidation 163 positron emission tomography 12, 124, 138, 142
patient and occupational exposure 74 postmortem image analysis 73
patient and occupational radiation exposure 133 postmortem imaging 72
patient simulators 100 pouchitis 128
patient support by monitering in long distance 146 pre-symptomatic detection and preemptic therapy 124
patient-derived tumor xenograft 34 preanalytical factor 149
patients survey 63 preclinical study 92
patulous eustachian tube 47 prediction of aortic rupture 175
PCR 168 preemptive medicine 169
pediatric cancer 26, 27 prefrontal cortex, motor-related area,
pediatric endocrinology 104 and parietal cortex 10
pediatric kidney and endocrine disorders 26 pregnant women 68
pediatric neurologic disorders 26 prenatal comfort scale 68
pediatric oncology 65 preparing intracellular membranes 9
xvi Keyword Index

prevention 163 quality assurance and quality control (QA, QC) 74, 133
prevention and treatment of cardiac arrest and quality control of medical image display 72
brain disorder 55 quality management 83
preventive psychiatry 44 quality management of biological specimens 149
primary aldosteronism 16 quality of care 64
(primary) cell culture 179 quality of life 50, 63, 64
prion 95 quantitation of metal ions 144
prion disease 96 quantitative genetics 152
prion protein 96 quantitative PCR 24, 132
probiotics 183 questionnaire 108
professionalization 57 questionnaire survey 126, 135
prognostic factors 60
program development 58, 61 R
prorenin receptor 78 radiation 159
prorenin-renin-angiotensin-aldosterone system 16 radiation dosimetry 74, 133
prospective large scale cohort study 147 radiation safety management 74, 133
prostate cancer 159 radioactivity 74, 133
prostatectomy 159 radiofrequency ablation 19
prosthetics & orthotics 50 radiotherapy 20
protein analysis 4, 94, 115, 117, 135 ral 114
protein chemistry 90 randomized controlled study 102
protein citrullination 114 randomized controlled trial 181
protein misfolding cyclic amplification 96 RASopathies 85
protein phosphatase 156 reactive oxygen species 11, 87
proteolysis 90 reactive sulfur species 87
proteome 87 recombinant protein 128
proto-oncogene 85 reconstruction after pelvic surgery 36
proxy assessment 38 recovery 106
Pseudomonas aeruginosa 183 recovery of brain function 50
psychoeducation 66 recurrent cancer 158
psychological assessment 184 regenerative medicine 3, 6, 170
psychological tests 126 regenerative medicine of the lung 120
psychometric test 49 regional brain activity 138
psychosocial intervention 134, 186 regional healthcare 84
psychosocial support 65 regional medical facilities 108
psychosomatic medicine 49, 109 regional medical network 182
psychotherapy 44 regional medicine 108
PTSD 134 registry 165
public health 167 regression analysis 169
public health ethics 89 regulation of gene expression 81
public health nurse 61 regulation of metabolism 121
public health nurses training 59 regulation of vascular degeneration 30
publicness 59 regulatory mechanism of stem cell differentiation 17
pulmonary hypertension 23, 120 regulatory science 83
pulmonary tuberculosis 168 rehabilitation 63
pulse sequence 70 rehabilitative audiology 127
pyrosequencing 141 relationship between medicine and traffic network 182
remote operation 164
Q renal biopsy 16
QOL 159 renal cancer 159
qualitative research 57 renal failure 179
qualitative study 100 renal function 179
quality assurance 64 renal hemodynamics 16
Keyword Index xvii

renal replacement therapy 179 skin care 160
renal transplantation 146 sleep apnea syndrome 25
repairing medicine 3, 6 sleep monitoring 51
repetitive transcranial magnetic stimulation 109 small animal surgery 33
reproductive endocrinology 28 small shin incision 164
reproductive medicine 29 small-intestinal transplantation 27
research ethics 89 smear 168
researcher training 100 SNP arrays 150
resistance to molecular target drug 162 sociality 122
resonance 54 sodium ion 94
respiration 56 sound 54
respiratory function test 25 sound (shock wave and ultrasound) 170
respiratory infection 168 spinal cord injury 32
respiratory infectious disease 25 spinal cord protection 35
respiratory virus 172 SS-MIX2 137
respiratory virus infection 172 standardization 84, 137
response to oxidative stress and xenobiotics 111 standardized clinical information 182
retina 4, 178 statistical analysis 83, 147, 171
retinal diseases 93 statistical genetics 152
retinal function 178 statistics 82, 148
retinitis pigmentosa 174 stem cell biology 46, 172
revascularization surgery 30 stem cells 3, 6
risk analysis 103 stent 43, 72
risk determination 103 stereotactic body radiation therapy 75
risk factors 60 stereotactic body radiotherapy 20
RNA microarray 13 steroids 13
RNA sequence 101 stigma 66
robot 131 stochastic differential equation 55
robotic assisted surgery 30 stress 49
robotic surgery 36, 164 stress hormone 135
role play 153 stress-related disorders 109
stroke 53
S structural optimization 92
sarcopenia 48 subtle energy 54
satellite cells 48 Suita study 165
scale development 57 support receiving capacity 131
scanning acoustic microscope 177 supportive therapy in the chemo-radiotherapy 160
schizophrenia 155 surgical devices 42
scientific visualization 138 survey 58, 64
screening 31 survey research 57
senior citizen/ elderly 58 survival curve 169
sequencing and phylogenetic analyses 14 susceptibility gene 141
severe mental illness 163 swallowing reflex 185
severe sepsis 39 synapse 139
sex steroid dependent tumor 13 synaptic transmission 97
shock wave 170 synaptic transmission in cerebellum 8
shoulder joint 32 synthesis of fluorescence nanoparticle with
sialidase 159 high luminance 173
signaling molecule 176 systematic review 153
signaling pathway 85 systemic inflammatory response syndrome 39
silent aspiration 185
skills lab 180 T
skills laboratory center 106 T cell costimulatory signal 15
xviii Keyword Index

T cell memory 15 ultrasound 37, 170
T cells 113 ultrasound microscopy 130
T-RFLP 128 upper respiratory tract 47
tactile pattern 139 urinary function 36
target validation 92 urologic oncology 36
TCR repertoire 113
team medication 180 V
technical innovation 63 vaccination 167
teleconference 131 vaccine 77
telemedicine 146, 180 valve repair 164
telenursing 63 valvular heart disease 164
terminal care 64 vascular aging 116
testicular tumor 159 vascular biology 23
theory / concept development 61 vascular remodeling 173
therapeutic approach 85 vasohibin 116
therapeutic drug monitoring (TDM) 110 vibration 54
therapeutic target gene of lung cancer 120 vibrational medicine 54
thermo data logger 88 virus vector 46
thoracoabdominal aortic aneurysm 35 viruses 14
thoracoscopic esophageal surgery 30 visceral impairment 52
thyroid cancer 31 visceral perception 49
tinnitus 127 visiting nursing 58
tissue and cell isolation 145 vitrectomy 178
tissue engineering and cell transplantation 30 vitreoretinal surgical instruments 178
Tohoku great earthquake victims 82 voluntary action 10
tolerance 15
traditional chinese medicine 106 W
transcranial magnetic stimulation 50 Warburg effect 156
transcription factor 5, 7, 111, 176 wearable sensors 48
transcriptional regulation 125 western blot 15
transcriptome 125 western blot analysis 78, 96
transgenic animals 120 western blotting 1
transgenic mouse 7, 40, 111 whole genome sequencing 151
translational research 119, 120, 155 wnt 115
transmission experiment 96 wound healing 40, 56
transplantation 27
transporter 110, 129 X
treatment 79 X ray exposure monitoring 73
treatment and education 65 X-irradiation 1
trend in cancer incidence 60 X-ray CT 71
TRI 84
tRNA 129 Y
TSLP-producing cell 144 young cancer patients 158
tuberculosis 24, 132
tumor immunity 45 Z
tumor infiltrating lymphocyte 31 zoonosis 24, 132
tumor suppressor gene 118
two-photon imaging 97
type 1 collagen 104
U
ulcerative colitis 128
ultrasonography 166, 181
Keyword Index xix

Radiation Biology Saves the Society
Radiation Biology Medical Sciences Course

Master / Doctoral Degree
HOSOI, Yoshio URL:

http://www.radbio.med.tohoku.ac.jp/index.html
Professor, M.D. Ph.D.
Contact:
TEL +81-22-717-8132
E-Mail hosoi@med.tohoku.ac.jp
Research Theme
Radiosensitization through modification of DNA double strand breaks repair enzymes
Activity of mTOR under nutrient starvation condition and cellar radiation sensitivity
Effects of low doses of ionizing radiation
Research Keywords: ionizing radiation, ATM, DNA-PK, mTOR, low dose radiation
Technical Keywords: X-irradiation, western blotting, cell culture
1. Basic research for radiation oncology.

(1). Radiosensitization through modification of DNA double strand breaks repair enzymes.
ATM, which is the responsible gene for radiosensitive human genetic disease, ataxia-telangiectasia (AT), contributes to DNA
double-strand breaks repair. We are investing relationship between ATM and radioresistance of cancer stem cell.
(2). Activity of mTOR under nutrient starvation condition and cellar radiation sensitivity.
The presence of radiation resistant cells in solid human tumors is one of the major reasons why radiotherapy fails to eradiate
such neoplasms. The presence of unperfused regions containing cells under hypoxic and nutrient-starvation conditions may
contribute to resistance to ionizing radiation. To investigate the effects or nutrient-starvation conditions on radiation sensitivity,
we are investigating relationship between activity of mammalian target of rapamycin complex 1 (mTORC1), whichi functions as a
nutrient/energy/redox sensor, and radiation sensitivity.
2. Effects of low doses of ionizing radiation
Low dose (0-0.5 Gy) total body irradiation (TBI) has been reported to have different effects from those induced by high dose
TBI, such as radioadaptive response and augmentation of immune response. It has been reported that low dose rate TBI increased
incidences of myocardial infarction and brain infarction. To clarify the molecular mechanisms underlying increased incidences of
these diseases, we are investigating effects of ionizing radiation on cultured human endothelial cells.
Figure 1. A 250 kV X-ray generator for irradiation of animals Figure 2. A 150 kV X-ray generator for irradiation of cells
Recent Publications
- Morita A, Murakami T, Morinaga T, Tanimoto K, Hosoi Y: Requirement of mitochondria for ATM activation by extranuclear oxidative stress in cultured human hepatoblastoma cell line HepG2 cells.
Biochemical and Biophysical Research Communications 443: 1286-90, 2014.
- Enomoto A, Fukasawa T, Takamatsub N, Itob M, Moritac A, Hosoi Y, Miyagawa K: The HSP90 inhibitor 17-allylamino-17-demethoxygeldanamycin modulates radiosensitivity by downregulating serine/
threonine kinase 38 via Sp1 inhibition. European Journal of Cancer 49: 3547-3558, 2013.
- Tanigawa K, Hosoi Y, Hirohashi N, Iwasaki Y, Kamiya K: Loss of life after evacuation: lessons learned from the Fukushima accident. Lnacet 379: 889-891, 2012.
Radiation Biology 1
To clarify the molecular basis of the interactions between the fatty acids and a number of
physiological responses by focusing on the biological role of intracellular lipid binding proteins
Organ Anatomy Medical Sciences Course

OWADA, Yuji URL:

Contact:
TEL +81-22-717-8039
E-Mail owada@med.tohoku.ac.jp
Research Theme
Role of cellular lipid homeostasis in the higher brain function
Mechanism underlying cortical develoipment
Role of intraepithelial lymphocytes in the digestive sysytem
Research Keywords: fatty acid binding protein, lipid, cerebral cortex, lymphocyte, gene knockout mouse
Technical Keywords: immunohistochemistry, electronmicroscopy, cell culture, live cell imaging, gene targeting
Fatty acids are important nutrients for various biological reactions. Recent epidemiological evidence suggests that dietary
consumption of some long chain fatty acids such as DHA and EPA, commonly found in fish oil, may modify the risk for
certain disorders. However, the molecular basis of their actions is still to be clarified.
Long chain fatty acids (LCFA), are key players in cell functions, including membrane remodeling, control of receptor
activity and signal transduction. Therefore it is to be expected that fatty acid binding proteins, due to their ability to binding
LCFAs with high affinity, participate in neural, immune and other cell functions as modulators for their homeostatic
regulation. The major goal of our laboratory is to clarify the molecular basis of the interactions between the fatty acids and a
number of physiological responses by focusing on the biological role of intracellular lipid binding proteins.
Figure 1. Role of FABP in the cellular fatty acid metabolism Figure 2. Regulation of membrane lipid raft formation by FABP7
Recent Publications
- Kagawa, Y., et al. Fatty acid-binding protein 7 regulates function of caveolae in astrocytes through expression of caveolin-1. Glia, 63, 780-794, 2015
- Islam, A., et al. Fatty acid binding protein 3 is involved in n-3 and n-6 PUFA transport in mouse trophoblasts. J Nutr, 144, 1509-1516, 2014
- Shimamoto, C., et al. Functional characterization of FABP3, 5 and 7 gene variants identified in schizophrenia and autism spectrum disorder and mouse behavioral studies. Hum Mol Genet, 23, 6495-6511, 2014
- Miyazaki, H., et al. Fatty acid binding protein 7 regulates phagocytosis and cytokine production in Kupffer cells during liver injury. Am J Pathol, 184, 2505-2515, 2014
- Shioda, N., et al. FABP3 protein promotes -synuclein oligomerization associated with 1-methyl-1,2,3,6-tetrahydropiridine-induced neurotoxicity. J Biol Chem, 289, 18957-18965, 2014
2 Organ Anatomy
Lets Shift the Paradigm of Regenerative Medicine by Using Muse Cells, Novel Type of
Non-Tumorigenic Pluripotent Stem Cells
Stem Cell Biology and Medical Sciences Course

Histology Master / Doctoral Degree
URL:
http://www.stemcells.med.tohoku.ac.jp/english/
DEZAWA, Mari index.html
Contact:
Professor, M.D. Ph.D. TEL +81-22-717-8025
E-Mail mdezawa@med.tohoku.ac.jp
Research Theme
Evaluation of Muse cell efficiency and safety in various disease models
In vivo function of Muse cells and development of factors to regulate Muse cell mobility
Development and evolution of Muse cells
Research Keywords: regenerative medicine, pluripotent stem cells, repairing medicine, differentiation, stem cells
Technical Keywords: cell culture, gene expression analysis, cell kinetics, animal experiment, histological analysis
We discovered a new type of pluripotent stem cells in adult human mesenchymal tissue and termed them "Multilineage-
differentiating stress-enduring (Muse)" cells. These cells can be obtained from easy accessible tissues, such as bone marrow,
skin, and adipose, as well as from commercially available mesenchymal cultured cells. They are characterized by the ability
to differentiate into various types of somatic cells, and the potential to self-renew. One of the major advantages of Muse cells
is their non-tumorigenic propertiy because they are naturally existing cells. Mesenchymal stem cells, from which Muse cells
are collected, have been used in a large number of clinical studies around the world. The results of these studies suggest the
safety of the Muse cell-based approach. Clinical applications of ES cells and iPS cells must overcome two major hurdles:
successful differentiation into the target cell type, and elimination of undifferentiated cells with tumorigenic potential.
By contrast, Muse cells do not need these prerequisite. Furthermore, Muse cells administered in vivo will recognize and
integrate into damaged sites and start to differentiate into cells that match the tissue. Therefore, they do not necessarily
require maneuvers, aimed at inducing differentiation, at a cell-processing center. These advantages make Muse cells
practical and plausible candidates for regenerative medicine. We are conducting studies in cooperation with many national
and international research organizations to promote regenerative medicine.
Figure 1. Pluripotency and self-renewal of Muse cells Figure 2. Muse cells are non-tumorigenic
Recent Publications
- Kuroda Y, et al. Isolation, culture and evaluation of Multilineage-differentiating Stress Enduring (Muse) cells. Nature Protocols. 8(7):1391-415, 2013.
- Hayashi T, et al. Autologous engraftment of A9 dopaminergic neurons induced from mesenchymal stem cells in parkinsonian rhesus macaques. J. Clin. Invest. 123(1):272-84, 2013.
- Tsuchiyama K, et al. Functional melanocytes are readily reprogrammable from multilineage-differentiating stress-enduring (Muse) cells, distinct stem cells in human fibroblasts. J Invest. Dermatol.
133(10):2425-2435, 2013.
- Wakao S et al. Multilineage-differentiating stress-enduring (Muse) cells are a primary source of induced pluripotent stem cells in human fibroblasts. Proc. Natl. Acad. Sci. USA. 108(24):9875-9880, 2011.
- Kuroda Y, et al, Unique multipotent cells in adult human mesenchymal cell populations. Proc. Natl. Acad. Sci. USA. 107(19):8639-8643, 2010.
Stem Cell Biology and Histology 3

Fascinating Pigment Cells: The Sensing System for Sunlight, Sound, and Stress
Molecular Biology and Applied Medical Sciences Course

Physiology Master / Doctoral Degree
URL:
http://www.mbap.med.tohoku.ac.jp
IGARASHI, Kazuhiko
Contact:
E-Mail
Research Theme
Regulation of heme catabolism
Differentiation of pigment cells
Stress response
Research Keywords: heme, melanin, retina, mitf, pigment cell

Technical Keywords: gene technology, protein analysis, cell culture, animal experiments
We have a longstanding interest in the molecular bases of oxygen sensing and cellular responses against hypoxia and
oxidative stress. Oxygen is toxic gas with high reactivity, and the primitive organism had invented heme and melanin to
coexist with oxygen. Heme is essential for all living organisms, as heme is involved in many cellular processes that use or
sense oxygen. Accordingly, heme is synthesized and degraded in all nucleated cells. Bilirubin is a final heme degradation
product with the strong antioxidant activity. On the other hand, the melanization is a defense mechanism using oxygen, as
evident from the darkening of damaged plants, such as a wounded apple. In the higher animals, melanin is produced by
pigment cells, including melanocytes and retinal pigment epithelium that are derived from the neural crest and the optic
cup of developing brain, respectively. The importance of melanization is apparent in the natural world, such as nuptial
coloration, cryptic color, and the seasonal change of the body color. Melanin is also important in the protection against
solar UV. To achieve good quality of life, we are working on the differentiation and the survival of pigment cells that are
distributed over retina, inner ear, skin, and heart.
Figure 1. Non-pigmentary functions of the melanocyte Figure 2. Black-eyed white mouse as a symbol of good luck
Recent Publications
- Chantarawong, W., Takeda, K., Sangartit, W., Yoshizawa, M., Pradermwong, K. and Shibahara, S. (2014) Microphthalmia-associated transcription factor as the molecular target of cadmium toxicity in
human melanocytes. Biochem. Biophys. Res. Commun. 454, 594599.
- Takeda, K., Hozumi, H., Nakai, K., Yoshizawa, M., Satoh, H., Yamamoto, H. and Shibahara, S. (2014) Insertion of long interspersed element-1 in the Mitf gene is associated with altered neurobehavior of
the black-eyed white Mitfmi-bw mouse. Genes Cells 19, 126-140.
- Kaneko, K., Furuyama, K., Fujiwara, T., Kobayashi, R., Ishida, H., Harigae, H. and Shibahara, S. (2014) Identification of the novel erythroid-specific enhancer for ALAS2 gene and its loss-of-function
mutation associated with congenital sideroblastic anemia. Haematologica. 99, 252-261.
- Shimanuki, M., Takeda, K., Kawaguchi, M., Suzuki, T., and Shibahara, S. (2012) Lipocalin-type prostaglandin D synthase as a marker for the proliferative potential of melanocyte-lineage cells in the human
skin. J. Dermatol. 39, 699-704.
- Hozumi, H., Takeda, K., Yoshida-Amano, Y., Takemoto, Y., Kusumi, R., Fukuzaki-Dohi, U., Higashitani, A., Yamamoto, H., and Shibahara, S. (2012) Impaired development of melanoblasts in the black-
eyed white Mitfmi-bw mouse, a model for auditory-pigmentary disorders. Genes to Cells 17, 494-508.
4 Molecular Biology and Applied Physiology

We Try to Understand Disease Processes through Exploration of the Regulatory
Mechanisms of Gene Expression and Epigenome
Biochemistry Medical Sciences Course

IGARASHI, Kazuhiko URL:

http://www.biochem.med.tohoku.ac.jp/
Contact:
TEL +81-22-717-7596
E-Mail igarashi@med.tohoku.ac.jp
Research Theme
Regulation of the development and differentiation of immune cells by transcription factors and epigenome, and its
pathological implications
Regulation of erythropoiesis and immune cells by the prosthetic group heme, and its pathological implications
Nuclear proteins network for histone methylation, and its pathological implications
Research Keywords: transcription factors, chromatin, epigenome, B lymphoid cell, macrophage, erythroid cell,
Technical Keywords: mass spectrometry analysis, next generation sequencing, bioinformatics, mouse, molecular biology
Cell differentiation is dependent on transcription factors and epigenetic modifications of chromatin that together regulate lineage-
and stage-specific gene expression. Using immune cells as a model, we are trying to understand their differentiation based on
transcription factors. Our recent major findings include 1) regulation of antibody class switching, somatic hypermutation, and
plasma cell differentiation by a gene regulatory network (GRN) involving the transcription repressor Bach2, 2) regulation of the
bifurcation of B and myeloid cells by Bach2 and Bach1 in the common lymphoid progenitor cells, and 3) regulation of tissue
specific macrophages such as alveolar macrophages by Bach2 and its implication in the pathology of alveolar proteinosis. We are
currently trying to extend these findings to the field of tumor immunity. Since we have also found that heme regulates both Bach1
and Bach2, the role of heme as a signaling molecule in the immune system is another focus of the laboratory.
Another line of the research is the regulation of methylation of histone and DNA by the transcription factors. We found that
methionine adenosyltransferase II (MATII) is present in the nuclei. This enzyme synthesizes S-adenosylmethionine (SAM)
which provides the methyl group for the transmethylation reactions. We are trying to understand how the nuclear and chromatin
localizations of MATII regulate chromatin function.
Figure 1. Gene regulatory network for B cell differentiation and responses Figure 2. Heme as a signaling molecule in the immune system
Recent Publications
- Igarashi, K. et al. Orchestration of plasma cell differentiation by Bach2 and its gene regulatory network. Immunol. Rev. 261, 116-125 (2014)
- Itoh-Nakadai, A. et al. The transcription repressors Bach2 and Bach1 promote B cell development by repressing myeloid program. Nature Immunol. 15, 1171-1180 (2014).
- Nakamura, A. et al. The transcription repressor Bach2 is required for pulmonary surfactant homeostasis and alveolar macrophage function. J. Exp. Med. 210, 2191-2204 (2013).
- Watanabe-Matsui, M. et al. Heme regulates B cell differentiation, antibody class switch, and heme oxygenase-1 expression in B cells as a ligand of Bach2. Blood 117, 5438-5448 (2011).
- Katoh, Y. et al. Methionine adenosyltransferase II serves as a transcriptional corepressor of Maf oncoprotein. Mol. Cell 41, 554-566 (2011).
Biochemistry 5
To Understand the Principal Mechanisms that Underlie the Key Biological Processes of
Differentiation, Cell Homeostasis, and Cellular Defense
Medical Biochemistry Medical Sciences Course

URL:
YAMAMOTO, Masayuki http://www.dmbc.med.tohoku.ac.jp/official/
Professor, M.D. Ph.D. index_E.html
Contact:
TEL +81-22-717-8084
E-Mail masiyamamoto@med.tohoku.ac.jp
Research Theme
The mechanisms of cellular defense against oxidative stress that occurs via the Keap1-Nrf2 system
GATA1 and GATA2 regulation of erythroid and megakaryocytic cell differentiation
The transcriptional regulation of the erythropoietin gene
Research Keywords: transcription factor, environmental response, hematopoietic differentiation, Keap1-Nrf2, GATA
Technical Keywords: knockout mouse, transgenic mouse, cell culture, flow cytometry
The Human Genome Project recently revealed that our species has approximately thirty thousand genes. The individual
identity of each cell is carefully scripted based a set of transcriptionally activated genes that occurs during differentiation.
We regard this transcriptional gene regulation as one of the fundamental tenets accounting for the diversity and the
mystery surrounding our own existence. Our personal goal as scientists is to decipher the principal mechanisms that
underlie the key biological processes of differentiation, cell homeostasis, and cellular defense by elucidating the
actions of these transcriptional gene pathways and networks. With each new discovery, we work towards increasing our
understanding of human disease processes. The specific focus of our research is to illuminate mechanisms revolving around:
1) The mechanisms of cellular defense against oxidative stress that occurs via the Keap1-Nrf2 system
2) GATA1 and GATA2 regulation of erythroid and megakaryocytic cell differentiation
3) The transcriptional regulation of the erythropoietin gene
Figure 1. Molecular mechanism of Keap1/Nrf2 system Figure 2. The function of GATA factors
Recent Publications
- Yamazaki H, et al. A remote GATA2 hematopoietic enhancer drives leukemogenesis in inv(3)(q21;q26) by activating EVI1 expression. Cancer Cell 25, 415-427 , 2014
- Suzuki N, et al. Erythropoietin production in neuroepithelial and euralcrest cells during primitive erythropoiesis. Nature Commun 4: 2902, 2013
- Yamazaki S, et al. A mouse model of adult-onset anaemia due to erythropoietin deficiency. Nature Commun 4, 1950 ,2013
- Mitsuishi Y, et al. Nrf2 redirects glucose and glutamine into anabolic pathways in metabolic reprogramming. Cancer Cell 22, 66-79, 2012
- Taguchi K, et al. Keap1 degradation by autophagy for the maintenance of redox homeostasis. Proc Natl Acad Sci USA 109, 13561-13566, 2012
6 Medical Biochemistry
To Understand Brain Function at the Molecular Level
Neurophysiology Medical Sciences Course

MUSHIAKE, Hajime URL:

http://www.neurophys.med.tohoku.ac.jp/
Contact:
TEL +81-22-717-8073
E-Mail hmushiak@med.tohoku.ac.jp
Research Theme
Molecular basis of synaptic function
Synaptic plasticity in the hippocampus and the cerebellum
Research Keywords: synaptic transmission in cerebellum, developmental changes in synapses, physiological models
Technical Keywords: patch-clamp, cerebellar slices, electromicroscopy
In the brain the neural information is carried from neuron to neuron at synapses. A single neuron has typically hundreds
to thousands synapses. Activity of a neuron is thus determined by the integration of synaptic activities, some of which
are excitatory and others are inhibitory. Brain functions such as learning and memory are explained by the plastic change
of synapses. Despite the importance of synapse, there remains a vast unrevealed field in the physiology of presynaptic
terminal. The progress of research is hampered by three major difficulties, (1) the small size of presynaptic terminal that is
typically 0.5-2 um, (2) the functional heterogeneity and (3) the biochemical complexity of presynaptic functions. We plan to
break through these difficulties by developing new methods to visualize presynaptic functions under microscope. Thus, the
visualization of presynaptic functions would enable us to reveal the morphological and physiological changes of presynaptic
terminal during a process of learning and memory and facilitate us to understand the molecular mechanisms underlying the
presynaptic plasticity. We are now studying these processes at molecular level using hippocampal slice , cerebellar slice and
isolated cell preparation of non-excitable tissues including megakaryocytes and hematic cell lines (ex. Meg-01 cell).
Figure 1. Evoked glycinergic currents in cerebellar nuclei Figure 2. Presence of glycinergic synapses in cerebellar nuclei
Recent Publications
- Kawa, K. Inhibitory synaptic transmission in area postrema neurons of the rat showing robust presynaptic facilitation mediated by nicotinic ACh receptors. Brain Research, 1130, 83-94, 2007.
- Kawa, K. Discrete but simultaneous release of adenine nucleotides and serotonin from mouse megakaryocytes as detected with patch and carbon-fiber electrodes. American Journal of Physiology-Cell, 286,
C119-C128, 2004.
- Kawa, K. Glycine receptors and glycinergic synaptic transmission in the deep cerebellar nuclei of the rat: a patch-clamp study J Neurophysiol. 90: 3490-3500, 2003.
Neurophysiology 7
Ion Channels Operating Multiple Ways in Every Membranes in Every Cells
Cell Physiology Medical Sciences Course

URL:
MUSHIAKE, Hajime http://www.med.tohoku.ac.jp/org/medical/09/
Professor, M.D. Ph.D. index.html
Contact:
TEL +81-22-717-8066
E-Mail
Research Theme
Pathophysiological implications of potassium ion channels in lymphocytes
Structure-function coupling in TRP channels
Orientation of ion channels across the membrane of endoplasmic reticulum
Research Keywords: ion channel function, endoplasmic reticulum membrane, ion channel structure,
organ pathophysiology relating to ion channels
Technical Keywords: patch-clamping, cell imaging, disease modelling, preparing intracellular membranes
The laboratory is based on the electrophysiology evolving with the patch-clamp techniques providing a rapid and high-
resolved data-set from membranes including the plasma, nuclear, and mitochondrial inner membrane. By keeping high
quality of data-obtaining techniques, we apply them to any types of membranes, and have had many experiences in the
membrane of pancreatic, salivary, and lacrimal acinar cells, blood platelets, megakaryocytes, mast cells, lymphocytes,
adrenal gland cells, pericytes of microvessels, and a variety of cultured cells.
Figure 1. Apparatus for patch-clamping the membrane
Recent Publications
- Kazama I. Physiological Significance of Delayed Rectifier K+-Channels (Kv1.3) Expressed in T lymphocytes and Their Pathological Significance in Chronic Kidney Disease. J Physiol Sci, 2014 .
- Kazama I et al.. Voltage-Dependent Biphasic Effects of Chloroquine on Delayed Rectifier K+-Channel Currents in Murine Thymocytes. J Physiol Sci, 62, pp267-274, 2012
- Ohsaga A et al. Asymmetry of Rb+ conduction emerged under bi-ionic conditions in epithelial Maxi-K+ channels. J. Physiol. Sci. 58: 363-369, 2008.
- Murata Y. et al Phosphoinositide phosphatase activity coupled to an intrinsic voltage sensor. Nature. 435(7046):1239-43. 2005.
- Oshiro, T. et al. Delayed expression of large conductance K+ channels reshaping agonist-induced currents in mouse pancreatic acinar cells. Journal of Physiology, 563:379-391, 2005.
8 Cell Physiology
System NeuroscienceFrom Neurons to Cognitive Function
Systems Neuroscience Medical Sciences Course

URL:
MUSHIAKE, Hajime http://www.neurophysiology.med.tohoku.ac.jp/
Professor, M.D. Ph.D. index_e.html
Contact:
TEL +81-22-717-8073
E-Mail hmushiak@med.tohoku.ac.jp
Research Theme
Neural mechanisms underlying voluntary action -How multiple cortical areas coordinate bodily movements?-
Theoretical study of cortical networks -How mind emerges from collective activities of neurons?-
Development of neuro-engineering tools -How neural state is monitored and manipulated by multi-disciplinary tools?-
Research Keywords: prefrontal cortex, motor-related area, and parietal cortex, voluntary action, cognitive function, local cortical circuits, optogenetics
Technical Keywords: electrophysiology, multi-channel recording, cognitive behavioral task, computational neuroscience, optogenetics
Recent progress in neuroscience allows us to address big issues like mind-body problem scientifically. We have been studying
how mind works ( cognition, action, memory emotion) by recoding neuronal activities. Our aim of study is to understand how
mind emerge from interactions of neurons under dynamics of brain- body-environment by multidisciplinary approaches.
Simple behaviors such as reaching movements results from interactions of many motor-related areas of the cerebral cortex. If
so many areas try to control one arm, why is it possible to feel that I am acting as a single agent. One aim of our research is to
understand how parallel and hierarchical cortical areas are integrated to one coordinated action.
Brain activities appear to fluctuate, synchronize together, or oscillate when the subject are engaged in various task. According
to recent studies fluctuations, oscillations are very important for communications among different parts of the brain.. But the
mechanisms are not clear.
We define emergence when interactions of components give rise to new functions beyond summations of components. In this
sense, mind is an emergent property of brains, because mind is a new function beyond summations of neurons . But how? It is a
big question.
Neuroscience has been expanding its research field by multidisciplinary approaches with various research disciplines . We are
looking for candidates for neuroscience course from various field of academic field .
Figure 1. Problem-solving behavior and optical neural manipulation/ multi-channel Figure 2. Neural oscillation and cortical circuits
recording
Recent Publications
- Kawaguchi N, Sakamoto K, Saito N, Furusawa Y, Tanji J, Aoki M, Mushiake H. Surprise Signals in the Supplementary Eye Field: Rectified Prediction Errors Drive Exploration-Exploitation Transitions. J
Neurophysiol. 113:1001-14, 2015
- Osawa S, Iwasaki M, Hosaka R, Matsuzaka Y, Tomita H, Ishizuka T, Sugano E, Okumura E, Yawo H, Nakasato N, Tominaga T, Mushiake H. Optogenetically induced seizure and the longitudinal
hippocampal network dynamics. PLoS One.8:e60928. 2013
- Matsuzaka Y, Akiyama T, Tanji J, Mushiake H. Neuronal activity in the primate dorsomedial prefrontal cortex contributes to strategic selection of response tactics. Proc Natl Acad Sci U S A. 109:4633-8. 2012
- Mita A, Mushiake H, Shima K, Matsuzaka Y, Tanji J. Interval time coding by neurons in the presupplementary and supplementary motor areas. Nat Neurosci. 12:502-7. 2009
- Mushiake H, Sakamoto K, Saito N, Inui T, Aihara K, Tanji J. Involvement of the prefrontal cortex in problem solving. Int Rev Neurobiol.;85:1-11. 2009
Systems Neuroscience 9
To Explore the Molecular Targets for the New Drug Therapy, Especially in Cardiovascular
Diseases
Molecular Pharmacology Medical Sciences Course

URL:
YANAI,Kazuhiko http://www.molpharm.med.tohoku.ac.jp/
Professor, M.D. Ph.D. fen_zi_yao_lihomupeji/HOME.html
Contact:
TEL +81-22-717-8064
E-Mail tksato@med.tohoku.ac.jp
Research Theme
Regulation of intracellular signaling and dynamics of G protein-coupled receptor (GPCR) by GPCR-interacting proteins
Mitochondrial quality control and drug-induced cardiotoxicity
Physiological roles of primary cilium and its regulatory mechanisms
Research Keywords: mitochondrialdisease,GPCR-mediatedsignaltransduction,primaryciliarydyskinesia

Technical Keywords: autophagy,molecularbiology,cellularbiology,reactiveoxygenspecies
We have developed various novel cardiovascular and neurological drugs including Ca2+ channel blockers, nicorandil, and
new cardiotonic agents. Recently we have investigated molecular mechanisms of GPCR-mediated signal transduction
and primary cilium, a new concept of signal acceptor, using state-of-the-art techniques. We have also investigated a new
concept relating with the quality control of mitochondria. Thus, we have a point of view to develop new drugs to treat
intractable diseases, including mitochondrial disease. You can also catch both pharmacology and molecular basis of
pharmacotherapeutics in our laboratory. Please join us for the future area to develop new drugs and diagnostic maneuvers.
Figure 1. Regulation of functions mediated through GPCR and primary cilium Figure 2. Effect of cardiotoxic agents on mitochondrial quality control
Recent Publications
- Suzuki T., et al. Mitochonic acid MA-5 binds to mitochondria and ameliorates renal tubular and cardiac myocyte damages. J Am Soc Nephrol. doi: 10.1681/ASN.2015060623
- Murakami M, et al. Involvement of the histamine H1 receptor in the regulation of sympathetic nerve activity. Biochem Biophys Res Commun., 458, 584-589 (2015).
- Sato T, et al. Evaluation of bystander cell killing effects in suicide gene therapy of cancer: Engineered thymidylate kinase (TMPK)/AZT enzyme-prodrug axis. Methods Mol Biol., 1317:55-67(2015).
- Suzuki T, et al. Mitochonic acid 5 (MA-5), a derivative of the plant hormone indole-3-acetic acid, improves survival of fibroblasts from patients with mitochondrial diseases. Tohoku J Exp Med. 236, 225-
232 (2015).
- Sato T., et al. The Engineered Thymidylate Kinase (TMPK)/AZT Enzyme-Prodrug Axis Offers Efficient Bystander Cell Killing for Suicide Gene Therapy of Cancer. PLOS ONE 8, e78711 (2013).
- Katsushima Y., et al. Interaction of PICK1 with C-Terminus of Growth HormoneReleasing Hormone Receptor (GHRHR) Modulates Trafficking and Signal Transduction of Human GHRHR. J. Pharmacol.
Sci., 122, 193-204 (2013).
- Goto T, et al. Suppression of adenylyl cyclase-mediated cAMP production by plasma membrane associated cytoskeletal protein 4.1G. Cell Signal. 25, 690-697 (2013).
- Yeh C., et al. IGF-1 activates a cilium-localized non-canonical G signaling pathway that regulates cell cycle progression. Dev Cell., 26, 358368 (2013).
10 Molecular Pharmacology
Comprehensive Challenge on both Molecular Imaging from Basic Development to Clinical
Application and Molecular and Psychopharmacological Research of Histamine
Pharmacology Medical Sciences Course

URL:
YANAI, Kazuhiko http://www.med.tohoku.ac.jp/english/org/
Professor, M.D. Ph.D. medical/12/index.html
Contact:
TEL +81-22-717-8056
E-Mail yanai@med.tohoku.ac.jp
Research Theme
Comprehensive molecular imaging study from basic probe screening to clinical application in humans
New functional study on histamine as a good guy using molecular and psychopharmacological methods
Development and application of early clinical diagnosis in Alzheimer disease using Positron Emission Tomography (PET)
Research Keywords: molecular imaging, Alzheimer disease, drug development, histamine,

positron emission tomography
Technical Keywords: non-invasive molecular imaging, molecular and behavioral pharmacology,
clinical study, genetically engineered mouse, neurochemistry
The Division is dedicated to carry out basic and clinical research at the highest quality, originality and creativity relevant
to Pharmacology and Clinical Pharmacology. The Division is also committed to providing the highest quality of basic and
clinical Pharmacology including appropriate ethical standards to medical students, graduate students, residents, fellows
and researchers. Our main research topics are as follows: 1) Molecular pharmacology (main focus on histamine system). 2)
Functional and molecular imaging in the living human brain by positron emission tomography (PET): the basic development
and clinical application. 3) In vivo amyloid and tau imaging: their fundamental development and clinical application to
Alzheimer disease. 4) Behavioral and neurochemical studies of histamine-related genes knockout mice. 5) Functions of the
histaminergic neuron system in the CNS.
Figure 1. Roles of histamine on various functions as a good guy Figure 2. Molecular imaging by positron emission tomography in humans
Recent Publications
- Okamura N, et al. Non-invasive assessment of Alzheimer's disease neurofibrillary pathology using 18F-THK5105 PET. Brain. 2014; 137(Pt 6): 1762-1771
- Yoshikawa T, et al. Molecular mechanism of histamine clearance by primary human astrocytes. Glia. 2013; 61(6): 905-916.
- Nakamura T, et al. The expression and function of histamine H receptors in pancreatic beta cells. Br J Pharmacol. 2014; 171(1): 171-185.
- Yanai K, et al. Positron emission tomography evaluation of sedative properties of antihistamines. Expert Opinion on Drug Safety 2011; 10(4): 613-622.
- Zhang D, et al. Next-day Residual Sedative Effect after Nighttime Administration of an OTC Antihistamine Sleepaid, Diphenhydramine, Measured by Positron Emission Tomography. J Clin
Psychopharmacol 2010; 30(6): 694-701.
Pharmacology 11
Exploring What is Unknown in Steroid-Hormones-Related Tissues and Tumors
Anatomic Pathology Medical Sciences Course

SASANO, Hironobu URL:

http://plaza.umin.ac.jp/~steroid/
Contact:
TEL +81-22-717-8050
E-Mail hsasano@patholo2.med.tohoku.ac.jp
Research Theme
Intracrinology of sex steroid dependent neoplasms
Analysis of the steroidogenesis in adrenocortical diseases
Pathological analysis of neuroendocrine tumor
Research Keywords: steroids, adrenal cortex, sex steroid dependent tumor, neuroendocrine tumor
Technical Keywords: immunohistochemistry, RNA microarray, co-culture, LCM
We have been and are working in the following areas.

1. Intracrinology of estrogen dependent neoplasms: Intracrinology is one of the newly established fields of steroid hormone
actions in which precursor steroids are converted to biologically active steroids in their target tissues. This is why estrogen
dependent breast cancer can develop and survive with few estradiol in circulation. We are one of the pioneers in establishing
this concept. These achievements and on-going research activities are contributing to the establishment of endocrine therapy.
2. Functional pathology of adrenocortical disorders: We were the first one to identify the sites of specific steroidogenesis
in human adrenal cortex and its disorders. We have also recently revealed the characterization of aldosterone production
and metabolism in the zone glomerulosa of human adrenal and primary aldosteronism, which leads to the novel mode of
antihypertensive agents.
3. Pathological analysis of neuroendocrine tumors: We are currently working on molecular pathological and in vitro analysis
of human neuroendocrine tumors in order to identify new surrogate markers.
Through these research activitiesincluding numerous domestic and international collaborative works, we have published
more than 500 original reports in peer-reviewed English journals, since the establishment of our laboratory in 1998.
Figure 1. Intracrinology and Endocrinology. In situ production of steroids in cancer Figure 2. Adrenal Triple Stain (CYP11B1,CYP11B2,CYP17) with DAPI
Recent Publications
- Nakamura Y, et al. Intratumoral heterogeneity of steroidogenesis in aldosterone-producing adenoma revealed by intensive double- and triple-immunostaining for CYP11B2/B1 and CYP17. Mol Cell
Endocrinol. 2015. ( in press)
- Guestini F, et al. Triple Negative Breast Cancer Chemosensitivity and Chemoresistance: Current Advances in Biomarkers Indentification. Expert Opin Ther Targets. 2015.
- Nakamura Y, et al. Aldosterone biosynthesis in the human adrenal cortex and associated disorders. J Steroid Biochem Mol Biol. 153:57-62. 2015.
- Adachi K, et al. Intracrine steroid production and mammalian target of rapamycin pathways in pulmonary lymphangioleiomyomatosis. Hum Pathol. 46(11):1685-93. 2015.
- Yazdani S, et al. Progesterone Receptor Isoforms A and B in Pancreatic Neuroendocrine Tumor. Neuroendocrinology. 101(4):309-20. 2015.
12 Anatomic Pathology
Cross-Border Researches on Infectious Diseases
Virology Medical Sciences Course

OSHITANI, Hitoshi URL:

http://www.virology.med.tohoku.ac.jp/en/
Professor, M.D. Ph.D. M.P.H.
Contact:
TEL +81-22-717-8211
E-Mail info@virology.med.tohoku.ac.jp
Research Theme
Molecular epidemiology and evolutionary dynamics of respiratory viruses as well as pathogenesis of respiratory
viral diseases
Genomic surveillance of respiratory and diarrheal viruses, and overseas field researches on infectious diseases
Infectious diseases epidemiology and outbreak investigation for public health measures
Research Keywords: viruses, infectious diseases, field epidemiology, molecular epidemiology, pathogenesis
Technical Keywords: data management and statistical analyses, pathogen detection and isolation,
sequencing and phylogenetic analyses, molecular and cellular biology
We mainly focus on the evolution and pathogenesis of viral infectious diseases and their public health consequences. Basic principles of our
activities are as followings:
1) Research on controlling infectious diseases: Our research themes are relevant, not only in the basic science, but also in the field of infectious
diseases response and preparedness.
2) Field-based Studies: We believe in looking at an infectious disease from different perspectives for its better management. We are therefore
conducting not only laboratory-based studies, but also field studies based in the community, public health centers, clinical set-ups, and even in the
environment.
3) Conducting researches in broader perspective: We are always open to conduct researches on any viral infectious diseases in any perspectives
to better understanding the evolution of emerging and reemerging infectious diseases. We are therefore not always focused on our expertise to a
particular infectious disease; we rather respond to a wide variety of infectious diseases depending on their public health importance.
4) Research on global perspectives: We are conducting collaborating studies in the Philippines, Peru and Mongolia. We also contribute to
the emergency response and preparedness activities of World Health Organization and other international organizations. Besides, we are also
conducting collaborating researches with other domestic institutions and universities. We believe in the theme that spreading of infectious agents
cannot be limited to any geographical boundaries, thus, there is no limit for conducting research on infectious diseases as well.
Figure 1. Laboratory activities Figure 2. Field activities
Recent Publications
- Imamura T, et al. Antigenic and receptor binding properties of enterovirus 68. J Virol. 2014 Mar;88(5):2374-84.
- Kamigaki T, et al. Investigation of an Influenza A (H3N2) outbreak in evacuation centres following the Great East Japan earthquake, 2011. BMC Public Health. 2014 Jan 14;14:34.
- Saito M, et al. Genetic diversity and geographic distribution of genetically distinct rabies viruses in the Philippines. PLoS Negl Trop Dis. 2013 Apr 4;7(4):e2144.
- Furuse Y, et al. Comparison of selection pressures on the HA gene of pandemic (2009) and seasonal human and swine influenza A H1 subtype viruses. Virology. 2010 Sep 30;405(2):314-21.
- Oshitani H, Kamigaki T, Suzuki A. Major issues and challenges of influenza pandemic preparedness in developing countries. Emerg Infect Dis. 2008 Jun; 14(6):875-80.
Virology 13
Understanding the Key Cellular and Molecular Processes which Help the Body Control
Immune-mediated Diseases
Microbiology and Immunology Medical Sciences Course

URL:
ISHII, Naoto http://www.immunol.med.tohoku.ac.jp//English/
Professor, M.D. Ph.D. indexE.html
Contact:
TEL +81-22-717-8096
E-Mail ishiin@med.tohoku.ac.jp
Research Theme
Immunological memory
T cell-mediated autoimmune diseases
Inflammatory signal in T cells
Research Keywords: autoimmunity, inflammation, T cell costimulatory signal, T cell memory, tolerance
Technical Keywords: flowcytometry, western blot, mouse handling, cell culture, gene manipulation
The key function of the immune system is to attack microbes, infected cells, and tumors while ignoring the bodys own
healthy cells. T cells are a subset of lymphocytes and carry out multiple functions, including activating macrophages,
helping B cells produce antibody, killing infected cells, and preventing adverse immune activation. Thus, T cells play
fundamental roles in controlling immunity. Our laboratory discovered two important molecules for T cells, i.e., the
common chain (c, CD132, IL2RG) and a co-stimulatory molecule gp34 (OX40L, CD252, TNFSF4). c serves as a shared
signaling receptor for cytokines, such as IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21, and plays essential roles for development,
differentiation, and growth of T cells. gp34 is the ligand of OX40 receptor expressed on the surface of activated T cells and
promotes the differentiation of antigen-primed effector and memory T cells. Although the T cell response is critical for host
defense against infection and cancer, if it becomes too extensive, it can lead to immune-mediated inflammatory diseases,
such as allergic asthma and rheumatoid arthritis. Since cytokine and co-stimulatory signaling pathways are attractive targets
for intervention in the clinic, our laboratory seeks to understand how these pathways operate in the immune system.
Figure 1. Immunologica roles of OX40 co-stimulation Figure 2. Novel role of TRAF5 in controlling IL-6 signal
Recent Publications
- Fujita T, Burwitz BJ, Chew GM, et al: Expansion of dysfunctional Tim-3 expressing effector memory CD8+ T cells during SIV infection in Rhesus Macaques. J. Immunol. 193:5576-5583(2014)
- Yamaki S, Ine, S, Kawabe T, et al: OX40 and IL-7 play synergistic roles in the homeostatic proliferation of effector memory CD4+ T cells. Eur. J. Immunol., 44: 3015-3025 (2014)
- Nagashima H, Okuyama Y, Asao A, et al: TNF receptor-associated factor 5 limits inflammatory CD4+ T cell differentiation by antagonizing IL-6-receptor signaling. Nat Immunol, 15: 449-456 (2014)
- Sun SL, Horino S, Itoh-Nakadai A, et al: Y-chromosome-linked B- and NK-cell deficiency in mice. J. Immunol, 190: 6209-6220 (2013)
- Kawabe T, Sun SL, Fujita T, et al: Homeostatic proliferation of nave CD4+ T cells in mesenteric lymph nodes generates gut-tropic Th17 cells. J. Immunol. 190: 5788-5798 (2013)
14 Microbiology and Immunology

Through Basic and Clinical Research Activities, We Foster Each Ones Competency in
Order to Contribute to and Lead the Society
Nephrology Endocrinology Medical Sciences Course

and Vascular Medicine Master / Doctoral Degree
URL:
http://www.int2.med.tohoku.ac.jp/index-en.html
ITO, Sadayoshi
Contact:
E-Mail m-daigakuin@bureau.tohoku.ac.jp
Research Theme
Pathogenesis of renal damages induced by hypertension, diabetes and nephritis
Protection against uremic toxin by controlling its generation and removal
Pathogenesis and treatment of endocrine disorders
Research Keywords: large-scale clinical study, prorenin-renin-angiotensin-aldosterone system,

renal hemodynamics, cardiorenal syndrome, primary aldosteronism
Technical Keywords: microperfusion of renal tuble, laser-doppler method, adrenal venous sampling,
renal biopsy
By promoting basic and clinical investigations on the pathophysiology, diagnosis and treatment of renal and endocrine
diseases and hypertension, we aim to foster excellent and competent medical doctors and scientists with integrative basic
and clinical knowledge/skill. One of the features of the division is an excellent international network. There are many
opportunities to study abroad. In addition, world-renown researches often visit us, and they not only discuss about researches
but also do round of visit of inpatients. Below are some of our research projects.
1. By using the-state-of the art renal physiological methods, molecular biology and gene technologies, we investigate: a) the
detailed mechanisms of renal and cardiovascular damages caused by various disease (hypertension, diabetes, nephritis; b)
mechanism of uremic toxin production and its clinical significance. In addition, we conduct various clinical studies in order
to analyze risk factors in chronic kidney disease and examine the effects of specific treatment.
2. Primary aldosteronism is common (5~10% of hypertension) and is associated with high incidence of cardiovascular
events. However, it is underdiagnosed. Our division is one of the world-leading groups in this field.
Figure 1. Strain vessel linking microalbuminuria and stroke Figure 2. Demonstration of macula densa-mediated glomerular hemodynamics
Recent Publications
- Haller H, et al.; ROADMAP Trial Investigators: Olmesartan for the delay or prevention of microalbuminuria in type 2 diabetes. N Engl J Med. 364: 907-917, 2011
- Satoh F, et al. Primary aldosteronism : A Japanese perspective. Rev Endocr Metab Disord. 12; 11-14, 2011
- Ito S. Cardiorenal syndrome; an evolutionary point of view; Hypertension. 60; 589-595, 2012
- Fujihara M, et al. Clinical Outcomes of Renal Artery Stenting for Hypertension and Chronic Kidney Disease over 12 Months in J-RAS study; A Prospective, Single-Arm, Multi-center Clinical Study.
Circulation J. (In Press)
- Academic Award (2010, The Kidney Foundation Japan), The trustees lectureship award (2012, Asia-Pacific Society of Hypertension), Arthur C Corcoran Memorial lectureship Award (2014, American Heart
Association)
Nephrology Endocrinology and Vascular Medicine 15

Our Mission is to Overcome Hematological Diseases and Autoimmune Diseases by Clinical
and Basic Researches
Hematology and Medical Sciences Course

Rheumatology Master / Doctoral Degree
URL:
http://www.rh.med.tohoku.ac.jp/
HARIGAE, Hideo
Contact:
E-Mail harigae@med.tohoku.ac.jp
Research Theme
Pathophysiology of hematological diseases and autoimmune diseases
Development of novel therapies for hematological diseases and autoimmune diseases
Research Keywords: erythroid differentiation and iron metabolism, regulatory mechanism of stem cell
differentiation, identification and characterization of autoantibody, clarification of
pathological characteristics of immune cells in autoimmune diseases , clinical studies of
hematological and autoimmune diseases
Technical Keywords: in vitro hematopoietic cell differentiation, generation of model mouse,
hematopoietic cell sorting, gene expression analysis
The mission of Department of Hematology and Rheumatology is to overcome hematological diseases including
hematological malignancies, anemia, hemorrhagic disorders, and autoimmune diseases including rheumatoid arthritis, SLE,
and closely related disorders. To achieve this goal, we perform clinical trial and research, and provide educational programs
and comprehensive treatment with up-to-date therapies including molecular targeting therapy and stem cell transplantation.
The treatment of these diseases has been rapidly progressed these ten years, with the consequence that survival rate
and quality life of patients is dramatically improved, however, still unsatisfactory. We are making every effort towards
developing the novel therapy to provide better outcome for patients. Our research field contains competitive and attractive
themes including hematopoiesis, immunology, regenerative medicine, and oncology. In these themes, we are specially
focusing on the regulatory mechanism of erythropoiesis, iron metabolism, biology of hematopoietic and mesenchymal stem
cells, molecular and cellular mechanism for development of autoimmune diseases.
Figure 1. Transcription factor, GATA2, bone marrow failure Figure 2. Shock wave, skin ulcer, collagen disease
Recent Publications
- Kamata M,et al.GATA2 regulates differentiation of bone marrow-derived mesenchymal stem cells. Haematologica.;99:1686-1696. 2014
- Fujiwara T, et al. 3-Deazaneplanocin A (DZNep), an inhibitor of S-adenosyl methionine-dependent methyltransferase, promotes erythroid differentiation. J Biol Chem.;289:8121-8134. 2014
- Nakamura K, et al. Fratricide of natural killer cells dressed with tumor-derived NKG2D ligand. Proc Natl Acad Sci U S A. ;110:9421-9426. 2013
- Ohba R, et al.Clinical and genetic characteristics of congenital sideroblastic anemia: comparison with myelodysplastic syndrome with ring sideroblast (MDS-RS). Ann Hematol.;92:1-9. 2013
- Shirai T, et al. A novel autoantibody against fibronectin leucine-rich transmembrane protein 2 expressed on the endothelial cell surface identified by retroviral vector system in systemic lupus erythematosus.
Arthritis Res Ther.;14:R157. 2012
16 Hematology and Rheumatology

To Establish Global-Level Infectious Diseases Research and Management
Infection Control and Medical Sciences Course

Laboratory Diagnostics Master / Doctoral Degree
URL:
http://www.tohoku-icnet.ac/
KAKU, Mitsuo
Contact:
E-Mail kaku-m77@med.tohoku.ac.jp
Research Theme
Control and prevention of infectious diseases
Analysis and control of drug resistance of microorganism
Establishment of network of infection prevention and control
Research Keywords: infection control network, antimicrobial resistance, experimental animal model,
control of infectious diseases, infection crisis management
Technical Keywords: genetical analysis, epidemiological analysis, clinical microbiology, network medicine,
crisis management
The mission of the department of Infection Control and Laboratory Diagnostics is to carry out basic and clinical research,
education and back up of in the area of Infection Control and Laboratory Medicine. The problem of infectious diseases is not
limited to healthcare institution, and it is a crisis of the whole community widely now. In our department, basic and clinical
reseach on "Infection Control " : the diagnosis, treatment and prevention of infectious diseases and clinical microbiology
were carried out. In addition, education programs for medical student and specialist having general correspondence ability
to relate to a diagnosis / treatment / the prevention of infectious diseases were carried out. And Regional Infection Control
Network was established since 2000, and also our department is responsible for the management of this Regional Infection
Control Network.
Figure 1. Tohoku Infection Control network Figure 2. New animal model of acute respiratory distress syndrome
Recent Publications
- Aoyagi T, et al. Impact of psm-mec in the mobile genetic element on the clinical characteristics and outcome of SCCmec-II methicillin-resistant Staphylococcus aureus bacteremia in Japan. Clin Microbiol
Infect 20:912-919,2014.
- Endo S et al. High frequency of Acinetobacter soli among Acinetobacter isolates causing bacteremia at a Japanese tertiary hospital. J Clin Microbiol 52: 911-915, 2014.
- Kanamori H et al. Lessons learned from a tuberculosis contact investigation associated with a disaster volunteer after the 2011 Great East Japan Earthquake. Am J Respir Crit Care Med 187: 1278-9, 2013.
- Aoyagi T et al. Characteristics of infectious diseases in hospitalized patients during the early phase after the 2011 Great East Japan earthquake: pneumonia as a significant reason for hospital care.
CHEST143: 349-356, 2013.
- Hatta M et al. Post-Tsunami Outbreaks of Influenza in Evacuation Centers in Miyagi Prefecture, Japan. Clin Infect Dis. Oct 5. [Epub ahead of print] ,2011.
Infection Control and Laboratory Diagnostics 17

Advanced Clinical Diagnostic Radiology Using Computed Tomography, Magnetic Resonance Imaging, Nuclear
Medicine, and Development of Minimally-invasive Therapy with Interventional Radiology
Diagnostic Radiology Medical Sciences Course

Doctoral Degree
URL:
TAKASE, Kei http://www.radiol.med.tohoku.ac.jp/
Professor, M.D. Ph.D. Diagnostic_radiology/
Contact:
TEL +81-22-717-7312
E-Mail ktakase@rad.med.tohoku.ac.jp
Research Theme
Clinical diagnostic imaging research and investigation of disease condition based on advanced image analysis
Imaging and clinical application of visualizing fine vascular and organic structures using tomography, magnetic
resonance imaging, and nuclear medicine
Development of novel interventional radiological devices and its clinical application based on industry-academia
and medical-engineering collaboration
Research Keywords: neuroradiology, general radiology, clinical imaging, radiofrequency ablation, cancer imaging
Technical Keywords: computed tomography, magnetic resonance imaging, nuclear medicine,
interventional radiology, diagnostic radiology
Our department belongs to field of clinical medicine. In Tohoku University Hospital, we perform clinical radiological
diagnosis and Interventional Radiology (IR) which is a minimally invasive image-guided therapy. We comprehensively
think over symptoms and imaging findings, making differential diagnosis, diagnosing disease extension and curative
effect. Our department consists of more than 30 medical doctors, including 17 authorized specialists of diagnostic
radiology. We perform CT, MRI, angiography, RI, and PET to diagnose and treat many patients. Our research works are
based on advanced clinical radiology in various subspecialties such as neuro, head and neck, chest, abdomen, urogenital,
gynecological, cardiovascular, musculoskeletal, emergency, cardiovascular, and pediatric radiology, nuclear medicine and
IR. We have two pillars, "Clinical studies based on detailed image analysis" and "Development of novel therapeutic methods
by industry-academia and medical-engineering collaboration". We have enabled assessment and diagnosis of lesions and
structures that had been impossible. The result of such studies of image diagnosis improved the treatment result of the
disease because they changed treatment policies and surgical method, influencing the contents of guidelines.
We can deal with the wide variety of IVR including head and neck, cardiovascular, systemic tumor, emergency, and
pediatrics. Based on such technology of IVR, we continue to develop innovative medical treatment.
Figure 1. Analysis of fine vascular structuresneurovascular and cardiovascular Figure 2. Radiofrequency ablation of aldosterone producing adenoma
structures
Recent Publications
- Mori N, et.al. Luminal-type breast cancer: correlation of apparent diffusion coefficients with the ki-67 labeling index. Radiology. 2015;274(1):66-73.
- Mata-Mbemba D, et.al Intraventricular Hemorrhage on Initial Computed Tomography as Marker of Diffuse Axonal Injury after Traumatic Brain Injury. J Neurotrauma. 2014 Jul 15. [Epub ahead of print]
- Takasawa C, et.al Properties of N-butyl cyanoacrylate-iodized oil mixtures for arterial embolization: in vitro and in vivo experiments. J Vasc Interv Radiol. 2012 ;23(9):1215-1221
- Li L, Mori S, et.al. Enhanced sonographic imaging to diagnose lymph node metastasis: importance of blood vessel volume and density. Cancer Res. 2013 ;73(7):2082-2092
- Mugikura S, et al. MR Imaging of Subcallosal Artery Infarct Causing Amnesia after Surgery for Anterior Communicating Artery Aneurysm. AJNR Am J Neuroradiol. 2014;35(12):2293-2301.
18 Diagnostic Radiology
To Challenge to Establish Radiotherapy for Cancer and to Improve QOL of Cancer Survivor
Radiation Oncology Medical Sciences Course

JINGU, Keiichi URL:

http://www.radiol.med.tohoku.ac.jp/chiryo/
Contact:
TEL +81-22-717-7312
E-Mail kjingu-jr@rad.med.tohoku.ac.jp
Research Theme
To establish radiotherapy for intestinal cancer
Prognostic value of functional imaging before radiotherapy
To establish salvage radiotherapy for postoperative recurrent cancer
Research Keywords: radiotherapy, esophageal cancer, nasopharyngeal cancer, stereotactic body radiotherapy,
adaptive radiotherapy
Technical Keywords: intensity modulated radiotherapy, image-guide radiotherapy, deformable image registration
Our department performs mainly clinical study regarding radiation oncology to produce clinical radiation oncologists.
Especially, we are intended to establish radiotherapy for esophageal cancer, nasopharyngeal cancer and prostate cancer.
Otherwise, we lead and participate many multi-institutional trials. And we, radiation oncologists and physicists, try to
establish radiation oncology with higher accuracy technology and to improve treatment results and QOL of survivors. And
our department develops salvage radiotherapy for postoperative recurrent or metastases also. Furthermore, we investigate
occurrence mechanism of radiation-induced injury and the treatment methods for radiation-induced injury.
Figure 1. Radiation dose-distribution of stereotactic radiotherapy for primary lung Figure 2. R adiation dose-distribution of intensity modulated radiotherapy for
cancer prostate cancer
Recent Publications
- Yamamoto T, et al. Outcomes after stereotactic body radiotherapy for lung tumors, with emphasis on comparison of primary lung cancer and metastatic lung tumors. BMC Cancer. 2014 Jun 23;14:464.
- Kadoya N, et al. Evaluation of various deformable image registration algorithms for thoracic images. J Radiat Res. 2014 Jan 1;55(1):175-82.
- Jingu K, et al. Long-term results of radiotherapy combined with nedaplatin and 5-fluorouracil for postoperative loco-regional recurrent esophageal cancer: update on a phase II study. BMC Cancer. 2012 Nov
22;12:542.
- Jingu K, et al. Results of chemoradiotherapy for stage I esophageal cancer in medically inoperable patients compared with results in operable patients. Dis Esophagus. 2013 Jul;26(5):522-7.
- Ariga H, et al. Prospective comparison of surgery alone and chemoradiotherapy with selective surgery in resectable squamous cell carcinoma of the esophagus. Int J Radiat Oncol Biol Phys. 2009 Oct
1;75(2):348-56.
Radiation Oncology 19
To Conquer Diabetes, Obesity, Metabolic Syndrome and Atherosclerosis:Elucidation of the
Mechanisms Maintaining Metabolic Homeostasis at a WHOLE BODY Level
Metabolism and Diabetes Medical Sciences Course

Doctoral Degree
KATAGIRI,Hideki URL:
http://www.diabetes.med.tohoku.ac.jp/_____english/
Contact:
TEL +81-22-717-7611
E-Mail katagiri@med.tohoku.ac.jp
Research Theme
Inter-organ neuronal communication achieving metabolic fine-tuning
Vascular research for increasing healthy life-spans
Clinical studies designed to conquer metabolic diseases in humans
Research Keywords: inter-organmetaboliccommunication,dynamichomeostasisofsystemicmetabolism,

pancreaticbetacellregeneration,diabetes,obesity
Technical Keywords: analysesofsystemicglucosemetabolism,analysesofsystemicenergymetabolism,
hyperinsulinemiceuglycemicclamp,analysesofbrainfunction,
inducibletissue-specificknockoutmice
The aim of our research is to conquer metabolic diseases such as diabetes, obesity, metabolic syndrome and atherosclerosis. For
this purpose, we strive to elucidate the precise mechanisms whereby multi-organ creatures maintain metabolic homeostasis at
a whole body level. We have recently discovered that INTER-ORGAN METABOLIC COMMUNICATION via NEURONAL
RELAYS, consisting of afferent and efferent nerves, play important roles in coordinating metabolism in several organs,
leading to maintaining dynamic homeostasis at a WHOLE BODY level(Fig.1). For example, increased lipid accumulation
in the liver reducesperipheral adiposity via increasedbasal metabolic rates (Science 2006), while increased glucose uptake
into the liver suppresses thermogenesis in brown adipose tissue (Cell Metabolism 2012). In addition, hepatic ERK activation
promotes pancreatic cell proliferation (Science 2008) (Fig.2). Based on our original findings, we have proposed that inter-
organ communication via neuronal relays achieves METABOLIC FINE-TUNING at the whole body level (Circ Res 2007).
Using this system, the brain functions as a conductor coordinating systemic metabolism among many organs. These inter-organ
mechanisms constitute potential therapeutic targets for obesity and diabetes by regulating energy expenditure and inducing
pancreatic cell regeneration. Our highest aspiration is for the research we have conducted to develop novel therapies for these
common metabolic diseases and senescence by manipulating these inter-organ communication mechanisms.
Figure 1. The inter-organ metabolic communication via neuronal relays Figure 2. Induction of pancreatic cell proliferation by pancreatic ERK activation
Recent Publications
- Yamada T, et al. Signals from intra-abdominal fat modulate insulin and leptin sensitivity through different mechanisms: Neuronal involvement in food intake regulation. Cell Metab 3(3): 223-229, 2006
- Uno K, et al. Neuronal pathway from the liver modulates energy expenditure and systemic insulin sensitivity. Science 312(5780): 1656-1659, 2006
- Imai J, et al. Regulation of pancreatic cell mass by neuronal signalsfrom the liver. Science 322(5905): 1250-4, 2008
- Imai J, et al. Eradication of insulin resistance. The Lancet 374: 264, 2009
- Tsukita S, et al. Hepatic glucokinase modulates obesity predisposition by regulating BAT thermogenesis via neural signals. Cell Metab 16(6): 825-832, 2012
20 Metabolism and Diabetes

Overcoming Intractable Gastrointestinal, Liver, Pancreatic and Biliary Diseases by
Translational Research
Gastroenterology Medical Sciences Course

Doctoral Degree
SHIMOSEGAWA, Toru URL:

Contact:
TEL +81-22-717-7171
E-Mail manager@gastroente.med.tohoku.ac.jp
Research Theme
Analysis of gene mutations relating to the pathophysiology of the digestive diseases
Investigation of genetic mechanisms and pathology of the carcinogenesis and progress of cancer in the digestive
organs
Innovation of novel gastrointestinal scopes and devices
Research Keywords: organ fibrosis, disease susceptibility gene, epithelial to mesenchymal transition (EMT),
gastric acid secretion, hepatic virus
Technical Keywords: cell culture, animal model, next generation sequencer, gastrointestinal endoscopy,
pathological analysis
We have 4 research groups, an upper gastrointestinal disease group, lower gastrointestinal disease group, liver disease group
and pancreatic and biliary disease group. The research themes of the upper gastrointestinal disease group include molecular
analysis of the pathophysiology through the immune response to acid exposure and Helicobacter pylori in the esophagus
and stomach, clinical investigation of gastroesophageal reflux disease and Barretts esophagus and the development of
new gastrointestinal endoscopes. The research themes of the lower gastrointestinal group include the pathogenesis and
pathophysiology of inflammatory bowel diseases by identifying disease susceptibility genes and analyzing their functions.
The research themes of the liver disease group include molecular biological analysis of hepatitis virus and the analysis and
treatment of the biological immune system, the molecular biological and immunological analysis of hepatocellular carcinoma
and the pathogenesis and pathophysiological analysis of non-alcoholic steatohepatitis (NASH). The research themes of
pancreatic and biliary disease group include the molecular mechanism of pancreatic fibrosis, focusing on the cell biology of
pancreatic stellate cells, analysis of the gene mutations related to the pathophysiology of pancreatitis and investigation of the
genetic mechanisms and pathology of the carcinogenesis and progress of pancreatic ductal carcinoma.
Figure 1. Interactive translational research with genetics Figure 2. Cumulative mutations lead to the malignant phenotype
Recent Publications
- Masamune A, et al. Common variants at PRSS1-PRSS2 and CLDN2-MORC4 loci associate with chronic pancreatitis in Japan. Gut.64(8):1345-1346,2015.
- Nakagawa K, et al. Comparison of the long-term outcomes of endoscopic resection for superficial squamous cell carcinoma and adenocarcinoma of the esophagus in Japan. Am J Gastroenterol. 109(3):348-
356, 2014.
- Masamune A, et al. PRSS1 c.623G>C (p.G208A) variant is associated with pancreatitis in Japan. Gut. 63(2):366, 2014.
- Ara N, et al. Serious laryngeal edema during endoscopic resection for squamous cell carcinoma of the esophagus. Endoscopy. 45(4):313-315, 2013.
- Masamune A, et al. Identification of novel missense CTRC variants in Japanese patients with chronic pancreatitis. Gut. 62(4):653-4. 2013.
Gastroenterology 21
Fighting Cardiovascular Disease: From Bench to Innovative Medicine
Cardiovascular Medicine Medical Sciences Course

URL:
SHIMOKAWA, Hiroaki http://www.cardio.med.tohoku.ac.jp/english/
Contact:
TEL +81-22-717-7153
Research Theme
Mechanisms of coronary vasospasm and atherosclerosis, Endothelial function
Development of innovative medical devices
Large-scale cohort studies on cardiovascular disease
Research Keywords: c
oronary vasospasm, ischemic heart disease, chronic heart failure,
pulmonary hypertension, arrhythmia
Technical Keywords: m
olecular biology, vascular biology, medical devices, catheter ablation,
large-scale cohort study
The research policy of our department is to conduct translational research, ranging from basic science to clinical research with high originality.
In basic research, we have been studying the role of Rho-kinase pathway, which we have demonstrated plays important roles in various cellular
functions, including contraction and relaxation of vascular smooth muscle. We were able to demonstrate that Rho-kinase is a novel therapeutic
target in a wide range of cardiovascular disease, including coronary artery spasm, hypertension, pulmonary hypertension, and ischemia/
reperfusion injury, leading to global development of Rho-kinase inhibitors. In our vascular biology research, we are the first to identify that
the nature of EDHF (endothelium-derived hyperpolarizing factor) is H2O2 derived from the endothelium at physiological concentrations, thus
leading this research filed in the world. Furthermore, we have developed the extracorporeal low-energy shock wave therapy for angina pectoris
and are now developing a new catheter ablation system for fatal tachyarrhythmias. In clinical research, we are conducting the large-scale
chronic heart failure (CHF) cohort study with 10,000 patients, which is one of the largest CHF cohort studies in the world. Furthermore, we
have greatly contributed to the launch of the Japanese Coronary Spasm Association and the Japanese Pulmonary Circulation Society, aiming
to elucidate the pathogenesis of coronary vasospasm and pulmonary hypertension. Thus, we are proud of our original translational research,
ranging from basic to global clinical studies, aiming to apply our research achievements to clinical applications.
Figure 1. R ho-kinase pathway as a new therapeutic target in cardiovascular Figure 2. Synthesis and roles of endothelium-derived relaxing factors
medicine
Recent Publications
- Sakata Y, et al. Clinical impacts of additive use of olmesartan in hypertensive patients with chronic heart failure. -The supplemental benefit of an angiotensin receptor blocker in hypertensive patients with
stable heart failure using olmesartan (SUPPORT) Trial. Eur Heart J. 2015;36:915-923
- Godo S, et al. Disruption of physiological balance between nitric oxide and endothelium-dependent hyperpolarization impairs cardiovascular homeostasis in mice. Arterioscler Thromb Vasc Biol. 2015 (in
press)
- Takahashi J, et al. Prognostic impact of chronic nitrate therapy in patients with vasospastic angina: multicentre registry study of the Japanese coronary spasm association. Eur Heart J. 36(4):228-37, 2015
- Shimokawa H. 2014 Williams Harvey Lecture: importance of coronary vasomotion abnormalities-from bench to bedside. Eur Heart J. 35(45):3180-93, 2014
- Satoh K, et al. Basigin mediates pulmonary hypertension by promoting inflammation and vascular smooth muscle cell proliferation. Circ Res.115(8):738-50, 2014
22 Cardiovascular Medicine
To Establish Global-Level Infectious Diseases Research and Management
Infection Diseases Medical Sciences Course

KAKU, Mitsuo URL:

http://www.tohoku-icnet.ac/
Contact:
TEL +81-22-717-7373
E-Mail kaku-m77@med.tohoku.ac.jp
Research Theme
Control and prevention of infectious diseases
Analysis and control of drug resistance of microorganism
Establishment of network of infection prevention and control
Research Keywords: infection control network, antimicrobial resistance, experimental animal model,
control of infectious diseases, infection crisis management
Technical Keywords: genetical analysis, epidemiological analysis, clinical microbiology, network medicine,
crisis management
The mission of the department of Infection Control and Laboratory Diagnostics is to carry out basic and clinical research,
education and back up of in the area of Infection Control and Laboratory Medicine. The problem of infectious diseases is not
limited to healthcare institution, and it is a crisis of the whole community widely now. In our department, basic and clinical
reseach on "Infection Control " : the diagnosis, treatment and prevention of infectious diseases and clinical microbiology
were carried out. In addition, education programs for medical student and specialist having general correspondence ability
to relate to a diagnosis / treatment / the prevention of infectious diseases were carried out. And Regional Infection Control
Network was established since 2000, and also our department is responsible for the management of this Regional Infection
Control Network.
Figure 1. Tohoku Infection Control network Figure 2. New animal model of acute respiratory distress syndrome
Recent Publications
- Aoyagi T, et al. Impact of psm-mec in the mobile genetic element on the clinical characteristics and outcome of SCCmec-II methicillin-resistant Staphylococcus aureus bacteremia in Japan. Clin Microbiol
Infect 20:912-919,2014.
- Endo S et al. High frequency of Acinetobacter soli among Acinetobacter isolates causing bacteremia at a Japanese tertiary hospital. J Clin Microbiol 52: 911-915, 2014.
- Kanamori H et al. Lessons learned from a tuberculosis contact investigation associated with a disaster volunteer after the 2011 Great East Japan Earthquake. Am J Respir Crit Care Med 187: 1278-9, 2013.
- Aoyagi T et al. Characteristics of infectious diseases in hospitalized patients during the early phase after the 2011 Great East Japan earthquake: pneumonia as a significant reason for hospital care.
CHEST143: 349-356, 2013.
- Hatta M et al. Post-Tsunami Outbreaks of Influenza in Evacuation Centers in Miyagi Prefecture, Japan. Clin Infect Dis. Oct 5. [Epub ahead of print] ,2011.
Infection Diseases 23
To Explore the Pathogenesis of Respiratory Diseases- Our Challen ge is to Find New
Therapeutic Targets for Respiratory Diseases
Respiratory Medicine Medical Sciences Course

ICHINOSE, Masakazu URL:

http://www.rm.med.tohoku.ac.jp/english/index.html
Contact:
TEL +81-22-717-8539
E-Mail kokyu@rm.med.tohoku.ac.jp
Research Theme
To explore new therapeutic targets in obstructive pulmonary disease
To explore new treatments for lung cancer
To elucidate the pathophysiology of diffusive lung diseases
Research Keywords: obstructive pulmonary disease, lung cancer, diffusive lung disease,
sleep apnea syndrome, respiratory infectious disease
Technical Keywords: biomarker, respiratory function test, bronchoscopy, immune mechanism, gene analysis
Respiratory medicine handles a broad range of diseases from chronic diseases, such as bronchial asthma and chronic
obstructive pulmonary diseaseCOPD, to pneumonia and lung cancer. Our challenge is to elucidate the pathogenesis
of these respiratory diseases and to explore the new therapeutic targets using approaches based on diverse foundations
including respiratory physiology, such as the mechanics of breathing or alveolar diffusing capacity, immunology (allergy),
oncology, and pharmacology.
Figure 1. Pathogenesis of COPD involvement of reactive nitrogen species
Recent Publications
- Nihei M, Okazaki T, Ebihara S, Kobayashi M, Niu K, Gui P, Tamai T, Nukiwa T, Yamaya M, Kikuchi T, Nagatomi R, Ebihara T, Ichinose M, . Chronic inflammation, lymphangiogenesis, and effect of an
anti-VEGFR therapy in a mouse model and in human patients with aspiration pneumonia. J Pathol 2015; 235:632-645
- Ono M, Ohkouchi S, Kanehira M, Tode N, Kobayashi M, Ebina M, Nukiwa T, Irokawa T, Ogawa H, Akaike T, Okada Y, Kurosawa H, Kikuchi T, Ichinose M. Mesenchymal Stem Cells Correct Inappropriate
Epithelial-mesenchyme Relation in Pulmonary Fibrosis Using Stanniocalcin-1. Mol Ther .2015; 23: 549-560.
- Tojo Y, Sekine H, Hirano I, Pan X, Souma T, Tsujita T, Kawaguchi S, Takeda N, Takeda K, Fong GH, Dan T, Ichinose M, Miyata T, Yamamoto M, Suzuki N. Hypoxia Signaling Cascade for Erythropoietin
Production in Hepatocytes. Mol Cell Biol 2015; 35: 2658-2672.
- Santoso A, Kikuchi T, Tode N, Hirano T, Komatsu R, Damayanti T, Motohashi H, Yamamoto M, Kojima T, Uede T, Nukiwa T, Ichinose M. Syndecan 4 Mediates Nrf2-dependent Expansion of Bronchiolar
Progenitors That Protect Against Lung Inflammation. Mol Ther. 2015; doi: 10.1038/mt.2015.153.
- Saito R, Suzuki T, Hiramoto K, Asami S, Naganuma E, Suda H, Iso T, Yamamoto H, Morita M, Furusawa Y, Negishi T,Ichinose M, Yamamoto M. Characterizations of Three Major Cysteine Sensors of
Keap1 in Stress Response. Mol Cell Biol. 2015; 2: 00868-15
24 Respiratory Medicine
Clinical and Genetic Research to Elucidate the Pathogenesis of Pediatric Disorders for
Sick Children
Pediatrics Medical Sciences Course

Doctoral Degree
KURE, Shigeo URL:

http://www.ped.med.tohoku.ac.jp
Contact:
TEL +81-22-717-7287
E-Mail kure@med.tohoku.ac.jp
Research Theme
Pediatric hematology/oncology/immunology
Pediatric neurology
Newborn errors of metabolism
Research Keywords: pediatric cancer, blood and immune disorders, pediatric neurologic disorders,
newborn errors of metabolism, pediatric kidney and endocrine disorders, newborn disorders
Technical Keywords: exome analysis, CGH array technique, cell culture, molecular biology, animal models
Our research projects in hematology/oncology/immunology are focused on molecular pathogenesis of primary

immunodeficiency (Figure 1) and pediatric leukemias by using molecular biology techniques and NOG mice.Projects in
neurology include molecular pathogenesis of pediatric neurologic disorders by the methods of whole exome analysis and
CGH array (Figure 2). We have been also published many new insights into newborn errors of metabolism.
The goal of our research is to elucidate the pathogenesis of pediatric disorders and link them to clinical applications for sick
children.
Figure 1. Molecular pathogenesis of primary immunodeficiency Figure 2. Genentic analysis of pediatric disorders
Recent Publications
- Open conformation of WASP regulates its nuclear localization and gene transcription in myeloid cells. Int. Immunol., 26(6): 341-352, 2014.
- T cell receptor ligation causes Wiskott-Aldrich syndrome protein degradation and F-actin assembly downregulation. J. Allergy Clin. Immunol., 132: 648-655, 2013.
- Gene therapy model of X-linked severe combined immunodeficiency using a modified foamy virus vector. PLos One, 8(8): e71594, 2013.
- Development of a multi-step leukemogenesis model of MLL-rearranged leukemia using humanized mice. PLoS One,7(6): e37892,2012.
- Casitas B-cell lymphoma mutation in childhood T-cell acute lymphoblastic leukemia. Leukemia Res. 36(8):1009-1015, 2012.
Pediatrics 25
Working for Infants and Children with Disorders that Require Surgery
Pediatric Surgery Medical Sciences Course

NIO, Masaki URL:

http://www.ped-surg.med.tohoku.ac.jp/index.html
Contact:
TEL +81-22-717-7237
Research Theme
Etiology and pathology of biliary atresia
Rehabilitation for gastrointestinal dysfunction and small intestinal transplantation
Etiology of pediatric cancers and developing novel therapies
Research Keywords: biliary atresia, small-intestinal transplantation, pediatric cancer, endoscopic surgery,
neonatal surgery
Technical Keywords: neonatal surgery, endoscopic surgery, transplantation
The Department of Pediatric Surgery deals with the clinical treatment of neonates, infants, and young children with
disorders that require surgical treatment, with the exception of cardiac, neurological, and musculoskeletal conditions.
Our clinical research focuses on biliary atresia, gastrointestinal dysfunction, pediatric cancer, and pediatric endoscopic
surgery.
In terms of basic research, we are engaged in studies of regenerative medicine with the goal of regenerating tracheal
cartilage, small intestinal transplant rejection control, and etiology and pathology of biliary atresia.
In recent years, we have also focused on the need for sociopsychological support for patients and their families. We are
pursuing ideal sociopsychological support by multidisciplinary support team.
Figure 1. Apoptosis of intrahepatic bile duct in biliary atresia Figure 2. Endoscopic surgery
Recent Publications
- Ando R, et al. The Transcription Factor Bach2 Is Phosphorylated at Multiple Sites in Murine B Cells but a Single Site Prevents Its Nuclear Localization. J Biol Chem. 2015. [Epub ahead of print]
- Nio M, et al. Long-term outcomes of biliary atresia with splenic malformation. J Pediatr Surg. 2015. [Epub ahead of print]
- Sato T, et al. Mediastinal tumor resection via open or video-assisted surgery in 31 pediatric cases: Experiences at a single institution. J Pediatr Surg. 2015. [Epub ahead of print]
- Nio M, et al. Does hepatic hilum morphology influence long-term prognosis in type I/I cyst biliary atresia? Pediatr. Surg. Int. (10):931-6. 2015.
- Shoji W, et al. NCYM promotes calpain-mediated Myc-nick production in human MYCN-amplified neuroblastoma cells. Biochem Biophys Res Commun. 461(3):501-6. 2015.
- Tanaka H, et al. Postnatal management of prenatally diagnosed biliary cystic malformation. J Pediatr Surg. 50(4):507-10. 2015.
- Nio M, et al. Effects of age at Kasai portoenterostomy on the surgical outcome: a review of the literature. Surg Today. 45(7):813-8. 2015.
26 Pediatric Surgery
Bring Up Gynecologists to World-class
Gynecology Medical Sciences Course

YAEGASHI, Nobuo URL:

www.ob-gy.med.tohoku.ac.jp
Contact:
TEL +81-22-717-7252
E-Mail ob-gy@med.tohoku.ac.jp
Research Theme
Gynecological oncology
Reproductive endocrinology
Women's health medical
Research Keywords: obstetrics and gynecology, gynecological oncology, reproductive endocrinology,

female chinese medicine
Technical Keywords: pathology, autopsy, endocrinology, advanced medical technology
We are doing the diagnosis and treatment of a wide range of diseases including gynecological malignancy (uterine cancer and ovarian
cancer), gynecological benign tumor (ovarian cyst, uterine myoma), gynecological endocrine disease (ovulation disorder, infertility,
menopause disability), sexually transmitted infection, abnormal formation and position of the genitals (vagina atresia, absence of the
vagina, uterine anomaly, uterine prolapse). Especially the number of new patients with gynecological tumor are more than two hundred
in a year. We are also working actively in minimally invasive surgery. We are evaluating effectiveness of sentinel lymph node biopsy to
gynecological malignancy, preservation of urination function by nerve-sparing surgery using intraoperative electrical stimulation, fertility
preservation by pervasive cervical hysterectomy. We have started endoscopic surgery of gynecological malignancy, especially the robot-
assisted radical surgery of endometrial cancer to aim for further minimally invasive surgery. We are verifying new treatments and doctor-
led clinical trials to the refractory cases such as recurrent cancers and rare cases. On the other hand, we are also actively involved in
palliative medicine to make the patients feel relief until last moment by the advantage of the characteristics as a university hospital with
a palliation wards. In the reproductive endocrine area, we are working on advanced medicine such as advanced assisted reproductive
technology (in vitro fertilization microinsemination), endoscopic surgery (laparoscopic and hysteroscopic) in infertility cases, and
salpingoscopic tuboplasty. In the area of puberty menstrual abnormalitiessexual differentiation disorders and gender identity disorders,
we have also performed the specific surgeries, such as colpopoiesis which are difficult in the general hospitals in cooperation with other
departments.
Figure 1. Immunohistochemistry for androgen receptor (AR) Figure 2. 5-reductase 1 (5R1)
Recent Publications
- Tanaka S, et al. The role of 5-reductase type1 associated with intratumoral dihydrotestosterone concentration in human endometrial carcinoma Molecular and Cellular Endocrinology.2014. Nov. 29 in press
- Tadakawa M, et al.The anti-diabetic drug metformin inhibits vascular endothelial growth factor expression via the mammalian target of rapamycin 1/hypoxia inducible factor-1 signaling pathway in ELT-
3 cellsMolecular and Cellular Endocrinology. 5;399:1-8 ,2015
- Sato T, et al. Pregnancy outcomes in women with type 1 and type 2 diabetes mellitus in a retrospective multi-institutional study in Japan. Endocrine Journal 61(8):759-64,2014
- Sugiyama T, et al. A retrospective multi-institutional study of treatment for mild gestational diabetes in Japan. Diabetes Research and Clinical Practice. 103:412-418, 2014
- Saito M, et al. Polymyxin B Agonist Capture Therapy for Intrauterine Inflammation: Proof-of-Principle in a Fetal Ovine Model. Reproductive Science (5):623-31,2014
Gynecology 27
Bring Up Perinatal Specialists to World-class
Obstetrics Medical Sciences Course

YAEGASHI, Nobuo URL:

www.ob-gy.med.tohoku.ac.jp
Contact:
TEL +81-22-717-7251
E-Mail ob-gy@med.tohoku.ac.jp
Research Theme
Fetal physiology
Pathology of the placenta
Maternal complication
Research Keywords: obstetrics and gynecology, perinatal medicine, reproductive medicine, clinical genetics
Technical Keywords: physiology, pathology, advanced medical technology, animal experimentation
We are treating a lot of pregnant women with the many underlying diseases and responding to fetal abnormalities and lifesaving
diseases in cooperation with many special doctors of the internal medicine, psychiatry, surgery, IVR department, emergency
medical care center, anesthesiology and laboratory technicians.
We have about 1,000 of labors per year (of which 400 cases were cesarean section) in addition, two hundred cases of emergency
transport.
As a basic research that was conscious of clinical application, we are studying as follows,
mechanism of placental dysplasia and pathogeneses of pregnancy hypertension syndrome, management of postpartum
hemorrhage, mechanism the maternal glucose and lipid metabolism and endocrine environment affect to the fetus, influence the
maternal drug during pregnancy to psychomotor development of children, new extraction of postpartum depression of parents
and various harmful effects that affect the psychomotor development of children, and creation of the intrauterine acute-chronic
inflammation model with pregnancy sheep which will ultimately develop more strategic appropriate method for diagnosis,
kinetic analysis, and treatment of intrauterine inflammation during pregnancy.
Figure 1. Effects of metformin on VEGF protein expression in ELT-3 cells Figure 2. Effects of metformin on VEGF expression induced by hypoxia-mimicking
conditions
Recent Publications
- Tanaka S, et al. The role of 5-reductase type1 associated with intratumoral dihydrotestosterone concentration in human endometrial carcinoma Molecular and Cellular Endocrinology.2014. Nov. 29 in press
- Tadakawa M, et al.The anti-diabetic drug metformin inhibits vascular endothelial growth factor expression via the mammalian target of rapamycin 1/hypoxia inducible factor-1 signaling pathway in ELT-
3 cellsMolecular and Cellular Endocrinology. 5;399:1-8 ,2015
- Sato T, et al. Pregnancy outcomes in women with type 1 and type 2 diabetes mellitus in a retrospective multi-institutional study in Japan. Endocrine Journal 61(8):759-64,2014
- Sugiyama T, et al. A retrospective multi-institutional study of treatment for mild gestational diabetes in Japan. Diabetes Research and Clinical Practice. 103:412-418, 2014
- Saito M, et al. Polymyxin B Agonist Capture Therapy for Intrauterine Inflammation: Proof-of-Principle in a Fetal Ovine Model. Reproductive Science (5):623-31,2014
28 Obstetrics
Enterprising Spirit -To Challenge Organ Regeneration, Neovascularization, and
Development of Surgical Device-
Advanced Surgical Science Medical Sciences Course

and Technology Master / Doctoral Degree
URL:
http://www.surg2.med.tohoku.ac.jp/
OHUCHI, Noriaki
Contact:
Research Theme
Establishment of new treatment strategy for esophageal diseases including minimally invasive surgery and
advanced perioperative management
Organ transplantation, cell transplantation, non-heart-beating donor transplantation, and tissue engineering
Elucidation of Mechanism and risk factors on the progression of abdominal aortic aneurysm
Research Keywords: minimally invasive surgery for upper gastrointestinal tract and liver, tissue engineering and cell transplantation,
regulation of vascular degeneration, surgical stress and nutrition science, development of new surgical devices
Technical Keywords: Thoracoscopic esophageal surgery, Organ and cell transplantation, Endovascular therapy and revascularization
surgery, Per-oral endoscopic myotomy (POEM) , Robot assisted endoscopic surgery
We performed 164 cases of liver transplantation from 1991 to 2014. In addition, we performed a large number of renal transplantation including
seven cases of simultaneous pancreas and kidney transplantation. We aggressively apply these vascular reconstruction techniques on hepato-
biliary-pancreatic surgery. Furthermore, we research the tissue engineering and cell transplantation technique forcefully.
As the field of digestive surgery, we introduced the thoracoscopic esophageal surgery in 1994 on the first time in Japan and have performed more
than 650 cases until now. Recently, for a more reduction of surgical invasiveness, we introduced robot assisted esophageal surgery, laparoscopic
hepatectomy. Furthermore, we have innovated per-oral endoscopic myotomy (POEM) for achalasia operation, it is one of the natural orifice
translumenal endoscopic surgery (NOTES). As the field of vascular surgery, we promote the minimally invasive surgery such as intravascular
therapy. Recently we introduced endovascular aortic repair (EVAR) in the abdominal aortic aneurysm and the number of the operation were
increased drastically.
As the future prospects,
We become the multidisciplinary study of esophageal cancer and hepatocellular carcinoma, and promote the minimally invasive surgery.
We promote liver transplantation, islet cell transplantation, stem cell transplantation, and tissue engineering.
We create the shock wave treatment for the purpose of neovascularization.
We will make efforts on medical education more and aim at the training of the surgeon who can treat the whole body of the patient with a high
professionalism.
Figure 1. Robot assisted thoracoscopic esophagectomy Figure 2. Living donor liver transplantation
Recent Publications
- Teshima J, et al.Comparison of short-term outcomes between prone and lateral decubitous positions for thoracoscopic esophagectomy. Surg Endoscopy 2014 Dec 6. [Epub ahead of print]
- Jimbo T, et al, total 10. A novel resting strategy for improving islet engraftment in the liver. Transplantation. Feb 15;97(3):280-6, 2014
- Ichikawa H, et al. Esophagectomy using a thoracoscopic approach with an open laparotomic or hand-assisted laparoscopic abdominal stage for esophageal cancer: analysis of survival and prognostic factors
in 315 patients. Ann Surg. 257(5): 873-85, 2013
- Hamada Y, et al. total 8. In vivo imaging of the molecular distribution of the VEGF receptor during angiogenesis in a mouse model of ischemia. Blood. 118(13):e93-e100. 2011
- Award: Miyagi S. 21th Japanese Society of Hepato-Biliary-Pancreatic Surgery, Chairman`s award 2009. Tokodai K. XXIII International Congress of Transplantation Society, Young investigator award 2010.
Advanced Surgical Science and Technology 29

Our Mission is to Cure Breast and Thyroid Cancer by Advancing the Promising Research
of J-START and Nano-medicine
Surgical Oncology Medical Sciences Course

OHUCHI, Noriaki URL:

http://www.surg2.med.tohoku.ac.jp/
Contact:
TEL +81-22-717-7214
Research Theme
Molecular biology and pathology: Basic investigation of breast and thyroid diseases based on genetics, molecular
biology and pathology
Nanomedicine: As a industrial academic government cooperation research, we promote an nanomedicine
research with fluorescence nanoparticles
Strategic Anti-Cancer Randomized Trial: Japan Strategic Anti-Cancer Randomized Trial (J-START) to certify
effectiveness of ultrasonography for breast cancer screening
Research Keywords: breast cancer, mammography, nano medicine, screening, thyroid cancer
Technical Keywords: tumor infiltrating lymphocyte, fluorescence nano-imaging, large randomized controlled trial, J-START
The Division of Surgical Oncology, succeeding the former Second Department of Surgery aims to contribute to human health
improvement through cancer research in the lights of basic and clinical sciences, and education of young fellows.
Diseases covered: Breast, thyroid and others.
Researches highlighted:
Molecular Biology and pathology: Basic investigation of breast and thyroid diseases based on genetics, molecular biology and clinical
pathology.
Nanomedical Science: As a translational research, we promote an interdisciplinary alliance to apply nanotechnology on novel medical
science, with investigators specializing material, engineering, and physical sciences.
Evaluation of Cancer Screening: We have established mammography screening in Japan on the basis of effectiveness analysis. Now, we
are promoting a large-scaled clinical trial to establish new modality for cancer screening.
Strategic Anti-Cancer Randomized Trial: As a leader of the National Project The 3rd Anti-cancer Comprehensive Strategic Research
by the MHLW, we are currently conducting "Japan Strategic Anti-Cancer Randomized Trial (J-START) to certify effectiveness of
ultrasonography for breast cancer screening.
We are forwarding to authorize graduate students and young fellows for next generation as researchers, to develop new techniques for
cancer diagnosis and therapy, and contribute to public health with providing outcomes internationally.
Figure 1. J-START: RCT on effectiveness of ultrasonography for breast cancer screening Figure 2. Quantitative analysis of cancer protein by fluorescence nanoparticle
Recent Publications
- Miyashita M, Sasano H, Tamaki K, et al. Tumor-infiltrating CD8+ and FOXP3+ lymphocytes in triple-negative breast cancer: its correlation with pathological complete response to neoadjuvant
chemotherapy. Breast Cancer Res Treat 148: 525-534, 2014
- Sato K, Miyashita M, Ishida T, et.al.: Prognostic significance of the progesterone receptor status in Ki67-high and -low Luminal B-like HER2-negative breast cancers. Breast Cancer, DOI 10.1007/s12282-
014-0575-6. 2014
- Ishida T, Suzuki A, Kawai M, et.al. A randomized controlled trial to verify the efficacy of the use of ultrasonography in breast cancer screening aged 40-49 (J-START): 76 196 women registered. Jpn J Clin
Oncol 44: 134-140, 2014
- Fujii R, Hanamura T, Suzuki T, et al. Increased androgen receptor activity and cell proliferation in aromatase inhibitor-resistant breast carcinoma. J Steroid Biochem Mol Biol 144 Pt B: 513-522, 2014
- Suzuki A, Ishida T, Ohuchi N. Controversies in breast cancer screening for women aged 40-49 years. Jpn J Clin Oncol 44: 613-618, 2014
30 Surgical Oncology
Challenge to Reveal Unknown Pathology and Develop Novel Therapeutic Strategy for
Orthopaedic Diseases: To Improve Patients Quality of Life
Orthopaedic Surgery Medical Sciences Course

Disability Sciences Course
ITOI, Eiji URL:
Professor, M.D. Ph.D. http://www.ortho.med.tohoku.ac.jp/english.php
Contact:
TEL +81-22-717-7245
E-Mail captain@ortho.med.tohoku.ac.jp
Research Theme
Biomechanical studies of the shoulder joint and development of novel clinical assessment and treatment of rotator cuff tear
Analyses of bone metabolism and fracture healing and development of novel prosthesis for hip joint
Analysis of molecular mechanism in neural tissue damage and development of novel therapeutic strategy for
spinal cord injury
Research Keywords: shoulder joint, bone metabolism, osteoporosis, spinal cord injury
Technical Keywords: biomechanical analysis, molecular biological analysis, histological analysis, finite element method
In shoulder group, we are perfoming biomechanical studies using fresh frozen cadavers. We are trying to clarify the stabilizing
mechanisms of the shoulder and to evaluate the initial strength of rotator cuff repair with use of the latest magnetic sensor, strain sensor
and MTS machine.
The hip and knee group is developing a new system of total hip arthroplasty using new low Young's modulus alloy. We evaluate safety
and efficacy of the new material with animal experimental models and perform clinical trial of new prosthesis. We also analyze bone
fracture healing with suppression of inflammation and osteoclast function for delineation of therapeutic procedure of failed bone union.
The cartilage biology group is aiming to clarify the pathogenesis or mechanism of progression of osteoarthritis (OA). We are investigating
gene control of cartilage-destroying proteins related to OA via DNA methylation, one of epigenetic mechanisms.
The spinal cord injury research group is aiming to reveal molecular mechanism in neural tissue damage and develop novel therapeutic
strategy for spinal cord injury. We try to clarify the novel cell death mechanism associated with autophagy and necroptosis. We also
evaluate clinical usefulness of extra-corporeal shock wave therapy and mTOR inhibitor for treatment of spinal cord injury.
Figure 1. Stem cell differentiation in fracture healing Figure 2. Novel cell death mechanism after spinal cord injury
Recent Publications
- Yamamoto N, et al. The stabilizing mechanism of the Latarjet procedure: a cadaveric study. J Bone Joint Surg Am. 95(15):1390-1397, 2013
- Mori Y, et al.Efficacy of methotrexate and tumor necrosis factor inhibitors in Japanese patients with active psoriatic arthritis. Mod Rheumatol. 2014 [Epub ahead of print]
- Hashimoto K, et al. Regulated transcription of human matrix metalloproteinase 13 (MMP13) and interleukin-1 (IL1B) genes in chondrocytes depends on methylation of specific proximal promoter CpG
sites. J Biol Chem. 288(14):10061-10072, 2013
- Kanno H, et al. Combination of engineered Schwann cell grafts to secrete neurotrophin and chondroitinase promotes axonal regeneration and locomotion after spinal cord injury. J Neurosci. 34(5): 1838-
1855, 2014
- Miura K, et al. The bone tissue compatibility of a new Ti-Nb-Sn alloy with a low Young's modulus. Acta Biomater. 7(5):2320-2326, 2011
Orthopaedic Surgery 31
Odyssey of an Academic Surgeon
Gastrointestinal Surgery Medical Sciences Course

Doctoral Degree
UNNO, Michiaki URL:

http://www.surg1.med.tohoku.ac.jp
Contact:
TEL +81-22-717-7205
E-Mail ikyokucho@surg1.med.tohoku.ac.jp
Research Theme
Elucidation of mechanism of multidrug resistance (MDR) in cancer cells
Identification of novel prognostic factors associated with clinical outcome in colorectal cancer patients
Elucidation of mechanism of ameliorating effect of diabetes mellitus (DM)/nonalcoholic steatohepatitis (NASH) by
bariatric surgery
Research Keywords: multidrug resistance (MDR), ATP binding cassette (ABC) transporters,
personalized medicine, energy metabolism in cancer cells, obesity as a disease
Technical Keywords: next generation sequencing (NGS), duodenojejunal bypass (DJB), pharmacogenomics,
immunohistochemistry, small animal surgery
We, as gastroenterological surgeons, dedicate our efforts to surgical treatments for the patients with gastrointestinal and hepato-biliary
pancreatic diseases. While at the same time, our department supports the development of new-generation of gastroenterological surgeons
who are involved in both our basic and clinical research to answer the questions arisen from daily clinical practice. The word for our
department is to be Academic Surgeon. We respect the seven faiths by an American neurosurgeon, Dr. Harvey Williams Cushing (1869
1939).
Dr. Cushing said that;
1. He must be a researcher.
2. He must be able to inoculate others with a spirit for research.
3. He must be a tried (reliable) teacher.
4. He must be a capable administrator of his large staff and department.
5. He must, of course, be a good operating surgeon.
6. He must be co-operative.
7. He must have high ideals, social standing and an agreeable wife.
Based on vast knowledge from state-of-the-art minimally invasive surgical procedures and the findings from our current research projects,
our department will support next generation of surgeons and researchers who will lead the world in the field of medical research.
Figure 1. Identification of splice site mutation Figure 2. Duodenojejunal bypass (DJB)
Recent Publications
- Komura T et. al., Usefulness of alternate-day administration of S-1 and leucovorin in a xenograft mouse model of colorectal cancer: a shorter drug-free interval leads to more efficient antitumor effects. Int J
Clin Oncol. 2014 May 8
- Yamamura A et.al., Suppressed expression of NDRG2 correlates with poor prognosis in pancreatic cancer. Biochem Biophys Res Commun. 441(1):102-7. 2013
- Sase T et. al., Runt-related transcription factor 2 in human colon carcinoma: a potent prognostic factor associated with estrogen receptor. Int J Cancer. 131(10):2284-93. 2012
32 Gastrointestinal Surgery
Odyssey of an Academic Surgeon
epato-BiliaryPancreatic
H Medical Sciences Course
Surgery Master / Doctoral Degree
URL:
http://www.surg1.med.tohoku.ac.jp
UNNO,Michiaki
Contact:
E-Mail ikyokucho@surg1.med.tohoku.ac.jp
Research Theme
The role of cancer microenvironment in the progression and chemosensitivity of gastrointestinal cancer
Translational research in pancreatobiliary malignancies
We aim to cure diabetes mellitus by progressing studies of pancreatic islet transplant and pancreas regeneration
Research Keywords: cancermicroenvironment,invasionandmetastasis,pancreatobiliarymalignancies,

chemosensitivity,islettransplantation
Technical Keywords: patient-derivedtumorxenograft,molecularbiologytechniques,extracellularmatrix,
mesenchymal stem cell, immunity isolating
We, as gastroenterological surgeons, dedicate our efforts to surgical treatments for the patients with gastrointestinal and hepato-biliary
pancreatic diseases. While at the same time, our department supports the development of new-generation of gastroenterological surgeons
who are involved in both our basic and clinical research to answer the questions arisen from daily clinical practice. The word for our
department is to be Academic Surgeon. We respect the seven faiths by an American neurosurgeon, Dr. Harvey Williams Cushing (1869
1939).
Dr. Cushing said that;
1. He must be a researcher.
2. He must be able to inoculate others with a spirit for research.
3. He must be a tried (reliable) teacher.
4. He must be a capable administrator of his large staff and department.
5. He must, of course, be a good operating surgeon.
6. He must be co-operative.
7. He must have high ideals, social standing and an agreeable wife.
Based on vast knowledge from state-of-the-art minimally invasive surgical procedures and the findings from our current research projects,
our department will support next generation of surgeons and researchers who will lead the world in the field of medical research.
Figure 1. Pancreatic islet transplantation Figure 2. NOG-EGFP mice
Recent Publications
- Shirasaki K et. al, NF-E2-related factor 2 promotes compensatory liver hypertrophy after portal vein branch ligation in mice. Hepatology. 59(6):2371-82. 2014
- Motoi F et. al., Neoadjuvant chemotherapy with gemcitabine and S-1 for resectable and borderline pancreatic ductal adenocarcinoma: results from a prospective multi-institutional phase 2 trial. Ann Surg
Oncol. 20(12):3794-801. 2013
- Motoi F et. al., Randomized clinical trial of external stent drainage of the pancreatic duct to reduce postoperative pancreatic fistula after pancreaticojejunostomy. Br J Surg. 99(4):524-31. 2012
- Shima K et. al., Potential Utility of NOG Mice with Ubiquitous eGFP Expression (NOG-EGFP) as a High Quality Cancer Sampling System. J Exp Clin Cancer Res.;31(1):2012
Hepato-Biliary Pancreatic Surgery 33

Challenges for the Last Frontier of Cardiovascular Medicine to Establish the Novel
Strategies Based on Basic Research
Cardiovascular Surgery Medical Sciences Course

SAIKI, Yoshikatsu URL:

Contact:
TEL +81-22-717-7222
E-Mail yoshisaiki@med.tohoku.ac.jp
Research Theme
Multi-disciplinary research to improve outcomes of thoracic aortic aneurysm repair
Application of drug delivery system to control intimal hyperplasia after vascular anastomosis
Development of novel blood-flow sensor and analysis of key molecule to establish new strategies for organ
protection from ischemic-reperfusion injury
Research Keywords: thoracoabdominal aortic aneurysm, spinal cord protection, anastomotic stenosis,
organ protection, ischemic-reperfusion injury
Technical Keywords: blood flow sensor, drug delivery system, large animal model, medical engineering
Multi-disciplinary research has been conducted to improve the outcomes of thoracic aortic aneurysm repair, including
exploration of risk factors for aneurysm development, modulation of aneurysm progression by cell therapy, development of
non-invasive screening system for aortic aneurysm, development of new method for spinal cord protection and regeneration of
medial tissue after acute aortic dissection. Some of our achievements are described below. By applying drug delivery system
during vascular anastomosis, diminished intimal hyperplasia resulting in improved patency of anastomotic site was achieved
as shown in a canine model. To establish new strategies for organ protection against ischemic-reperfusion injury, a real-time
monitoring blood flow sensor has been developed using MEMS (Micro electro mechanical systems) technique collaborating
with the biomedical engineering team, and also modulation of key molecules for organ protection has been pursued. We have
worked on these research themes as pre-clinical tests especially utilizing large animal models such as canine and swine.
Figure 1. Medial regeneration using a biodegradable felt Figure 2. Aortic dissection in canine model
Recent Publications
- Sato M, Kawamoto S, Watanabe M, Sakamoto N, Sato M, Tabata Y, Saiki Y. Medial regeneration using a biodegradable felt as a scaffold preserves integrity and compliance of a canine dissected aorta.
Circulation. 2012;126:S102-S109
- Hayatsu Y, Kawamoto S, Matsunaga T, Haga Y, Saiki Y. Real-time monitoring of spinal cord blood flow with a novel sensor mounted on a cerebrospinal fluid drainage catheter in an animal model. J Thorac
Cardiovasc Surg 2014; 148(4):1726-1731.
- Matsuo S, Saiki Y, Adachi O, Kawamoto S, Fukushige S, Horii A, Saiki Y. Single-dose rosuvastatin ameliorates lung ischemia-reperfusion injury via upregulation of endothelial nitric oxide synthase and
inhibition of macrophage infiltration in rats with pulmonary hypertension. J Thorac Cardiovasc Surg. 2014;Oct 15 DOI: 10.1016/j.jtcvs.2014.10.030
34 Cardiovascular Surgery
To Challenge Urologic Oncology, Develop Minimally Invasive Therapy and Functional
Reconstruction after Pelvic Surgery
Urology Medical Sciences Course

ARAI, Yoichi URL:
Professor, M.D. Ph.D. http://www.uro.med.tohoku.ac.jp
Contact:
TEL +81-22-717-7282
E-Mail yarai@uro.med.tohoku.ac.jp
Research Theme
Development of minimally invasive urologic surgery
Urologic oncology
Urinary function and reconstruction after pelvic surgery
Research Keywords: urologic oncology, minimally invasive surgery, reconstruction after pelvic surgery,
urinary function, glycobiology
Technical Keywords: laparoscopic surgery, robotic surgery, glycobiology, nerve-sparing surgery,
lower urinary tract symptoms
With dramatic increase in urologic malignancy cases, the main focus of research has been urologic oncology. We have had a
long history of glycobiologic approach to urologic cancer, research on mechanism of carcinogenesis and its invasive growth.
Prostate cancer is a top cancer in number at Tohoku University Hospital. We developed minimally invasive treatment
including robotic surgery for localized prostate cancer.
Our research on function-sparing approach and reconstruction after pelvic surgery has contributed to further improvement of
outcome after treatment. The basic and clinical research on voiding dysfunction is also well organized. We have established
research network in Northeast area Japan and many multi-institutional clinical triasl are now on going.
Figure 1. Robot-assisted partial nephrectomy Figure 2. Intarevesical chemotherapy for prevention of bladder recurrence after
nephroureterectomy
Recent Publications
- Ito A, et al. Prospective randomized phase II trial of a single early intravesical instillation of pirarubicin (THP) in the prevention of bladder recurrence after nephroureterectomy for upper urinary tract
urothelial carcinoma: the THP Monotherapy Study Group Trial. J Clin Oncol. 2013 Apr 10;31(11):1422-7.
- Mitsuzuka K, Arai Y. Controversies associated with the evaluation of elderly men with localized prostate cancer when considering radical prostatectomy. Int J Clin Oncol. 2014 Oct;19(5):793-9.
- Sasaki M, et al. Low Percentage of Free Prostate-specific Antigen (PSA) Is a Strong Predictor of Later Detection of Prostate Cancer Among Japanese Men With Serum Levels of Total PSA of 4.0 ng/mL or
Less. Urology. 2014 Nov;84(5):1163-7
- Kawamorita, et al. Roles of the spinal glutamatergic pathway activated through AMPA receptors and its interactions with spinal noradrenergic and serotonergic pathways in the rat urethral continence
mechanisms. Neurourol Urodyn. 2015;34: 75-81.
- Kaiho Y, et al. Optimization of sexual function outcome after radical prostatectomy using phosphodiesterase type 5 inhibitors.Int J Urol. 2013 Mar;20(3):285-9.
Urology 35
Innovative Research in Anesthesiology Based on Excellent Anesthesia Care
Anesthesiology and Medical Sciences Course

PerioperativeMedicine Disability Sciences Course
URL:
YAMAUCHI, Masanori http://www.anes.med.tohoku.ac.jp
Contact:
E-Mail anes@med.tohoku.ac.jp
Research Theme
Omics research in perioperative medicine for surgical patients
Identification of novel biomarkers in critically ill patients with ARDS
Development of regenerative medicine for neuropathic pain
Research Keywords: o
pioidsensitivity,anesthetic,PONV,SNPs,ARDS,sepsis,EMPs,neuropathicpain,
Multilineage-differentiatingstressenduringcell
Technical Keywords: n
ext-generationDNAsequencing,omics,invivoimaging,animalmodelsofpain,cell
transplantation
Are you seeking a postgraduate student position? Tohoku University Anesthesia offers some research programs run by dedicated mentors
in anesthesiology, critical care medicine, and pain medicine. The programs are four-year courses of training for young anesthesiologists to
acquire a Ph.D. degree. We believe that our programs can promote your career as an anesthesia professional.
He /she will be given some research themes such as the following:

1) Perioperative genetics and genomics
2) Translational research for critically ill patients with organ failure
3) Gene and cell therapy for patients with neuropathic pain
4) Or your own research theme!
Anesthesiology is inextricably linked to physiology, pharmacology and immunology. Also, our departmental policy is to conduct
innovative research in anesthesiology based on excellent anesthesia care. Our goal is to provide valuable research (Fig. 1).
You can work for doctoral research at our orbital laboratory (Fig. 2), and you can also live in Sendai, Japan. Sendai is very beautiful city
and we promise that you would enjoy a fulfilling life in Sendai.
If you have any further questions, please do not hesitate to let me know. Join us! Email me today!!
Figure 1. Anesthesiology and our departmental goal Figure 1. A student conducting research in our laboratory.
Recent Publications
- Toyama H, et al. Two cases of bilateral lung transplantation combined with intracardiac repair and pulmonary artery replacement: perioperative managements based on the left ventricular function. J Anesth.
29(6):957-961, 2015
- Sugino S, et al. Peripartum Anesthetic Management and Genomic Analysis of Rare Variants in a Patient with Familial Pulmonary Fibrosis. A A Case Rep. 5(10):169-172, 2015
- Sugino S, et al. Pharmacogenetics of chemotherapy-induced nausea and vomiting. Pharmacogenomics. 16(2):149-160, 2015
- Adachi K, et al. Anesthetic management of pulmonary valve replacement for pulmonary regurgitation in six patients with surgically repaired tetralogy of Fallot. J Anesth. 28(6):928-931, 2014
- Sugino S, et al. Association of -opioid receptor gene (OPRM1) haplotypes with postoperative nausea and vomiting. Exp Brain Res. 232(8):2627-2635, 2014
36 Anesthesiology and Perioperative Medicine

Our Department Provides Both Clinical and Research Experience Regarding Palliative
Medicine to Become a Palliative Care Specialist and to Obtain a Degree.
PalliativeMedicine Medical Sciences Course

Doctoral Degree
INOUE,Akira URL:
Professor, M.D., Ph.D.

Contact:
TEL +81-22-717-7366
E-Mail akinoue@idac.tohoku.ac.jp
Research Theme
Prospective interventional studies or observational studies regarding anti-cancer agents or other drugs for patients
with advanced cancer.
Clinical studies regarding symptom management or psycho-social pain for cancer patients in terminal stage.
Analysis of big data regarding cancer-related information and research for family of cancer patients.
Research Keywords: earlypalliativecare,molecular-targetingagents,psycho-socialpain,cachexia

Technical Keywords: prospectiveinterventionalstudy,observationalstudy,researchforfamiliesofcancerpatients
In October 2000, the first palliative care unit in national universities in Japan opened in Tohoku University and our
department was founded in 2008. Since the establishment of the Cancer Control Act, the needs for palliative medicine
have steadily increased. We are practicing the early palliative care in cooperate with an appropriate cancer treatment and
addressing clinical trials to improve palliative medicine. Our department is one of the core members of nation-wide research
group, J support, and also conducting other clinical trials. Thus our graduate students will have many research themes to
obtain degrees.
Our department has a palliative care specialist certified by the Japanese Society for Palliative Medicine who can educate
young doctors to get the certification. They can also learn how to cooperate with other doctors and medical staffs through
activities in palliative care team, or have valuable experiences with skillful home care doctors or pain clinic doctors.
In our department, doctors can tackle both general practice and clinical research in their favorite balance. We will provide
various educational plan for palliative care
Figure 1. Dramatic improvement by molecular-targeting agent in end-stage lung Figure 2. Organization chart of Japan Supportive, Palliative and Psychosocial
cancer patients. Oncology Group.
Recent Publications
- Inoue A, Kobayashi K, Maemondo M, et al. Updated Overall Survival Results from A Randomized Phase III Trial Comparing Gefitinib with Carboplatin-Paclitaxel for Chemo-Nave Non-Small Cell Lung
Cancer with Sensitive EGFR Gene Mutations (NEJ002). Ann Oncol 24: 54-9, 2013
- Maemondo M, Inoue A, Kobayashi K, et al. Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med 362, 2380-8, 2010
- Inoue A, Kobayashi K, Usui K, et al. First-line Gefitinib for Advanced Non-Small Cell Lung Cancer Patients Harboring Epidermal Growth Factor Receptor Mutations without Indication for Chemotherapy.
J Clin Oncol 27:1394-400, 2009
- Inoue A, Sugawara S, Yamazaki K, et al. Randomized Phase II Trial Comparing Amrubicin with Topotecan in Patients with Previously Treated Small Cell Lung Cancer: Report of North Japan Lung Cancer
Study Group Trial 0402. J Clin Oncol 26:5401-6, 2008
- Inoue A, Suzuki T, Fukuhara T, et al. Prospective phase II study of gefitinib for chemotherapy-nave patients with advanced non-small-cell lung cancer with epidermal growth factor receptor gene mutations.
J Clin Oncol 24: 3340-3346, 2006
Palliative Medicine 37
To Provide Innovation and Leadership across the Spectrum of Critical Care: From Basic
Science to Large Clinical Trials
Emergency and Critical Care Medical Sciences Course

Medicine Master / Doctoral Degree
URL:
http://www.emergency-medicine.med.tohoku.ac.jp/
KUSHIMOTO, Shigeki
Contact:
E-Mail information@emergency-medicine.med.tohoku.ac.jp
Research Theme
Pathophysiology of acute stress condition and damage-associated molecular patterns
Coagulo-fibrinolytic abnormalities in acute stress conditions with systemic inflammation
Innovative treatments for severe sepsis
Research Keywords: systemic inflammatory response syndrome, damage-associated molecular patterns,

coagulo-fibrinolytic abnormalities, critical care, severe sepsis
Technical Keywords: bio-monitoring, artificial organ support, cell-based therapy, disaster medicine
Our faculty continues to provide innovation and leadership across the spectrum of emergency medicine and critical care, from basic science to clinical
trials, disaster medicine. Our research activities are grouped into three primary domains: clinical, translational research and Big Data analysis.
1) Clinical research
An important theme is pathophysiology of acute stress condition. We are investigating the role of damage-associated molecular patterns, such as
mitochondrial DNA and HMGB1, in sepsis, trauma and post cardiac arrest syndrome. Coagulo-fibrinolytic abnormalities in critical ill patients has been
a centerpiece of research, and we are evaluating the molecular mechanism and managing large multicenter clinical trials to establish the strategy of
damage control resuscitation.
2) Translational research
Anti-inflammatory strategies have failed to improve outcome in patients with sepsis. Cell-based strategy, especially mesenchymal stem cell (MSC),
has been reported to decrease inflammation and organ dysfunction and also to improve outcome. These effects are believed to be mediated by soluble
factors secreted by MSC. Multilineage-differentiating stress-enduring (Muse) cells are distinct stem cells in MSC populations with the capacity to self-
renew, to differentiate into cells representative of all three germ layers from a single cell, and to repair damaged tissues by spontaneous differentiation
into tissue-specific cells. We are investigating the role of Muse cell in sepsis and examining the effect of Muse cell-focused MCS treatments for severe
sepsis.
3) Big Data Analysis and Disaster Medicine
A novel theme in our multidisciplinary department is Big Data Analysis. We are analyzing the big bio-monitoring data to prevent secondary injury in
patients with traumatic brain injury and to improve patient management. Our investigators also is developing Business Continuity Plan for disaster-
base institution based on the big data of Great East Earth Quake.
Figure 1. Plasma levels of mitochondrial DNA in critically ill patients Figure 2. Muse cell-focused cell based strategy for sepsis
Recent Publications
- Kushimoto S, et al. Body temperature abnormalities in non-neurological critically ill patients: a review of the literature. Journal of Intensive Care. 2:14, 2014
- Kushimoto S, et al. The impact of body temperature abnormalities on the disease severity and outcome in patients with severe sepsis: an analysis from a multicenter, prospective survey of severe sepsis. Crit
Care. 2013, 17:R271
- Yamanouchi S, et al. Plasma mitochondrial DNA levels in patients with trauma and severe sepsis: Time-course and the association with clinical status. J Crit Care. 28(6):1027-31, 2013
- Kushimoto S, et al. Relationship between extravascular lung water and severity categories of acute respiratory distress syndrome by the Berlin definition. Critical Care. 17:R132, 2013
- Kudo D, et al. Low-dose interferon- treatment improves survival and inflammatory responsesin a mouse model of fulminant acute respiratory distress syndrome. Inflammation.812-20, 2013
38 Emergency and Critical Care Medicine

Wide Variety of Research Programs, Including Wound Healing, Ischemia-reperfusion
Injuries, Absorbable Metal Plates
Plastic and Reconstructive Medical Sciences Course

URL:
http://www.prs.med.tohoku.ac.jp/
TACHI, Masahiro
Contact:
Research Theme
Evaluation of the role of NKT cells in wound healing
Development of absorbable metal plate for craniofacial surgery
Multicenter cohort trial of functioning reconstruction of head and neck cancer
Research Keywords: wound healing, biofilm, absorbable plate, NKT cell

Technical Keywords: animal experiment, transgenic mouse, pathology
We are addressing the role of leucocytes in the wound healing process. Inoculation of Pseudomonas aeruginosa PAO1 significantly accelerated
the wound healing and inflammatory response on day 3 post-wounding. These responses were cancelled when inoculated with lasI in place
of PAO1or treated with anti-3-oxo-C12-HSL antiserum. By contrast, administration of 3-oxo-C12-HSL in the absence of PAO1 significantly
promoted the wound healing and inflammatory response. These results strongly suggest that a quorum-sensing molecule, 3-oxo-C12-HSL, may be
deeply involved in the skin wound healing under infection with P. aeruginosa.
We elucidated the contribution of tumor necrosis factor-alpha (TNF-alpha) and invariant natural killer T (iNKT) cells to wound healing. Wound
healing was significantly delayed on day 3 in mice treated with ant-TNF-alphamAb, compared with mice that received control IgG. In contrast,
wound healing was accelerated on day 3 when mice were treated with bioactive human TNF-alpha. On the other hand, in J alpha18KO mice
lacking iNKT cells, wound healing was significantly delayed on days 3 and 7, compared with wild-type mice. These results indicate that TNF-
alpha and iNKT cells are both involved in the process of wound healing and suggest that iNKT cells may act independently of TNF-alpha.
Figure 1. Bacterial burden accelerates wound healing Figure 2. Presence of biofilm demonstrated by bacterial staining and rhodamine-
concanavalin A
Recent Publications
- Shibuya N, et al. Acute Rejection of Knee Joint Articular Cartilage in a Rat Composite Tissue Allotransplantation Model. The Journal of Bone & Joint Surgery,96(12): 1033-1039, 2013
- Kochi T, et al. Characterization of the arterial anatomy of the murine hindlimb: functional role in the design and understanding of ischemia models.PLoS One, 8(12):e84047, 2013
- Kanno E, et al. Neutrophil-derived tumor necrosis factor- contributes to acute wound healing promoted by N-(3-oxododecanoyl)-L-homoserine lactone from Pseudomonas aeruginosa. J Dermatol Sci.
70(2), 130-138, 2013
- Hayashi D, et al. Low-energy extracorporeal shock wave therapy enhances skin wound healing in diabetic mice: a critical role of endothelial nitric oxide synthase. Wound Repair Regen, 20(6): 887-95, 2012
- Tachi M, et al. Versatility of chimeric flap based on thoracodorsal vessels incorporating vascularized scapular bone and latissimus dorsi myocutaneous flap in reconstructing lower-extremity bone defects due
to osteomyelitis.J Reconstr Microsurg, 26(6):417-24, 2010
Plastic and Reconstructive Surgery 39

Translational Studies for Discovery of Earlier Diagnosis and Novel Therapies for Life-threatening
Neuromuscular Diseases: From Basic Research to Clinical Applications
Neurology Medical Sciences Course

AOKI, Masashi URL:

http://www.neurol.med.tohoku.ac.jp/index.html
Contact:
TEL +81-22-717-7189
Research Theme
Identification of molecular mechanisms and exploration of novel therapeutics for neuromuscular diseases
Studies on etiopathogenesis of neuroimmunological diseases
Research Keywords: MND/ALS,Parkinsonsdiseaseandrelateddisorders,musculardiseases,multiplesclerosis,

neuromyelitisoptica
Technical Keywords: next-generationsequencer,iPSCtechnologyandregenerativemedicine,
pathologyandbiochemistrytechniques,cellularandanimalmodel,molecularandfunctionalimaging
Intractable neurological diseases became an increasingly worrisome burden for our aging population. We are currently
focusing on the neurodegenerative diseases including amyotrophic lateral sclerosis (ALS) and Parkinsons disease (PD),
muscular diseases such as distal myopathies, and neuroimmunological disorders such as multiple sclerosis (MS) and
neuromyelitis optica (NMO).
Most of the neurodegenerative diseases are characterized by progressive dysfunction and loss of neuronal subpopulations
that affect specific neural systems, including ALS and PD. The currently available treatments for these diseases are only
the palliative/symptomatic therapy, and no disease-modifying therapy has yet been approved. However, the identification
of several genes linked to familial forms of neuromuscular diseases has offered insight into the biochemical and molecular
mechanisms of the disease. To obtain better understanding of disease pathomechanisms, variety of cellular and animal
models including patient-derived iPSC have been established in our lab. Furthermore, we are employing the next-generation
sequencing to identify novel genes associated with the disease. In addition to basic researches, our faculty has strength in
the area of clinical studies including biomarker and molecular imaging. MS and NMO are neuroimmunological disease in
which oligodendroglial or astrocytes in the CNS is damaged by inflammatory response. The interrelationship between MS
and NMO has long been controversial; however, after the discovery of NMO-specific autoantibody against aquaporin-4
(AQP4), NMO is considered as a distinct clinical entity. To find novel surrogate marker and disease-modifying therapy, we
are investigating pathological role of anti-AQP4 antibody, diagnostic marker of NMO.
Figure 1. Basic technology in neurological research Figure 2. Our goal via translational research
Recent Publications
- Sato DK, et al. Distinction between MOG antibody-positive and AQP4 antibody-positive NMO spectrum disorders. Neurology. 2014 Feb 11;82(6):474-81.
- Izumi R, et al. Genetic profile for suspected dysferlinopathy identified by targeted next-generation sequencing. Neurol Genet. 2015 Dec 10;1 (4):e39
- Kurosawa K et al. Severely exacerbated neuromyelitis optica rat model with extensive astrocytopathy by high affinity anti-aquaporin-4 monoclonal antibody. Acta Neuropathol Comun 2015 Dec 4;3(1):82
- Sugeno N, et al. Lys-63-linked ubiquitination by E3 ubiquitin ligase Nedd4-1 facilitates endosomal sequestration of internalized -synuclein. J Biol Chem. 2014 Jun 27;289(26):18137-51.
- Kitajima Y, et al. Proteasome dysfunction induces muscle growth defects and protein aggregation. J Cell Sci. 2014 Dec 15;127(24):5204-17.
40 Neurology
Research-driven Neurosurgery: Development of Novel Neurosurgical Therapeutics to Meet
Future Needs
Neurosurgery Medical Sciences Course

TOMINAGA, Teiji URL:

http://www.nsg.med.tohoku.ac.jp/
Contact:
TEL +81-22-717-7230
E-Mail edu@nsg.med.tohoku.ac.jp
Research Theme
Development of new neurosurgical devices
Development of less invasive neurosurgery
Pathogenesis and treatment of central nervous system diseases
Research Keywords: malignant brain tumors, cerebrovascular diseases, epilepsy, surgical devices,
academic-industry partnership
Technical Keywords: convection enhanced delivery, medical device development, computational fluid dynamics,
genetic analysis, animal experiment
We perform both basic and clinical research on all specialized fields of neurosurgery, in collaboration with other laboratories
and institutions. Major research topics are as follows.
- Covection-enhanced delivery (CED) for malignant brain tumors and spinal cord tumors
- Genetic analysis of malignant brain tumors and its clinical application
- Immunotherapy of malignant brain tumors
- Development of new surgical devices (pulsed-water jet mess)
- Computational fluid dynamics of cerebro-vascular diseases
- Development of new drugs for acute ischemic stroke
- Genetics of Moyamoya disease
- Development of new models of epilepsy and seizures using optogenetics
Figure 1. Development of new surgical devices (pulsed-water jet mess) Figure 2. Covection-enhanced delivery (CED) for malignant brain tumors
Recent Publications
- Nakagawa A, et al. Pulsed Laser-induced Liquid Jet System for Treatment of Sellar and Parasellar Tumors: Safety Evaluation. J Neurol Surg A Cent Eur Neurosurg. 2015 Jan 16. [Epub ahead of print]
- Saito R, et al. Convection-enhanced delivery: from mechanisms to clinical drug delivery for diseases of the central nervous system. Neurol Med Chir (Tokyo). 52(8):531-8, 2012
- Shibahara I, et al. Malignant clinical features of anaplastic gliomas without IDH mutation. Neuro Oncol. 17(1):136-44, 2015
- Osawa S, et al. Optogenetically induced seizure and the longitudinal hippocampal network dynamics. PLoS One. 10;8(4):e60928, 2013
- Ito A, et al. Enhanced post-ischemic angiogenesis in mice lacking RNF213; a susceptibility gene for moyamoya disease. Brain Res. 12;1594:310-20, 2015
Neurosurgery 41
Best Use of Computational Fluid Dynamics of Cerebral Aneurysms
Neuroendovascular Therapy Medical Sciences Course

URL:
TOMINAGA, Teiji http://www.med.tohoku.ac.jp/english/org/
Professor, M.D. Ph.D. medical/48/index.html
Contact:
TEL +81-22-717-7195
E-Mail
Research Theme
Risk evaluation of intracranial aneurysms using computational fluid dynamics
Neuroendovascular therapy
Research Keywords: endovascular therapy, cerebral aneurysm, computational fluid dynamics, stent, coil
Technical Keywords: computational fluid dynamics, stent, coil, embolization
Our clinical works include endovascular treatment of cerebral aneurysms, carotid artery stenosis, arteriovenous
malformations, brain tumors and others, and its field is still increasing dramatically. Our research interests have been
computational fluid dynamics of cerebral aneurysms (collaboration with the department of engineering) and many basic
researches using experimental cerebral aneurysms in rodents. All of you are welcome to visit our department and laboratory.
Figure 1. CFD analysis
Recent Publications
- Relative residence time prolongation in intracranial aneurysms: a possible association with atherosclerosis. Sugiyama et al., Neurosurgery 73:767-776, 2013
- Use of microscope-integrated near-infrared indocyanine green videoangiography in the surgical treatment of intramedullary cavernous malformations: report of 8 cases. Endo et al., J Neurosurg Spine
18:443-449, 2013
- Local hemodynamics at the rupture point of cerebral aneurysms determined by computational fluid dynamics analysis. Omodaka et al., Cerebrovasc Dis 34:121-129, 2012
- Computational Simulation of Therapeutic Parent Artery Occlusion to Treat Giant Vertebrobasilar Aneurysm. Hassan et al., AJNR Am J Neuroradiol 25:63-68, 2004
- Hemodynamic analysis of an adult vein of Galen aneurysm malformation by use of 3D image-based computational fluid dynamics. Hassan et al., AJNR Am J Neuroradiol 24:1075-1082, 2003
42 Neuroendovascular Therapy
Protect Mental Health and Prevent Mental Illness
Psychiatry Medical Sciences Course

MATSUOKA, Hiroo URL:
Professor, M.D. Ph.D. http://www.psytohoku.ac
Contact:
TEL +81-22-717-7262
E-Mail info@psytohoku.ac
Research Theme
Research on psychiatric treatment to children and their family
Early intervention and prevention in psychiatry
Research Keywords: child and adolescent psychiatry, neurodevelopmental disorders,

early intervention in psychiatry, preventive psychiatry, early psychosis
Technical Keywords: psychotherapy, play therapy, neuroimaging, cognitive function, cognitive behavioral therapy
(1) Child and adolescent psychiatry: We have various research targets: developmental disorders, problem in school and
society, child abuse, eating disorder, anxiety disorder and psychosis. We are undertaking some collaborative studies: 1)
psychiatric issues in children with pediatric surgery diseases; 2) trauma and resilience after the Great East Japan Earthquake
with the team in Miyagi Psychiatric Center.
(2) Early intervention in psychiatry: We are conducting researches on early intervention and prevention in psychiatry. We
are now doing comprehensive clinical studies on first episode psychosis (FEP) and at-risk mental state (ARMS). We are
interested in biological and psychological mechanism in the early course of psychosis and developing intervention for
the population. Current main research themes are as follows: 1) longitudinal clinical follow-up study of ARMS and FEP;
2) brain structural study using MRI in ARMS and FEP; 3) feasibility study of Cognitive Behavioral Therapy for ARMS
in Japan: an open-label pilot study; 4) effect of cognitive training on cognition and brain structure in schizophrenia; 5)
functional MRI study on ego disturbance of schizophrenia.
Figure 1. Course of ARMS in relation to psychosis/schizophrenia Figure 2. Regional alterations in brain gray matter after brain training
Recent Publications
- Honda N et al: Physical and psychological outcome in long-term survivors of childhood malignant solid tumor in Japan. Pediatr Surg Int 27(7): 713-720, 2011
- Honda N: Trauma- and stressor-related disorders. Jpn J Child Adolesc Psychiatry 55(5): 579-588, 2014 [Jpn]
- Ohmuro N et al: The association between cognitive deficits and depressive symptoms in at-risk mental state: A comparison with first-episode psychosis. Schizophr Res (in press)
- Katsura M et al: A naturalistic longitudinal study of at-risk mental state with 2.4 years follow-up at a specialized clinic setting in Japan. Schizophr Res 158 (1-3): 32-38, 2014
- Matsumoto K et al: Frequency and neural correlates of pauses in patients with formal thought disorder. Front Psychiatry 10(4), doi:10.3389/fpsyt.2013.00127
Psychiatry 43
Seach for the Mechanism of the Charm of Skin
Dermatology Medical Sciences Course

AIBA, Setsuya URL:

http://www.derma.med.tohoku.ac.jp/
Contact:
TEL +81-22-717-7271
E-Mail saiba@med.tohoku.ac.jp
Research Theme
Analysis of the mechanism of allergic contact dermatitis
Analysis of melanocyte development using MUSE cells
Analysis of the biological roles of antimicrobial peptides, and development of effective anti-tumor immune
response for skin cancers
Research Keywords: contact dermatitis, Muse cell, melanogenesis, immunotoxicity, tumor immunity
Technical Keywords: lucife assay, DNA array, in vivo imaging of ATP, microdissection, Muse cell
The main theme of our department is to understand the biology of skin, the most outer layer of the body. Regarding the
pathogenesis of allergic contact dermatitis (ACD), we elucidated that allergens for ACD, i.e., haptens, react with thiol
residues in keratinocytes or dendritic cells in the skin, which triggers the activation of mitogen activated protein kinase
leading to dendritic cell activation and opens the pannexin-1 channel to release ATP from keratinocytes. On the other
hand, in the lesional skin of ACD, keratinocytes stimulated by T cell cytokines actively produce hyalulonan, which results
in intercellular edema of epidermis, i.e., spongiosis. Regarding melanocyte development, we succeeded in developing
melanocytes from human skin fat cells. Now we are ready to explore melanocyte stem cells and factors to augment or
suppress melanogenesis. Recently, we have elucidated the mechanism by which human cathelicidin antimicrobial peptide
(CAMP) initiates skin inflammation via the induction of various chemokines and IL-36 by keratinocytes. In the research
on anti-tumor immune response, we found that Paget cells of extramammary Paget disease create immunosuppressive
environment by producing receptor activator of nuclear factor kappa-B ligand (RANKL).
Figure 1. Molecular mechanism of spongiosis Figure 2. Melanocyte induction from human adipose cells
Recent Publications
- Kambayashi, Y., Fujimura, T., Furudate, S., Asano, M., Kakizaki, A., Aiba, S., 2015. The Possible Interaction between Receptor Activator of Nuclear Factor Kappa-B Ligand Expressed by Extramammary Paget Cells
and its Ligand on Dermal Macrophages. J Invest Dermatol 135, 2547-2550.
- Kimura, Y., Fujimura, C., Ito, Y., Takahashi, T., Nakajima, S., Ohmiya, Y., Aiba, S., 2015. Optimization of the IL-8 Luc assay as an in vitro test for sin sensitization. Toxicol In Vitro in press.
44 Dermatology
Unraveling Pathomechanisms of and Developing Treatments for Intractable Ocular
Disease ~Aiming toward ZERO Blindness~
Ophthalmology Medical Sciences Course

NAKAZAWA, Toru URL:
Professor, M.D. Ph.D. http://www.oph.med.tohoku.ac.jp/
Contact:
TEL +81-22-274-7294
E-Mail eye@oph.med.tohoku.ac.jp
Research Theme
Analysis of glaucoma pathomechanisms for early diagnosis and treatment of the disease and development of
drugs for neuroprotection
Technical development for an efficient gene therapy for retinal neurodegenerative disorders
Generation of disease models using iPS cells
Research Keywords: glaucoma, neuroprotection, drug development, gene therapy, iPS cells
Technical Keywords: comprehensive gene expression analysis, drug screening, genome analysis, virus vector,
stem cell biology
Glaucoma, the second common cause of blindness in 1990s, has now become the most frequent blinding disease, owing to the rapid
expansion of the aging population. Therefore, the prevention of visual loss due to glaucoma is of a paramount importance considering the
welfare of the elderly people.
Currently, the only evidence-backed treatment for glaucoma is to reduce intraocular pressure (IOP), although the disease often progress
despite achieving a sufficiently low IOP. In order to develop neuroprotective drugs for treating glaucoma that act independently of IOP,
we are employing both comprehensive gene expression analysis and molecular biology approach on animal models of glaucoma to select
candidate therapeutic molecules. Neuroprotective agents effectively targeting the candidate molecules are sought through screening of
large drug libraries equipped at Tohoku University. Other than glaucoma, our research interest extends to various other intractable ocular
diseases including age-related macular degeneration, diabetic retinopathy, retinal dystrophies, uveitis, and corneal diseases. Our laboratory
focuses on translational research through combining multidisciplinary technologies from pharmacology, engineering, agriculture, and ips
cell biology etc., and developing novel neuroprotective agents, gene therapies, cell therapies, drug delivery systems, and surgical devices.
Through clinical research, we are also studying ocular blood flow, oxidative stress, and genetic influence as IOP-independent glaucoma
factors to allow sensitive detection of glaucoma progression.
Figure 1. Development of neuroprotective drugs using an animal axonal injury Figure 2. C omprehensive gene expression analysis and development of
model neuroprotective drugs
Recent Publications
- Yasuda M, et al. Retinal transcriptome profiling at transcription start sites: a cap analysis of gene expression early after axonal injury. BMC Genomics. 18(15):982, 2014
- Aizawa N, et al. Laser speckle and hydrogen gas clearance measurements of optic nerve circulation in albino and pigmented rabbits with or without optic disc atrophy. Invest Ophthalmol Vis Sci.
55(12):7991-7996, 2014
- Yamamoto K, et al. The novel Rho kinase (ROCK) inhibitor K-115: a new candidate drug for neuroprotective treatment in glaucoma. Invest Ophthalmol Vis Sci. 55(11):7126-7136, 2014
- Omodaka K, et al. Artemin augments survival and axon regeneration in axotomized retinal ganglion cells. J Neurosci Res. 92(12):1637-1646, 2014
- Nakazawa T. Medical Research Encouragement Prize of The Japan Medical Association. 2014
Ophthalmology 45
Get Progression of Medical Treatment and Research for Otolaryngology & Head-and-Neck
Surgery
Otolaryngology-Head and Medical Sciences Course

Neck Surgery Disability Sciences Course
URL:
KATORI, Yukio http://www.med.tohoku.ac.jp/english/org/
medical/53/index.html
Professor, M.D. Ph.D. Contact:
TEL +81-22-717-7301
E-Mail yukatori@orl.med.tohoku.ac.jp
Research Theme
Mechanism of inner ear and hearing loss due to its dysfunction
Pathogenesis of head and neck cancer and function preservation treatments
Treatments of swallowing dysfunction
Research Keywords: inner ear dysfunction, patulous eustachian tube, upper respiratory tract,
pathogenesis of head and neck cancer, dysphagia and voice disorders
Technical Keywords: cochlear implant, molecular biology, histochemistry, electrophysiology, endoscopic surgery
Three main research themes are progressing by our medical staffs and posgraduate students; 1)Protection and therapy of
hearing disturbance due to dysfunctions of both peripheral and central auditory pathway. 2)Molecular biology of head
and neck cancer, and function preservation therapy for head and neck cancer. 3)Evaluation and therapy of swallowing
dysfunctions.
Each theme concerns to clinical problems and therapy of disease in the field of otolaryngology & head-and-neck surgery.
Figure 1. Brainstem auditory implant with 260 multi channels electrode Figure 2. Functional anatomy for phonation: Elastica-Masson staining of crico-
thyroid joint
Recent Publications
- Oshima H, Ikeda R, Nomura K, Yamazaki M, Hidaka H, Katori Y, Oshima T, Kawase T, Kobayashi T. (2014) Change in endocochlear potential during experimental insertion of a simulated cochlear implant
electrode in the guinea pig. Otol Neurotol. 35(2):234-40.
- Kawamoto A, Katori Y, Honkura Y, Kakuta R, Higashi K, Ogura M, Miyazaki M, Arakawa K, Kashima K, Asada Y, Matsuura K. (2014) Central-part laryngectomy is a useful and less invasive surgical
procedure for resolution of intractable aspiration. Eur Arch Otorhinolaryngol. 271(5):1149-55.
- Hidaka H, Yamaguchi T, Hasegawa J,Yano H, Kakuta R, Ozawa D, Katori Y. (2014) Clinical and bacteriological influence of diabetes mellitus on deep neck infection: a systematic review and meta-analysis.
Head Neck, Epub ahead of print.
- Yamauchi D, Yamazaki M, Ohta J, Kadowaki S, Nomura K, Hidaka H, Oshima T, Kawase T, Katori Y. (2014) Closure technique for labyrinthine fistula by underwater endoscopic ear surgery.
Laryngoscope. Epub ahead of print.
- Kakuta R, Yano H, Hidaka H, Miyazaki H, Irimada M, Oda K, Arai K, Ozawa D, Takahashi T, Kaku M, Katori Y. (2014) Severe acute otitis media caused by mucoid streptococcus pyogenes in a previously
healthy adult. Tohoku J Exp Med. 232(4):301-4.
46 Otolaryngology-Head and Neck Surgery

Multidisciplinary Approach to Health and Sports Science Covering Molecular Biology to
Epidemiology
Medicine and Science in Disability Sciences Course

SportsandExercise Medical Sciences Course
URL:
NAGATOMI, Ryoichi www.sports.med.tohoku.ac.jp
Contact:
E-Mail nagatomi@med.tohoku.ac.jp
Research Theme
Cellular basis of skeletal muscle adaption focusing on satellite cells
Investigation of risk factors for sarcopenia, cardiovascular diseases and depression
Investigation and prevention of chronic sports injuries
Research Keywords: satellitecells,hypoxicpathway,sarcopenia,physicalactivity,microbiome

Technical Keywords: wearable sensors, motion analysis, metagenomic analysis, cohort studies
Professor Ryoichi Nagatomi, a member of the board of directors of Japanese Society of Physical Fitness and Sports
Medicine, a Fellow of European College of Sports Science (ECSS) and the past president of International Society of
Exercise and Immunology, has been making significant contributions to exercise and sports science, using multidisciplinary
approach covering molecular and cellular biology, immunology, cardiovascular physiology, biomechanics, and epidemiology
and bioinformatics. He is targeting a wide range of research questions involving physical activity/inactivity, exercise and
sports, cardiovascular diseases and sarcopenia. Current topics are 1) role of protein disposal systems in skeletal muscles,
2) contribution of hypoxic responsive pathway on exercise capacity, 3) cross talk of skeletal muscle and gut microbiome,
4) investigation of risk factors for cardiovascular diseases and sarcopenia, 5) investigation of risk factors for chronic sports
injury of children and youths, 6) biomechanical approach for sports injury prevention utilizing wearable sensors.
Students from abroad are most welcome. Students from China, Korea, Indonesia, Mexico, Russia, and Finland had
previously joined our lab. Full English conversation in research conferences is guaranteed.
Figure 1. Multidisciplinary approach to health and sports science Figure 2. Investigation of skeletal muscle adaptation from molecules to human body
and population
Recent Publications
- Kitajima Y, Tashiro Y, Suzuki N, Warita H, Kato M, Tateyama M, Ando R, Izumi R, Yamazaki M, Abe M, Sakimura K, Ito H, Urushitani M, Nagatomi R, Takahashi R, Aoki M. Proteasome dysfunction
induces muscle growth defects and protein aggregation. Journal of cell science 2014;127:5204-5217
- Momma H, Niu K, Kobayashi Y, Huang C, Otomo A, Chujo M, Tadaura H, Nagatomi R. Leg extension power is a pre-disaster modifiable risk factor for post-traumatic stress disorder among survivors of the
Great East Japan Earthquake: a retrospective cohort study. PloS one 2014;9:e96131
- Huang C, Niu K, Momma H, Kobayashi Y, Guan L, Chujo M, Otomo A, Cui Y, Nagatomi R. Breakfast consumption frequency is associated with grip strength in a population of healthy Japanese adults.
Nutrition, metabolism, and cardiovascular diseases : NMCD 2014;24:648-655
- Momma H, Niu K, Kobayashi Y, Huang C, Chujo M, Otomo A, Tadaura H, Miyata T, Nagatomi R. Lower serum endogenous secretory receptor for advanced glycation end product level as a risk factor of
metabolic syndrome among Japanese adult men: a 2-year longitudinal study. The Journal of clinical endocrinology and metabolism 2014;99:587-593
- Niu K, Kobayashi Y, Guan L, Momma H, Guo H, Cui Y, Otomo A, Chujo M, Nagatomi R. Longitudinal changes in the relationship between serum adiponectin concentration and cardiovascular risk factors among
apparently healthy middle-aged adults. International journal of cardiology 2013;167:2318-2320
Medicine and Science in Sports and Exercise 47

To Promote Basic and Clinical Research on the Relationships among Health, Illness, and
Behavior: Exploring Coping Strategies for Stress-related Disorders
Behavioral Medicine Disability Sciences Course

Medical Sciences Course
FUKUDO, Shin URL:
Professor, M.D. Ph.D. http://www.med.tohoku.ac.jp/english/org/
disability/61/index.html
Contact:
TEL +81-22-717-8214
E-Mail sfukudo@med.tohoku.ac.jp
Research Theme
Elucidation of pathophysiology on brain-gut interaction in irritable bowel syndrome (IBS)
Elucidation of role of brain-gut peptide on stress-related disorders
Development of novel treatment for psychosomatic diseases
Research Keywords: behavioral medicine, psychosomatic medicine, stress, brain-gut interactions,

corticotropin-releasing hormone (CRH), irritable bowel syndrome (IBS), emotion
Technical Keywords: brain imaging, gastrointestinal motility, visceral perception, genetic research,
psychometric test, animal study
The great social benefit is expected if we can clarify the pathophysiology of stress-related disorders and coping program
against it with brain science. The mission of the Department of Behavioral Medicine is to promote basic and clinical
research on the relationships among health, illness, and behavior. Our research targets at any diseases that are influenced by
psychosocial stress but mainly focuses on physiology of stress and pathophysiology of stress-related disorders. Individuals
cope with environmental changes by behavior. The magnitude of the response is regulated in the normal range as the healthy
condition. Deviated response out of the normal range is manifested as the stress-related disorder.
This concept is well applicable to irritable bowel syndrome (IBS), one of disorders of brain-gut interactions. Patients with
IBS show aberrant regional activation of the brain in response to the visceral stimulation. We have succeeded to prove
it using cerebral evoked potential and PET imaging. We are also exploring psychological trauma, maternal deprivation,
alexithymia, and mucosal sensitization on the pathophysiology of the stress-related disorders. We plan to proceed to further
clarification of the pathophysiology of stress-related disorders, finding way of regulation of key molecule of stress response,
and developing coping program against it with brain science.
Figure 1. Brain-gut interactions published in Nat Rev Gastroenterol Hepatol Figure 2. Functional MRI in IBS patients showed less activation of the prefrontal
cortex
Recent Publications
- Aizawa E, et al. Altered cognitive function of prefrontal cortex during error feedback in irritable bowel syndrome: fMRI and dynamic causal modeling. Gastroenterology 143: 1188-1198, 2012.
- Sato N, et al. Corticotropin-releasing hormone receptor 1 gene variants in irritable bowel syndrome. PLos ONE 7: e42450, 2012.
- Seino S, et al. Enhanced auditory brainstem response and parental bonding style in children with gastrointestinal symptoms. PLos ONE 7: e32913, 2012.
- Fukudo S. IBS: Autonomic dysregulation in IBS. Nat Rev Gastroenterol Hepatol 10:569-571, 2013.
- Su J, et al. Injection of corticotropin-releasing hormone into the amygdala aggravates visceral nociception and induces noradrenaline release in rats. Neurogastroenterol Motil 27: 30-39, 2015.
48 Behavioral Medicine
To Contribute for Development in Rehabilitation Science and to Achieve Happiness of
Oneself, One's Family and the Community
Physical Medicine and Disability Sciences Course

Rehabilitation Medical Sciences Course
URL:
IZUMI, Shin-ichi http://www.reha.med.tohoku.ac.jp/modules/
tohoku/index.php?id=2
TEL +81-22-717-7338
E-Mail reha@med.tohoku.ac.jp
Research Theme
Study on rehabilitation program based on cognitive and neuroscience
Non-invasive brain stimulation for patients with central nervous system disorders
Study for pathology and management of musculoskeletal disorders
Research Keywords: recovery of brain function, body schema, phantom limb pain, musculoskeletal disorder,
quality of life
Technical Keywords: transcranial magnetic stimulation, diffusion tensor imaging, prosthetics & orthotics,
intrathecal baclofen therapy
Our goal is to develop a new technology based on medicine and engineering for preventing and minimizing disabilities
resulting from neuromusculoskeletal disorders through studies on plastic changes in human central nervous system induced
by noninvasive brain stimulation, optimization of motor control using motion analysis and computational neuroscience,
network science for community-based rehabilitation, and psycho-social intervention for patient-centered medical
management.
Our research subjects are as follows; 1) Clinical Neurophysiology (EEG, EMG, gait analysis, electromagnetic stimulation), 2)
Pathophysiology of peripheral nerves and muscles, 3) Exercise physiology, 4) Molecular biology (regenerative medicine), 5)
Rehabilitation system, 6) Rehabilitation psychology, 7) Rehabilitation engineering, prosthetics & orthotics, 8) Rehabilitation
of swallowing disorder.
Figure 1. Cognitive-neuroscientific intervention to abnormality on body scheme in Figure 2. Diffusion tensor imaging
motor-sensory impairment
Recent Publications
- Izumi SI, Saitoh E. A brief history and international perspective of the Japanese Association of Rehabilitation Medicine: the 50th anniversary in 2013. PM&R 6, 1044-1047, 2014.
- Michimata A, Suzukamo Y, Izumi SI. Development of Clinicians Communication Skills Influences the Satisfaction, Motivation, and Quality of Life of Patients with Stroke. Int J Phys Med Rehabil,1:174.
doi: 10.4172/2329-9096.1000174, 2014
- Sugiyama K et al. Clinical utility of diffusion tensor imaging and fibre tractography for evaluating diffuse axonal injury with hemiparesis. Case Rep Med 321496, 5page. 2013.
- Takeuchi N et al. Motor Control and Neural Plasticity through Interhemispheric Interactions. Neural Plast.:823285, 2012.
- Abe H et al. Prevalence and length of recovery of pusher syndrome based on cerebral hemispheric lesion side in patients with acute stroke.Stroke.;43(6):1654-6, 2012
Physical Medicine and Rehabilitation 49

We are Life Changers
Epileptology Disability Sciences Course

NAKASATO,Nobukazu URL:
Professor, M.D. Ph.D. http://www.epilepsy.med.tohoku.ac.jp
Contact:
TEL +81-22-717-7343
E-Mail nkst@med.tohoku.ac.jp
Research Theme
Seizure semiology and clinical neurophysiology
Relationship among epilepsy, sleep and the autonomic nervous system
Rehabilitation psychology of epilepsy
Research Keywords: epilepsymonitoringunit,sleepmonitoring,highfrequencyoscillation,ictaltachycardia,

functionalbrainmapping
Technical Keywords: epilepsymonitoringunit,electroencephalography,magnetoencephalography,
electrocorticography,electricalcorticalstimulation
The new Department of Epileptology began operations in February 2010, under the newly appointed Chairman, Nobukazu
Nakasato, MD, PhD. Epilepsy is a disorder characterized by recurrent episodes of paroxysmal brain dysfunction caused
by sudden, disorderly, and excessive neuronal discharges. Epilepsy is also associated with various interictal neurological,
mental, and physical symptoms. The prevalence of epilepsy is about 1% worldwide. Patients and the public generally
misunderstand that epilepsy is an untreatable disease. In addition, general physicians and even specialists in other
neurological diseases often fail to consult specialists in epilepsy to establish the correct diagnosis before starting treatment.
The new Department of Epileptology is intended to establish a comprehensive epilepsy program, including group medical
services provided by neurologists, neurophysiologists, radiologists, pediatricians, psychiatrists, neurosurgeons, specialized
nurses, pharmacists, and social workers; advance both basic and clinical research into epilepsy and related brain functions;
develop human resources for these medical services; and provide education about epilepsy for patients, their families,
the public, general physicians, and specialists in neurological diseases. The Department of Epileptology will provide
international facilities for physicians, researchers, students, and social workers intending to study the many aspects of
epilepsy to provide treatments to normalize the lives of patients with epilepsy.
Figure 1. The purple day 2014 Figure 2. Kato K, et al. Neurology 2014
Recent Publications
- Kato K, et al. Earlier tachycardia onset in right than left mesial temporal lobe seizures. Neurology 83: 1232-1236, 2014
- Itabashi H, et al. Electro- and magneto-encephalographic spike source localization of small focal cortical dysplasia in the dorsal peri-rolandic region. Clin Neurophysiol 125: 2358-2363, 2014
- Okumura E, et al. Time-varying inter-hemispheric coherence during corpus callosotomy. Clin Neurophysiol 124: 2091-2100, 2013
- Osawa S, et al. Optogenetically induced seizure and the longitudinal hippocampal network dynamics. PLoS One. 10;8(4):e60928, 2013
- Tanji K, et al. Face specific broadband electrocorticographic spectral power change in the rhinal cortex. Neurosci Lett 515: 66-70. 2012
50 Epileptology
A New Rehabilitation Concept for Patients with Visceral Impairment: Adding Life to Years
and Years to Life
Internal Medicine and Disability Sciences Course

Rehabilitation Science Medical Sciences Course
URL:
KOHZUKI, Masahiro http://www.naibu.med.tohoku.ac.jp/index.html
Contact:
E-Mail kohzuki@med.tohoku.ac.jp
Research Theme
To elucidate the mechanism of organ protection of rehabilitation medicine in Lung, Heart, Brain, Kidney, Liver and
Intestine disease
To analyze the effects of rehabilitation medicine before and after transplant surgery
To demonstrate the mechanism of organ protection of chronic exercise in animal disease models by utilizing
molecular biological techniques
Research Keywords: visceral impairment, comprehensive rehabilitation, exercise therapy,

organ damage and protection, multi-organ connection
Technical Keywords: clinical research, exercising test, animal research, molecular biological approaches,
pathologic analysis
Our laboratory is the sole laboratory in Japan to elucidate effects of rehabilitation medicine for patients with visceral
impairment such as cardiac, pulmonary, renal and hepatic disorders.
Additionally, we have demonstrated the mechanism of organ protection of exercise training in human and animal models
with chronic diseases by utilizing molecular biological techniques.
The goal of our research is to establish new comprehensive rehabilitation programs, which improve exercise performance,
quality of life, cardiovascular risk factors and prognosis, for patients with visceral impairment.
Figure 1. Cardiopulmonary exercising test to evaluate an exercise tolerance Figure 2. Exercise training for animal disease models
Recent Publications
- Suzuki T, et al. Mitochonic Acid 5 Binds Mitochondria and Ameliorates Renal Tubular and Cardiac Myocyte Damage. J Am Soc Nephrol. pii: ASN.2015060623. 2015 Nov 25.
- Ito D, et al. Chronic Running Exercise Alleviates Early Progression of Nephropathy with Upregulation of Nitric Oxide Synthases and Suppression of Glycation in Zucker Diabetic Rats.PLoS One.
10(9):e0138037, 2015.
- Kohzuki M ed. Renal Rehabilitation. Ishiyaku Pabulishers, Inc., Tokyo, Japan, 2012 [Jpn]
- Muroya Y, et al. Disorders of fatty acid metabolism in the kidney of puromycin aminonucleoside-induced nephrotic rats. Am J Physiol Renal Physiol 303: F1070-F1079, 2012
- Ebihara S. Infectious disease in the aging. Lancet Infect Dis 11: 271, 2011
Internal Medicine and Rehabilitation Science 51

Training and Research of Behavioral Neurology
Behavioral Neurology and Disability Sciences Course

Cognitive Neuroscience Medical Sciences Course
URL:
MORI, Etsuro http://www.med.tohoku.ac.jp/org/disability/65/

TEL +81-22-717-7356
E-Mail morie@med.tohoku.ac.jp
Research Theme
Clinical study of dementia
Neuropsychological and neuroimaging research of brain disease
Brain injury and stroke
Research Keywords: behavioral neurology, neuropsychology, cognitive neuroscience, neuroimaging, dementia

Technical Keywords: Alzheimer's disease, Parkinson's disease, dementia with Lewy bodies, stroke,
normal pressure hydrocephalus
Department of Behavioral Neurology and Congnitive Neuroscience was founded in 1994 as a part of Division of Disability
Sciences, Tohoku University Graduate School of Medicine. We also have a responsibility for the clinic of the Tohoku
University Hospital. Our section have graduate programs for medical students and postgraduate programs for graduate
students from various areas including neuroscience, psychology, rehabilitation sciences, and education, and provides unique
opportunities to study and research functions of the brain and mind and its relation. The research fields include clinical
neuropsychology, neuroimaging studies, research on neurobehavioral aspects of neurological diseases, and clinical trial for
neurological and cognitive disorders. We have achieved many successes in each research field, publishing more than 30
papers in each year. The backgrounds the graduate students are quite multidisciplinary, including medicine, health sciences
(PT, OT, ST, nursing, radiographer), biology, psychology, and education.
Figure 1. Amnesia-related neural tracts in the brain with thalamic infarction Figure 2. White matter abnormality in the brain with idiopathic normal pressure
hydrocephalus
Recent Publications
- Ishioka T, et al. Illusory misidentifications and cortical hypometabolism in Parkinson's disease. Mov Disord. 2011 Apr;26(5):837-43.
- Hayashi A, et al. Neural substrates for writing impairments in Japanese patients with mild Alzheimer's disease: a SPECT study. Neuropsychologia. 2011 Jun;49(7):1962-8.
- Nishio Y, et al. Neuroanatomy of a neurobehavioral disturbance in the left anterior thalamic infarction. J Neurol Neurosurg Psychiatry. 2011 Nov;82(11):1195-200.
- Uchiyama M, et al. Pareidolias: complex visual illusions in dementia with Lewy bodies. Brain. 2012 Aug;135(Pt 8):2458-69.
- Mori E, et al. Donepezil for dementia with Lewy bodies: a randomized, placebo-controlled trial. Ann Neurol. 2012 Jul;72(1):41-52.
52 Behavioral Neurology and Cognitive Neuroscience

Creating Future Medicine Concerning How Music and Sound Affect Human Body by Means
of Vibration and Subtle Energy
Music and Acoustical Medicine Disability Sciences Course

ICHIE, Masayoshi URL:
Professor, M.D. Ph.D. http://www.music.med.tohoku.ac.jp
Contact:
TEL +81-22-717-8010
E-Mail inform123@music.med.tohoku.ac.jp
Research Theme
Wellness through music activity
CAM (complementary and alternative medicine) in medical fields
Resonance of human body by music, sound and vibration
Research Keywords: music,sound,vibration,subtleenergy,resonance

Technical Keywords: near-infraredspectroscopy(NIRS),heartratevariability(HRV),vibrationalmedicine
Music therapy has been well known, however, music therapist is not medical license in Japan. There are many restrictions
for music therapists to do session in the fields of medicine because of Japanese law. We propose how to do music therapy in
the medical fields and have published a textbook of medical music therapy. We also propose that music activities are very
effective for health promotion in various manners.
Acoustic sound, vibrational medicine and subtle energy are our other interests concerning to resonance of human body. Our
purpose is to apply them to future medicine. Subtle energy can be easily caught by some kind of skin sensor, however, no
instruments can detect such energy. Developing the detector of human subtle energy will be done as a industry-university
research project.
Figure 1. Textbook of medical music therapy Figure 2. Experiment of detecting subtle energy
Recent Publications
- Otera M, et al. Expected effects of listening to music among Japanese and American college students. Music and Medicine. (In press)
- Ichie M. How to apply music therapy into Japanese medical fields, p.23-27. In Go T (ed), Medical Music Therapy from basic to clinical approaches, Kitaohji-shobou, Kyoto, Japan, 2014 [Jpn]
- Ichie M. Music and Atopic Dermatitis : Approaches from Complementary and Alternative Medicine. Skin research suppl 20: 7-12, 2013 [Jpn]
- Otera M, et al. Musical life review for the elderly with dementia as spiritual care -Clinical functions and roles of meaningful or memorable songs. The Arts in Psychotherapy. 40(3):285-290, 2013
- Ichie M. Music, Brain and Music Therapy, p.183-196, In Iwata M (ed.), Brain and Social, Igaku-shoin, Tokyo, Japan, 2012 [Jpn]
Music and Acoustical Medicine 53

Make Next Generation Fetal and Neonatal Medicine Based on the New Science of Cell
Differentiation, Development and Growth
Advanced Interdisciplinary Disability Sciences Course

Biomedical Engineering Medical Sciences Course
URL:
KIMURA, Yoshitaka http://www.fetalecg.med.tohoku.ac.jp/kimuralab/
kimuralab_top_en.html
TEL +81-22-717-7575
E-Mail ykimura@med.tohoku.ac.jp
Research Theme
Development of fetal electrocardiogram and fetal heart rate variability analysis from fetal ECG
The gene expression of fetal development and its adaptation to environment
The mathematical analysis of gene expression in single cells by using stochastic differential equations
Research Keywords: extraction algorithm of fetal electrocardiogram, the abdominal fetal ECG device,
gene expression analysis of fetal dysfunction, prevention and treatment of cardiac arrest
and brain disorder, mathematical analysis of single-cell gene expression
Technical Keywords: blind source separation, blind source separation with reference signal,
mouse model for diseases, gene expression analysis/protein analysis,
stochastic differential equation
Diseases such as autism, juvenile diabetes, asthma in children have increased in recent years. It has been thought that
maternal environment during pregnancy is very important for the pathogenesis of those diseases. However, for fetus is in the
complex context of development, it is very difficult to clarify the relation between the pathogenesis and fetal conditions.
In addition, it is known that the same protein works greatly variously in developmental stages. In our laboratory, we
investigate the gene expressions, gene regulatory networks and physiological responses under several conditions such
as hypoxia, infection, undernutrition. We studied the relation between fetal development and its responses to such
environmental changes in uterus. Our aims are to find the useful clinical applications to save babies and next generation in
uterus.
Figure 1. The actual measurement equipment Figure 2. The abstract of our experimental systems with model mouse
Recent Publications
- Dong Y, et al. Intrauterine Ischemic Reperfusion Switches the Fetal Transcriptional Pattern from HIF-1- to P53-Dependent Regulation in the Murine Brain. PLoS One. 9(10):1-7, 2014
- Velayo C, et al. Molecular patterns of neurodevelopmental preconditioning: a study of the effects of antenatal steroid therapy in a protein-restriction mouse model. ISRN Obstet Gynecol. 2014:1-13, 2014
doi:10.1155/2014/193816
- [IEEE Australia Council 2013-2014 second best student paper award] Marzbanrad F, et al. Automated estimation of fetal cardiac timing events from Doppler ultrasound signal using hybrid models. IEEE J
Biomed Health Inform. 18(4):1169-77, 2014
- [Good presentation award] Sugibayashi R, et al. Outcomes of 51 cases of twin reversed arterial perfusion sequence. The 66th Japan Society of Obstetrics and Gynecology. Tokyo. April 18th-20th, 2014 [Jpn]
- [Patent] Kimura Y, et al. Single extracting apparatus. USA. US 8,808,192B2. 2014
54 Advanced Interdisciplinary Biomedical Engineering

To Challenge the Effects of Physiology and Immunology on Nursing Practice
Science of Nursing Practice Health Sciences Course

MARUYAMA, Ryoko URL:

http://www.snp.med.tohoku.ac.jp/
Professor, R.N. Ph.D.
Contact:
TEL +81-22-717-7484
E-Mail maruyama@med.tohoku.ac.jp
Research Theme
Physiological effects on nursing practice
Relationship between sexual hormone and autonomic nervous activity
Immunological study of skin wound healing
Research Keywords: respiration, autonomic nervous activity, nursing care, wound healing, infection
Technical Keywords: heart rate variability, animal experiment, immunology
The purpose of our research will build the scientific knowledge base of advancement of nursing practice. Evidence- based
practice is nursing care provide that is supported by reliable research- based evidence. Our members are now a Professor, a
Lecture and graduate students. Our research interests are as follows,
1) Physiological effects on nursing practice
2) The effect of sexual hormone on autonomic nervous activity
3) Immunological study of skin wound healing
Figure 1. Wound healing related factors Figure 2. Effects of microbial load on the wound healing
Recent Publications
- Sasaki K, Maruyama R. Consciously controlled breathing decreases the high-frequency component of heart rate variability by inhibiting cardiac parasympathetic nerve activity. Tohoku J Exp Med. 233(3):
155-163, 2014
- Yamamoto H, et al. Defect of CARD9 leads to impaired accumulation of IFN--producing memory-phenotype T cells in lungs and increased susceptibility to pulmonary infection with Cryptococcus
neoformans. Infect Immun. 82(4): 1606-1615, 2014
- Kanno E, et al. Neutrophil-derived tumor necrosis factor- contributes to acute wound healing promoted by N-(3-oxododecanoyl)-L-homoserine lactone from Pseudomonas aeruginosa. J Dermatol Sci.
70(2): 130-138, 2013
- Denso Hayashi, et al. Low-energy extracorporeal shock wave therapy enhances skin wound healing in diabetic mice: a critical role of endothelial nitric oxide synthase. Wound Rep Regen. 20(6): 887-895,
2012
- Kanno E, et al. Wound healing in skin promoted by inoculation with Pseudomonas aeruginosa PAO1: the critical role of tumor necrosis factor- secreted from infiltrating neutrophils. Wound Rep Regen.
19(5): 608-621, 2011
Science of Nursing Practice 55

Challenge Professionalization among Nurses
Nursing Education and Health Sciences Course

Administration Master / Doctoral Degree
URL:
http://www.nem.med.tohoku.ac.jp/index.html
ASAKURA, Kyoko
Contact:
Professor, R.N. Ph.D. TEL +81-22-717-8674
E-Mail asakura@med.tohoku.ac.jp
Research Theme
Elucidation of the predictors of psychosocial working environment among nurses occupational mobility
Analysis by gender perspective of nursing phenomena
Elucidation of professional autonomy of nurses, autonomous clinical judgment of nurses, reflective thinking of
nurses
Research Keywords: professionalization, autonomy, occupational mobility, clinical judgment

Technical Keywords: scale development, survey research, qualitative research, gender analysis
Elucidation of the predictors of psychosocial working environment among nurses occupational mobility. To show off nurses
abilities and provide high quality care continuously, it is needed that nurses satisfy their work environment and continue to
work. We are engaging to elucidate the predictors of psychosocial working environment among nurses occupational mobility.
Analysis by gender perspective of nursing phenomena. Nursing has been constructed as an occupation for women since
modern times, and then 94% of nurses are female at the present time in Japan. We are analyzing phenomena of nursing by
gender perspective. Thus, we are engaging to analyze nursing phenomena by gender perspective and to aim nurses social status
in Japan moved up.
Elucidation of professional autonomy of nurses, autonomous clinical judgment of nurses, reflective thinking of nurses.
To become a complete profession, nurses should fulfill the three conditions for profession which are autonomy, publicity
and original and established knowledge. Especially for nurses, getting autonomy is really difficult. We are conceptualizing
professionalism of nurses, including autonomy, and exploring the predictors of professionalism.
Figure 1. Confirmatory factor analysis for the concept of autonomy among nurses Figure 2. Seminar at a lodging-house in Zao, Yamagata Pref
Recent Publications
- Asakura K, Kago R. Autonomous Clinical Judgment in Mid-Career Japanese Generalist Nurses, 33(4): 43-52, 2013. [Jpn]
- Tei-Tominaga M, Asakura T, Asakura K. Stigma towards nurses with mental illnesses: A study of nurses and nurse managers in hospitals in Japan. International Journal of Mental Health Nursing, 23:316-
325, 2013.
- Asakura K, Watanabe I. The Survival Strategy of Male Nurses in Rural Areas of Japan. Japan Journal of Nursing Science, 8(2): 194-202, 2011.
- Asakura K. Conservative Attitudes toward Nursing Professionalism in Japan. The Japanese Journal of Health Behavioral Science. 22: 106-120, 2007.
- Asakura K, A Study of the Development of the Attitudes Toward Sexuality Scale. The Japanese Journal of Health Behavioral Science, 17: 85-113, 2002. [Jpn]
56 Nursing Education and Administration

To Realize the Society Enable the Individuals to Keep Living in their Communities, even
with Diseases and Disabilities
Gerontological and Home Health Sciences Course

Healthcare Nursing Master / Doctoral Degree
URL:
OZAKI, Akiko
Contact:
Professor, R.N. Ph.D. TEL +81-22-717-7480
E-Mail aozaki@med.tohoku.ac.jp
Research Theme
Study on unification of cure and care in visiting nursing
Development of model for promoting sleep of evidence-based nursing among elderly
Development of the participation in community activity support program for elderly men after retirement at the age limit
Research Keywords: senior citizen/ elderly, community health, in-home care,

facility care/ residential care/ long-term care, visiting nursing
Technical Keywords: program development, education, survey, interview
Japan has the highest proportion of the elderly in the world. It is the pressing issue to reform and restructure the social
security system and the health care system in connection with super-aged and depopulation. To realize the idea that the
elderly keep on living in their familiar surroundings to the last breath, organizing the comprehensive community care system
in recent years has been advanced. Under this situation, Gerontological and home health care nursing is expected much to
play important roles. Gerontological and home health care nursing is practical science to support those who could have their
time in their community they settle in for long time. We have studied about how to support healthy aging with dignity and
about the nursing care in several places where are at home, in the community, and in the elderly facility.
Figure 1. State of the simulation experience of the elderly person Figure 2. Conference scenery in the laboratory
Recent Publications
- Nishizaki M, et al. Learning outcome of discharge support practical training of nursing students, Journal of Japan Academy Nursing for Home Care, in press.
- Saito M, et al. Demands by visiting nurses for nursing education about medical practices. Bulletin of School of Health Sciences Tohoku University, 23(2): 73-82, 2014
- Sakagawa N. The second report on the visiting of Elderly facilities in Oregon: Consideration of the actual life and self-determination for the elderly who need care in Oregon, in the United States. Bulletin of
School of Health Sciences Tohoku University. 23(1): 1-8, 2014
- Asaoka S, et al. Factors associated with shift-work disorder in nurses working with rapid rotation schedules in Japan: The nurses sleep health project. Chronobiology International, 30(4), 628-636, 2013.
- Saito M, et al. Visiting nurses' reasons for conducting pressure ulcer care of elderly patients independently during medical practice. Journal of North Japan Academy of Nursing Science, 16(1): 33-42, 2013
- Sakagawa N. Report on the visiting of elderly facilities in Oregon: Consideration of the challenge facing the quality of care in Japanese elderly facilities through observation of the management system for
quality of care in Oregon. Bulletin of School of Health Sciences Tohoku University, 22(2): 51-60, 2013
Gerontological and Home Healthcare Nursing 57

To Create the New Publicness for Solving Community Health Problems: Development
Methodology of Collaboration
Nursing Science of Health Sciences Course

Community Health Care Master / Doctoral Degree
System
URL:
http://www.med.tohoku.ac.jp/org/health/72/
Contact:
OMORI, Junko TEL +81-22-717-7930
Professor, Ph.D. R.N. P.H.N. E-Mail
Research Theme
Methodology of collaboration in community health activities
Public health nurses activities at the disaster area
Community empowerment at the disaster area
Research Keywords: higher the quality of life, publicness, methodology of collaboration,

community health activity at the disaster area, public health nurses training
Technical Keywords: health promotion, advocacy, empowerment, consensus building, management
We work on education and study about methodology of the collaboration to create the new publicness for solving
community health problemEspecially, we place emphasize on public health nurses and students training, who can develop
community health care system for improvement of the quality of life and community empowermentMain themes are
community health activity methodology of collaboration, inhabitants independency, career development of public health
nurse, social support network and construction of community health care systemAfter East Japan great earthquakewe
work on the community health nurse activity support in the stricken area, and activities for the community reproduction
through the collaboration with inhabitants / people concerned.
Also, Beginning in April 2014, the Tohoku University Graduate School of Medicine is offering a Public Health Nurse
Master's Course in the early part of its doctoral program.
The goal of this course is to provide opportunities to students hoping to become public health nurses or to brush up their skills
as public health nursesThe community health nurse training course is pioneer, and therefore we want to practice better
community health nurse education in future while testing the result.
Figure 1. Collaboration / empowerment: education, studies and community health Figure 2. Discussion toward regional revitalization by public collaboration
activities
Recent Publications
- Takahashi KSuenaga KKurimoto A. The establishment of the public healthnurse masters course tohoku university graduate school of medicine1expectations to the public health nurse masters
course. Bull. Sch. Health. Sci. Tohoku Univ.23(2)53-63,2014 [Jpn]
- Ito KSuenaga K.A study of communities of practice superintended by public healthnursesBull. Sch. Health. Sci. Tohoku Univ. 21(1):41-49,2012 [Jpn]
- Suenaga K. Disability and social welfare.p.90-106. Masuda MShimada Med,Nursingraphicus9health support and social security (3)social welfare and social security2nd edvol4.
MEDICUS SHUPPANOsaka,2012 [Jpn]
- Suenaga K. Leadership that is necessary for public health nurse managers.p.100-103Japanese Nursing Association(Ed.). New Publication Public Health Nurses Activities Handbook.2nd edJAPANESE
NURSING ASSOCIATION PUBLISHING COMPANY, LtdTokyo,2010 [Jpn]
- Kurimoto A et al. Reliability and validity of the Japanese version of the abbreviated lubben social network scale. Nihon Ronen Igakkai Zasshi.48(2):149-57,2011 [Jpn]
58 Nursing Science of Community Health Care System

To Elucidate Risk Factors and Prognostic Factors of Cancer Aiming at Cancer Prevention
and Improvement of Prognosis
Community Health Health Sciences Course

URL:
MIYASHITA, Mitsunori http://www.med.tohoku.ac.jp/english/org/
Professor, R.N. P.H.N. Ph.D. health/162/index.html
Contact:
TEL +81-22-717-7479
E-Mail
Research Theme
Elucidation of risk factors and prognostic factors of cancer on the basis of epidemiologic studies
Identification of factors affecting trend and distribution of cancer, using statistical models
Development of new methodologies to overcome difficulties in the health and medical care sector
Research Keywords: cancer, risk factors, prognostic factors, lifestyles, trend in cancer incidence
Technical Keywords: epidemiology, biostatistics, case-control studies, cohort studies, cancer registry
Since 1981, malignant neoplasms have been a leading cause of death in Japan. Our research interests are to elucidate risk
factors and prognostic factors of cancer and to identify determinants of the geographical distribution and the trend in cancer
incidence, using epidemiologic study methods. Finally, we wish to provide useful evidence for improving medical care
and promoting cancer prevention. The aim of our recent study is to clarify risk factors of cancer including those of the
stomach, lung, and breast, which are major cancers in Japan. With regard to breast cancer, we have performed several case-
control studies and cohort studies and identified risk factors. In subsequent studies, we plan to investigate the interactions
between biomarkers including hormone levels, the genetic polymorphisms and environmental factors. On the other hand, it
is assumed that the prevalence of cancer will increase. We must therefore elucidate not only risk factors but also prognostic
factors. A new technology including genetic screening and the innovative drug development advances, but "what kind of
lifestyle is connected with long-term survival?" is an important concern for cancer patients. To clarify prognostic factors of
cancer, we are conducting a patient cohort study.
Figure 1. Cohort effect on breast cancer incidence in Miyagi, based on statistical Figure 2. Prevalence of risk factors for breast cancer explaining cohort effect in
models Figure 1
Recent Publications
- Minami Y, et al. Family history, body mass index and survival in Japanese patients with stomach cancer: a prospective study. Int J Cancer. 136(2):411-424, 2015
- Seki T, et al. Cigarette smoking and lung cancer risk according to histologic type in Japanese men and women. Cancer Sci. 104(11): 1515-1522, 2013
- Kawai M, et al. Anthropometric factors, physical activity, and breast cancer risk in relation to hormone receptor and menopausal status in Japanese women: a case-control study. Cancer Causes Control.
24(5): 1033-1044, 2013
- Kawai M, et al. Body mass index and survival after breast cancer diagnosis in Japanese women. BMC Cancer, 2012 Apr 17;12:149. doi: 10.1186/1471-2407-12-149
- Minami Y, et al. Being breastfed in infancy and adult breast cancer risk among Japanese women. Cancer Causes Control. 23(2):389-398, 2012
Community Health 59
Co-creative Health Promotion Activities to Enrich Social Capitals with Local Residents for
Future of their Community
Public Health Nursing Health Sciences Course

URL:
OMORI, Junko http://www.med.tohoku.ac.jp/english/org/
Professor, Ph.D. R.N. P.H.N. health/73/index.html
Contact:
TEL +81-22-717-8010
E-Mail junko-omori@med.tohoku.ac.jp
Research Theme
Development of health promotion programs to nurture the "attachment to the local community"
Development of programs to promote the exchange of neighborhood residents
Development of collaboration model with community organizations and the profession
Research Keywords: culture, health belief, attachment to the local community, health promotion, public health nurse
Technical Keywords: CBPR (community based participatory research), mixed method, ethnography, program development,
theory / concept development
Public health is a practical science that promote local residents and professionals to collaborate in protecting the shared property of
society, namely, human life, living and livelihood. Nurses working in this field are experts in health, questioning the true meaning
of auence and quality of life (QOL) at a particular time and place, providing preventive care, and supporting to create a culture
of health as members of the ever-changing local community. Our discipline is built on the principle that health is not provided by
experts, but is a culture that must be developed as part of peoples daily life.
Our study focuses on the perception of health as culture and health promotion for different socio-cultural groups. Each community
consists of various socio-cultural groups (sub-communities), and each sub-community has its own perceptions of health depending
on a wide range of factors including age, circumstances, diseases and disabilities. We develop care and support techniques by
identifying key health drivers by asking the question, When do people feel more alive, energy and relief? We believe that
research should respect cultural diversity and learn from peoples ways of life.
Adopting the Community-Based Participatory Research (CBPR) approach, a mainstream research style prevailing in the public
health community in the US, we are promoting personal and social transformation, working with local residents and health
administrators such as public health nurses in various projects including: Development of a Health Promotion Program to Nurture
Attachment to the Local Community.
Figure 1. Program to facilitate conversation on attachment to their community Figure 2. Health education by community health workers
Recent Publications
- Omori J. Development of Strategies for Healthy Community Building through Accumulation of Evidence, The 2nd JAPAN- KOREA Joint Conference on Community Health Nursing,Hyogo, Japan,
2011.7.17.Invited lecture
- Omori J. Emerging Policy Issues for Elderly Health Promotion in Japan,International Conference on Evidence-Based Research and Practice in Older Adults,Kaohsiung Medical University, Kaohsiung,
Taiwan,2012.5.26.Invited lecture
- Omori J, et al. Concept Analysis of "Attachment to the local community" for Public Health Nursing, Japanese Journal of Public Health Nursing, 3(1), 40-48, 2014. [Jpn]
- Taguchi A, et al. Home visiting nurse agencies for community dwelling elderly at nighttime in Japan. Home Health Care Management & Practice, 25(6), 256-63, 2013.
- Taguchi A, et al. Identification of the need for home visiting nurse: development of a new assessment tool. International Journal of Integrated Care 2014; 14.
60 Public Health Nursing

Cross Talk between Gastrointestinal Epithelial Cells and Immune System in
Transdifferentiation and Carcinogenesis
Adult Health Nursing Health Sciences Course

IMATANI, Akira URL:

Contact:
TEL +81-22-717-8010
Research Theme
Molecular analyses of the carcinogenesis through the immune response to Helicobacter pylori infection in the
stomach
Molecular mechanisms of the differentiation of gastric epithelial cells under the chronic inflammation and aging
Influence of gene polymorphisms on the susceptibility of gastrointestinal diseases
Research Keywords: gastric cancer, Helicobacter, mucosal immunology, differentiation, gene polymorphism
Technical Keywords: immunohistochemistry, cell culture, molecular biology, animal experiment, genotyping
Host immune response to Helicobacter pylori (H. pylori) infection causes chronic inflammation and this influences on
the transdifferentiation from gastric oxyntic glands to atrophic gastritis and intestinal metaplasia. The deviation from this
transdifferentiation may lead to gastric cancer. Therefore, the major interest of our research is to clarify the molecular
mechanisms of the differentiation and carcinogenesis of gastric epithelial cells under chronic inflammation and aging. We
focus on key molecules related with the differentiation of gastrointestinal tract, especially homeobox genes Sox2 and Cdx2
as well as a transmembrane receptor Notch1, and investigate the expression pattern and cell signaling pathways of these
molecules by the immune response to H.pylori infection using in vitro and in vivo analyses. In addition, we are investigating
about signaling pathways that are involved in tumorigenesis such as NF-B, STAT3, SHP-2 and Wnt/-catenin signaling.
On the other hand, host genetic factors, i.e. gene polymorphisms, affect interindividual variation in the gastric
carcinogenesis sequence. After identifying novel genes related with the transdifferentiation and carcinogenesis in the
stomach, we are searching for the gene polymorphisms as biomarkers useful for early diagnosis of gastric cancer and for
preventive medicine.
Figure 1. Transdifferentiation and carcinogenesis in gastric epithelial cells by Figure 2. Expression of differentiation related transcriptional factors in the stomach
chronic inflammation
Recent Publications
- Oikawa T et al, Gene polymorphisms of NOD1 and interleukin-8 influence the susceptibility to erosive esophagitis in Helicobacter pylori infected Japanese population. Hum Immunol. 73:1184-1189, 2012
- Asonuma S, et al. Helicobacter pylori induces gastric mucosal intestinal metaplasia through the inhibition of interleukin-4-mediated HMG box protein Sox2 expression. Am J Physiol Gastrointest Liver
Physiol. 297:G312-322, 2009
Adult Health Nursing 61

Realizing Care to Improve Cancer Patients' Quality of Life: Developing Telenursing
Systems and Care for Rebuilding Life after Cancer Treatment
Oncology Nursing Health Sciences Course

SATO, Fumiko URL:

http://www.oncolnurs.med.tohoku.ac.jp
Contact:
TEL +81-22-717-7926
E-Mail fsato@med.tohoku.ac.jp
Research Theme
Intervention to prevent and improve impaired upper limb function following surgery for breast cancer
Stress and quality of life in cancer patients
Telenursing system for cancer patients
Research Keywords: oncology nursing, quality of life, telenursing, rehabilitation

Technical Keywords: intervention study, patients survey, technical innovation
We are conducting multifaceted research to develop care for improving cancer patients quality of life (QOL). An
intervention study is currently underway on building a comprehensive long-term rehabilitation care program based on the
effects and outcomes of long-term interventions at 5 years after surgery. This work is being done as part of developing
an intervention program to prevent and improve impaired upper limb function in breast cancer survivors. Findings at 3
years after surgery suggest that interventions to facilitate self-care through daily self-monitoring of upper limb function,
and consultation with doctors on adjusting rehabilitation and lifestyle, may help prevent and improve impaired upper limb
function after surgery. Since 2014 we have also been developing a telenursing system for prostate cancer surgery patients.
Doctors and nurses in a remote location check data sent via the cloud and manage ongoing rehabilitation, providing advice
and other such nursing care. This system provides effective complementary assistance for patients receiving treatment
at home. Using studies and surveys on QOL in various cancer patients, we hope to investigate care for rebuilding cancer
patients lives after surgery.
Figure 1. Comparison of subjective evaluation of an upper arm dysfunction Figure 2. Comparison of the disability of the arm, shoulder hand
Recent Publications
- Sato N, et al. Immunolocalization of corticotropin-releasing hormone (CRH) and its receptors (CRHR1 and CRHR2) in human endometrial carcinoma: CRHR1 as a potent prognostic factor. .Int. J. Gynecol.
Cancer Nov; 24(9):1549-57, 2014
- Sato F, Ishida T, Ohuchi N. The Perioperative Educational Program for Improving Upper Arm Dysfunction in Patients with Breast Cancer: A Controlled Trial, Tohoku J. Exp. Med. 232,115-122, 2014
- Sato N, et al. Corticotropin-Releasing Hormone Receptor 1 Gene Variants in Irritable Bowel Syndrome. PLoS ONE, 7(9): e42450.doi:10.1371/journal.pone.0042450, 2012
- Sato F. Facters Related to Pain in the Arm on the Affected Side in Breast Cancer Survivors Who Had Undergone Surgrery within the Past Year. The Japanese Health Behavioral Science,27,157-170, 2012 [Jpn]
- Sato N, Minakawa S, Fukudo S. Development of a Terminal Phase Patient Support Cognitive-Behavioral Scale for Medical Professionals. Jpn Psychosom Med,52,5-33, 2012 [Jpn]
62 Oncology Nursing
At the Department of Palliative Nursing, We Study on Palliative Care, One of the Most
Needed Specialties in Cancer Nursing
Palliative Nursing Health Sciences Course

MIYASHITA, Mitsunori URL:

http://www.pn.med.tohoku.ac.jp/index.html
Professor, R.N. P.H.N. Ph.D.
Contact:
TEL +81-22-717-7924
E-Mail miya@med.tohoku.ac.jp
Research Theme
Evaluation of quality of palliative care
Evaluation of quality of life in patients and families with cancer
Survey on end-of-life care
Research Keywords: palliative care, terminal care, nursing, quality of life, quality of care
Technical Keywords: survey, measurement, quality assurance, evaluation study
At the Department of Palliative Nursing, we study on various topics related to palliative care, one of the most needed
specialties in cancer nursing. One of our major mission is to develop and provide palliative nursing care, which improves
the quality of life of patients and their families facing the problem associated with life-threatening illness, through the
prevention and relief of suffering by means of early identification and impeccable assessment and treatment of pain and
other problems, physical, psychosocial and spiritual. Graduate students are qualified for an examination of certified nurse
specialist in cancer nursing.
Figure 1. Illness trajectry and palliative care in onclogy Figure 2. Major topics of research
Recent Publications
- Kinoshita H, Maeda I, Morita T, Miyashita M, Yamagishi A, Shirahige Y, Takebayashi T, Yamaguchi T, Igarashi A, Eguchi K. Place of Death and the Differences in Patient Quality of Death and Dying and
Caregiver Burden. J Clin Oncol. 2015;33(4):357-63.
- Morita T, Miyashita M, Yamagishi A, Akiyama M, Akizuki N, Hirai K, Imura C, Kato M, Kizawa Y, Shirahige Y, Yamaguchi T, Eguchi K. Effects of a programme of interventions on regional comprehensive
palliative care for patients with cancer: a mixed-methods study. Lancet Oncol. 2013;14(7): 638-46.
- Miyashita M, Morita T, Sato K, Tsuneto S, Shima Y. A nationwide survey of quality of end-of-life cancer care in designated cancer centers, inpatient palliative care units and home hospices in Japan: the
J-HOPE study. J Pain Symptom Manage. (in press)
- Sato K, Miyashita M, Morita T, Tsuneto S, Shima Y. Family member perspectives of deceased relatives' end-of-life options on admission to a palliative care unit in Japan. Support Care Cancer.
2012;20(5):893-900
- Miyashita M, Morita T, Hirai K. Evaluation of end-of-life cancer care from the perspective of bereaved family members: The Japanese experience. J Clin Oncol. 2008; 26(23): 3845-52.
Palliative Nursing 63
To Explore Child Health Nursing as a "Future Genesis of Science" which Works to Create
a Future for Human Being
Child Health Nursing Health Sciences Course

SHIWAKU, Hitoshi URL:

http://www.chn.med.tohoku.ac.jp/
Contact:
TEL +81-22-717-7921
E-Mail inquiry@chn.med.tohoku.ac.jp
Research Theme
The psychosocial support nursing for child and their family
The mental health care for children with neurosis or developmental disorder (ADHD, ASD, etc.) and their family
The total care for children with malignancy and their family
Research Keywords: child, family, psychosocial support, developmental disorder, pediatric oncology
Technical Keywords: notification, decision making, treatment and education, autistic spectrum disorder, end of life care
The purpose of this study is to clarify the kinds of images that children hold about disease in general and the diseases that
they have actually suffered. The total number of subjects(child and parent) in this study was 1298.They ranged from 4th
graders to 9th graders. We have collected 357 valid responses.
The result of our analysis is as follows.
1.Children image "cancer" with the highest frequency when they heard the word "disease" (130 children, 38.7%), followed
by influenza (77 children, 22.9%) and common cold (34 children, 10.1%).
2.While children in elementary school tend to image minor diseases, students of junior high school image diseases that are
more serious.
3.Children who imaged serious diseases showed more negative images, such as "scary," "tough and hard," "painful," and
"fatal," about the diseases that they had listed than those who imaged minor diseases and chronic diseases.
4.While 82.2% of children answered that they would like to know about their own serious diseases, 14.1% of them responded that they
would not like to know.
5.Children who imaged serious diseases showed a stronger interest in knowing about their own diseases than those who
imagined minor diseases.
Figure 1. The children want to know own serious diseases Figure 2. Recognition about the disease notification of child and parent
Recent Publications
- Nagoya Y, et al. Barriers and Difficulties felt by Pediatric Nurses Providing End-of-Life Care. Journal of Japanese Society of Child Health Nursing 23(3):49-55,2014[Jpn]
- Nagoya Y, et al. How did the parents informed that their child with incurable cancermake decisions about treatment course of their child? Journal of North Japan Academyof Nursing Science 17(1)
11-17.2014[Jpn]
- Nagoya Y, Shiwaku H, Suzuki Y. Nurses' Conflicts in Caring for End-of-Life Children with Cancer and Their Parents. Journal of Japanese Society of Child Health Nursing 22(2):41-47.2013 [Jpn]
- Irie W, et al. Fathers Feeling and Thought towards Their Interaction during the Hospitalization of Their Children with Cancer-Comparison between Fathers of Childhood Cancer Patients and the Others of
Children on Long Hospitalization-.J.JSPON 7:28-38.2012[Jpn]
- Shiho S, Yukiko S, Hitoshi S. Factors Associated with Childrens Ineffective Coping Behavior during Blood Sampling. Japanese journal of nursing research 34(4):23-31.2011[Jpn]
64 Child Health Nursing

Psychiatric Nursing is an Important Study in Modern Times when Mental Health is Likely to
be Impaired
Psychiatric Nursing Health Sciences Course

URL:
SAITO, Hidemitsu http://www.med.tohoku.ac.jp/org/health/164/
Contact:
TEL +81-22-717-7916
E-Mail saito-h@med.tohoku.ac.jp
Research Theme
Support of reducing the incidence or the relapse of mental disorders
Mental health support for nurses and family of patients
Provision against stigma toward persons with mental disorders
Research Keywords: mental health, nurses, persons with mental disorders, stigma, family
Technical Keywords: educational program development, internet questionnaire survey, psychoeducation
Early detection and intervention in schizophrenia are important in improving quality of life after treatment and are major
issues in psychiatric care. Our study's aim is investigate the effectiveness of a web-based education program that aimed to
improve understanding of schizophrenia among parents of adolescents. The content of the education program consisted of 10
units: characteristics, causes, symptoms, classification, course of the disease and its characteristic clinical features, treatment,
prognosis, how to prevent progression and exacerbation of the disorder, signs of progression, and consultation facilities.
Education program show included 12 slides with narration and required 13 minutes to complete. The program resulted in
an improvement in basic knowledge of schizophrenia, discrimination of schizophrenia symptoms, and discrimination of
prodromal symptoms (P < 0.001 for all) (Fig 1).
In addition, as part of an effort to develop an education program to combat stigma toward schizophrenia, we surveyed
1,309 mothers of junior and senior high school students in Japan. The mean (SD) score for the Devaluation-Discrimination
Measure (DDM) was 32.74.4, which was similar to scores reported in other studies. Among mothers, stigma toward
schizophrenia was associated with contact with people with the disorder. The findings disproved our hypothesis that having
contact and communication with a person with schizophrenia would reduce stigma (Fig2).
Figure 1. Rates of correct answers on knowledge and discrimination between Figure 2. Associations between DDM and demographic characteristics of
disorders respondents
Recent Publications
- Yoshii H, et al. Effect of an education program on improving knowledge of schizophrenia among parents of junior and senior high school students in Japan. BMC Public Health. 11: 323, 2011
- Yoshii H, et al. Stigma toward schizophrenia among parents of junior and senior high school students in Japan. BMC Res Notes. 4: 558, 2011
- Norika M, et al. Implementation of a psychological program during the recovery phase of first-episode psychosis in a Japanese clinical setting, Psychiatric Nursing.44: 137-140,2014 [Jpn]
- Saito H, et al. Support for midwives in midwife-led care clinic. Japanese Journal of Psychiatric Treatment.28(6):715-720, 2013 [Jpn]
- Saito H, et al. Family Support in the Palliative Care Center. Clin Psychiatry. 54(4):419-426, 2012 [Jpn]
Psychiatric Nursing 65
Providing Full Support which Makes Perinatal Women More Comfortable and Safe and
Overcoming a Declining Birthrate
Maternal Nursing Health Sciences Course

SATO, Kineko URL:

http://www.med.tohoku.ac.jp/org/health/69/
Contact:
TEL +81-22-717-7956
E-Mail satokine@med.tohoku.ac.jp
Research Theme
Maternal mental health care
Perinatal women in stricken area of the East Japan Great Earthquake
Educational history of nursing and midwifery
Research Keywords: perinatal nursing, mental health care, history of nursing education,
history of midwifery education, disaster nursing, medical system
Technical Keywords: counseling, education for perinatal women, advanced life support in obstetrics
During pregnancy and child bearing, hormonal changes can significantly influence a womans mental state. Postpartum
depression occurs in 10-15% of Japanese women. Our research studied the effect the East Japan Great Earthquake of 2011
had on the rate of postpartum depression on our participants. Using the Edinburgh Postnatal Depression Scale and the
General Health Questionnaire 28, two efficient screening tools for psychiatric distress, we evaluated 886 parents of children
born in Miyagi between February and October 2011. Ten months after the earthquake 21.5% of these mothers scored over
nine on the Edinburgh Postnatal Depression Scale as compared with the average of mothers who gave birth during other
time periods. The average percentage of people who score over the cutoff value is 10-14% of Japanese. We found the that
percentage of parents who scored high for depression on the General Health Questionnaire 28 was greater at 16, 24, and
36 months postpartum than in parents whose child was born outside the earthquake period. (65.3%, 55.3%, and 56.4% for
mothers and 46.2%, 48.2%, and 60.0% for fathers) Continued research is needed to understand the mental health of women
who have given birth during periods of natural disaster and to be able to propose relevant supportive long term help.
Figure 1. Comparison before and after the disaster area Figure 2. GHQ28 score of the parents after the disaster
Recent Publications
- Sato K. Effects of the Great East Japan Earthquake gave the mother of mental health. The Japanese Journal for Midwives.66(10)858-863,2012[Jpn]
- Sato K, et al.Mental and physical health for women one year and four months after the Great East Japan Earthquake, who were in the peripartum period at the time In relation to the degree of satisfaction of
couples-. J Jp Soc Psychosom Obstet Gynecol 19(2)197-203.2014[Jpn]
- Yoshii H,et al.Maternal Anxiety 16 Months after the Great East Japan Earthquake Disaster Area:First Report.Health 870-878,2014
- Oyamada N, et al.Process of nurse education system and the status defining law establishment in Miyagi of the Meiji period -Background until the nurses' training school opening of a school attached to the
Miyagi Prefectural hospital- .The Journal of Japan Society of Nursing History.21:56-67,2008 [Jpn]
- Kikuchi A, et al. Paternal consciousness for a family member at two months after the birth of a second -born child. Journal of North Japan Academy of Nursing Science.16(1):1-12,2013[Jpn]
66 Maternal Nursing
Challenging Womens Health Research to Enhance the Radiance of Health in All Women:
Innovations in Nursing for the Next Generation
Women's Health Nursing Health Sciences Course

URL:
YOSHIZAWA, Toyoko http://www.med.tohoku.ac.jp/english/org/
Professor, R.N. C.N.M. Ph.D. health/70/index.html
Contact:
TEL +81-22-717-7915
E-Mail info@womens.med.tohoku.ac.jp
Research Theme
Womens lower limb edema and their health-related quality of life (QOL)
Development of an intervention program for learning coparenting skills
The cognition of fertility in men and women
Research Keywords: lower limb edema, coparenting, couple communications, pregnant women, comfort fertility
Technical Keywords: LYMQOL, fundamental family program, prenatal comfort scale
In the field of women's health nursing, our research has focused not only on the health of perinatal women and their babies,
but also on the health of women at all life stages. That includes womens gynecological health problems (i.e., those issues
related to menarche, pregnancy, sexual functioning, and menopause) as well as gender-related social issues (gender roles,
sexuality).
Since 2013, we have adopted the idea of the benefits of coparenting, and we have shifted to research about choices that
can help families in maintaining a balance between working and child rearing and enhance the health radiance of both
women and men. Such projects will enhance the development of a healthy new generation. We also have just undertaken
the development of a program to promote parenting abilities for pregnant couples which will cover basic research regarding
becoming a father, the child rearing abilities of fathers, etc.
We are currently undertaking the study of a variety of other research topics, including specific problems of women under
disaster conditions, lower limb edema trouble in women, QOL and health issues for hospitalized pregnant women who have
been prescribed activity restriction, male infertility, and fertility in men and women.
Figure 1. Our original concept model of copearenting Figure 2. Example of daily activity count over time using actiwatch2
Recent Publications
- Nakamura Y, Takeishi Y, Ito N, Ito M, Atogami F, Yoshizawa T: Comfort with Motherhood in Late Pregnancy Facilitates Maternal Role Attainment in Early Postpartum, The Tohoku Journal of Experimental
Medicine, 235(1), 2015, in press.
- Yoshizawa T. Pathways to a distinguished young researcher in nursing science. Nursing Research 47(1):6-13,2014[Jpn]
- Sato M, Atogami F, Nakamura Y, Yoshizawa T. Remote community-based public health nursing a disaster: an ethnographic case study in Japan.Australas Emerg Nurs J.17(3):106-11,2014.
- Atgami F, ,Nakamura Y, Takeishi Y, Ito N, Yoshizawa T. Change of vomfort during pregnancy for women who married after they were pregnant. Journal of Japan Maternity Nurisng(14)1:50-56,2014[Jpn]
- Takeuchi M, Yoshizawa T,Kusaka Y, Furusawa Y, Nakamura Y, Atogami F, Niikura H. Detecting subclinical secondary lymphedema using bioimpedance: A preliminary Study, Journal of Lymphoedema
8(2):16-20,2013.
Women's Health Nursing 67

High Accuracy Imaging of Cancer, Peripheral Artery Disease, and Dementia: Clarification of Disease
Mechanisms and Development of Disease Diagnosis Methods
Medical Physics Health Sciences Course

URL:
GONDA, Kohsuke http://www.med.tohoku.ac.jp/english/org/
Professor, Ph.D. health/159/index.html
Contact:
TEL +81-22-717-8010
Research Theme
Development of high resolution and accuracy imaging using nanotechnology
Medical study of cancer and peripheral artery disease with nano-imaging
Simulation study of pharmacokinetic and radiation physics in human body using PET and SPECT
Research Keywords: nanomedicine, imaging, nuclear medicine (PET/SPECT), cancer, peripheral artery disease
Technical Keywords: high accuracy, early diagnosis, evaluation of drug efficacy, pharmacokinetic analysis,
image processing
Cancer and arterial sclerosis are main cause of the death in Japan. Imaging technology is very important for the
effective development of diagnosis in early stage and treatment methods for these diseases. We have been developing
the nanomedicine-based technologies for X-ray computed tomography (CT) imaging or fluorescence imaging with high
accuracy and highly-quantitative sensitivity to clarify the mechanism and develop the diagnostic methods for these diseases.
Both imaging technologies have highly-quantitative sensitivity because X-ray absorption coefficients is proportional to the
volume of contrast agents and fluorescence signal intensity is proportional to the intensity of the photon excitation energy.
We previously found that the tumor cells showed increases in membrane fluidity (over 1000-fold) (J. Biol. Chem. 2010)
and the three-fold difference in VEGF receptor distribution on the vascular wall is important for the formation of branched
vasculature from a linear vessel in angiogenesis.of arteriosclerosis (Blood, 2011). Then, we have been developing the
technique to diagnose efficacy of anticancer drugs with high certainty by imaging of surgical specimens (Biochem. Biophys.
Res. Commun., 2012). In addition, increase of dementia is considered a social problem in Japan. To design new diagnostic
drug for dementia, we aims to develop beneficial methodologies on quantitative PET and SPECT imaging.
Figure 1. Development of X-ray CT imaging of micro tumor Figure 2. Fluorescence imaging of tumor cells for evaluation of drug efficacy
Recent Publications
- Gonda K, et al. In vivo nano-imaging of membrane dynamics in metastatic tumor cells using quantum dots. J. Biol. Chem. 285(4): 2750-2757, 2010.
- Hamada Y, et al. In vivo imaging of the molecular distribution of the VEGF receptor during angiogenesis in a mouse model of ischemia. Blood 118: 118(13):e93-e100, 2011
- Gonda K, et al. Development of a quantitative diagnostic method of estrogen receptor expression levels by immunohistochemistry using organic fluorescent material-assembled nanoparticles. Biochem.
Biophys. Res. Commun. 426(3):409-414, 2012
- Shidahara M, et al. Wavelet-based resolution recovery using anatomical prior provides quantitative recovery for human population phantom PET [11C]raclopride data. Phys Med Biol. 57(10):3107-22, 2012
- Shidahara M, et al. Evaluation of the biodistribution and radiation dosimetry of the F-18 labelled amyloid imaging probe [18F]FACT in humans. EJNMMI res. 3(1):32, 2013
68 Medical Physics
To Investigate Image Quality of Medical Images Aiming at Clinical Applications
Mededical Imaging and Health Sciences Course

Applied Radiology Master / Doctoral Degree
URL:
MACHIDA, Yoshio
Contact:
Professor, Ph.D. TEL +81-22-717-7937
E-Mail info@miar.med.tohoku.ac.jp
Research Theme
Evaluation and improvement of image quality in MR fast imaging such as Propeller MRI or compressed sensing
MRI
Investigation of fundamental image characteristics in MR applications such as diffusion-weighted imaging or non-
contrast MR angiography
Investigation of cancer therapy with neuromodulation
Research Keywords: MRI, image quality, MR fast imaging, compressed sensing, neuromodulation
Technical Keywords: image reconstruction, pulse sequence, numerical experiment, electrical stimulation
As morphological and functional information of the human organs can be obtained noninvasively with magnetic resonance
imaging (MRI), it is anticipated that MRI techniques will develop further in the field of medical imaging. The Department
of Medical Imaging and Applied Radiology has strong interests in the MR imaging techniques and its clinical applications.
One of the topics the department is focusing on is evaluation and improvement of MR image quality, especially in MR fast
imaging such as Propeller MRI or compressed sensing MRI.
Figure 1. Analysis of noise characteristics of MR images by NPS Figure 2. Analysis of CS reconstructed images by numerical experiments
Recent Publications
- Saito T, et al. Evaluating image quality of compressed sensing MRI aiming at clinical applications, 100th RSNA, PHE024-b, 2014/12, Chicago, "CERTIFICATE of MERIT" AWARD
- Ichinoseki Y, et al. Noise power spectrum in PROPELLER MR imaging, Magn Reson Med Sci, In Press
- Nakai T, et al. The Tsunami Disaster to MR Scanners in the Great East Japan Earthquake in 2011, Magn Reson Med Sci, 13(3): 197-198, 2014
- Mori I, et al. Photon starvation artifacts of X-ray CT: their true cause and a solution, Radiological Physics and Technology,6: 130-141, 2013
- Machida Y, et al. Parallel imaging based on expanded unfolding technique USP7,205,765, 2007
Mededical Imaging and Applied Radiology 69

Revelation of Fundamental Mechanisms and Origin of Intelligence in Neural Information Processing
by Biomedical Imaging and Computational Intelligence Techniques
Radiological Imaging and Health Sciences Course

Informatics Master / Doctoral Degree
URL:
http://www.med.tohoku.ac.jp/english/org/
HOMMA, Noriyasu health/75/index.html
Contact:
E-Mail secretary@rii.med.tohoku.ac.jp
Research Theme
Revelation of the information processing mechanisms in the neuronal circuit of cortico-basal ganglia loop
Development of highly intelligent medical instruments
Improvement of X-ray CT image quality
Research Keywords: basal ganglia, Parkinsons disease, calcium, image-guided radiation therapy, computer-aided diagnosis
Technical Keywords: calcium imaging, MRI, X-ray CT, computational intelligence, machine learning
By using multi-modal imaging techniques, we aim to accurately visualize wide range of biomedical phenomena such as
microscopic neurophysiological activities as well as macroscopic whole brain ones. The images can then be utilized for
not only extracting useful information for medical and life sciences, but also revealing mechanisms of neural information
processing and implementing them. For example, the basal ganglia receives the input from cortex and sends the output to
cortex, and is thought to play a crucial role in motor control, reward prediction, learning, and memory. The basal ganglia
also related to the symptoms of Parkinsons disease. However, the fundamentals of information processing in the basal
ganglia and the pathophysiological mechanisms of Parkinsons disease are not fully elucidated. Therefore, we conduct
the studies for revelation of the information processing mechanisms in the neuronal circuit of cortico-basal ganglia loop,
and pathophysiological characteristic of Parkinsons disease. In addition to the neurophysiological analysis, we also build
computational models of neural information processing inspired by highly intellectual skills of human specialists such as
radiologists. Based on the models and some machine learning techniques, we develop intelligent computer-aided systems for
medical image diagnosis, interventional radiology, and image-guided therapy.
Figure 1. Visualization of the neuronal activity changes by qAIM- MRI Figure 2. Novel intelligent fluoroscopic imaging: Tumor
extraction (right) from the X-ray image (left)
Recent Publications
- Zhang X, et al, Tracking tumor boundary in MV-EPID images without implanted markers: A feasibility study, Medical Physics, 42(5): 2510-2523, 2015
- Kikuta S, et al. Quantitative activation-induced manganese-enhanced MRI reveals severity of Parkinsons disease in mice. Scientific Reports 5: 12800, 2015
70 Radiological Imaging and Informatics

To Challenge Disease Detection and Cause of Death Investigation using Medical Imaging
Clinical Imaging Health Sciences Course

ISHIBASHI, Tadashi URL:

Contact:
TEL +81-22-717-7481
Research Theme
Development of the diagnostic support system for digital mammography
Non-invasive treatment, especially development of the device for intravascular stenosis
Cause-of-death investigation using postmortem imaging
Research Keywords: digital radiography, computed assisted detection, image display, non-invasive therapy,
forensic imaging
Technical Keywords: digital mammography, automated computer diagnosis, quality control of medical image
display, stent, postmortem imaging
In this field, the imaging-diagnostic-technology is broadly studied from fundamental to clinical application.
1) The digital diagnostic techniques using a flat panel or a computed radiography, especially in mammography are studied.
Moreover, joint research with engineering is performed about computer assisted detection and systems.
2) In cooperation with forensic medicine, we develop a technique for the
interpretation of postmortem imaging and investigate a cause of death
Figure 1. A case of CAD detection in digital mammography Figure 2. Images of postmortem CT scans
Recent Publications
- Ishibashi T, et.al. Digital mammographic screening in Japan. Breast Cancer. 17(3):159-62.2010
- Zhang X, et,al. A Hybrid Image Filtering Method for Computer-Aided Detection of Microcalcification Clusters in Mammograms. Journal of Medical Engineering. Volume Article ID 615254, 8 pages. 2013
- Sato M, et,al. Cost-effectiveness analysis for breast cancer screening: double reading versus single + CAD reading. Breast Cancer. 2014 Sep;21(5):532-41
- Kawasumi Y,et,al. Hypothermic death: possibility of diagnosis by post-mortem computed tomography.Eur J Radiol. 2013 Feb;82(2):361-5
- Kawasumi Y, et,al. Diagnosis of drowning using post-mortem computed tomography based on the volume and density of fluid accumulation in the maxillary and sphenoid sinuses Eur J Radiol. 2013
Oct;82(10):e562-6
Clinical Imaging 71
To Optimize Modern Imaging Modalities for Various Diseases, and Coach Academic
Writing Skills for Students
Diagnostic Image Analysis Health Sciences Course

SAITO, Haruo URL:

Contact:
TEL +81-22-717-7938
E-Mail hsaito@med.tohoku.ac.jp
Research Theme
Optimization of the modern imaging modalities, magnetic resonance imaging and MDCT, for the evaluation of the
cardiovascular system
Optimization of postmortem imaging before forensic autopsy, and revealing its advantages and disadvantages
Development of a new monitoring system of exposure dose in the radiotherapy using ruby scintillator
Research Keywords: cardiovascular MRI, cardiovascular MDCT, postmortem image analysis,

functional brain imaging, X ray exposure monitoring
Technical Keywords: MRI, MDCT, PET, IVR
The aim of our studies are follows:

1Autopsy imaging: optimization of postmortem imaging before autopsy , and revealing its advantages and disadvantages.
2Optimization of the modern imaging modalities, magnetic resonance imaging and multi-detector-row CT, for the
evaluation of the cardiovascular system. The function of the heart is to provide energy and perfuse organ vascular beds.
The vascular system plays an important role as the distributed conduit. Modern development of the imaging technologies,
enables us to obtain precise images of the heart and great vessels less invasively. We focus on the regional myocardial
motion and stress-strain state of the aorta.
3) Analysis of brain function imaging: using PET, SPECT and MRI; to determine the presence and the patterns of the
differences between neurodegenerative disease patients and normal controls.
4) To research of the precision management by PET/CT, SPECT equipments with Tohoku University Hospital.
5) Development of a new monitoring system of exposure dose in the radiotherapy using ruby scintillator.
Figure 1. Poster presentation in Malaysia Figure 2. Image analysis of MDCT with cardiac phantom
Recent Publications
- Hosokai Y, et al. Distinct patterns of regional cerebral glucose metabolism in Parkinsons disease with and without mild cognitive impairment. Mov Disord 24:854-862, 2009
- Usui A, et al. Usefulness of postmortem computed tomography before forensic autopsy for alerting forensic personnel totuberculous infection. Jpn J Radiol 30: 612-5, 2012
- Konno M, et al. Cardiac output obtained from test bolus injections as a factor in contrast injection rate revision of following coronary CT angiography. Acta Radiol. 53:1107-11, 2012
- Nakajima A, et al. The prevalence of morphological changes in the thoracolumbar spine on whole-spine computed tomographic images Insights Imaging. 5:77-83, 2014
- Usui A, et al. Postmortem lung features in drowning cases on computed tomography.Jpn J Radiol. Jul;32(7):414-20. 2014
72 Diagnostic Image Analysis

Radiation Protection and Dosimetry
Radiological Examination Health Sciences Course

and Technology Master / Doctoral Degree
URL:
http://irides.tohoku.ac.jp/eng/organization/
CHIDA, Koichi medicine/03.html
Contact:
E-Mail chida@med.tohoku.ac.jp
Research Theme
Radiation safety management and radiological protection in medicine
QC and QA for radiation equipment and optimization of radiation dose and image performance
Radiation disaster medicine
Research Keywords: patient and occupational exposure, radiation safety management, optimization of radiation dose and
image quality, interventional radiology, deterministic and stochastic effects
Technical Keywords: radiation dosimetry, energy and beam quality, phantom and image performance,
effective dose and equivalent dose, radioactivity, quality assurance and quality control (QA, QC)
The Division of Radiological Examinations and Technology, Tohoku University Graduate School of Medicine, has provided a course
in radiological technology since 2009.Our division researches management of the radiation dose and quality control/assurance of the
radiation equipment used in radiological examinations, including interventional radiology (IVR).
In particular, our main fields of education and research are:
1Radiation safety and risk management during radiological examinations (patients and staff).
2Quality control and quality assurance of medical X-ray systems and radiographic images.
3Optimization of the radiation dose and X-ray image quality.
4Development of dosimeters and evaluation methods for radiation exposure in radiological examinations.
5Radiation protection for pediatric patients.
6Avoidance of radiation-induced injury (deterministic and stochastic effects) in radiological examinations.
7Optimization of medical radiation exposure and radiation protection.
8Justification of radiological procedures.
Our laboratory evaluates radiation doses and radiation effects in humans, analyzes the management of radiation exposure from nuclear
hazards, and develops diagnostic imaging systems for use in disasters. Specifically, our main areas of research and education are:
1Radiation safety and risk management;
2Evaluation/measurement of radiation doses and radiation effects in humans;
3Development of diagnostic imaging systems for use in disasters;
4Public education regarding radiation and radioactivity.
Educating students in the technologies of radiology and medical physics is also an important aspect of our division.
Figure 1. New real-time patient radiation dosimeter (multichannel sensors) Figure 2. Glass dosimeter system measuring the direct patient entrance dose
Recent Publications
- Nakamura M, Chida K. Red emission phosphor for real-time skin dosimeter for fluoroscopy and interventional radiology. Med Phys. 2014;41(10):101913. 1-5.
- Chida, K. et alOccupational dose in interventional radiology procedures. Am J Roentgenol. (AJR) 200, 138-41 (2013)
- Chida, K. et alClarifying and visualizing sources of staff-received scattered radiation in interventional procedures. Am J Roentgenol. (AJR). 197, 900-3 (2011)
- Chida, K. et alRadiation dose to the pediatric cardiac catheterization and intervention patient. Am J Roentgenol. (AJR). 195, 1175-9 (2010)
- Chida, K. et alRadiation dose of interventional radiology system using a flat-panel detector. Am J Roentgenol. (AJR). 193, 1680-5 (2009)
Radiological Examination and Technology 73

For Aiming at Delivering Adequate and Safer Radiation Therapy
Therapeutic Radiology Health Sciences Course

TAKEDA, Ken URL:

Contact:
TEL +81-22-717-8010
Research Theme
Technology of adaptive radiotherapy for head and neck cancer
Development of dose calculation algorithm using parallel computing technique
Development of 3D printing process of patient immobilization devices in radiation therapy
Research Keywords: high-precision radiotherapy, adaptive radiotherapy, dose calculation algorithm

Technical Keywords: image-guided radiation therapy, intensity-modulated radiation therapy,
stereotactic body radiation therapy, Monte Carlo method, 3D printing
At present in Japan, one person in two people in the life is diagnosed as cancer and it accounts for about 30 percent of the
overall death. Furthermore, its death rate keeps rising and elderly cancer patients will increase. Therefore, the role of radiation
therapy (RT) which can reduce burden of cancer patients is expected to be promoted more from now on. Recent technological
development of high-precision RT such as stereotactic body RT, intensity-modulated RT, image-guided RT and adaptive
RT confirmed the advantages of delivering adequate doses to achieve optimal treatment outcomes and reduction of severe
adverse event. With the development of high-precision RT, the precise dose calculation is getting more and more important.
Nevertheless, there remain problems regarding its accuracy in inhomogeneous regions as well as its speed in dose optimization.
To overcome these problems, it is necessary to fully understand the details of the dose calculation algorithms. However, the
details of the algorithms used in commercial treatment planning systems are not open to the public. In our research group, we
have implemented the dose calculation algorithm from scratch, and based on the implementation, we are now researching and
developing a high speed and high accuracy dose calculation system.
Figure 1. A linac accelerator, dose distribution and a 3D-printed immobilization Figure 2. Dose distribution and iso-dose lines in lung stereotactic body therapy
device
Recent Publications
- Dobashi S and Mori S, Evaluation of respiratory pattern during respiratory-gated radiotherapy. Australas Phys Eng Sci Med. 2014 [Epub ahead of print]
- Komori S, et al. Clinical factors relevant to regional body volume changes during radical external beam radiotherapy for head and neck cancer. Jpn J Clin Radiol. 59(5): 733-739, 2014 [Jpn]
- Takeda K, et al. Treatment outcome of high-dose image-guided intensity-modulated radiotherapy using intra-prostate fiducial markers for localized prostate cancer at a single institute in Japan. Radiat Oncol.
7:105, 2012
- Dobashi S, et al. Intrafractional respiratory motion for charged particle lung therapy with immobilization assessed by four-dimensional computed tomography. J Radiat Res. 52(1):96-102, 2011
- Takeda K, et al. Predicting the severity of acute urinary toxicity after brachytherapy with iodine-125 for localized prostate cancer. Tohoku J Exp Med. 223(1):55-60, 2011
74 Therapeutic Radiology
Development of Medical Technology for Overcoming Breast Cancer
~ Basic Research for Diagnosis and Therapy of Breast Cancer ~
Molecular and Functional Health Sciences Course

Dynamics Master / Doctoral Degree
URL:
http://www.mfd.med.tohoku.ac.jp/
HAYASHI, Shin-ichi
Contact:
E-Mail shin@med.tohoku.ac.jp
Research Theme
Molecular mechanism of tumorigenesis and progression of hormone-dependent cancer
Mechanism of hormonal therapy-resistance and development of novel molecular target therapy
Development of new molecular biomarker and diagnosis for breast cancer
Research Keywords: breast cancer, estrogen, hormonal therapy, molecular target therapy, nuclear receptor
Technical Keywords: cell culture, molecular biology, biochemistry
The mission of our laboratory is education and research for the science underlying the field of clinical laboratory medicine:
especially biochemistry, molecular biology, clinical chemistry, and analytical chemistry. Our main research projects are
focused on steroid hormone-dependent tumors such as breast cancer. Recently, the number of breast cancer patients is rapidly
increasing in Japan. The pathogenic mechanism is not fully understood. However, it is well known that female hormone,
estrogen plays important roles. Estrogen is an important signaling molecule to regulate cell proliferation, differentiation, and
homeostasis in various organs. On the other hand, estrogen acts for the occurrence and proliferation of breast and endometrial
cancers. In these cancer cells, the pathogenesis is closely related to the nuclear estrogen receptor function. In fact, it is well
known as hormone therapy, widely employed and show good efficacy in clinical treatment to block the function of estrogen
receptor by the anti-hormonal agents.
We are studying in the molecular mechanisms of breast cancer progression, predicting the effect of hormone therapy,
mechanisms of resistance to hormone therapy, breast cancer stem cell research. Our aim is to contribute to the patients with
breast cancer and the society through these studies.
Figure 1. Mechanism of hormonal therapy for breast cancer and its resistance Figure 2. Visualized ER activity by GFP in breast cancer
Recent Publications
- Hanamura T, et al. Androgen metabolite-dependent growth of hormone receptor-positive breast cancer as a possible aromatase inhibitor-resistance mechanism. Breast Cancer Res. Treat. 139: 731-740, 2013
- Fujiki N, et al. Estrogen response element-GFP (ERE-GFP) introduced MCF-7 cells demonstrated the coexistence of multiple estrogen-deprivation resistant mechanisms. J. Steriod Biochem. Mol. Biol.,
139: 61-72, 2014
- Hanamura T, et al. Possible role of the aromatase-independent steroid metabolism pathways in hormone responsive primary breast cancers. Breast Cancer Res. Treat. 143: 69-80, 2014
- Yamaguchi Y, et al. Detection of estrogen-independent growth-stimulating activity in breast cancer tissues: implication for tumor aggressiveness. Cancer Microenvironment, 7: 23-21, 2014
- Fujii R, et al. Increased androgen receptor activity and cell proliferation in aromatase inhibitor-resistant breast carcinoma. J. Steriod Biochem. Mol. Biol., 144: 513-522, 2014
Molecular and Functional Dynamics 75

To Challenge Mechanism of Immune System for Protecting Host from Microbial Infection:
Development of Novel Vaccines and Stealth Nanoparticles
Medical Microbiology, Health Sciences Course

Mycology and Immunology Master / Doctoral Degree
URL:
http://www.infect-immun.med.tohoku.ac.jp/
KAWAKAMI, Kazuyoshi
Contact:
E-Mail kawakami@med.tohoku.ac.jp
Research Theme
Clarification of host immune mechanism against microbial infection
Development of novel vaccines
Development of stealth nanoparticles for novel therapy of malignant diseases
Research Keywords: infection and immunity, immune memory, fungus, vaccine, nanoparticle
Technical Keywords: experiment with microbial infection, animal experiment, immunological analysis,
molecular biological analysis, pathological analysis
In our laboratory, we aim to clarify the immune mechanism against infection with microbial pathogens such as fungi and
bacteria from the perspectives of innate immunity, acquired immunity and immune memory. We also attempt to extend the
results obtained from these studies to development of novel vaccines and that of stealth nanoparticles for novel anti-cancer
therapies which make it possible to bring them more efficiently to cancer tissues without trapped by reticuloendothelial
system and without stimulating immune response.
Figure 1. Possible relationship of microbial infection with various diseases Figure 2. Intracellular signaling in TLR9-mediated activation of macrophages and
dendritic cells by Cryptococcus neoformans
Recent Publications
- Yamamoto H, et al. Defect of CARD9 leads to impaired accumulation of IFN--producing memory-phenotype T cells in lungs and increased susceptibility to pulmonary infection with Cryptococcus
neoformans, Infect Immun 82: 1606-1615, 2014
- Miyasaka T, et al. Dectin-2-dependent NKT cell activation and serotype-specific antibody production in mice immunized with pneumococcal polysaccharide vaccine. PLoS One 8:e78611, 2013
- Togashi T, et al. Continuous hydrothermal synthesis of 3,4-dihydroxyhydrocinnamic acid-modified magnetite nanoparticles with stealth-functionality against immunological response. J Materials Chemi 22:
9041-9045, 2012
- Kinjo Y, et al. Invariant NKT cells recognize glycolipids from pathogenic gram-positive bacteria. Nat Immunol 12: 966-974, 2011
- Saijo S, et al. Dectin-2 is crucial for the defense against Candida albicans in mice by recognizing alpha-mannans and inducing Th17 differentiation. Immunity 32: 681-691, 2010
76 Medical Microbiology, Mycology and Immunology

To Clarify Pathophysiology via the Research in Biologically Active Peptides, and to Aim at
the Translational Research in Laboratory Medicine
Endocrinology and Applied Health Sciences Course

Medical Science Master / Doctoral Degree
URL:
TAKAHASHI, Kazuhiro health/81/index.html
Contact:
E-Mail ktaka-md@med.tohoku.ac.jp
Research Theme
Studies on neuropeptides and cardiovascular peptides in the pathophysiology of cardiovascular diseases, and
neuroendocrine diseases
(Patho)physiology of prorenin receptor in cancer, erythropoiesis and sleep apnea syndrome
Translational research in laboratory medicine
Research Keywords: neuropeptide, prorenin receptor, physiological function, neuroendocrinology, cardiovascular

endocrinology
Technical Keywords: cell culture, molecular biology, immunohistochemistry, western blot analysis, ELISA
The Department of Endocrinology & Applied Medical Science is studying neuropeptides and cardiovascular peptides in order to
clarify (patho) physiological roles of biologically active peptides in normal conditions and various diseases.
Biologically active peptides are produced and secreted not only by endocrine cells and neurons, but also by cardiomyocytes (atrial natriuretic
peptide and B-type natriuretic peptide), vascular endothelial cells (endothelins), immune cells (ACTH and corticotropin-releasing hormone),
adipocytes (leptin and resistin), etc. We aim at the translational research in the fields of neuroendocrinology and cardiovascular endocrinology to
develop novel test methods in laboratory medicine and treatments for various diseases, such as the metabolic syndrome, hypertension, diabetes
mellitus, chronic kidney diseases, and malignant neoplasm.
In these recent years, we have focused on the research in prorenin receptor, receptor for renin precursor. In particular, we have been
studying pathophysiological roles of prorenin receptor in cancers, relationship between erythropoiesis and prorenin receptor, and plasma
levels of soluble prorenin receptor in patients with obstructive sleep apnea syndrome. Studies on obstructive sleep apnea syndrome have
been done in co-operation with Division of Behavioral Sleep Medicine, Iwate Medical University School of Medicine, Morioka, Japan
(directed by Prof. Shigeru Sakurai).
Figure 1. Immunohistochemistory of prorenin receptor in invasive breast cancer Figure 2. Correlation between plasma soluble prorenin receptor and apnea
hypopnea index
Recent Publications
- Ohba K, et al. Expression of (pro)renin receptor in breast cancers and its effect on cancer cell proliferation. Biomed Res (Tokyo), 35:117-126; 2014
- Nishijima T, Tajima K, Takahashi K, Sakurai S. Elevated plasma levels of soluble (pro)renin receptor in patients with obstructive sleep apnea syndrome: Association with polysomnographic parameters.
Peptides, 56:14-21; 2014
- Yamamoto H, et al. Increased expression of (pro)renin receptor in aldosterone-producing adenomas. Peptides, 49:68-73; 2013
- Kaneko K, et al. Expression of (pro)renin receptor in human erythroid cell lines and its increased protein accumulation by interferon-. Peptides, 37:285-289; 2012
- Takahashi K, Totsune K. Urotensin peptides, p. 1437-1442. In Kastin AJ (ed), Handbook of Biologically Active Peptides, Second Edition. Elsevier, Amsterdam, Boston, Heidelberg, London, New York,
Oxford, Paris, San Diego, San Francisco, Singapore, Sydney, Tokyo 2013
Endocrinology and Applied Medical Science 77

Analysis of Hormone Actions in Breast Cancer
Pathology and Health Sciences Course

Histotechnology Master / Doctoral Degree
URL:
SUZUKI, Takashi health/82/index.html
Contact:
E-Mail t-suzuki@patholo2.med.tohoku.ac.jp
Research Theme
Analysis of invasion and metastatic processes in breast cancer
Analysis of resistance mechanisms after endocrine therapy and/or chemotherapy in breast cancer
Analysis of hormone actions in various human cancers
Research Keywords: breast cancer, hormone, invasion, metastasis, treatment

Technical Keywords: immunohistochemistry, pathology, microarray, cell culture, animal experiment
Breast cancer is one of the most common malignancies in women worldwide. Therefore, it is very important to investigate
biological features of breast carcinoma in order to improve clinical outcome of the patients. It is well known that estrogens
play important roles in the development of human breast carcinomas, and endocrine therapies are frequently used in these
patients to block the intratumoral estrogen actions. In the Division of Pathology and Histotechnology, we analyze hormone
actions in breast carcinoma by pathological methods as well as various molecular biological techniques.
Figure 1. in situ estrogen synthesis in breast carcinoma tissue Figure 2. Identification of molecular mechanism of estrogen-mediated invasion
Recent Publications
- Onodera Y, et al. NRF2 immunolocalization in human breast cancer patients as a prognostic factor. Endocr Relat Cancer. 21 (2): 241-252.2014
- Takayama K, et al. CtBP2 modulates the androgen receptor to promote prostate cancer progression. Cancer Res. 74(22):6542-6553. 2014
- Sato-Tadano A, et al. Hexokinase II in breast carcinoma: A potent prognostic factor associated with hypoxia-inducible factor-1alpha and Ki-67. Cancer Sci. 104 (10): 1380-1388.2013
- Takagi K, et al. Intratumoral concentration of estrogens and clinicopathological changes in ductal carcinoma in situ following aromatase inhibitor letrozole treatment. Br J Cancer.109 (1): 100-108.2013
- Takagi K, et al. BUB1 immunolocalization in breast carcinoma: its nuclear localization as a potent prognostic factor of the patients. Horm Cancer.4 (2): 92-102.2013
78 Pathology and Histotechnology

To Investigate Contractile Properties in Diaphragm and Heart Muscle
Clinical Physiology Health Sciences Course

URL:
SHINDOH, Chiyohiko http://www.med.tohoku.ac.jp/english/org/
Professor, M.D. Ph.D. health/83/index.html
Contact:
TEL +81-22-717-7948
E-Mail cshindoh@med.tohoku.ac.jp
Research Theme
Elucidation of endotoxin effects on diaphragm muscle contractility using MyD88KO mice
Relationship between muscle contraction and arrhythmogenesis
Diaphragm muscle contractility in bronchial asthma model
Research Keywords: diaphragm muscle contractility, endotoxin, MyD88KO mice, arrhythmias, intracellular calcium
Technical Keywords: dissected diaphragm muscle, electrical stimulation, knockout mice,
multicellular cardiac muscle preparation, fluorescent dye loading
This department teaches medical technology related to respiratory and cardiac physiology and basically investigates
diaphragm and heart muscle contractility using animal models as follows: (1) The respiratory muscle is an organ to drive
lung movements, and the decreased muscle contractility is closely related to a respiratory failure, therefore, to prevent
respiratory failure is a very important research theme. To investigate respiratory failure in septic shock, we have measured
force-frequency curves (Figure.1) as a diaphragm muscle contractility after endotoxin injection in normal mice and
MyD88KO mice. (2) Almost 60,000 people suddenly die chiefly due to lethal arrhythmias in Japan, but we have no effective
therapy except for ICD implantation. It is well known that in ventricular muscle, intracellular Ca2+ is deeply involved in the
occurrence of such arrhythmias by enhancing delayed afterdepolarizations (Figure.2). In this department, we thus focus on
intracellular Ca2+ dynamics during muscle contraction, investigating how lethal arrhythmias occur in diseased hearts using
rat ventricular muscle.
Figure 1. Example of force-frequency curve measurement Figure 2. Induction of arrhythmias due to disturbance of intracellular Ca2+
Recent Publications
- Miura M, et al. Role of reactive oxygen species and Ca2+ dissociation from the myofilaments in determination of Ca2+ wave propagation in rat cardiac muscle. J Mol Cell Cardiol. 56:97-105, 2013
- Shindoh C, et al. Inhalation of Budesonide/Formoterol Increases Diaphragm Muscle Contractility. Allergol Int. 61:439-449, 2012
- Miura M, et al. Regional increase in extracellular potassium can be arrhythmogenic due to nonuniform muscle contraction in rat ventricular muscle. Am J Physiol 302:H2301-H2309, 2012
- Shindoh C, et al. Effects of inhalation or incubation of oxitropium bromide on diaphragm muscle contractility in mice. Allergol Int. 60: 365-372, 2011
- Miura M, et al. Effect of non-uniform muscle contraction on sustainability and frequency of triggered arrhythmias in rat cardiac muscle. Circulation 121:2711-2717, 2010
Clinical Physiology 79
To Understand the Molecular Mechanisms Underlying Pathogenesis of GATA-factor-related Diseases;
How Transcriptional Regulatory Network Governs Maintenance of Hematopoietic Homeostasis in Mammals
Molecular Hematology Health Sciences Course

URL:
SHIMIZU, Ritsuko http://www.exphem.med.tohoku.ac.jp/
Professor, M.D. Ph.D. toppage.html
Contact:
TEL +81-22-717-8080
E-Mail rshimizu@med.tohoku.ac.jp
Research Theme
Research on the vital roles of transcription factors GATA1 and GATA2 during mammalian hematopoiesis
Research on the mechanisms underlying pathogenesis of leukemias caused by quantitative and qualitative
dysfunction in GATA factors
Drug discovery research of GATA-factor-related diseases
Research Keywords: regulation of gene expression, GATA factors, leukemias, drug discovery
Technical Keywords: gene editing in mice, fluorescent activated cell sorter, experimental hematological analysis;
e.g. transplantation, colony assay, cell culture, high-throughput screening
In 1988, Prof. Weintraub identified MyoD as a key transcription factor that had a potential to directly reprogram fibroblasts
to myocytes. Since then, a large number of scientists have rushed into cloning races of transcription factors that is vital
for cell fate decision. In this process, GATA1 and GATA2 were identified as transcription factors indispensable for
hematopoiesis.
GATA2 is expressed in hematopoietic stem/progenitors and important for maintenance of pluripotent stem cells, whereas
GATA1 is mainly expressed in cells committed to erythroid and megakaryocytic lineages and requisite for differentiation,
control of proliferation and cell survival. In 21 century, multiple cases of germline and somatic mutations on GATA1 and
GATA2 genes have been discovered in humans suffering hematopoietic abnormalities/malignancies. However, it remains
to be uncertain how the dysfunction of GATA factors contributes to the onset of the diseases. We are now challenging to
clarify the molecular mechanisms on the pathogenesis of the hematopoietic diseases caused by quantitative and qualitative
dysfunction of GATA factors, focusing on the vital roles of GATA1 and GATA2 in transcriptional regulatory network during
mammalian hematopoiesis. Furthermore, we are interesting in drug discovery against diseases involving GATA factors.
Figure 1. Hematologic diseases caused by dysfunctions of GATA factors Figure 2. Drug discovery targeting for GATA factors
Recent Publications
- Shimizu R, Engel JD, Yamamoto M. GATA1-related leukemias. Nat Rev Cancer, 8(4):279-287, 2008
- Hasegawa A, et al. Mature erythrocyte membrane homeostasis is compromised by loss of the GATA1-FOG1 interaction. Blood, 119(11):2615-2623, 2012
- Kaneko H, et al. N- and C-terminal transactivation domains of GATA1 protein coordinate hematopoietic program. J Biol Chem, 287(25):21439-21449, 2012
- Toki T, et al. Naturally occurring oncogenic GATA1 mutants with internal deletions in transient abnormal myelopoiesis in Down syndrome. Blood. 121(16):3181-3184, 2013
- Yamazaki H, et al. A Remote GATA2 Hematopoietic Enhancer Drives Leukemogenesis in inv(3)(q21;q26) by Activating EVI1 Expression. Cancer Cell, 25(4) 415-427, 2014
80 Molecular Hematology
Extending Healthy Life Expectancy through Prevention of Lifestyle-related Diseases and
Aging From Epidemiological Evidence to Healthcare Policy
Epidemiology School of Public Health Course

TSUJI, Ichiro URL:
Professor, M.D. Ph.D. http://www.pbhealth.med.tohoku.ac.jp/
Contact:
TEL +81-22-717-8123
E-Mail thkpbh-office@umin.ac.jp
Research Theme
Large-scale cohort studies to identify risk factors for lifestyle-related diseases
Cohort and intervention studies for prevention of aging (such as disability and dementia)
Doctorial Course, Tohoku University Graduate School of Medicine
Research Keywords: healthy life expectancy, cancer, cardiovascular disease, aging, Tohoku great earthquake victims
Technical Keywords: epidemiology, statistics, cohort study, intervention study
Our main research themes involve identifying risk factors for cancer, cardiovascular disease, and aging (including disability
and dementia) using observational epidemiology methods, and verifying the effectiveness of preventive health services
using intervention epidemiology methods. Our division manages two cohort study datasets covering 50,000 subjects each.
For more than 20 years we have investigated associations between this detailed lifestyle and diagnostic data, and subsequent
mortality risk, incident risk of cancer, healthcare costs, risk of certificate of long-term care insurance, and incident risk of
dementia. The only sites in Japan covering cohorts of this magnitude at a single institution are the National Cancer Center
and our division. We have fully utilized this abundant resource to publish in journals such as the New England Journal of
Medicine and JAMA, and our findings have received attention worldwide. We propose policies for the extension of a healthy
life expectancy based on this epidemiological evidence.
We conduct health studies of Tohoku great earthquake victims every six months in cooperation with the Center for
Community Health. We identify factors that affect the mental and physical health of victims and propose suitable policies
for supporting their resilience. In addition, we are actively involved in the health support of victims such as in health check-
up, health education, and classroom to improve nutrition and exercise.
We also believe it is very important to educate and train the next generation of human resources in epidemiology and public
health such as epidemiologists, health policy administrators, clinicians, and other healthcare professionals who are mindful
of disease prevention.
Figure 1. Association between Japanese dietary pattern and incident functional Figure 2. Community survey for disaster victims in Sendai on Feb 2012
disability
Recent Publications
- Sugiyama K, et al. Association between Coffee Consumption and Incident Risk of Disabling Dementia in Elderly Japanese: The Ohsaki Cohort 2006 Study. J Alzheimers Dis. 2015 Dec 2. [Epub ahead of print]
- Tomata Y, et al. Long-term impact of the 2011 Great East Japan Earthquake and tsunami on functional disability among older people: A 3-year longitudinal comparison of disability prevalence among
Japanese municipalities. Soc Sci Med. 2015;147:296-9.
- Tanji F, et al. Personality and suicide risk: the impact of economic crisis in Japan. Psychol Med. 2015;45(3):559-73.
- Kumagai Y, et al. Dietary patterns and colorectal cancer risk in Japan: the Ohsaki Cohort Study. Cancer Causes Control. 2014;25(6):727-36.
- Chen Y, et al. Association between body mass index and cardiovascular disease mortality in east Asians and south Asians: pooled analysis of prospective data from the Asia Cohort Consortium. BMJ. 2013
Oct 1;347:f5446
Epidemiology 81
To Bridge the Gap between Theory and Practice in Medical Research!
Biostatistics School of Public Health Course

YAMAGUCHI, Takuhiro URL:
Professor, Ph.D. http://www.biostat.med.tohoku.ac.jp/
Contact:
TEL +81-22-717-7659
E-Mail yamaguchi@med.tohoku.ac.jp
Research Theme
Design and analysis of clinical / epidemiological studies
Information management system
Clinical database study
Research Keywords: biostatistics, information management, clinical research methodology, pharmacoepidemiology, regulatory science
Technical Keywords: statistical analysis, clinical data management, clinical research support system, quality management
Biostatistics is the application of statistics to a wide range of topics in medical researches. It encompasses how to collect,
analyze and report (interpret) the data from medical studies. Methodological research, collaboration, and education are
three pillars of our division. We conduct methodological research in a broad range of areas, including design and analysis of
clinical/epidemiological studies, information (data) management, survival data analysis and so on. Members in our Division
direct the Clinical Research Data Center, Tohoku University Hospital, and are providing research support in design, data
management and statistical analysis in many projects inside/outside the university. We provide some undergraduate courses
such as introduction to medical statistics and medical data analyses to students work in many medical fields.
Figure 1. Our Lab Figure 2. Clinical Research Data Center
Recent Publications
- Kurosawa S, Yamaguchi T et al. Blood 2010; 117(7): 2113-20.
- Mieno MN, Yamaguchi T et al. BMC Medical Research Methodology 2011; 26(11): 80-5.
- Morita T, Yamaguchi T et al. Lancet Oncology 2013; 14(7): 638-46.
- Ooba N, Yamaguchi T et al. PLoS One 2014; 9(5): e96919. doi: 10.1371/journal.pone.0096919. eCollection 2014.
82 Biostatistics
Development of -type Persons who can Cope with Both Clinical and Omics Informations
Medical Informatics School of Public Health Course

TSUJI, Ichiro URL:
Professor, M.D. Ph.D. http://www.med.tohoku.ac.jp/english/org/
sph/235/index.html
Contact:
TEL +81-22-717-7501
E-Mail secretary@msi.med.tohoku.ac.jp
Research Theme
Medical Informatics
Research Keywords: medical semantics, regional healthcare, ontology, TRI, standardization

Technical Keywords: medical informatics, next generation EHR, medical information network,
medical safety control, information security
We pursue what Informatics and ITC infrastructure should be in medical science and clinical medicine through integrated
network system with fundamental infrastructures such as Tohoku University School of Medicine, Tohoku Medical
Megabank Organization, Miyagi Medical and Welfare Information Network, Tohoku University Hospital and Clinical
Research, Innovation and Education Center.
We aim to produce excellent graduates who can cope with both clinical informatics and bio informatics using the above
mentioned infrastructures effectively.
Figure 1. Tohoku Medical Information Highway
Recent Publications
- Jun Nakaya, Takeshi Imai, Michiyo Kamata, Kaei Hiroi, Hiroshi Tanaka. Clinical Omics sub information model for ICD11(iCOs). WHO-FAMILY OF INTERNATIONAL CLASSIFICATIONS NETWORK
ANNUAL MEETING 2014. C319. 2014
- J.Nakaya, M. Kimura, S. Ogishima, A. Shabo, I. K. Kim, C. Parisot, B. de Faria Leao. Future Direction of IMIA Standardization, IMIA Yearbook of Medical Informatics 2014. P105-109. 2014
- Jun Nakaya, Teiji Tominaga, Hiroshi Tanaka, Masayuki Yamamoto. Disaster-tolerant features of ICT Architecture in Tohoku Medical Megabank. APRU 8.2012, 32-33 , 2012.
- Jun Nakaya, Michio Kimura, Riichiro Mizoguchi, Kouji Kozaki and Hiroshi Tanaka. Semantic Mechanisms in Clinical Omics DB. InterOntology2012, p81-91. 2012
- Nakaya, J., Hiroi, K., Yang, W., Ido, K., Kimura, M.. Genomic Sequence Variation Markup Language (GSVML). International Journal of Medical Informatics. Vol.79. Issue2. p130-142. Feb 2010.
Medical Informatics 83
To Identify Novel Genes and Explore the Pathogenetic Mechanisms of Genetic Disorders
Medical Genetics School of Public Health Course

AOKI, Yoko URL:
Professor, M.D. Ph.D. http://www.medgen.med.tohoku.ac.jp/
RasMapk syndromes.html
Contact:
TEL +81-22-717-8139
E-Mail info@medgen.med.tohoku.ac.jp
Research Theme
Molecular analysis of disorders with dysregulation of signaling pathways
Genetic analysis of intractable and rare diseases using massive parallel sequencing
Generation of mouse modeling and development of therapeutic approaches to treat genetic disorders
Research Keywords: signaling pathway, proto-oncogene, intractable and rare disease, Human development, RASopathies
Technical Keywords: genetic analysis, massively parallel sequencing, therapeutic approach, mouse modeling, cell culture
In 2005 and 2006, we discovered that germline mutations in HRAS cause Costello syndrome, a congenital anomaly
syndrome, and KRAS and BRAF mutations cause cardio-facio-cutaneous syndrome (Aoki Y, et al. Nature Genetics, 2005,
Niihori T, et al. Nature Genetics, 2006). We proposed that disorders with mutations of molecules in the RAS/MAPK cascade
may be comprehensively termed "the RAS/MAPK syndromes (Aoki Y, et al. Hum Mutat, 2008). These disorders are also
called RASopathies. In 2013, we identified a novel gene of Noonan syndrome, RIT1, using next generation sequencer. We
are now studying molecular analysis and mouse modeling of RASopathies (Inoue SI, et al Hum Mol Genet, 2014, Moriya M
et al. Hum Mol Genet, 2015).
Another project is to identify causative genes for rare genetic disorders using next generation sequencer. Since 2010, we
have developed technical and bioinformatic WES pipeline to identify new genes for intractable and rare diseases, including
congenital anomaly syndromes, genetic neuromuscular disorders and chronic pancreatitis. Samples were sent from clinical
departments of our university as well as other collaborators. Our lab plays a central role in evaluating clinical manifestations,
performing exon capture reaction and filtering variants to identify causative genes in the WES pipeline.
Figure 1. RASopathies Figure 2. WES analysis pipeline
Recent Publications
- Niihori T, Ouchi-Uchiyama M, Sasahara Y, Kaneko T, Hashii Y, Irie M, Sato A, Saito-Nanjo Y, Funayama R, Nagashima T, Inoue S, Nakayama K, Ozono K, Kure S, Matsubara Y, Imaizumi M, Aoki Y.
Mutations in MECOM, Encoding Oncoprotein EVI1, Cause Radioulnar Synostosis with Amegakaryocytic Thrombocytopenia. Am J Hum Genet. 97(6):848-54, 2015
- Moriya M, Inoue SI, Miyagawa-Tomita S, Nakashima Y, Oba D, Niihori T, Hashi M, Ohnishi H, Kure S, Matsubara Y, Aoki Y.Adult mice expressing a Braf Q241R mutation on an ICR/CD-1 background
exhibit a cardio-facio-cutaneous syndrome phenotype. Hum Mol Genet. 24(25):7349-60, 2015
- Izumi R, Niihori T, Takahashi T, Suzuki N, Tateyama M, Watanabe C, Sugie K, Nakanishi H, Sobue G, Kato M, Warita H, Aoki Y, Aoki M. Genetic profile for suspected dysferlinopathy identified by
targeted nextgeneration sequencing. Neurol Genet. 1(4):e39, 2015
- Inoue SI, et al. New BRAF knock-in mice provide a pathogenetic mechanism of developmental defects and a therapeutic approach in cardio-facio-cutaneous syndrome. Hum Mol Genet. 23:6553-66, 2014
- Aoki Y, et al. Gain-of-function mutations in RIT1 cause Noonan syndrome, a RAS/MAPK pathway syndrome. Am J Hum Genet. 93:173-180, 2013
84 Medical Genetics
To Challenge Big Data for Discovering Healthcare System by National Database
(All Japan Medical e-claim Data)
Health Administration and School of Public Health Course

Policy Medical Sciences Course
URL:
FUJIMORI, Kenji
Contact:
E-Mail iryoukanri@policy.med.tohoku.ac.jp
Research Theme
DPCDiagnosis Procedure Combination) and e-claim data; evaluation of payment system, medical procedure,
healthcare expenditure
Patients behavior and regional healthcare program
Research Keywords: healthcare policy, national database, DPC/PDPS

Technical Keywords: medical e-claim data, database, data analysis, big data
Department of Health Administration & Policy was established in 1952. Our department is the first national laboratory to
study health policy and health economics in Japan.
Prof. FUJIMORI (2013- ) energetically constructed a new approach for medicine in this dynamic period in 21st century.
Principal research themes currently headed up by the Department are as follows: study with DPCDiagnosis Procedure
Combination) and e-claim data; evaluation of payment system, medical procedure, health care expenditure and regional
medical program.
We investigate that, how to change clinical performance to improve the quality of care, and the efficiency of hospital.
We have a plan to build up the National Database (medical, long-term care e-claim and health checkup information
database) Center in TOHOKU University.
Figure 1. Outpatients chemotherapy in Japan by national database Figure 2. Regional medical cooperation of stroke by e-claim data
Health Administration and Policy 85

Exploring of Physiologically Oriented Reactive Oxygen Species in Life Science and
Molecular Toxicology
Environmental Health School of Public Health Course

Sciences and Molecular Medical Sciences Course
Toxicology Master / Doctoral Degree
URL:
http://www.toxicosci.med.tohoku.ac.jp
AKAIKE, Takaaki Contact:
TEL +81-22-717-8164
Professor, M.D. Ph.D. E-Mail secretariat@toxicosci.med.tohoku.ac.jp
Research Theme
Chemical biology of nitric oxide and reactive oxygen species and regulation of oxidative stress
Pathogenesis and epidemiology of emerging pathogen Helicobacter cinaedi
Research Keywords: reactive oxygen species, oxidative stress, reactive sulfur species, metabolic syndrome,
molecular toxicology
Technical Keywords: chemical biology, proteome, metabolome
Reactive oxygen species (ROS) produced in excess in cells induces oxidative stress and is involved in various
diseases including infection and inflammation, cancer, metabolic syndrome such as atherosclerosis and diabetes, and
neurodegenerative disorders like Alzheimer's disease. In recent years, ROS are recognized as signaling molecules regulating
various biological phenomena. ROS exerts various physiological functions such as adaptive response to oxidative stress,
autophagy induction, and regulation of cell senescence and cell death, via well-organized signaling pathways consisted with
receptor molecules and effector proteins. To clarify the regulation mechanism of ROS signaling is a high-priority subject in
research on the pathogenesis of oxidative stress-related diseases.
Our laboratory investigates the molecular mechanism of infectious diseases as an environmental factor, toxicology of
environmental pollutants, and cellular responses to environmental and oxidative stress, by using the advanced analytical
techniques, such as chemical biology, proteomes, metabolomes, etc. Recent progresses in our study include the discoveries
of the reactive sulfur species as new regulator of oxidative stress and the promotion of atherosclerosis by the infection of
emerging pathogen Helicobacter cinaedi.
Based on these high-impact achievements, we are seeking to develop novel strategies of diagnosis, remedy, and prevention
for various diseases, in view of the defense mechanism in response to oxidative stress.
Figure 1. Regulation of oxidative stress by reactive sulfur species Figure 2. Promotion of atherosclerosis by Helicobacter cinaedi infection
Recent Publications
- Ida T, et al. Reactive cysteine persulfides and S-polythiolation regulate oxidative stress and redox signaling. Proc Natl Acad Sci USA. 111(21):7606-7611, 2014
- Khan S, et al. Promotion of atherosclerosis by Helicobacter cinaedi infection that involves macrophage-driven proinflammatory responses. Sci Rep. 4:4680, 2014
- Yoshizawa T, et al. SIRT7 controls hepatic lipid metabolism by regulating the ubiquitin-proteasome pathway. Cell Metab. 19(4):712-721, 2014
- Ito C, et al. Endogenous nitrated nucleotide is a key mediator of autophagy and innate defense against bacteria. Mol Cell. 52(6):794-804, 2013
- Nishida M, et al. Hydrogen sulfide anion regulates redox signaling via electrophile sulfhydration. Nature Chem Biol. 8(8):714-724, 2012
86 Environmental Health Sciences and Molecular Toxicology

Forensic Medicine is Commonly Used to Describe All Aspects of Forensic Work within
Criminal Justice System
Forensic Medicine School of Public Health Course

FUNAYAMA, Masato URL:
Contact:
TEL +81-22-717-8010
Research Theme
Time of death
Rapid drug extraction and analysis
Human identification using CT images
Research Keywords: forensic pathology, forensic toxicology, forensic radiology

Technical Keywords: thermo data logger, liquid chromatography-tandem mass spectrometry, computed tomography
Forensic pathology
Molecular analysis of excited delirium syndrome.
Estimation of time of death using thermo data logger.
Studies on gas dispersal potential of infant bedding of sudden death cases.
Forensic toxicology:
Rapid drug extraction from human materials using a modified extraction method.
Forensic radiology:
Sex and age determination using postmortem CT images.
Relationship between causes of death and postmortem CT images.
Recent Publications
- Hayashizaki Y et.al. Sex determination of the pelvis using Fourier analysis of postmortem CT images, Forensic Sci Int, 246, 122e1-e9, 2015.
- Usui K et.al. Rapid drug extraction from human whole blood using a modified QuEChERS extraction method Legal Med 2012;14: 286-296.
- Usui A et.al. Postmortem lung features in drowning cases on computed tomography Jpn J Radiol 32, 414-20, 2014.
- Usui K et.al. Application of modified QuEChERS method to liver samples for forensic toxicological analysis Forensic toxicology, 32, 139-47, 2014
- Sakai J et.al. Gas dispersal potential of bedding as a cause for sudden infant death. Forensic Sci Int 2008; 180:93-97
Forensic Medicine 87
We Conduct Education, Research, and Actions to Aim to Develop Clinical Ethics, Research
Ethics, Public Health Ethics, and Medical Professionalism
Medical Ethics School of Public Health Course

ASAI, Atsushi URL:
Professor, M.D. Ph.D., M. Bioeth. http://www.med.tohoku.ac.jp/english/org/
sph/240/index.html
Contact:
TEL +81-22-717-8196
E-Mail aasai@med.tohoku.ac.jp
Research Theme
Research on ethical problems in contemporary Japanese society
Studies to develop clinical ethics consultation in Japanese clinical settings
Investigation concerning public heath ethics and human rights
Research Keywords: clinical ethics, research ethics, public health ethics, medical professionalism,
contemporary ethics issues
Technical Keywords: normative analysis, descriptive ethics methods, ethics committee activities,
ethics consultation interventions, medical humanities approach
The Department of Medical Ethics at Tohoku University was established in April, 2014. The main area of topics are: (1)
Clinical Ethics including ethics consultation and end-of-life decisions, (2) Research Ethics including ethics committee
activities and misconducts, (3) Public Health Ethics, (4) Medical Professionalism and medical ethics education, (5) Medical
Humanities Research focusing on films and other forms of art, and (6) Normative analysis concerning contemporary ethics
issues. Our department also aims to train a clinician-ethicist, especially a physician-ethicist.
Recent Publications
- Asai A, Ishimoto H, Masaki S. An ethical review of the production of human skeleton models from autopsied patients with Hansens disease in pre-war Japan. Ritsumeikan Journal of Asia Pacific Studies
2014; 33: 153-161.
- Masaki S, Ishimoto H, Asai A. Contemporary issues concerning informed consent in Japan based on a review of court decisions and characteristics of Japanese culture. BMC Medical Ethics 2014, 15:8
- Asai A. Commentry Tsunami-tendenko and morality in disasters Journal of Medical Ethics 2013-101629Published Online First: 22 July 2013 doi:10.1136/medethics-2013-101629
- Asai A, Ishimoto H. Should we maintain baby hatches in our society? BMC Medical Ethics 2013, 14:9
- Asai A. Kadooka Y. Reexamination of the ethics of placebo use in clinical practice. Bioethics 2013;27:186-193.
88 Medical Ethics
Elucidation of Molecular Mechanisms of Cell Proliferation and Cell Differentiation:
Unlock the Secret of Life
Cell Proliferation Medical Sciences Course

NAKAYAMA, Keiko URL:

http://www.devgen.med.tohoku.ac.jp/
Contact:
TEL +81-22-717-8227
E-Mail nakayak2@med.tohoku.ac.jp
Research Theme
Regulation of epigenetics during development and oncogenesis
Regulation of protein stability related to cell proliferation and differentiation
Research Keywords: cell cycle, epigenetics, proteolysis, bioinformatics

Technical Keywords: next generation sequencer, gene engineering mouse, cell biology, protein chemistry
We are interested in molecular mechanisms of cell cycle regulation by proteolysis, as well as epigenetic change during
differentiation or oncogenesis.
We, multicellular organisms develop and differentiate from only one fertilized egg to adult tissues. During cell cycle, various
regulatory proteins express in adequate amounts at the right time. This elaborate regulation partly depends on ubiquitin-
proteasome system. We generate and analyze gene-engineered mouse related this system to elucidate the physiological
functions of these molecules and biological and pathological significance of these molecules and system.
On another front, we address cell cycle and differentiation from the perspective of epigenetics. Our bodies are comprised
of various kinds of cells. These cells share the same genome, but they function differently. It is suggested that diverse
epigenomic profiles make cells function differently. We analyze epigenome comprehensively using the next-generation
sequencer to understand what makes change epigenomic profiles and how maintain these profiles.
At the research field of life science and medicine, novel methods of study develop in rapid-fire succession, resulting in
generation of many novel findings. We will learn and take these new methods and expand our view of research.
Figure 1. Effect of oncogene Ras on Histone H3K27me3 Figure 2. Deletion of Geminin in ES cells and bone marrow cells
Recent Publications
- Nakagawa, T. et al. S6 Kinase- and beta-TrCP2-Dependent Degradation of p19Arf Is Required for Cell Proliferation. Mol Cell Biol 35, 3517-3527, 2015
- Nakagawa T, et al. CRL4 E3 Ligase Promotes Monoubiquitylation and Chromatin Binding of TET Dioxygenases. Mol Cell 57, 247-260, 2015
- Nakagawa, T. & Nakayama, K. Protein monoubiquitylation: targets and diverse functions. Genes cells 20, 543-562 2015
- Hosogane M, et al. Ras-induced changes in H3K27me3 occur after those in transcriptional activity. PLoS Genetics. 9: e1003698, 2013
- Ishikawa Y, et al. Opposing functions of Fbxw7 in keratinocyte growth-differentiation and skin tumorigenesis mediated through negative regulation of c-Myc and Notch. Oncogene. 32: 1921-1932, 2013
Cell Proliferation 89
Where Do Brains Come From? What Are Brains? Where Are Brains Going?
Thats Why We Challenge Research in Developmental Neuroscience
Developmental Medical Sciences Course

Neuroscience Master / Doctoral Degree
URL:
http://www.dev-neurobio.med.tohoku.ac.jp/
OSUMI, Noriko english/
Contact:
Professor, D.D.S. Ph.D. TEL +81-22-717-8203
E-Mail osumi@med.tohoku.ac.jp
Research Theme
Molecular and cellular mechanisms of cortical development and neurogenesis in regard with brain evolution
Lipid signals in glial cell differentiation and functions in healthy and unhealthy conditions
Genetical and epigenetical mechanisms underlying pathophysiology of autism spectrum disorder and related
neurodevelopmental disease
Research Keywords: brain development, neurogenesis, glial cell differentiation, autism spectrum disorder, epigenetics
Technical Keywords: animal experiment, genome editing, cell culture, epigenetics, bioinformatics
How our brain is formed? Our aim is to understand 1) the regulatory mechanisms of brain development, 2) lipid biology in the brain and
nervous system, and 3) transgenerational epigenetics underlying offsprings behavior (Figure 1).
We have identified multiple functions of a transcription factor Pax6 that regulates proliferation and differentiation of radial glia (i.e.,
neural stem/progenitor cells) via its specific downstream molecule including a fatty acid binding protein Fabp7 and a transcription factor
Dmrta1, respectively. Recently, we have found that FMRP, an RNA-binding protein responsible for fragile X syndrome, may also be
regulated under Pax6 and function to transport mRNA (e.g., of Cyclin D2) to the basal end of the radial glial processes.
We are also working on elucidation of lipid signals on neurogenesis and glial differentiation especially focusing on brain-rich fatty acids
such as docosahexanoic acid (DHA) and arachidonic acid (ARA) and their binding partner fatty acid binding protein (Fabp).
We are further challenging to understand genetic and epigenetic mechanisms for etiology of neurodevelopmental diseases such
as autism spectrum disorder (ASD). A hint has come from the possibility that Pax6 and paternal aging may be involved in the
pathophysiology of ASD. We are establishing mouse models for ASD to understand how paternal aging affects offsprings behavior.
Figure 1. Three major projects in our lab Figure 2. Working model for Cyclin D2 mRNA transport system in cortical neural
stem cells and evidence obtained by genome editing
Recent Publications
- Sugiyama, T., Osumi, N., Katsuyama, Y. A novel cell migratory zone in the developing hippocampal formation. J Comp Neurol. 522, 3520-3538, 2014.
- Kikkawa, T., Obayashi, T., Takahashi, M., Fukuzaki-Dohi, U., Numayama-Tsuruta, K., Osumi, N.: Dmrta1 regulates proneural gene expression downstream of Pax6 in the mammalian telencephalon. Genes
Cells. 18(8), 636-649. 2013.
- Guo, N., Yoshizaki, K., Kimura, R., Suto, F., Yanagawa, Y., Osumi, N.: A sensitive period for GABAergic interneurons in the dentate gyrus in modulating sensorimotor gating. J Neurosci. 33(15), 6691-
6704. 2013.
- Tsunekawa, Y., Britto, J.M., Takahashi, M., Polleux, F., Tan, S-S. and Osumi, N.: Cyclin D2 in the basal process of neural progenitors is linked to non-equivalent cell fates. EMBO J. 31(8), 1879-1892, 2012.
- Umeda, T., Takashima, N., Nakagawa, R., Maekawa, M., Ikegami, S., Yoshikawa, T., Kobayashi, K., Okanoya, K., Inokuchi, K. and Osumi, N.: Evaluation of Pax6 mutant rat as a model for autism. Plos
One. 5(12), e15500, 2010.
90 Developmental Neuroscience
Innovative Drug Development
~From Drug Discovery to Investigator-driven Clinical Trials in Academia~
Molecular Medicine and Medical Sciences Course

Therapy Master / Doctoral Degree
URL:
http://miyatalaben.jimdo.com/
MIYATA, Toshio
Contact:
E-Mail souyakulab@gmail.com
Research Theme
Development of inhibitors to carbonyl stress
Development of inhibitors to plasminogen activator inhibitor-1
Regulatory science
Research Keywords: drug discovery and development, exploratory clinical trial, microdose test, PAI-1, carbonyl stress
Technical Keywords: in silico drug design, structural optimization, target validation, preclinical study, clinical study
"Drug discovery" pursued by pharmaceutical companies follows a stereotyped pattern and operates within a very narrow
scope. For example, the same statin-type antihyperlipidemic and sartan-type antihypertensive drugs may be extensively
developed and formulated by drug companies, whereas orphan drugs or drugs that target diseases which are overlooked by
drug companies but are nonetheless of significant social impact (such as kidney diseases) are far from receiving the attention
they deserve in new drug development.
Our unit focuses on "academically driven drug discovery" via a cross-disciplinary approach involving inputs from biology,
structural biology, pharmacology, chemistry, and computer engineering.
Our research platform employs an array of state-of-the-art technologies including in silico hit discovery, lead optimization,
pre-clinical trials, human clinical trials (microdose trials, early-phase exploratory clinical trials, POC trials) to complement
rational drug discovery and development.
They should improve insights into human physiology/pharmacology and document the drug candidate's characteristics
and therapeutic target relevant to disease. Such an approach should alter the balance of risks during the drug development
dramatically, enable us to pursue many more promising compounds than is currently affordable, and develop them with a
much greater probability of success.
Figure 1. From drug discovery to investigator-driven clinical trials in academia
Recent Publications
- Eren M, et al. PAI-1-regulated extracellular proteolysis governs senescence and survival in Klotho mice. Proc Natl Acad Sci USA. 111(19):7090-7095,2014
- Miyata T, et al. Drug discovery in renal disease towards a more efficient framework. Nature Review Nephrology. 10(5):290-6,2014
- Remuzzi G, et al. Kidney failure: aims for the next 10 years and barriers to success. Lancet. 382(9899):353-362,2013
- Miyata T, Suzuki N, van Ypersele de Strihou C. Diabetic nephropathy: Are there new and potentially promising therapies targeting oxygen biology? Kidney Int. 84(4):693-702,2013
- Mori T, Miyata T, Ito S. Oxidative/Carbonyl stress in the renal circulation and cardiovascular renal injury, p.305-320. In Oxidative Stress in Applied Basic Research and Clinical Practice Studies on Renal
Disorders, edited by Miyata T, Eckardt KU, Nangaku M. 1st ed, vol 1. Springer Science+Business Media, New York, NY, 2011
Molecular Medicine and Therapy 91

Drug Delivery System and Prevention for Blindness
Clinical Cell Therapy Medical Sciences Course

ABE, Toshiaki URL:

http://www.ctaar.med.tohoku.ac.jp/dcct/index.htm
Contact:
TEL +81-22-717-8234
E-Mail toshi@oph.med.tohoku.ac.jp
Research Theme
Drug delivery system for retinal diseases
Deployment type nanosheets creation technology development for biopharmaceutical local sustained release
Screening of the new vessel stimulant in the retina
Research Keywords: drug delivery, nano-sheet, retinal diseases, blindness prevention, neuroprotection
Technical Keywords: micro fabrication, controlled drug delivery, animal experiments,
cell culture and gene manipulation, cell transplantation
We have been developing drug and/or cell delivery system. Although we performed these studies for eye diseases, these
techniques will be able to expand other organs. Because most of the blindness is attributed to retinal diseases, administration
of some drugs to treat degenerating retina has been tried. Using our novel device, we can perform sustained long-term drug
administration to the retina. We have performed our work in collaboration with Prof Nishizawa and Associate Prof. Kaji
(Department of Bioengineering and Robotics) and Prof Nakazawa (Department of Ophthalmology).
We have also developed a biodegradable and transplantable sheet that can culture the cells using microfabrication
techniques. We developed micropatterned nanosheets that can be ejected from a syringe through the needle. It can be
expanded to conform to the local space according to the necessity. The sheet is gene- and drug-containable and is easily
attached to the target tissue, which enable the target molecules could be released locally.
Figure 1. Trans-scleral sustained drug delivery system Figure 2. Biodegradable and transplantable micropatterned conforming nanosheets
Recent Publications
- Nagai N, et al. A Platform for Controlled Dual-Drug Delivery to the Retina: Protective Effects against Light-Induced Retinal Damage in Rats. Adv Healthc Mater. 2014 19. doi: 10.1002/adhm.201400114.
[Epub ahead of print]
- Fujie T, et al.Micropatterned polymeric nanosheets for local delivery of an engineered epithelial monolayer. Adv Mater. 2014;26:1699-705.
- Nagai N, et al. A polymeric device for controlled transscleral multi-drug delivery to the posterior segment of the eye.Acta Biomater. 2014;10:680-7.
- Onami H, et al. Transscleral sustained vasohibin-1 delivery by a novel device suppressed experimentally-induced choroidal neovascularization.PLoS One. 2013;8:e58580. doi: 10.1371/journal.
pone.0058580. Epub 2013.
- Kawashima, et al. A scalable controlled release device for transscleral drug delivery to the retina.Biomaterials 32(7):1950-1956, 2011.
92 Clinical Cell Therapy

Slow and Steady
Gene Therapy Medical Sciences Course

MATSUBARA, Mitsunobu URL:
Associate Professor, M.D. Ph.D.

Contact:
TEL +81-22-717-8231
E-Mail mmitsu2i@gmail.com
Research Theme
Blood pressure regulation
Body fluid regulation
Research Keywords: blood pressure, body fluid, sodium ion

Technical Keywords: gene analysis, protein analysis, physiological analysis
We have been working on the reseach for blood pressure regulation and body fluid regulation. We have been focusing on the
infuence of renal function on such regulations. Especially the movement of sodium ions in renal tubule would be the major
factor. Now we are interested in the sodium trenaport in distal tubule, which might induce the focal release of bioactive
proteins and following physiological reaction of small artery.
Gene Therapy 93
The Establishment of Next-Generation Cell Therapy Based on Islet Transplantation
Transplantation and Medical Sciences Course

Regenerative Medicine Master / Doctoral Degree
URL:
GOTO, Masafumi cooperate/184/index.html
Contact:
E-Mail masafumi.goto.c6@tohoku.ac.jp
Research Theme
Development of newly recombinant digesting enzymes for islets and various types of cell isolation
Development of an immunoisolating device for Bioartificial pancreatic islets
Establishment of novel effective protocols for performing hepatocyte transplantation
Research Keywords: islet transplantation, hepatocyte transplantation, cell islolation enzymes,

bioartificial pancreatic islets, next-generation cell therapy
Technical Keywords: cell culture, tissue and cell isolation, cell transplantation, in vivo / in vitro imaging,
histopathology
Islet transplantation is a less invasive type of tissue transplantation which is used to treat diabetic patients. In contrast to pancreas transplantation, islet
transplantation only requires the use of local anaesthesia and percutaneous cannulation to transplant isolated islets. The major obstacle associated with
islet transplantation is a the need to obtain multiple donors in order to cure one diabetic patient. This is mainly due to the unstable and insufficient
islet yield which is related to such factors as the poor quality of islet isolating enzymes, a low islet functionality, and poor engraftment. The need to
administer immunosuppressants to prevent graft rejection also results in the occurrence of several adverse effects experienced by the recipients.
Our main research interests focus on addressing these problems. We have developed genetically engineered cell isolating enzymes produced by
recombinant DNA technology. These novel enzymes can eliminate batch to batch differences, consequently making it possible to optimize the
enzyme components according to the structure of specific tissues. Improvements in the islet yield and function have already been reported in pre-
clinical study and clinical trials that are currently going on. Such improvements are expected to also be applicable for other types of cell therapy, such
as hepatocyte transplantation. Several studies from our laboratory, including the development of a novel evaluation method for the islet function and
a novel regimen for facilitating engraftment by resting transplanted islet grafts, are already being used in clinical practice. We are also attempting to
develop a bioartificial pancreatic islet device to enable patients to avoid the use of immunosuppressants.
Our ultimate goal is to make islet transplantation the standard therapy for diabetes, and also establish new types of next-generation cell therapy for
various diseases.
Figure 1. Development of safe and efficient enzymes for cell isolation Figure 2. High-sensitive imaging system for islet grafts
Recent Publications
- Maeda, et, al. Cloning a neutral protease of Clostridium histolyticum, determining its substrate specificity, and designing a specific substrate. Applied Microbiology and Biotechnology 2015 Aug 26 (Epub
ahead oh print)
- Dendo M, et al. Synergistic effect of neutral protease and clostripain on pancreatic islet isolation. Transplantation. in press, 2015
- Jimbo T, et al. A novel resting strategy for improving islet engraftment in the liver. Transplantation. 97(3):280-286, 2014
- Fujio A, et al. Collagenase H is crucial for isolation of rat pancreatic islets. Cell Transplantation. 23(10):1187-1198, 2014
- Nishimura R, et al. Tacrolimus inhibits the revascularization of isolated pancreatic islets. PLOS ONE. 8(4):e56799, 2013
94 Transplantation and Regenerative Medicine

To Challenge Intractable Brain Diseases Caused by Mysterious Misfolded Proteins:
Discovery of Remedies for Prion and Prion-like Diseases
Neurochemistry Medical Sciences Course

DOH-URA, Katsumi URL:

http://www.neurochemistry.med.tohoku.ac.jp/
Contact:
TEL +81-22-717-8233
E-Mail doh-ura@med.tohoku.ac.jp
Research Theme
Development of preventive and therapeutic methods, and search for novel drug targets and novel surrogate
markers for prion disease
Elucidation of molecular mechanism of prion formation, by means of chemical biology and molecular biology
Elucidation of molecular mechanism of neuronal cell death caused by misfolded protein accumulation and aging
Research Keywords: prion, misfolded protein, drug discovery, neuronal cell death, aging
Technical Keywords: cell culture, animal experiment, chemical biology, molecular biology, pathology
Our research interests are basic science and applied medical science related to the diseases caused by misfolded protein
accumulation in the brain, including prion disease and prion-like diseases (Alzheimers disease, Parkinsons disease, and
others). All these incurable brain diseases appear age-dependently in a sporadic fashion in most cases, and the pathological
processes of the diseases are proposed to share similar molecular degenerative pathways in the brain, which are not fully
elucidated. The nature of misfolded proteins, especially prion, is still one of the most challenging enigmas in science,
because misfolded proteins which are free of genomes transmit the pathological conditions into normal nerve cells, and even
into healthy individuals. Actually, recent outbreaks of new types of prion disease in animals and humans have demonstrated
that these kinds of misfolded proteins can be a real threat to the public health in the world. Concomitantly, development of
specific remedies for the diseases has been eagerly sought but has not been successfully achieved yet. Our research aims are
based on these circumstances, and we are working on the above research themes to disclose the molecular mechanisms of
the misfolded protein diseases, especially prion disease, and finally to make them curable.
Figure 1. Conceptual pathological pathway of brain disease caused by misfolded Figure 2. Accumulated misfolded protein in prion disease mouse brain (PET blot)
protein
Recent Publications
- Hamanaka T, et al. Structure-activity analysis and antiprion mechanism of isoprenoid compounds. Virology. 486:63-70, 2015
- Hamanaka T, et al. Anti-prion activity found in beetle grub hemolymph of Trypoxylus dichotomus septentrionalis. Biochemistry and Biophysics Reports. 3:3237, 2015
- Kimura T, et al. Secretin receptor involvement in prion-infected cells and animals. FEBS Lett. 589:2011-2018, 2015
- Teruya K, et al. Heparinase I-specific disaccharide unit of heparin is a key structure but insufficient for exerting anti-prion activity in prion-infected cells. BBRC. 460:989-995, 2015
- Nishizawa K, et al. Efficacy and mechanism of a glycoside compound inhibiting abnormal prion protein formation in prion-infected cells. J. Virol. 88:4083-4099, 2014
- Teruya K, Doh-ura K. Amyloid-Binding Compounds and their Anti-Prion Potency. Curr Top Med Chem. 13:2522-2532, 2013
Neurochemistry 95
To Understand the Molecular Mechanisms of Prion Protein Conversion
Neurological Science Medical Sciences Course

KITAMOTO, Tetsuyuki URL:

http://www.prion.med.tohoku.ac.jp/index.html
Contact:
TEL +81-22-717-8147
E-Mail kitamoto@med.tohoku.ac.jp
Research Theme
New diagnostic method to identify the acquired prion disease
Conversion-accelerating or inhibitory mechanism of prion protein
PrP polymorphism analysis in prion diseases
Research Keywords: prion protein, normal polymorphism and mutations, conversion, transmission experiment,
prion disease
Technical Keywords: histopathological analysis, humanized knock-in mouse, western blot analysis,
protein misfolding cyclic amplification, transmission experiments
We investigated prion diseases as a collaborating center of WHO (World Health Organization) since 1998 because of vCJD
emerging infection from 1996, also as a center for analyzing the PRNP gene and evaluating the histopathology of Japanese
CJD surveillance.
The recent achievements are as follows, the identification of the original prions (VV2 or MV2 prions) in dura-grafted CJD
with kuru plaques(2), the highly sensitive detection method to amplify vCJD prions from the plasma, and the structural
model of abnormal prion protein (5).
The future goals of our laboratory is to reveal the conversion mechanism of prion protein. By elucidation of this
mechanism, we can achieve to the treatment or the prevention of the prion diseases.
Figure 1. Transmission experiment with humanized PrP knock-in mouse Figure 2. Structural model of abnormal prion protein
Recent Publications
- Hizume M, et al. Human Prion Protein (PrP) 219K is converted to PrPSc but shows heterozygous inhibition in variant Creutzfeldt-Jakob disease infection. J Biol Chem. 284: 3603-3609, 2009.
- Kobayashi A, et al. Experimental verification of a traceback phenomenon in prion infection. J. Virol. 84:3230-3238, 2010.
- Takeuchi A, et al. Characterization of variant Creutzfeldt-Jakob disease prions in prion protein-humanized mice carrying distinct codon 129 genotypes. J Biol Chem. 288:21659-21666, 2013.
- Kobayashi A, et al. Deciphering the pathogenesis of sporadic Creutzfeldt-Jakob disease with codon 129 M/V and type 2 abnormal prion protein. Acta Neuropathol Commun. 1:74(1-11), 2013.
- Shirai T, et al. Evaluating prion models on comprehensive mutation data of mouse PrP Structure 22; 560-571, 2014.
- Kobayashi A. et al. Transmission properties of atypical Creutzfeldt-Jakob disease: a clue to disease etiology?. J Virol. 89(7):3939-46,2015.
96 Neurological Science
In Search for Our Mind: Pursuit of Optogenetic Approach to Reveal the Role of Neuron-
Glia Interactions in Mind Formation
Interdisciplinary Medical URL:

http://www.ims.med.tohoku.ac.jp/matsui/
Science Contact:
(Center for Neuroscience) TEL +81-22-717-8208
E-Mail matsui@med.tohoku.ac.jp
MATSUI, Ko
Associate Professor, Ph.D.
Research Theme
Glial modulation of synaptic transmission
Mechanism of glial release of transmitters
Determinant of signal transmission via microenvironment of synapse
Research Keywords: glia, synaptic transmission, intracellular ionic composition, brain ischemia, epilepsy
Technical Keywords: optogenetics, electrophysiology, acute brain slice, two-photon imaging, electroencephalogram
Every scientific endeavor starts with observation. However, observation alone can only lead to analysis of correlation.
Experimental perturbation is required to understand the causal relationship between the components that constitute the
system under study. The brain is a complex multicellular organ. Our current understanding of its function suggests that
communication between these cells underlies the formation of the mind. This is mainly deduced from studies of correlation
between cell activity and animal behavior. Recently developed tools enable specific control of cell activity. For example,
light-sensitive proteins found in microorganisms, such as channelrhodopsin-2, can now be genetically expressed in
mammalian brain cells which allow experimenters to optically control cell activity at will. We have introduced various
methods to study communication between neuron-to-neuron, neuron-to-glia, and glia-to-neuron. Our recent report using
transgenic mice shows that selective optogenetic stimulation of glia can lead to release of glutamate as gliotransmitter,
induce synaptic plasticity, and accelerate cerebellar modulated motor learning. This finding suggests that glia also
participates in information processing in the brain, a function once thought to be solely mediated by neuronal activity. These
reports demonstrate the use of optogenetic tools for exploring the causal relationship between brain activity and mind.
Figure 1. In vivo optogenetic manipulation of glial activity Figure 2. Suppression of ischemic damage by optogenetic glial activity
Recent Publications
- Nakamura Y, et al. Nanoscale distribution of presynaptic Ca2+ channels and its impact on vesicular release during development. Neuron 85(1):145-158, 2015
- Beppu K, et al. Optogenetic countering of glial acidosis suppresses glial glutamate release and ischemic brain damage. Neuron 81(2):314-320, 2014
- Budisantoso T, et al. Evaluation of glutamate concentration transient in the synaptic cleft of the rat calyx of Held. J Physiol 591(1):219-239, 2013
- Sasaki T, et al. Application of an optogenetic byway for perturbing neuronal activity via glial photostimulation. PNAS 109(50):20720-20725, 2012
- Tanaka KF, et al. Expanding the repertoire of optogenetically targeted cells with an enhanced gene expression system. Cell Rep 2(2):397-406, 2012.
Interdisciplinary Medical Science (Center for Neuroscience) 97

Development of Cancer-specific Monoclonal Antibodies without Side Effects
Regional Innovation Medical Sciences Course

Master Degree
URL:
KATO, Yukinari http://www.med.tohoku.ac.jp/english/org/196/
Contact:
TEL +81-22-717-8207
E-Mail yukinarikato@med.tohoku.ac.jp
Research Theme
Development of innovative next generation cancer-specific monoclonal antibodies and clinical application
Protein expression and antibody production using antibody-engineering technologies
Development of therapeutic devices using tumor-specific antibodies
Research Keywords: podoplanin, CLEC-2, PA tag, IDH1/2, CasMab

Technical Keywords: cancer-specific monoclonal antibody, glycobiology, development of therapeutic devices,
monoclonal antibody, antibody-engineering
Although many antigens are expressed highly in tumors, those antigens have been removed from the candidates of antibody-
drug targets because they were also expressed in normal tissues. When one protein in cancer cells and normal cells possesses
the same amino acid sequence, the post-translational difference such as glycans should be utilized to produce the cancer-
specific mAb (CasMab). The CasMab method is the platform to develop mAbs, which could attack only cancer cells.
Importantly, this method is useful for not only producing CasMabs against novel targets but also replace the existing mAbs
into the side effect-free ones. Podoplanin, a cancer metastasis-inducing protein, is expressed in many cancers, while it is
also expressed in normal cells such as lymphatic endothelial cells and lung type I alveolar cells. We have already produced
CasMabs against human podoplanin. We will refine our technologies and develop CasMabs against several molecular targets.
Figure 1. Podoplanin is expressed in many cancers Figure 2. Development of cancer-specific monoclonal antibodies
Recent Publications
- Kato Y, Kaneko MK. A Cancer-specific Monoclonal Antibody Recognizes the Aberrantly Glycosylated Podoplanin. Sci Rep. 4:5924, 2014
- Nagae M, et al. A novel platform of C-type lectin-like receptor CLEC-2 for binding O-glycosylated podoplanin and non-glycosylated rhodocytin. Structure. 22(12): 17111721, 2014
- Kaneko M, et al. IDH2 mutation is frequently observed in giant cell tumor of bone. Cancer Sci. 105(6):744-748, 2014
- Fujii Y, et al. PA tag: a versatile protein tagging system using a super high affinity antibody against a dodecapeptide derived from human podoplanin. Protein Expr Purif. 95:240-247, 2014
- Kato Y. Specific monoclonal antibodies against IDH1/2 mutations as diagnostic tools for gliomas. Brain Tumor Pathol. 32(1): 3-11, 2015
98 Regional Innovation
Development of Prevention, Diagnosis, and Treatment Methods for Various Diseases by
Understanding Pathogenic Mechanisms through Establishment of Innovative Animal Models
Laboratory Animal Medicine Medical Sciences Course

URL:
MIYOSHI, Ichiro http://www.med.tohoku.ac.jp/english/org/
Professor, D.V.M. Ph.D. DJCLAM medical/18/index.html
Contact:
TEL +81-22-717-8175
Research Theme
Identification and analysis of responsible genes for refractory diseases by reverse and forward genetics
Development of new genetically modified animal by developmental engineering technology
Development of new genetically modified animal to investigate the pathophysiological roles of cell surface
glycoconjugates
Research Keywords: comparative and experimental medicine, genetically engineered animal, disease-associated gene,
developmental engineering, cell-surface glycoconjugates
Technical Keywords: genetically engineered animal, developmental engineering, genome editing,
animal experimentation
The institute for Animal experimentation is a facility for rearing laboratory animals with about 30 care takers. We are
now maintaining about 30,000 laboratory animals including mice, rats, rabbits, dogs, pigs and monkeys. In our research
laboratory, we are investigating comparative and experimental medicine and educating graduate students in the field of
laboratory animal science and medicine. We perform research using laboratory animals to try to find out human characteristics.
We are studying the causes and pathology of hereditary diseases using spontaneous and transgenic animal models for human
diseases such as rats with diabetes mellitus, mice with congenital cataracts, mice with Menkes disease and rats with Wilson's
disease. In addition, one of the recent topics in our laboratory is pathophysiological role of glycosphingolipids (GSLs).
We found that aberrant expression of a GSLs synthase dramatically promotes proliferation of intestinal epithelial cells. It
is likely to be a model of initial stage of colon cancer. Other models reveal various changes in their phenotypes, including
metabolic disorder, dysontogenesis and cancer. We are exploring molecular events underlying these phenotypic change.
Figure 1. Specific pathogen-free (SPF) animal room of the facility Figure 2. Invasive serous carcinoma of the ovary of mOGP-Tag transgenic mice
Recent Publications
- Sherman-Baust CA, et al. A genetically engineered ovarian cancer mouse model based on fallopian tube transformation mimics human high-grade serous carcinoma development. J Pathol. 233(3):228-237,
2014
- Taguchi K, et al. Colony-stimulating factor-1 signaling suppresses renal crystal formation. J Am Soc Nephrol. 25(8):1680-1697, 2014
- Kitamura H, et al. Beneficial effects of Brazilian propolis on type 2 diabetes in ob/ob mice: Possible involvement of immune cells in mesenteric adipose tissue. Adipocyte. 2(4):227-36, 2013
- Kitamura H, et al. Ubiquitin-specific protease 2-69 in macrophages potentially modulates metainflammation. FASEB J. 27(12):4940-4953, 2013
- Okamura T, et al. Phenotypic Characterization of LEA Rat: A New Rat Model of Nonobese Type 2 Diabetes. J Diabetes Res. 2013:986462, 2013
Laboratory Animal Medicine 99

Medical Education to Produce Medical Professionals Ranging from World-class
Researchers to Leaders of High-quality Hospitals
Office of Medical Education URL:

http://www.med.tohoku.ac.jp/english/org/94/
index.html
Contact:
KAGAYA, Yutaka TEL +81-22-717-8508
E-Mail meduc-jimu@bureau.tohoku.ac.jp
Research Theme
Development of effective learning programs using medical simulation training
Development of a peer review system of medical records as an outcome evaluation of medical education
How does undergraduate education influence medical students choice of future specialties?
Research Keywords: researcher training, medical simulation, outcome evaluation, career choice
Technical Keywords: curriculum development, patient simulators, peer review, qualitative study
The future careers of our students vary from world-leading researcher to leader of a high-quality hospital. We develop advanced
learning programs for students and graduates to help them actively develop their own careers taking a broad view of things with a
spirit of inquiry.
Education of future leaders who will move medicine forward
To increase the number of MD researchers, which has decreased recently in Japan, we began a new Research Apprentice Course
to support students wishing to start research at M1, in addition to our Advanced Research Course for students who aim to continue
research after Long-term Research Training at M3.
Development of effective learning programs using medical simulation training
We provide effective and efficient learning programs regarding emergency medicine and cardiac physical examination using
high-quality simulators. Since using high-tech simulators alone is not sufficient for students to achieve good outcomes, we are
developing advanced new programs.
Development of a peer review system of medical records as an outcome evaluation of medical education
We are developing a peer review system of medical records as an outcome evaluation (performance after graduation) of medical
education. High inter-rater reliability has been obtained, and validity is being pursued.
How does undergraduate education influence medical students choice of future specialties?
The decreasing numbers of physicians in several clinical specialties and that of MD researchers in basic medical science are serious
problems in Japan. We are investigating the effect of undergraduate medical education on the students choice of future specialties.
Figure 1. Mission of Office of Medical Education Figure 2. Education of future leaders who will move medicine forward
Recent Publications
- Ishii S, et al. What should be altered in the newly introduced integrated preclinical curriculum: a qualitative study of curriculum reformation. CAHE Journal of Higher Education Tohoku University. 7: 25-34, 2012
- Kagaya Y, et al. Current perspectives on protective roles of erythropoietin in cardiovascular system: erythropoietin receptor as a novel therapeutic target. Tohoku J Exp Med. 227:83-91, 2012. Review
- Tabata M, et al. Effects of participation in medical support teams for areas devastated by the Great East Japan Earthquake on learning attitudes and future careers of medical students. Igaku Kyoiku. 43:309-
314, 2013[Jpn]
- Hasegawa S, et al. Password-protected secret-sharing schemes without random oracles. ISITA 2014. 579-583, 2014
- Kameoka J, et al. Development of a peer review system using patient records for outcome evaluation of medical education: reliability analysis. Tohoku J Exp Med. 233:180-195, 2014
- Kameoka J, et al. Number of papers published in English from the nursing departments of 42 national universities in Japan in the past ten years. Nurse Educ Today. 2016 in press.
100 Office of Medical Education

Genomic Imprinting in Mammals and Evolution
Informative Genetics Medical Sciences Course

URL:
http://www.ob-gy.med.tohoku.ac.jp/laboratory/
ARIMA, Takahiro t-arima.html / http://www.med.tohoku.ac.jp/org/
Professor, M.D. Ph.D. egrc/169/index.html
Contact:
TEL +81-22-717-7844
E-Mail tarima@med.tohoku.ac.jp
Research Theme
Genomic imprinting and mammalion evolution
Molecular mechanism of genomic imprinting phenomenon
Study on association between human assisted reproductive technology (ART) and congenital imprinting diseases
Research Keywords: Genomic imprinting, Epigenetics, Placenta, Assisted reproductive technology (ART),
Evolution
Technical Keywords: DNA methylation, Histone modification , RNA sequence
Our aim is to determine the normal epigenomes of the human placenta, which constitute the fetal-maternal interface,
for future use in studies of human diseases associated with reproduction and development. In the placenta, we focus on
cytotrophoblast and syncytiotrophoblast cells. To this end, we will develop and establish the technologies to isolate these
cells and analyze the epigenomic modifications. We will further try to determine the epigenomes of disease samples, to
search for disease-specific changes. We will also determine the methylomes of sperm from oligospermic patients for their
use in the improvement of assisted reproductive technology.
Figure 1. Incomplete erasure of germline DNA methylation in the human placenta Figure 2. HTS cells
Recent Publications
- Okae H, et al. Genome-wide analysis of DNA methylation dynamics during early human development. PLOS Genetics. 10(12): e1004868, 2014.
- Okae H, et al. RNA sequencing-based identification of aberrant imprinting in cloned mice. Hum Mol Genet.23. 992-1001. 2014.
- Okae H, et al. Re-investigation and RNA sequencing-based identification of genes with placenta-specific imprinted expression. Hum Mol Genet. 21: 548-558, 2012.
- Watanabe T, et al. Role for piRNAs and non-coding RNA in de novo DNA methylation of the imprinted mouse Rasgrf1 locus. Science. 332: 848-852, 2011.
- Borgel, J., et al. Targets and dynamics of promoter DNA methylation during early mouse development. Nat. Genet. 42: 1093-1100, 2010.
Informative Genetics 101

To Realize Holistic Medicine through Molecular and Social Epidemiology.
Molecular Epidemiology Medical Sciences Course

KURIYAMA, Shinichi URL:

Professor, M.D. Ph.D. egrc/170/index.html
Contact:
TEL +81-22-717-8104
E-Mail kuriyama@med.tohoku.ac.jp
Research Theme
Molecular epidemiological study regarding obesity and cancer
Molecular epidemiological study regarding autistic spectrum disorders
Methodological study of genome cohort and precision medicine
Research Keywords: molecular epidemiology, obesity, cancer, autistic spectrum disorders, genome cohort
Technical Keywords: family-based prospective cohort study, birth and three generation cohort study,
pyridoxine related diseases study, biobank, risk prediction and elucidate causation of diseases
We intend to realize personalized healthcare and medicine based on genetic and lifestyle information through genome cohort
studies.
1. Methodological study of genome cohort:
We have developed the Birth and Three-Generation Cohort Study (BirThree Cohort Study). The cohort could reveal the
causal relationship between genetic factors and environmental factors from fetus. In addition to the BirThree Cohort Study,
we conduct The Japan Environment and Children's Study and Kakegawa Study.
2. Autistic spectrum disorders study:
Through the BirThree Cohort Study and so on, we intend to elucidate the cause of autistic spectrum disorders. Pyridoxine
responsiveness is one of the clues to cluster the syndrome.
3. Obesity and cancer study:
Through the BirThree Cohort Study and so on, we intend to elucidate the cause of obesity and cancer.
Figure 1. The BirThree Cohort Study and medicine in the near future Figure 2. The aims of genome medicine
Recent Publications
- Ohuchi N, et al. Sensitivity and specificity of mammography and adjunctive ultrasonography to screen for breast cancer in the Japan Strategic Anti-cancer Randomized Trial (J-START): a randomized
controlled trial. Lancet 2015. pii: S0140-6736(15)00774-6.
- Nagasaki M, et al. ToMMo Japanese Reference Panel Project, Yamamoto M. Rare variant discovery by deep whole-genome sequencing of 1,070 Japanese individuals. Nat Commun. 2015;6:8018.
- Kikuya M, et al. Protocol and Research Perspectives of the ToMMo Child Health Study after the 2011 Great East Japan Earthquake. Tohoku J Exp Med. 2015;236:123-30.
- Nishigori H, et al. Correlation Between the Great East Japan Earthquake and Postpartum Depression: A Study in Miyako, Iwate, Japan. Disaster Med Public Health Prep. 2015;9:307-12.
- Hasegawa J, et al. Change in and long-term investigation of neuro-otologic disorders in disaster-stricken Fukushima prefecture: retrospective cohort study before and after the Great East Japan Earthquake. PLoS
One. 2015;10:e0122631.
102 Molecular Epidemiology

To Clarify the Association of Chemical Exposures with Child Development in Birth Cohort
Studies
Development and Medical Sciences Course

Environmental Medicine Master / Doctoral Degree
URL:
http://www.dem.med.tohoku.ac.jp
NAKAI, Kunihiko
Contact:
E-Mail nakai_k@dem.med.tohoku.ac.jp
Research Theme
To clarify the association of prenatal chemical exposures with child neurobehavioral development in birth cohort studies
To examine the adverse effects of exposures to methylmercury, lead and persistent organic pollutants
To elucidate the environmental radioactive contamination with biomonitoring approaches after Fukushima Daiichi
nuclear disaster
Research Keywords: behavioral teratology, chemical exposure, methylmercury, risk analysis, caddisfly watch
Technical Keywords: birth cohort study, risk determination, intelligence measurement,
mental development measurement, field research in the environment
Several previous studies have reported the association of prenatal/perinatal exposures to environmental chemicals with poorer
development in children. Especially, methylmercury (MeHg), lead, and persistent organic pollutants (POPs) including polychlorinated
biphenyls (PCBs) are the chemicals that may cause delay of neurobehavioral development and behavior problems like attention deficit/
hyperactivity disorder (ADHD) of children. Therefore, we have been performing two birth cohort studies; first, Tohoku Study of Child
Development (TSCD) was started in 2002 at the coastal areas of Miyagi prefecture, and second, we are participating to the Japan
Environment and Childrens Study (JECS) as Miyagi unit center. We are focusing on adverse effects on mental development, intelligence,
laungage ability, and behavioral problems such as ADHD and autism.
Since human are exposed to MeHg and PCBs through the consumption of fishes, we pay special attention to the risk/benefit balance
of fish intake. Especially, omega-3 polyunsaturated fatty acids such as DHA are considered to be beneficial to child development, while
eating a lot of fishes may invite chemical exposures. Risk communication including the ongoing risk monitoring is another subject.
Additionally, after the The Great East Japan Earthquake/tsunamis, we started two field studies to examine the tsunami-induced
environmental contamination by various kind of organic chemicals and to monitor the contamination of fresh water system with
radioactive materials by biomonitoring using aquatic insect larvae, caddishfly.
Figure 1. Risk and benefit balance of fish intake Figure 2. Prenatal exposure to PCB impaired intellectual ability in 42-month-old
boys
Recent Publications
- Tatsuta, et al. Impacts of the Great East Japan Earthquake on Child's IQ. J Pediatr. 167(3):745-751, 2015
- Hosaka, et al. Relationship between material gestational hypertension and home blood pressure in 7-year-old Children and their mothers: the Tohoku Study of Child Development. Hypertens Res. 38(11):776-
782, 2015
- Tatsuta N, et al. Impacts of prenatal exposures to polychlorinated biphenyls, methylmercury, and lead on intellectual ability of 42-month-old children in Japan. Environ Res. 133:321-326, 2014
- Yoshimasu K, et al. A meta-analysis of the evidence on the impact of prenatal and early infancy exposures to mercury on autism and attention deficit/hyperactivity disorder in the childhood. Neurotoxicology.
44:121-31, 2014
- Iwai-Shimada M, et al. Methylmercury in breast milk of Japanese mothers and lactational exposure of their infants. Chemosphere. 126:67-72, 2015
Development and Environmental Medicine 103

To Watch for Sound Growth and Development of Children (Research for Pediatric
Endocrinology and Japan Environmental and Childrens Study)
Pediatric Endocrinology Medical Sciences Course

and Environmental Medicine Master / Doctoral Degree
URL:
http://www.egrc.med.tohoku.ac.jp/index.html
FUJIWARA, Ikuma
Contact:
E-Mail ifujiwara-endo@umin.ac.jp
Research Theme
Genetic analysis of osteogenesis imperfect and uncovering of new causal genes
Establishing new treatments for osteogenesis imperfecta
Clinical research for pediatric endocrinology, diabetes, and bone diseases
Research Keywords: pediatric endocrinology, genetic skeletal disorders, diabetes mellitus,

osteogenesis imperfecta, type 1 collagen
Technical Keywords: genetic analysis, bone mineral density, medical therapy
We are working on Japan Environmental and Childrens Study. We also carry out clinical research for pediatric
endocrinology, diabetes, and congenital bone diseases in addition to genetic analyses for those disorders. Among skeletal
disorders, we focus on osteogenesis imperfecta and study for its genetic background and the efficacy of bisphosphonate
treatment. We have found that kinds of mutation in type 1 collagen genes do not affect the treatment efficacy on bone
mineral density. Around 20 % of the patients have no mutation in type 1 collagen genes, and we are now trying to find other
genetic aberrations in osteogenesis imperfecta by whole exome sequencing.
Figure 1. Pathogenesis of osteogenesis imperfecta Figure 2. Efficacy of pamidronate in patients with osteogenesis imperfecta
Recent Publications
- Fujiwara I, et al. Mutations in PIGL in a patient with hyperphosphatasia mental retardation syndrome. Am J Med Genet Part A, 2015 (in press).
- Kaga A, et al. Association of achondroplasia with Down syndrome: difficulty in prenatal diagnosis by sonographic and 3-D helical computed tomographic analyses. Cong Anomal, 2015 (in press).
- Takagi M, et al. Heterozygous defects in PAX6 gene and congenital hypopituitarism. Eur J Endocrinol 172(1);37-45, 2015
- Kamimura M, et al. Glycemic control in type 1 diabetic patients following the Great East Japan Earthquake and Tsunami. J Japan Diab Soc 57(1): 16-21, 2014 [Jpn]
104 Pediatric Endocrinology and Environmental Medicine

Trying to Assess the Detailed Forensic Diagnosis of Death and Accurate Individual
Identification Using CT and MRI
Autopsy Imaging Center URL:

http://www.ai.med.tohoku.ac.jp
Contact:
TEL +81-22-717-7481
ISHIBASHI, Tadashi E-Mail tisibasi@med.tohoku.ac.jp
Research Theme
Analysis of radiologic postmortem image findings
Establishment of forensic anthropologic individual identification method on postmortem images
Research Keywords: forensic medicine, diagnostic radiology, cause of death, individual identification
Technical Keywords: computed tomography, magnetic resonance imaging, forensic autopsy,
anthropologic measurement
In recent years, postmortem radiology using CT scanner, that is to say, Ai: Autopsy imaging in Japanese, has become
popular within the field of legal medicine. In our institute, more than 1,000 cases were analyzed using the multi-slice CT
scanner and the 3D workstation between 2009 and 2014. We have offered a lot of useful information to forensic pathologists
on the cause of death (e.g. hypothermic death and drowning death), the location of metal weapon(s) in the body, respiratory
infectious disease like tuberculosis and so on. In addition, we have carried out many studies on forensic anthropology, such
as sex and age determination using CT images.
Figure 1. 3D volume rendering image of skull fractures Figure 2. Multiple fractures of left upper extremity and pelvic bone
Recent Publications
- Usui A, et al. Postmortem lung features in drowning cases on computed tomography. Jpn J Radiol. Jul;32(7):414-20, 2014
- Kawasumi Y, et al. Hypothermic death: possibility of diagnosis by post-mortem computed tomography. Eur J Radiol. Feb;82(2):361-365, 2013
- Nakajima A, et al. The prevalence of morphological changes in the thoracolumbar spine on whole-spine computed tomographic images. Insights Imaging, Feb;5(1):77-83, 2014
- Hayashizaki Y, et al. Sex determination of the pelvis using Fourier analysis of postmortem CT images. Forensic Sci Int. Jan;246:122.e1-9, 2015
- Funayama M, Saito H, ed. Autopsy imaging; case presentation and imaging method. 1st ed. Ishiyaku publishers, inc., Tokyo, 2014[Jpn]
Autopsy Imaging Center 105

Toward the Recovery of Community Medicine after the Great East Japan Earthquake
Comprehensive Education URL:

http://www.ctc.med.tohoku.ac.jp/
Center for Community Contact:
Medicine TEL +81-22-717-8010
E-Mail ctc@med.tohoku.ac.jp
HARIGAE, Hideo
Research Theme
Accept personnel in medical fields from the disaster-stricken areas and educate them as high skill medical
professionals
Establish a new disaster medicine field and cultivate personnel who engage in regional and disaster medicine
Implement the medical education emphasis program for an increase in capacity at the School of Medicine
Research Keywords: community medicine, disaster medicine, recovery

Technical Keywords: skills laboratory center, cutting-edge medical technology, emergency, traditional chinese
medicine, pathology
The Great East Japan Earthquake of March 11, 2011 wreaked massive damage to the medical institutions located along the Pacific
coast of the Tohoku region. According to a Miyagi Medical Association survey taken in early April just after the disaster, six public
hospitals in Miyagi Prefecture suffered catastrophic damage resulting in the loss of some 600 beds.
In addition, since medical institutions damaged by the earthquake were forced to provide medical care at temporary medical
offices and their hospital bed capacities were decreased, many full-time doctors left their jobs. Faced with this serious situation,
many hospitals, medical institutions, and local governments addressed rebuilding and restoration of hospitals, and tried to secure
the employment of medical staff.
In order to prevent the outflow, overwork, and burnout of those capable personnel engaged in region-based medical services in the
disaster-stricken areas, it is necessary to secure jobs for healthcare professionals, promote exchange and circulation of personnel,
improve the levels of medical care services, and to send back to the region effectively reeducated healthcare workers with advanced
knowledge and skills.
Therefore, for the purpose of contributing to the revival of community medicine in the Tohoku region, Tohoku University
established the Assistance Project of the Comprehensive Education Center for Community Medicine. Through this initiative,
we shall build a circulating lifetime education and dispatching system for medical workers, help prevent the outflow of medical
workers from the disaster-stricken areas, and enhance the level of medical service provided in the entire region.
Figure 1. Kampo workshop Figure 2. Visiting Skills Laboratory
106 Comprehensive education center for community medicine

Networking Between University Hospitals and Community Cancer Center Hospitals
Tohoku Community Cancer URL:
Services Program Contact:

TEL +81-22-717-7087
E-Mail tamori@med.tohoku.ac.jp
MORI, Takahiro
Research Theme
Networking between University hospitals and community cancer center hospitals
Research Keywords: networking between University hospitals and community cancer center hospitals,
molecular biology of cancer , cancer immunotherapy
Technical Keywords: networking between University hospitals and community cancer center hospitals,
molecular biology of cancer , cancer immunotherapy
This Tohoku area has much more aged populations than average in Japan and aged population tend to obtain more
malignancies. Therefore, the increment of cancer patients in our community is expected in near future. However, we also
have a problem the shortage of oncology specialists compared with any other areas in Japan. Besides, this situation seems to
be worsened due to the Great East Japan Earthquake, which widely and strongly damaged this area in 2011.
Our department aims to strengthen the alliances of oncology networking systems between university hospital and community
cancer center hospitals, as this is essential to deliver quality care to cancer patients. We also have educational systems to
support and train oncology specialists including board-certified oncologists, certified cancer nursing specialists and other
oncology specialists in co-medicals and intend to develop the medical human resource with high level of knowledge and
skill in this community.
Figure 1. Scientific seminar Figure 2. Visiting Ishinomaki, after the Great Earthquake
Recent Publications
- The effectiveness of reducing affected arm volume by self-care program in patients with breast cancer treatment-related lymphoedema. Arinaga Y, Sato F, Sato N, Kashiwagura E. J. Jpn. Acad. Nurs. Sci.
2015; 35 (in press).
- IFN-gamma AU-rich element removal promotes chronic IFN-gamma expression and autoimmunity in mice. Hodge DL, Berthet C, Coppola V, Kastenmuller W, Buschman, MD, Schaughency PM, Shirota H,
Scarzello AJ, Subleski JJ, Anver MR, Ortaldo J R, Lin F, Reynolds DA, Sanford ME, Kaldis P, Tessarollo L, Klinman DM, Young HA. J Autoimmun 2014
- Recent progress concerning CpG DNA and its use as a vaccine adjuvant. Shirota H, Klinman DM. Expert Rev Vaccines 2014; 13: 299-312
- Curative resection of gastric tube cancer by hand-assisted thoracoscopic surgery. Kato T, Ohtani H, Ueki H, Mori T. Esophagus 2013; 10.1007/s10388-012-0358-0 (DOI) (Correspond. Author)
- Clinical usefulness of KRAS, BRAF, and PIK3CA mutations as predictive markers of cetuximab efficacy in irinotecan- and oxaliplatin-refractory Japanese patients with metastatic colorectal cancer. Soeda H,
Shimodaira H, Watanabe M, Suzuki T, Gamoh M, Mori T, Komine K, Iwama N, Kato S, Ishioka C. Int J Clin Oncol. 2012; May 26.
Tohoku Community Cancer Services Program 107

Building a Platform for Future Regional Medicine, Training Future Specialists of Regional
Care
Education and Support for Medical Sciences Course

Community Medicine Doctoral Degree
URL:
http://www.hosp.tohoku.ac.jp/departments/
ISHII, Tadashi 3207.html
Contact:
E-Mail administ@soushin.hosp.tohoku.ac.jp
Research Theme
Clinical Studies of Regional Medicine, Comprehensive Medicine, Disaster Medicine, traditional Japanese (Kampo)
medicine and the Clinical Questions in Daily Clinical Practice
Research Keywords: Regional Medicine, Disaster Medicine, Comprehensive Medicine,

traditional Japanese (Kampo) medicine, Clinical Studies
Technical Keywords: kampo drugs, information and communication technology, questionnaire,
regional medical facilities, education program
Our research projects are focused on regional, general and alternative medicine, and especially pertain to medical care in the disaster-stricken
areas after the Great East Japan Earthquake.
Based on our experience of the earthquake, we have been developing a mobile assessment system which collects the information that is
necessary for the health maintenance in a large-scale disaster using digital devices such as smartphones.
We are studying the influence of the spectrum of disease, before and after the earthquake, around the Taro area of Iwate Prefecture.
We are studying a questionnaire survey on community medicine in residency programs in the Tohoku region of Japan to clarify the benefits
of medical education in the disaster-stricken areas.
We are studying the epidemiological evaluation of the extraction from the latent population with esophagus achalasia (EA) among patients
diagnosed with anorexia nervosa (AN) in the regional area. This is because 10% of the EA patients are unfortunately misdiagnosed with AN.
For the management of patients with chronic kidney disease, our clinical trial on the evaluation of the renal protective effect of oral alkaizer
and the metabolome analysis has been collaborated with the other Division of Nephrology, Endocrinology and Vascular Medicine and Tohoku
Medical Megabank Organization.
Traditional Japanese (Kampo) medicine has been widely used in regional medicine for the treatment of multiple diseases; however, its efficacy
remains unclear. Our department has reported many clinical studies on traditional Japanese (Kampo) medicine, and we will continue to support
this area in order to discover new evidence.
Figure 1. Group photo of our team
Recent Publications
- Ishii T. Medical response to the Great East Japan Earthquake in Ishinomaki City. WPSAR 2(4): 1-7, 2011
- Kuroda H. Health care response to the tsunami in Taro District, Miyako City, Iwate Prefecture. WPSAR2(4):14-24, 2011
- Tanaka J, et al. An observational study of giant cell interstitial pneumonia and lung fibrosis in hard metal lung disease. BMJ Open. 4(3):e004407, 2014
- Takayama S, et al. The traditional kampo medicine tokishakuyakusan increases ocular blood flow in healthy subjects. Evidence-based Complementary and Alternative Medicine, doi:10.1155/2014/586857, 2014
- Numata T, et al. Traditional Japanese Medicine Daikenchuto Improves Functional Constipation in Poststroke Patients. Evidence-based Complementary and Alternative Medicine, doi:10.1155/2014/231258, 2014
108 Education and Support for Community Medicine

Active Research to Elucidate the Mechanism of Stress-related Disorders and Vigorous
Challenge to Develop Innovative Psychosomatic Treatment
Psychosomatic Medicine Medical Sciences Course

Doctoral Degree
URL:
FUKUDO, Shin http://square.umin.ac.jp/thkpsm/
Professor, M.D. Ph.D. english_index.htm
Contact:
TEL +81-22-717-7326
E-Mail sfukudo@med.tohoku.ac.jp
Research Theme
To widen perspective of brain-gut interaction with multimodal techniques and to uncover secrets of functional
gastrointestinal disorders
To investigate the neural mechanism behind the onset and maintenance of eating disorders by brain imaging
To bring a breakthrough to psychosomatic medicine through improvement of treatment for stress-related disorders
and development of innovative neuromodulation
Research Keywords: psychosomatic medicine, stress-related disorders,

functional gastroenterological disorders, brain-gut interaction, eating disorders
Technical Keywords: gastrointestinal manometry, barostat, functional neuroimaging,
cognitive behavior therapy, repetitive transcranial magnetic stimulation
We, Department of Psychosomatic Medicine, conduct clinical practice and research on stress-related disorders which include psychosomatic
diseases and some psychiatric diseases.
Functional gastrointestinal (GI) disorders are a typical model of psychosomatic diseases. Brain and digestive system are complicatedly
interconnected via neural and hormonal pathway (brain-gut interaction), and deeply affected by psychosocial stress. Functional gastrointestinal
disorders do not show any particular finding through ordinary gastroenterological tests. Functional examinations such as manometry and barostat
bring invaluable information on the pathophysiology of functional GI disorders. We accumulate data of functional GI examinations. In one of our
researches, we elucidated the role of corticotropin-releasing hormone on colonic motility and sensation.
Anorexia nervosa, typical eating disorder, is a life-threatening disease because of severe emaciation by drive for thinness. We are investigating
neural basis of the disorder using functinal neuroimaging techniques. We reported alteration of histamine receptor binding potential in the central
nervous system of anorexia nervosa patients, and hypoactivity of ventrolateral prefrontal cortex in the patients during cognitive set-shifting.
We put efforts into improvement of psychosomatic therapy (both pharmacotherapy and psychotherapy) and development of neuromodulation
technique such as repetitive transcranial magnetic stimulation.
Figure 1. Colonic motility in a patient with irritable bowel syndrome Figure 2. Brain activity of anorexia nervosa patients during cognitive flexibility task
Recent Publications
- Fukudo S. IBS: Autonomic dysregulation in IBS. Nat Rev Gastroenterol Hepatol. 10(10):569-71, 2013
- Sato Y, Saito N, Utsumi A, et al. Neural basis of impaired cognitive flexibility in patients with anorexia nervosa. PLoS One. 8(5):e61108. 2013
- Endo Y, Shoji T, Fukudo S, et al. The features of adolescent irritable bowel syndrome in Japan. J Gastroenterol Hepatol. 26(Suppl3):106-9, 2011
- Yoshizawa M, Tashiro M, Fukudo S, et al. Increased brain histamine H1 receptor binding in patients with anorexia nervosa. Biol Psychiatry. 2009 Feb 15;65(4):329-35.
- Sagami Y, Shimada Y, Tayama J, et al. Effect of a corticotropin releasing hormone receptor antagonist on colonic sensory and motor function in patients with irritable bowel syndrome. Gut. 53(7):958-64. 2004
Psychosomatic Medicine 109

For Providing Medical Therapies with Safe and High Quality and for Establishment the
Evidence-based Novel Therapies
Clinical Pharmaceutical Medical Sciences Course

Science Master / Doctoral Degree
URL:
http://www.pharm.hosp.tohoku.ac.jp/
MANO, Nariyasu
Contact:
E-Mail mano@hosp.tohoku.ac.jp
Research Theme
Construction of high sensitive analytical methods for abnormal bile acids in patients with lipid metabolism disorder
Development of the analytical methods for blood concentrations of drugs and their metabolites for clinical
application
Study on analysis of the pharmacokinetics change in patients with disease and optimization of the medical therapy
Research Keywords: bile acid, therapeutic drug monitoring (TDM), transporter, biomolecules
Technical Keywords: bioanalytical chemistry, metabolomics, pharmacokinetics, molecular biology
The primary aim of our research is to provide medical therapies with safe and high quality, and to accumulate the evidence
for novel therapies.
The metabolism abnormality of cholesterol affects arteriosclerosis, cardiac disorder, and progress of the cerebrovascular
disorder. It is known that the level of bile acids, which are synthesized from cholesterol, shows an abnormality and that most
of those bile acids are excreted in urine as salfate conjugations in patients with hepatobiliary diseases. Furthermore, the
relationship between bile acid and glucose metabolism and oxidative stress is pointed out. We currently study the basic and
clinical methodology for metabolomics to elucidate disease-relating biomolecules.
In addition, we are trying to develop the analytical methods for blood concentration of drugs and their metabolites using
chromatographic and mass spectrometric techniques. The blood concentration of the drugs including metabolites shows
the phenotype as a result of environmental factor such as age of the patient, sex, a lifestyle, taste, underlying diseases
or concomitant drug and genetic factor including polymorphisms. We mainly develop the determination methods for
antineoplastic drugs, immunosuppressive drugs, and antibiotics and measure the clinical specimens and push forward the
study that aimed at the adequacy of medical therapy.
Figure 1. Cholesterol metabolism and abnormal bile acids excreted into urine Figure 2. Development of analytical methods of drug blood concentrations
Recent Publications
- Tanaka N, Yamaguchi H, Mano N. Transport of eicosapentaenoic acid-derived PGE3, PGF3, and TXB3 by ABCC4. PLoS One. 9(10):e109270, 2014
- Sato T, et al. Organic anion transporting polypeptides 1B1 and 1B3 play an important role in uremic toxin handling and drug-uremic toxin interactions in the liver. J Pharm Pharm Sci. 17(4):475-484, 2014
- Maekawa M, et al. Tandem mass spectrometric characterization of bile acids and steroid conjugates based on low-energy collision-induced dissociation. Steroids. 80:80-91, 2014
- Shimada M, et al. A quantitative HPLC-UV method for determination of serum sorafenib and sorafenib N-oxide and its application in hepatocarcinoma patients. Tohoku J Exp Med. 233(2):103-112, 2014
- Maekawa M, et al. LC/ESI-MS/MS analysis of urinary 3-sulfooxy-7-N-acetylglucosaminyl-5-cholen-24-oic acid and its amides: new biomarkers for the detection of Niemann-Pick type C disease.
Steroids. 78(10):967-972, 2013
110 Clinical Pharmaceutical Science

Metabolic and Transcriptional Response to Redox Disturbance in Aging-related Disorders
Gene Expression Regulation Medical Sciences Course

MOTOHASHI, Hozumi URL:

http://www2.idac.tohoku.ac.jp/dep/ger/index.html
Contact:
TEL +81-22-717-8550
E-Mail hozumim@idac.tohoku.ac.jp
Research Theme
Regulatory mechanisms of stress response system during carcinogenesis
Roles of stress response system in hematopoietic stem cell aging
Functional interaction between intranuclear redox homeostasis and regulation of gene expression
Research Keywords: response to oxidative stress and xenobiotics, transcription factors, metabolic regulation
Technical Keywords: transgenic mice & knockout mice, metabolomic analysis, flow cytometry
Transcriptional regulation of gene expression is the key process in the stress response to extrinsic and intrinsic insults,
which is one of the critical determinants of organismal aging process. The KEAP1-NRF2 system plays a central role in the
protection from various stresses, including reactive oxygen species and xenobiotics. It has been shown that NRF2-activating
chemicals, either naturally occurring or artificially synthesized, are beneficial for our health. On the other hand, our recent
work revealed that NRF2 contributes to the malignant evolution of cancer cells by modulating cellular metabolic activity.
Based on this result, we are focusing on the function of NRF2 in carcinogenesis and malignant evolution of cancers,
especially in relation with epigenetic regulations. Our goal is to clarify specific molecular mechanisms of NRF2 function
in cancer cells that are distinguished from those in normal cells, which we believe would make an ideal molecular target of
anti-cancer therapy for patients with NRF2-positive cancers. Considering that disturbance of intranuclear redox balance
often causes genome instability resulting in carcinogenesis and progeria, we are also interested in the relation among aging
processes, intranuclear redox balance and NRF2-mediated antioxidant capacity. Thus, we are cultivating a new field of
intranuclear redox metabolism and its effect on gene expression via genetic and epigenetic alterations.
Figure 1. NRF2 mediates malignant evolution and proliferation of cancers
Recent Publications
- Honkura Y. et al. NRF2 is a key target for prevention of noise-induced hearing loss by reducing oxidative damage of cochlea. Sci Rep in press
- Sekine H. et al. The mediator subunit MED16 transduces NRF2-activating signals into antioxidant gene expression. Mol Cell Biol in press.
- Shirasaki K, et al. Nrf2 promotes compensatory liver hypertrophy after portal vein branch ligation in mice. Hepatology 59(6), 2371-2382, 2014.
- Taguchi K, et al. Nrf2 enhances cholangiocyte expansion in Pten-deficient livers. Mol Cell Biol 34(5), 900-913, 2014.
- Mitsuishi Y, et al. Nrf2 redirects glucose and glutamine into anabolic pathways in metabolic reprogramming. Cancer Cell 22(1), 66-79, 2012.
Gene Expression Regulation 111

To Understand the Molecular Mechanisms for Discrimination between Immunological Self
and Non-self and Memory Based on Immunoregulatory Receptors of Lymphocytes
Experimental Immunology Medical Sciences Course

TAKAI, Toshiyuki URL:

http://www2.idac.tohoku.ac.jp/dep/expimmu/
Professor, Ph.D.
Contact:
TEL +81-22-717-8501
E-Mail toshiyuki.takai.b8@tohoku.ac.jp
Research Theme
Immunoregulatory receptors on B lymphocytes in maintaining tolerance and immunological memory
Deregulated B cell tolerance in autoimmune diseases such as systemic lupus erythematosus
Development of therapeutic ligands for immunoregulatory receptors for treating allergic and autoimmune diseases
Research Keywords: immune regulation, B lymphocyte, immunological tolerance, immunological memory,

cell-surface receptor protein
Technical Keywords: gene-engineered mice, flow cytometric fine sorting of human peripheral blood cells,
allergy/inflammation/autoantibody, in vitro B cell development, in vitro molecular evolution technique
The Laboratory of Experimental Immunology aims to understand the molecular mechanisms by which our immune system
discriminates between immunological self and non-self, based on our detailed analysis of immunoregulatory receptors on
various cells such as B cells and T cells. We, for the first time, discovered the importance of immunoregulatory receptors (Takai
T. Nat. Rev. Immunol. 2:580, 2002; Nakamura A. et al. Nat. Immunol. 5:623, 2004). Studies are now in progress on the roles of
immunoregulatory receptors including FcR and PirB/LILRB in allergy and autoimmune diseases. Development of novel strategies
against these immune disorders has also been in progress. Our particular interest is now in 1) elucidating the molecular mechanism
of development of autoreactive B cells and generation of autoantibodies in various autoimmune diseases of humans as well as in
mouse models, and in 2) regulating the deregulated B cells by generating novel strategies such as development of synthetic ligands
for the receptors, generated by the In-Vitro Evolution technique.
Figure 1. Genes for FcRIIB and SLAM family proteins are juxtaposed Figure 2. Synergy of FcRIIB deficiency (RIIB) and SLAM129 augments
autoantibody production
Recent Publications
- Kanari Y, et al. Dichotomy in the FcRIIB deficiency and autoimmune-prone SLAM haplotype clarifies the roles of the Fc receptor in development of autoantibodies and glomerulonephritis. BMC Immunol
2014, 15:47.
- Mitsuhashi Y, et al. Regulation of plasmacytoid dendritic cell responses by PIR-B. Blood 120: 3256-9. 2012.
- Matsushita H, et al. Differential but competitive binding of Nogo protein and class I major histocompatibility complex (MHCI) to the PIR-B ectodomain provides an inhibition of cells. J. Biol. Chem. 2011;
286(29):25739-47.
- Arita K, et al. Transcriptional activation of the Pirb gene in B cells by PU.1 and Runx3. J. Immunol. 2011; 186(12): 7050-9.
- Kubo T, et al. Augmented TLR9-induced Btk activation in PIR-B-deficient B-1 cells provokes excessive autoantibody production and autoimmunity. J. Exp. Med. 2009; 206: 1971-82.
112 Experimental Immunology

To Explore the Immunological Functions of NK and T Cells in Diseases such as
Autoimmune, Tumor and Infection.
Immunobiology Medical Sciences Course

OGASAWARA, Koetsu URL:

http://www2.idac.tohoku.ac.jp/dep/imbio/
Professor, Ph.D.
Contact:
TEL +81-22-717-8579
E-Mail imbio1@idac.tohoku.ac.jp
Research Theme
Autoimmune diseases and allergy
Immune surveillance against tumor and infection
Dressed NK cells
Research Keywords: NK cells, T cells, dressed NK cells, TCR repertoire

Technical Keywords: image-cytometry, flow-cytometry, next generation sequences,
developmental engineering, molecular and cellular biology
Immune system contributes to defense from diseases such as infection and tumors. Natural Killer (NK) cells play important
roles in elimination of virally infected cells and tumors. NK cell functions are regulated by the opposing signals from
activating or inhibitory receptors. Our laboratory has focused on activating and inhibitory receptors on NK cells and T cells.
We will explore that the molecular mechanisms underlying recognition of NK cells and T cells against target cells in viral
immunity, tumor immunity and autoimmunity.
Figure 1. NK cell death by dressed NK cells Figure 2. Identification of pathogenic T cells in metal allergy
Recent Publications
- Kawano M, et al. NKG2D+IFN-+CD8+ T cells are responsible for palladium allergy. PLoS One ;9(2):e86810, 2014.
- Nakamura K, et al. Fratricide of natural killer cells dressed with tumor-derived NKG2D ligand. Proc Natl Acad Sci U S A. ; 110 (23): 9421-9426.2013.
- Nakamura K, et al. NK-cell fratricide-Dynamic crosstalk between NK and cancer cells OncoImmunology ; 2:11, e26529. 2013.
- Nakayama M, et al. Inhibitory receptor PIR-B is exploited by Staphylococcus aureus for virulence. J Immunol.; 189 (12): 5903-5911. 2012.
- Nakayama M, et al. NK-dendritic cell interactions generate MHC class II-dressed NK cells that regulate CD4+ T cells. Proc Natl Acad Sci U S A.; 108 (45): 18360-18365. 2011.
Immunobiology 113
Let's Enjoy Science Together!
Molecular and Cellular Biology Medical Sciences Course

HORIUCHI, Hisanori URL:

http://www2.idac.tohoku.ac.jp/dep/mcb/
Contact:
TEL +81-22-717-8463
E-Mail hisanori.horiuchi.e8@tohoku.ac.jp
Research Theme
Intracelluar signaling escpecially focusing on small GTPases
Innate immunity escpecially focusing on NET-formation of neutrophils
Research on hemostasis and thrombosis (anti platelet therapy and acquired von Willebrand syndrome)
Research Keywords: ral, mTOR, neutrophil NETs, protein citrullination, acquired von Willebrand syndrome
Technical Keywords: biochemistry, molecular biology, cell biology , mouse biology,
multimer analysis of von Willebrand factor
We have investigated molecular and cellular biology/medicine focusing on small GTPases by identifying critical molecules.
Recently we have identified Munc13-4 as a Rab27 effector and RalGAPs, negative regulators of small GTPase Ral
implicated in endo- and exocytosis and tumorigenesis. So, let's join us and enjoy science to have your own molecules/
projects.
We have focused on following projects:
1. To elucidate the evaluating system of cellular nutrition by focusing of small GTPase regulating mTOR pathway.
2. To elucidate molecular mechanism of NET formation of neutrophils, which is implicated in not only host defense but also
thrombosis, cancer metastasis and autoimmune diseases.
3. Clinically, we are evaluating heart disease-related acquired von Willebrand syndrome with bleeding tendency by multimer
analysis of von Willebrand factors.
Figure 1. The functions and regulatory mechanism of a small GTPase Ral Figure 2. RalGAP and its suppressing role of cancer metastasis
Recent Publications
- R. Shirakawa*, H. Horiuchi (2015) Ral GTPases: Crucial Mediators of Exocytosis and Tumorigensis.( a review) J Biochem (Tokyo) in press
- N. Yaoita, R. Shirakawa, Y. Fukumoto, K. Sugimura, S. Miyata, Y. Miura, K. Nochioka, M. Miura, S. Tatebe, T. Aoki, S. Yamamoto, K. Satoh, T. Kimura, H. Shimokawa, H. Horiuchi* (2014) Platelets are
highly activated in patients of chronic thromboembolic pulmonary hypertension (CTEPH) Arteriosclerosis Thromb Vasc Biol, 34, 2486-2494
- R Saito, R Shirakawa, H Nishiyama*, T Kobayashi, M Kawato, T Kanno, K Nishizawa, Y Matsui, T Ohbayashi, M Horiguchi, T Nakamura, T Ikeda, K Yamane, E Nakayama, E Nakamura, Y Toda, T
Kimura, T Kita, O Ogawa, H Horiuchi* (2013) Downregulation of Ral GTPase-activating-protein causes tumor invasion and metastasis of bladder cancer. Oncogene 32, 894-902
- Y. Murata, T. Yasumi*, R. Shirakawa, K. Izawa, H. Sakai, J. Abe, N. Tanaka, T. Kawai, K. Oshima, M. Saito, R. Nishikomori, O. Ohara, E. Ishii, T. Nakahata, H. Horiuchi*, T. Heike (2011) Rapid diagnosis
of familial hemophagocytic lymphohistiocytosis type 3 (FHL3) by flow cytometric detection of intraplatelet Munc13-4 protein. Blood 118, 1225-1230
- R. Shirakawa, S. Fukai, M. Kawato, T. Higashi, H. Kondo, T. Ikeda, E. Nakayama, K. Okawa, O. Nureki, T. Kimura, T. Kita, H. Horiuchi* (2009) Tuberous sclerosis tumor suppressor complex-like
complexes act as GTPase activating proteins for Ral GTPases. J. Biol. Chem., 284, 21580-21588.
114 Molecular and Cellular Biology

Aging and Metabolic Regulation
Metabolism Medical Sciences Course

URL:
YAMAMOTO, Tokuo http://www.idac.tohoku.ac.jp/ja/activities/
Professor, Ph.D. research/metabolism/index.html
Contact:
TEL +81-22-717-8010
Research Theme
Functional genomics of lipoprotein receptors
Functional genomics of acyl-CoA synthetases
Wnts and metabolic regulation
Research Keywords: cholesterol, atherosclerosis, aging, wnt, obesity

Technical Keywords: protein analysis, gene analysis, biochemical analysis
Studies with yeast, C. elegance, mouse and rhesus monkeys have shown that calorie restriction expands their life spans. In
human, excess food intake causes obesity and subsequently leads to metabolic syndrome that is characterized by decreased
glucose tolerance. In our laboratory, we have identified and characterized lipoprotein receptors that play a key role in the
plasma clearance of lipoproteins. We also identified and characterized several acyl-CoA synthetases that catalyze the initial
reaction of fatty acid metabolism. In addition to these molecules in the lipid metabolism, we are studying on the metabolic
regulation mediated by wnt proteins.
Recent Publications
- Sakakibara I, et al. Fasting-induced hypothermia and reduced energy production in mice lacking acetyl-CoA synthetase 2. Cell Metab. 2009 Feb;9(2):191-202. doi: 10.1016/j.cmet.2008.12.008.
Metabolism 115
Every organ in your body can be replaced with artificial organs
Medical Engineering and Medical Sciences Course

Cardiology Master / Doctoral Degree
URL:
http://mec1.idac.tohoku.ac.jp/?eng_top
YAMBE, Tomoyuki
Contact:
E-Mail tomoyuki.yambe.a4@tohoku.ac.jp
Research Theme
Artificial heart, circulatory assist
Artificial esophagus, artificial sphincter
Epilepsy control, Biomedical Engineering
Research Keywords: Total artificial heart, Ventricular assist device, Artificial sphincter, Artificial esophagus,
Epilepsy attack control
Technical Keywords: Transcutaneous energy transmission, Artificial muscle, Peltier elements
Tohoku University have a long term tradition in Bio-Medical Engineering area. First case of long term survival of the
patients with pneumatic ventricular assist device was reported from Tohoku University Hospital. Various kinds of artificial
organs are now under development
Figure 1. Total Artificial Heart Figure 2. Epilepsy attack control device
Recent Publications
- Sensorless cardiac phase detection for synchronized control of ventricular assist devices using nonlinear kernel regression model. Hirohashi Y, Tanaka A, Yoshizawa M, Sugita N, Abe M, Kato T, Shiraishi Y,
Miura H, Yambe T. J Artif Organs. 2016 Jan 13. [Epub ahead of print]
- Fundamental analysis and development of the current and voltage control method by changing the driving frequency for the transcutaneous energy transmission system. Miura H, Yamada A, Shiraishi Y, Yambe T.
Conf Proc IEEE Eng Med Biol Soc. 2015 Aug;2015:1319-22. doi: 10.1109/EMBC.2015.7318611.
- Effect of valsalva in the pulmonary prosthetic conduit valve on hemodynamic function in a mock circulatory system. Tsuboko Y, Shiraishi Y, Yamada A, Yambe T, Matsuo S, Saiki Y, Yamagishi M. Conf
Proc IEEE Eng Med Biol Soc. 2015 Aug;2015:278-81. doi: 10.1109/EMBC.2015.7318354.
- Initial Acute Animal Experiment Using a New Miniature Axial Flow Pump in Series With the Natural Heart. Okamoto E, Yano T, Shiraishi Y, Miura H, Yambe T, Mitamura Y. Artif Organs. 2015
Aug;39(8):701-4. doi: 10.1111/aor.12558.
- Hemodynamics of a functional centrifugal-flow total artificial heart with functional atrial contraction in goats. Shiga T, Shiraishi Y, Sano K, Taira Y, Tsuboko Y, Yamada A, Miura H, Katahira S, Akiyama M,
Saiki Y, Yambe T. J Artif Organs. 2015 Jul 22. [Epub ahead of print]
116 Medical Engineering and Cardiology

Control of Cancer and Aging via the Vascular System
Vascular Biology Medical Sciences Course

SATO, Yasufumi URL:

#N/A
Contact:
TEL +81-22-717-8532
E-Mail y-sato@idac.tohoku.ac.jp
Research Theme
Control of angiogenesis
Control of vascular aging
Research Keywords: angiogenesis, vascular aging, vasohibin

Technical Keywords: molecular biology, cell biology, biochemistry, experimental pathology
About 50% of the cause of death in Japan is related to either cancer or atherosclerosis. Our department is specialized in the
vascular biology, characterizing the mechanism of angiogenesis and endothelial cell senescence in order to control tumor
angiogenesis and vascular aging. We have recently isolated vasohibin-1 and vasohibin-2, the novel family of proteins that
relates to angiogenesis and endothelial cell senescence. We are now characterizing their functions and trying to develop
novel strategies for the treatment of cancer and atherosclerosis.
Figure 1. The vasohibin family Figure 2. The gene tree of vasohibin family
Recent Publications
- Watanabe K, et al. Vasohibin as an endothelium-derived negative feedback regulator of angiogenesis. J. Clin. Invest. 114: 898-907, 2004.
- Shibuya T, et al. Isolation and characterization of vasohibin-2 as a homologue of VEGF-inducible endothelium-derived angiogenesis inhibitor vasohibin. Arterioscler. Thromb. Vasc. Biol. 26: 1051-1057, 2006.
- Kimura H, et al. Distinctive localization and opposed roles of vasohibin-1 and vasohibin-2 in the regulation of angiogenesis. Blood 113:4810-4818, 2009.
- Miyashita H, et al. Angiogenesis inhibitor vasohibin-1 enhances stress resistance of endothelial cells via induction of SOD2 and SIRT1. PLoS One 7, e46459, 2012.
- Sato Y. A novel link between inhibition of angiogenesis and tolerance to vascular stress. J Atheroscler Thromb. 2015 (in press).
Vascular Biology 117

How Chromosomal Instability Arises and How It is Involved in Oncogenesis and Cancer
Progression: Detailed Analysis of Chromosome Motion
Molecular Oncology Medical Sciences Course

TANAKA, Kozo URL:

http://www2.idac.tohoku.ac.jp/dep/molonc/pg40.html
Contact:
TEL +81-22-717-8491
E-Mail k.tanaka@idac.tohoku.ac.jp
Research Theme
Mechanism of chromosomal instability in cancer
Mechanism of oncogenic transformation through chromosomal instability
Cancer therapy targeting mitosis
Research Keywords: chromosomal instability, oncogenesis, chromosome segregation, mitosis, cancer therapy
Technical Keywords: live cell imaging, cell culture, immunofluorescence staining, protein analysis,
genetically modified mouse
Cancer is characterized by unrestricted proliferation of cells. Our body is made up with sixty trillion cells as a result
of proliferation (division) of one fertilized egg. In each cell of our body, 46 chromosomes are properly transmitted. On
the other hand, most of the cancer cells show abnormalities in chromosome number and structure due to chromosomal
instability, which is increased rate of chromosome missegregation in mitosis. Chromosomal instability is not just a result
of oncogenic transformation, but supposed to be closely related to oncogenesis, although its detailed mechanism is elusive.
Chromosome segregation is a very dynamic process, and has been attracted scientists for over hundred years. We try to build
up and verify hypotheses through our observation of chromosome motion, avoiding preconceptions. We have discovered a
molecule involved in chromosome segregation, CAMP, and revealed that Nup188, a component of nuclear pore complex,
plays a role in chromosome segregation. Through these researches, using culture cells and mice, we are aiming to clarify
how chromosomal instability is related to oncogenesis. On the other hand, we are also trying to develop novel strategies to
cure cancer by targeting its characteristics like chromosomal instability.
Figure 1. Process of chromosome segregation Figure 2. Chromosome misalignment in CAMP-depleted cells
Recent Publications
- Iemura K, Tanaka K. Chromokinesin Kid and kinetochore kinesin CENP-E differentially support chromosome congression without end-on attachment to microtubules. Nat Commun. 6:6447, 2015.
- Amin MA, et al. CLIP-170 recruits PLK1 to kinetochores during early mitosis for chromosome alignment. J Cell Sci. 127(13):2818-2824, 2014.
- Itoh G, et al. CAMP (C13orf8, ZNF828) is a novel regulator of kinetochore-microtubule attachment. EMBO J. 30(1):130-144, 2011.
- Kawashima S, et al. Global analysis of core histones reveals nucleosomal surfaces required for chromosome bi-orientation. EMBO J. 30(16):3353-3367, 2011.
- Kitamura E, et al. Kinetochores generate microtubules with distal plus ends: their roles and limited lifetime in mitosis. Dev Cell 18(2):248-259, 2010.
118 Molecular Oncology

Elucidation of Genome Instability Due to the Failure of Cell Division and DNA Damage
Response
Cancer Biology Medical Sciences Course

URL:
CHIBA, Natsuko http://www.idac.tohoku.ac.jp/en/activities/
Professor, M.D. Ph.D. research/Cancer_Biology/index.html
Contact:
TEL +81-22-717-8477
E-Mail natsuko.chiba.c7@tohoku.ac.jp
Research Theme
Regulatory mechanism of breast cancer-related molecules in mitosis
Response of tumor suppressor molecules to DNA damage
Research Keywords: tumor suppressor gene, mitosis, DNA damage response, hereditary cancer,
centrosome regulation
Technical Keywords: cell biology, molecular biology, animal experiment
Five to seven percent of all breast cancers are inherited, and the two most important breast cancer susceptibility genes,
BRCA1 and BRCA2, were identified by linkage analysis of familial breast cancer. Mutations of BRCA1 and BRCA2 have
been found in 25% of hereditary breast cancer. Recently, these breast cancers are called Hereditary Breast and Ovarian
Cancer Syndrome (HBOC). In addition to hereditary cancer, it has been reported that BRCA1 is involved in a subtype of
sporadic breast cancer, Triple-negative breast cancer, and in chemosensitivity to various cancers.
BRCA1 is involved in many cellular processes, including DNA repair and centrosome regulation. Defects in the
regulatory mechanisms of centrosome and DNA repair result in defective mitoses, chromosome segregation errors, and the
accumulation of DNA damage. These are significant sources of genome instability, a hallmark of cancer.
Our research particularly focuses on the functions of BRCA1 in DNA repair and centrosome regulation. To analyze the
functions of BRCA1 and its related proteins, we perform cytological analyses, analyses using genetically modified mice,
and analyses of clinical specimens. This research will contribute to the further understanding of carcinogenesis and aid in
developing novel cancer therapies.
Figure 1. Dysfunction of BRCA1 causes cancer Figure 2. OLA1 localizes to centrosome and spindle poles
Recent Publications
- Matsuzawa A, Kanno S, Nakayama M, Mochiduki H, Wei L, Shimaoka T, Furukawa Y, Kato K, Shibata S, Yasui A, Ishioka C, and Chiba N. The BRCA1/BARD1-interacting protein OLA1 functions in
centrosome regulation. Molecular Cell, 53,101-114, 2014
- Kais Z, Chiba N, Ishioka C, Parvin J D. Functional differences among BRCA1 missense mutations in the control of centrosome duplication. Oncogene, 31(6): 799-804 2012
- Wei L, Lan L, Yasui A, Tanaka K, Saijo M, Matsuzawa A, Kashiwagi R, Maseki E, Hu Y, Parvin J D, Ishioka C and Chiba N. BRCA1 contributes to transcription-coupled repair of DNA damage through
polyubiquitination and degradation of Cockayne syndrome B protein. Cancer Science, 102(10): 1840-1847, 2011
- Ransburgh D*, Chiba N*, Ishioka C, Toland A, and Parvin J D. (*co-first author) Identification of breast tumor mutations in BRCA1 that abolish its function in homologous DNA recombination. Cancer
Res., 70(3): 988-995, 2010
- Wei L, Lan L, Hong Z, Yasui A, Ishioka C, and Chiba N. Rapid recruitment of BRCA1 to DNA double-strand breaks is dependent on its association with Ku80. Mol. Cell. Biol.28(24);7380-93, 2008
Cancer Biology 119

Research and Education Plan for Medical Oncologist: Translational Research to Develop
Molecular Target Drugs and Biomarkers for Cancer Treatment
Clinical Oncology Medical Sciences Course

Doctoral Degree
ISHIOKA, Chikashi URL:

http://www.co.idac.tohoku.ac.jp/
Contact:
TEL +81-22-717-8543
E-Mail chikashi@idac.tohoku.ac.jp
Research Theme
Development of novel molecular target drugs for cancer treatment
Development of novel molecular biomarkers for cancer treatment
Comprehensive and multidisciplinaly treatment including anti-cancer drugs for advanced cancer patients
Research Keywords: cancer chemotherapy, biomarker, molecular target drug, medical oncology,
cancer treatment
Technical Keywords: comprehensive expression analysis, genetic analysis, DNA methylation analysis,
clinical trial, translational research
In the Department of Clinical Oncology, we conduct translational research including development of cancer chemotherapy including
molecular target agents and molecular biomarkers to control refractory cancer. Our Department of Clinical Oncology wrestles for various
clinical studies while being engaged in practice of cancer chemotherapy of various solid tumor as the Division of Medical Oncology in the
Tohoku University Hospital (always in charge of the medical treatment of more than 600/month outpatients and more than 20 inpatients)
and brings up the medical oncologist to answer high social needs.
We welcome young talented person with strong motivation for the development of new anti-cancer agents and molecular biomarkers.
Figure 1. Molecular modeling of PI3K and FK228 complex (Cancer Sci., 2012) Figure 2. FK228 and its analogs are ATP-competitive PI3K-inhibitors (Cancer Sci.,
2015)
Recent Publications
- Saijo K, Imamura J, Narita K, Oda A, Shimodaira H, Katoh T, Ishioka C. Biochemical, biological, and structural properties of romidepsin (FK228) and its analogs as novel HDAC/PI3K dual inhibitors.
Cancer Sci. 2014 Dec 10. doi: 10.1111/cas.12585. [Epub ahead of print]
- Soeda H, Shimodaira H, Gamoh M, Ando H, Isobe H, Suto T, Takahashi S, Kakudo Y, Amagai K, Mori T, Watanabe M, Yamaguchi T, Kato S, Ishioka C. Phase II trial of cetuximab plus irinotecan for
oxaliplatin- and irinotecan-based chemotherapy-refractory patients with advanced and/or metastatic colorectal cancer: evaluation of efficacy and safety based on KRAS mutation status (T-CORE0801).
Oncology. 2014;87(1):7-20. doi: 10.1159/000360989. Epub 2014 Jun 24.
- Shiono M, Takahashi S, Kakudo Y, Takahashi M, Shimodaira H, Kato S, Ishioka C. Upper arm central venous port implantation: a 6-year single institutional retrospective analysis and pictorial essay of
procedures for insertion. PLoS One. 2014 Mar 10;9(3):e91335. doi: 10.1371/journal.pone.0091335. eCollection 2014.
- Soeda, H.Shimodaira, H.Watanabe, M.Suzuki, T.Gamoh, M.Mori, T.Komine, K.Iwama, N.Kato, S.Ishioka, C. Clinical usefulness of KRAS, BRAF, and PIK3CA mutations as
predictive markers of cetuximab efficacy in irinotecan- and oxaliplatin-refractory Japanese patients with metastatic colorectal cancer. Int J Clin Oncol 18: 670-7, 2013.
- Kato S, Andoh H, Gamoh M, Yamaguchi T, Murakawa Y, Shimodaira H, Takahashi S, Mori T, Ohori H, Maeda S, Suzuki T, Kato S, Akiyama S, Sasaki Y, Yoshioka T, Ishioka C; Tohoku Clinical Oncology
Research and Education. Safety verification trials of mFOLFIRI and sequential IRIS + bevacizumab as first- or second-line therapies for metastatic colorectal cancer in Japanese patients. Oncology 83:101-7, 2012.
120 Clinical Oncology

Basic and Clinical Researches to Improve Surgical Outcome of Lung Cancer Patients and
Lung Transplantation
Thoracic Surgery Medical Sciences Course

Doctoral Degree
OKADA, Yoshinori URL:

http://www2.idac.tohoku.ac.jp/dep/surg/index.html
Contact:
TEL +81-22-717-8520
E-Mail yoshinori.okada.a1@tohoku.ac.jp
Research Theme
Research for lung cancer
Research for lung transplantation
Lung physiology
Research Keywords: therapeutic target gene of lung cancer, ischemia-reperfusion lung injury, lung allograft rejection,
pulmonary hypertension, regenerative medicine of the lung
Technical Keywords: pathological analysis, physiological analysis, gene analysis, transgenic animals,
translational research
Department of Thoracic Surgery, Institute of Development, Aging and Cancer, Tohoku University is active in Sendai, one
of the most beautiful cities in Japan. We perform surgeries for lung cancer, mediastinal tumors, pneumothorax and lung
transplantation at Tohoku University Hospital. We also proceed with basic research for lung cancer, lung transplantation,
pulmonary hypertension, tumor immunology, and regenerative medicine. We look forward to ambitious colleagues to
achieve fruitful basic and clinical researches together with us.
Figure 1. Example of research in our department
Recent Publications
- Oishi H, et al. Successful bilateral lung transplantation after 16 h of lung preservation with EP-TU solution: report of a case. Surgery Today 45 (5): 630-633, 2015
- Hoshikawa Y, et al. Medical consultant system for improving lung transplantation opportunities and outcomes in Japan. Transplant Proc 47(3): 746-750, 2015
- Endo C, et al. A prospective study of surgical procedures for patients with oligometastasis non-small cell lung cancer. Annals of Thoracic Surgery 98: 258-264, 2014
- Notsuda H, at al. p190A RhoGAP is involved in EGFR pathways and promotes proliferation, invasion and migration in lung adenocarcinoma cells. International Journal of Oncology 43(5): 1569-1577, 2013
- Eba S, et al. The Nuclear Factor Erythroid 2-Related Factor 2 Activator Oltipraz Attenuates Chronic Hypoxia-Induced Cardiopulmonary Alterations in Mice. American Journal of Respiratory Cell and
Molecular Biology 49(2): 324-333, 2013
Thoracic Surgery 121

We Investigate the Functional Roles of Physical Forces in Development and Homeostasis
to Discover New Therapeutic Approaches
Developmental Neurobiology Medical Sciences Course

URL:
OGURA, Toshihiko http://www2.idac.tohoku.ac.jp/dep/devn/english/
Professor, M.D. Ph.D. index2.htm
Contact:
TEL +81-22-717-8564
E-Mail ogura@idac.tohoku.ac.jp
Research Theme
Mechano-transduction system that converts physical stimuli into biochemical/genetic responses
Development of exercise pills based on the novel mechano-transduction pathways
Mechanical regulation of metabolism and organogenesis
Research Keywords: physical forces, gene expression, exercise pill (exercise mimetics),
regulation of metabolism, force-sensing proteins
Technical Keywords: mechanical manipulation, gene knock-out, molecular biology
Physical forces regulate various aspects of embryogeneis and homeostasis, as embodied by massive bone atrophy of
astronauts and bedridden patients. Molecular mechanism by which living cells sense physical forces and convert them into
biochemical responses is largely unknown.
We have discovered several force-sensitive factors and are exploring the mechanism of signal transduction (mechano-
transduction) triggered by the mechanical stimuli. Interestingly, we found that these factors regulate various processes of
development, such as cardiogenesis and bone formation. More importantly, energy metabolism, regeneration and wound
healing are under the control of the force-sensitive factors. This indicates that these factors are good targets of therapeutic
drugs. Adopting physics and engineering techniques, we are exploring a new field of biology, in a hope of discovering new
drugs and therapies.
Figure 1. Haemodynamics-dependent valvuloganesis.
Recent Publications
- Inoue S et al., New BRAF knockin mice provide a pathogenetic mechanism of developmental defects and a therapeutic approach in cardio-facio-cutaneous syndrome. Hum Mol Genet. 23, 6553-6566, 2014
- Akira et al., Introducing Micrometer-Sized Artificial Objects into Live Cells: A Method for Cell-Giant Unilamellar Vesicle Electrofusion. PLoS ONE 9, e106853. doi; 10.1371/journal.pone.0106853, 2014
- Aoki Y. et al., Gain-of-Function Mutations in RIT1 Cause Noonan Syndrome, a RAS/MAPK Pathway Syndrome.The American Journal of Human Genetics, 93, 173-180, 2013.
- Banjo T. et al., Haemodynamically dependent valvulogenesis of zebrafish heart is mediated by flow-dependent expression of miR-21. Nature Communications, 4, Article number 1978, 2013 (doi:10.1038/
ncomms2978).
- Watanabe Y. et al., Fibroblast growth factor 10 gene regulation in the second heart field by Tbx1, Nkx2-5, and Islet1 reveals a genetic switch for down-regulation in the myocardium. Proc Natl Acad Sci U S
A. 109, 18273-18280, 2012
122 Developmental Neurobiology

To Reveal the Mechanism of Brain and Mind Using Neuroimaging:
Visualization of Mind and Exploration of Its Neural Dynamics
Functional Brain Imaging Medical Sciences Course

SUGIURA, Motoaki URL:

http://www.fbi.idac.tohoku.ac.jp/fbi/index.html?lang=en
Contact:
TEL +81-22-717-7988
E-Mail motoaki.sugiura@tohoku.ac.jp
Research Theme
Exploring the underlying mechanisms behind brain plasticity
Understanding the neural basis of higher mental function of the human
Application of the outcome of the basic brain research on education and welfare
Research Keywords: imaging, plasticity, perception, cognition, sociality

Technical Keywords: magnetic resonance imaging (MRI), magnetoencephalography (MEG), 7T-MRI for small animals
Researchers in our department have a variety of backgrounds including medicine, science, life science, engineering,
pharmacy, linguistics, pedagogy, and the arts. They work energetically on a wide range of studies of brain science, from
basic brain research in small animals (e.g., rats and mice), to functional brain imaging research, which creates images of the
workings of the brain, to social technology study, which applies the findings of these studies to the educational and welfare
fields.
In rodent brain imaging study, we try to combine macro-level neuroimaging methods using 7T-MRI and micro-level
techniques such as histological stain and gene analysis to understand biological mechanisms behind structural brain
plasticity.
In functional brain imaging research, using fMRI and MEG, we elucidate the neural underpinnings of cognitive functions,
such as perception, memory, motor, linguistic, and emotional processes, and reveal the mechanism of the mind that survives
the complicated physical and social environment around us.
In social technology research, we will open a new possible approach to education and social welfare from the viewpoint
of brain science. We develop welfare systems for the improvement and maintenance of brain function in the elderly and
education systems to best foster the healthy development of brain function in children.
Figure 1. Regional gray matter volume increases following exercise Figure 2. fMRI experiment (A and B) and brain activity (C)
Recent Publications
- Sumiyoshi A, et al. Regional gray matter volume increases following 7 days of voluntary wheel running exercise: A longitudinal VBM study in rats. NeuroImage, 98, 82-90, 2014.
- Sasaki K, et al. Specific regions display altered grey matter volume in -opioid receptor knockout mice: MRI voxel-based morphometry. Br J Pharmacol, 172, 654-67, 2015.
- Sugiura M, et al. Neural mechanism for mirrored self-face recognition. Cereb Cortex, in press
- Jeong H, et al. Neural correlates of second-language communication and the effect of language anxiety. Neuropsychologia, in press.
- Akimoto Y, et al. High-gamma activity in an attention network predicts individual differences in elderly adults' behavioral performance. Neuroimage, 100:290-300, 2014
Functional Brain Imaging 123

To Clarify What and How Several Factors such as Genetic Factors and Lifestyle Affect
Brain Structure and Functions
Nuclear Medicine and Medical Sciences Course

Radiology Master / Doctoral Degree
URL:
http://www.nmr.idac.tohoku.ac.jp/?lang=en
TAKI, Yasuyuki
Contact:
E-Mail ytaki@idac.tohoku.ac.jp
Research Theme
Revealing brain development and aging using large brain MRI database
Revealing relationships among genetic factor, environmental factors, brain structure and function, and cognitive
function
Early diagnosis of several disorders such as autism and dementia
Research Keywords: brain, magnetic resonance image, autism, dementia, development and aging
Technical Keywords: image analysis, big data analysis, database, genetic analysis
Now we confront a super aging society in Japan. In the situation, it is important to preserve our cognitive function for entire life
by preventing us from pathological brain aging. To perform the aim, we have built a large brain magnetic resonance imaging
(MRI) database from around 3,000 subjects aged from five to 80 in order to reveal how brain develops and ages. We have also
collected several cognitive functions, lifestyle such as eating and sleeping habits, and genetic data. Using the database, we have
revealed normal brain development and aging, and also have revealed what factors affect brain development and aging. These
findings help understanding the mechanism of brain development and aging as well as performing differential diagnosis or
diagnosis at an early stage of several diseases/disorders such as autism and Alzheimers disease.
Figure 1. Correlation between brain perfusion and age in each lobe.
Recent Publications
- Sekiguchi A, et al. Resilience after 3/11: Structural brain changes 1 year after the Japanese Earthquake. Molecular Psychiatry, in press.
- Mutoh T, et al. Early-intensive versus minimally-invasive approach to postoperative hemodynamic management after subarachnoid hemorrhage. Stroke, 45:1280-1284, 2014.
- Taki Y, et al. Linear and curvilinear correlations of brain white matter volume, fractional anisotropy, and mean diffusivity with age using voxel-based and region-of-interest analyses in 246 healthy children.
Human Brain Mapping, 34:1842-56, 2013.
- Taki Y, et al. Correlation between high-sensitivity C-reactive protein and brain gray matter volume in healthy elderly subjects. Human Brain Mapping, 34:2418-24, 2013.
- Taki Y, et al. A longitudinal study of the relationship between personality traits and the annual rate of volume changes in regional gray matter in healthy adults. Human Brain Mapping, 12:3347-53, 2013.
124 Nuclear Medicine and Radiology

To Develop Strategies that Enable Us to Fight Dementia Disorders: Pre-symptomatic
Detection and Drug Discovery of Disease-modifying Therapies
Geriatrics and Gerontology Medical Sciences Course

ARAI, Hiroyuki URL:

http://www2.idac.tohoku.ac.jp/dep/geriat/
Contact:
TEL +81-22-717-7182
E-Mail hiroyuki.arai.b5@tohoku.ac.jp
Research Theme
Amyloid and Tau PET imaging in dementia and Alzheimer disease
Blood and cerebrospinal fluid biomarkers in dementia and Alzheimer disease
Prospective cohort study of elderly people living in temporary apartments after the Great East Japan Earthquake
Research Keywords: Alzheimers disease and dementia, molecular neuroimaging, pre-symptomatic detection and
preemptic therapy, medication management in elderly people, disaster geriatric medicine
Technical Keywords: positron emission tomography, disease modifying drugs, development of imaging probes,
epidemiological study in earthquake-hit areas, development of ICT-based pill-box for frail elderly
1) Molecular imaging study

Since aging is strongly associated with an increased risk of developing dementia and cancer, the prevalence of dementia and cancer is
likely to increase in super-aged society. Deposition of amyloid- protein and phosphorylated tau may occur decades before clinical onset
of dementia symptoms. Since 1995 here in Department of Geriatrics & Gerontology (Prof.Arai H) and Department of Neuroimaging
(Prof. Kudo Y), we started research on biomarker development. Notably, we are currently successful to develop [18F]THK-5351 probe
to visualize tau pathology in Alzheimers brains. The [18F]THK-5351 will help us to conduct clinical trials of tau-directed drugs such as
anti-tau antibodies.
2) Development of fluid biomarkers
Expression of several micro-RNAs was significantly different between normal subjects and Alzheimer s patients. A unique N-glycan
on human transferrin in cerebrospinal fluid could be a possible biomarker for idiopathic normal pressure hydrocephalus.
3) Disaster Geriatric Medicine
We proposed Shelter-associated pneumonia in patients who developed pneumonia following moving to shelter. The shelter-associated
pneumonia may be multi-factorial including aspiration, mal-nutrition as well as loss of oral care due to limited supply of water and
medications. Cognitive decline was detectable in approximately 36% of elderly people aged 65 or older living in temporary houses.
Figure 1. Perspectives in the diagnosis and treatment of Alzheimers disease Figure 2. Human amyloid (Right) and tau PET imaging (Left)
Recent Publications
- 1.Arai H, et al. Geriatric Medicine, Japanese Alzheimer's Disease Neuroimaging Initiative and Biomarker Development. Tohoku J. Exp. Med. 221:87-95, 2010
- Suzuki M et al. Shelter acquired pneumonia after a catastrophic earthquake in Japan. J. Am. Geriatr. Soc. 59:1968-1969, 2011
- Futakawa S et al. A unique N-glycan on human transferrin in CSF: a possible biomarker for iNPH. Neurobiol Aging. 33:1807-1815, 2012
- Kiko T et al. MicroRNAs in Plasma and Cerebrospinal Fluid as Potential Markers for Alzheimer's Disease. J Alzheimers Dis. 39253-259, 2014
- Okamura N et al. Tau PET Imaging in Alzheimer's Disease. Curr Neurol Neurosci Rep. Nov;14(11):500. doi: 10.1007/s11910-014-0500-6. 2014
Geriatrics and Gerontology 125

Uncover the Mysteries of Germ Cell, the Origin of Successive Generations, and of
Pluripotential Stem Cells
Cell Resource Center for Medical Sciences Course

Biomedical Research Master / Doctoral Degree
URL:
http://www.idac.tohoku.ac.jp/en/activities/
MATSUI, Yasuhisa research/cancer_cell_repository/index.html
Contact:
E-Mail ymatsui@idac.tohoku.ac.jp
Research Theme
Molecular mechanisms ensuring germ cell to correctly transmit genetic and epigenetic information into successive
generations
Mechanisms regulating differences and common characteristics among germ cell, pluripotential stem cells and
cancer cells
Research Keywords: germ cells, pluripotential stem cells, cell differentiation, epigenetics,
transcriptional regulation
Technical Keywords: cell culture, genetically modified mouse, gene manipulation, transcriptome
Our goal is to elucidate the molecular mechanisms of germ cell formation and of their subsequent development to transmit
genetic and epigenetic information into successive generations. Germ cells undergo unique epigenetic changes during their
differentiation, and we are interested in epigenetic regulation of germ cell development. We also focus on relationship
among germ cells, pluripotential stem cells and cancer cells. Germ cells are differentiated form pluripotential stem cells in
early embryos, while germ cells can be easily reprogrammed into pluripotential stem cells in culture. It indicates that those
cells are closely correlated each other. In addition, germ cells and cancer cells commonly express a number of specific
genes though their functions are not fully understood. We therefore study molecular mechanisms regulating differences and
common characteristics of germ cells, pluripotential stem cells and cancer cells.
Figure 1. Relationship among pluripotential stem cells, germ cells and cancer cells Figure 2. Nascent primordial germ cells in early mouse embryo
Recent Publications
- Matsui Y, et al. The majority of early primordial germ cells acquire pluripotency by Akt activation. Development 141: 4457-4467, 2014
- Maeda, I, et al. Max is a repressor of germ-cell-related gene expression in mouse embryonic stem cells. Nature Commun.4: 1754, 2013
- Okamura D, et al. REST and its downstream molecule Mek5 regulate survival of primordial germ cells. Dev. Biol. 372: 190-202, 2012
- Okamura D, et al. Cell-cycle gene-specific control of transcription has a critical role in proliferation of primordial germ cells. Genes Dev. 26: 2477-2482, 2012
- Mochizuki K, et al. Implication of DNA demethylation and bivalent histone modification for selective gene regulation in mouse primordial germ cells. PLoS ONE 7: e46036, 2012
126 Cell Resource Center for Biomedical Research

To Read, Train, and Guide Neural Functions: Toward Realization of Smart Aging Society
Smart Ageing International Medical Sciences Course

Research Center Master / Doctoral Degree
URL:
http://www2.idac.tohoku.ac.jp/dep/sairc/index.html
KAWASHIMA, Ryuta
Contact:
Professor, M.D. TEL +81-22-717-7988
E-Mail ryuta@idac.tohoku.ac.jp
Research Theme
Intervention studies for improvement of cognitive functioning and mental health through a life
Advanced brain science studies for neural decoding of individual and collective mental states
Educational psychological studies to identify influential factors for childrens learning motivation
Research Keywords: brain aging, brain training, mental health, neural decoding, education and learning
Technical Keywords: magnetic resonance imaging (MRI), near-infrared spectroscopy (NIRS),
psychological tests, questionnaire survey, physiological measurements
Combining recent techniques of neuroimaging, cognitive neuroscience, psychology, sociology and other fields, we investigate how
to develop, maintain, and improve cognitive functions and mental health of children, young and elderly adults.
Intervention researches: We conduct intervention studies to investigate the effectiveness of physical exercise, cognitive trainings,
and other activities. To maintain and improve the brain functioning and mental health in a diverse and complicated society, we are
focusing on the prefrontal cortex (PFC), which plays a major role in the higher cognitive functions necessary for maintaining a
healthy social life.
Decoding of the mind: We develop technologies to decode ones state of mind, such as attention, mood, and intention, based on the
latest neuroimaging methods. We also extend the technologies to researches on social interactions. Simultaneous measurement of
multiple brains enables us to evaluate interaction and resonance among neural activities of individuals, leading to communication-
enhancing methods.
Research for healthy children: Based on a partnership with the Sendai education board, we are engaged in an interdisciplinary
research project, which aims to identify the factors affecting motivation for learning in children and adolescents. The goal of this
project is to develop an intervention program or a scientifically evidence-based policy for enhancing childrens autonomous learning.
Figure 1. Combination exercise training improved cognitive functions of healthy Figure 2. Evaluation of neural synchrony during verbal and non-verbal social
elderly interaction
Recent Publications
- Kawashima R, et al. Riding a motorcycle affects cognitive functions of healthy adults. International Journal of Automotive Engineering, 5:77-83, 2014.
- Nouchi R, et al. Four weeks combination exercise training improved executive functions, episodic memory and processing speed in healthy elderly people: Evidence from a randomized controlled trial.
AGE, 36(2):787-799, 2014.
- Nozawa T, et al. Ongoing activity in temporally coherent networks predicts intra-subject fluctuation of response time to sporadic executive control demands. PLoS One, 9(6):e99166, 2014.
- Yokoyama R. et al, The neural bases underlying social risk perception in purchase decisions. Neuroimage, 91:120-128, 2014.
- Kotozaki Y, et al, Biofeedback-based training for stress management in daily hassles: an intervention study. Brain Behav. 4:566-579, 2014.
Smart Ageing International Research Center 127

Hearing Restoration for Deafened Patients Using the Approach Based on the Biomedical
Engineering
Audiology Medical Sciences Course

KAWASE, Tetsuaki URL:

http://www.auditorylab.med.tohoku.ac.jp/index.html
Professor, M.D.
Contact:
TEL +81-22-717-7303
E-Mail kawase@orl.med.tohoku.ac.jp
Research Theme
Development of diagnostic tools based on the pathophysiology of hearing loss
Research on auditory rehabilitation
Research on audio-visual bimodal speech perception
Research Keywords: hearing loss, rehabilitative audiology, audio-visual speech perception, binaural hearing,
tinnitus
Technical Keywords: hearing aid, cochlear implant, magnetoencephalography
Sound information, which is converted to the electrical spike signal of the cochlear nerve in the inner ear, is transmitted to
the brain via the auditory system. Disturbance of any part of auditory system causes hearing impairment. In considering the
improvement of speech perceptibility of impaired listeners, it is important to understand the pathology and pathophysiology
of deafness. In our laboratory, researches being conducted on auditory prostheses and related auditory science to help
impaired listeners compensate for the deteriorated speech perception.
Ongoing principal research themes are as follows: binaural hearing and audio-visual bimodal speech perception
1) Research on binaural hearing and audio-visual bimodal speech perception
2) Development of diagnostic tools based on the pathophysiology of hearing loss
3) Research on auditory prosthesis (cochlear, brainstem and mid-brain implants, hearing aid)
4) Research on auditory rehabilitation
5) Research on tinnitus retraining therapy (TRT)
Figure 1. Electrophysiological mapping system for auditory brainstem implant Figure 2. Neuromagnetic investigation on auditory steady state respons
Recent Publications
- Kawase T, et al. Contra-noise suppresses 40-Hz auditory-steady-state fields without significant change of N100m. Neuroimage 59:1037-1042, 2011.
- Takata Y, et al. Auditory evoked magnetic fields in patients with absent brainstem responses due to auditory neuropathy with optic atrophy. Clin Neurophysiol. 123: 985-992, 2012.
- Oda K, et al. Masking effects in patients with auditory neuropathy -possible involvement of suppression mechanism caused by normal outer hair cell function- Otology & Neurotology 34: 868-876, 2013.
- Kawase T, et al. Positive auditory cortical responses in patients with absent brainstem response. Clinical Neurophysiology 125:148-53, 2014.
- Usubuchi H, et al. Effects of contralateral noise on the 20-Hz auditory steady state response - magnetoencephalography study. PLoS One 9: e99457, 2014.
128 Audiology
To Be or Not to Be a GI Investigator: That is No Question
Surgical and Molecular Medical Sciences Course

Pathophysiology Master / Doctoral Degree
URL:
http://www.fukushimalab.med.tohoku.ac.jp/
FUKUSHIMA, Kouhei aboutus.html
Contact:
E-Mail kouhei@surg1.med.tohoku.ac.jp
Research Theme
Inflammatory bowel disease (clinical and basic)
Intestinal adaptation after massive bowel resection
Drug delivery system
Research Keywords: ulcerative colitis, Crohn's disease, pouchitis, intestinal adaptation, intestinal flora
Technical Keywords: microarray, T-RFLP, recombinant protein, immunohistochemistry, electron microscopy
We aim to develop a novel research system and therapies to improve GI dysfunction due to massive bowel resection or
chronic intestinal diseases such as ulcerative colitis and Crohn's disease. We also try to understand mucosal defense system,
mechanism of nutrients and electrolytes transport, syn- and dysbiosis of enteric flora, and homeostasis of the host. We also
participate in the research group for intractable diseases in the Ministry of Health, Labour and Welfare of Japan.
Recent Publications
- 1992 Award of Japanese Society of Gastroenterology
- 2005 Award of Japanese Society of Gastroenterology
- 1999 Dr. Carl Lysis Research Award (Crohn and Colitis Foundation of America)
- Kohyama A, Ogawa H, Funayama Y, Takahashi K, Benno Y, Nagasawa K, Tomita S, Sasaki I, Fukushima K. Bacterial population moves toward a colon-like community in the pouch after total
proctocolectomy.Surgery. 2009;145(4):435-47
- Sasaki K, Igarashi M, Hinata M, Komori Y, Fukushima K. Simulation of drug release from PLGA particles in vivo. J Drug Delivery 2013;1:1-8.
Surgical and Molecular Pathophysiology 129

Development of the treatment of chronic renal failure and Mitochondria Medicine
Clinical Biology and Medical Sciences Course

Hormonal Regulation Master / Doctoral Degree
URL:
http://plaza.umin.ac.jp/~takaabe/takaakiabe.html
ABE, Takaaki
Contact:
E-Mail takaabe@med.tohoku.ac.jp
Research Theme
Mitochondrial Medicine
CKD and gut micorbiota
Transporter Medicine
Research Keywords: transporter, gut microbiota, tRNA, mitochondrial diseases, anti-fibrosis

Technical Keywords: transporter, mitochondria, flux analyzser, tRNA, 1-methyladenosine
Takaaki ABE studied and isolated various uremic solute transporters (e.g. SLCO4C1) and their pathophysiological roles
in chronic kidney disease (CKD) and now he is an editorial board member of the American Journal of Physiology (Renal
Physiology).
He found that various uremic toxins are generated in the gut and ClC-2 chloride channel activator lubiprostone, clinical used
as a laxative, ameliorates the progression of CKD and the accumulation of uremic toxins by improving the gut microbiota
andintestinal environment.
He also reported that have reported that indole acetic acid found in CKD patients increasederythropoietin production and
synthesized its analog mitochonic acid MA-5 increased cellular ATP and rescued fibroblasts from various mitochondrial
disease patients such as Leigh, MELAS, LHON, Kearns-Sayre syndrome (Suzuki T. et al. Tohoku J. Exp. Med. 2015). He
also found that MA-5 is also effective in the mitochondrial DNA defect disease model Mitomice resucuing cardimyocyte
and renal tubular respiration. MA-5 could be novel therapeutic drugs for the treatment of mitochondrial diseases that exerts
itseffect in a novel manner different from anti-oxidant therapy (Suzuki T. JANS 2015).
MA-5

Cytosol
OM
F
MA-5 O
Mitofilin / MINOS

COOH
N
complex
H
IM
CJ
ADP+ Pi
H+ H+
H+
H+
H+
H+ ATP
H+ 2013-209539
H+ ADP+ Pi

CJ: Crista junctions H+
OM: outer membrane
IM: inner membrane Crista ATP
CL:cardiolipin
PCTPCT/JP2014/5049

Suzuki T. THEM 2015
Suzuki T, JASN 2015
Figure 1. Development of drugs for mitochondrial diseases Figure 2. Alteration of gut microbiota modulates uremic toxins
Recent Publications
- Suzuki T., Yamaguchi H., Kikusato M., Hashizume O., Nagatoishi S., Matsuo A., Sato T., Kudo T., Matsuhashi T., MurayamaK., Ohba Y., Watanabe S., Kanno S.-I., Minaki D., Saigusa D., Shinbo H., Mori
N., Yuri A., Yokoro M., Mishima E., Shima H., Akiyama Y., Takeuchi Y., Kikuchi K., Toyohara T., Suzuki C., Ichimura T., Anzai J., Kohzuki M., Mano N., Kure S., Yanagisawa T., Tomioka Y., Tohyomizu M.,
Tsumoto K., Kazuto Nakata K., Bonventre J.V., Ito S., Osaka H., Hayashi K. and Abe T. Mitochonic acid MA-5 binds to mitochondria and ameliorates renal tubular and cardiac myocyte damages. J Am Soc
Nephrol. in press
- Suzuki T., Yamaguchi H., Kikusato M., Matsuhashi T., Matsuo A., Sato T., Oba Y., Watanabe S., Minaki D., Saigusa D., Shimbo H., Mori N., Mishima E., Shima H., Akiyama Y., Takeuchi Y., Yuri A.,
Kikuchi K., Toyohara T., Suzuki C., Kohzuki M., Anzai J., Mano N., Kure S., Yanagisawa T., Tomioka Y., Toyomizu M., Ito S., Osaka H., Hayashi K. and Abe T. Mitochonic Acid 5 (MA-5), a Derivative of
the Plant Hormone Indole-3-Acetic Acid, Improves Survival of Fibroblasts from Patients with Mitochondrial Diseases.Tohoku J Exp Med. 236: 225-232, 2015
- Mishima E., Fukuda S., Shima H., Hirayama A., Akiyama Y., Takeuchi Y., Fukuda N.N., Suzuki T., Suzuki C., Yuri A., Kikuchi K., Tomioka Y., Ito S., Soga T. and Abe T.Alteration of the Intestinal
Environment by Lubiprostone Is Associated with Amelioration of Adenine-Induced CKD. J Am Soc Nephrol. 26: 1787-94, 2015
- Takeuchi Y. Mishima E., Shima H., Akiyama Y., Suzuki C., Suzuki T., Kobayashi T., Suzuki Y., Nakayama T., Takeshima Y., Vazquez,N., Ito S., Gammba G. and Abe T.Exonic Mutations in the SLC12A3
Gene Cause Exon Skipping and Premature Termination in Gitelmans Syndrome. J. Am. Soc. Nephrol. 26: 271-279, 2015
- Toyohara T., Suzuki T., Akiyama Y., Takeuchi Y., Mishima E., Kikuchi K., Suzuki C., Tanemoto M., Ito S., Nagao S., Soga T. and ABE T. Metabolomic Profiling of the ADPKD rat model. Clin. Exp.
Nephrol. 15: 676-687, 2011
130 Clinical Biology and Hormonal Regulation

To Visualize Important Biomedical Information by Application of Advanced Engineering
Technologies
Biomedical Imaging Medical Sciences Course

SAIJO, Yoshifumi URL:

http://www.ecei.tohoku.ac.jp/imaging/index-e.html
Contact:
TEL +81-22-717-8514
E-Mail saijo@idac.tohoku.ac.jp
Research Theme
Imaging of biological tissue and cell with high frequency ultrasound
Evaluation of cardiovascular flow dynamics by ultrasound and MRI
Photoacoustic imaging of biological tissue
Research Keywords: ultrasound microscopy, blood flow imaging, photoacoustic imaging

Technical Keywords: high frequency ultrasound, fluid dynamics, photoacoustic effect, biomechanics
Our laboratory is studying novel signal and image processing methods of ultrasound, CT (computed tomography) and MRI
(magnetic resonance imaging) in order to realize 3D imaging, precise automatic diagnosis and cardiovascular blood flow
analysis. Besides analysis of conventional medical imaging modalities, we are investigating biomechanics of biological
tissues such as atherosclerosis, heart, tendon, cartilage, bone, tooth and living cell by our originally developed ultrasound
microscopes. Photoacoustic (PA) effect is a phenomenon in which ultrasound is generated by thermal expansion of the
tissue by nano-second pulsed laser irradiation. We have recently started a big research project on real time high resolution
PA imaging for visualization of vasculature of small vessels and slow blood flow that is not detectable by conventional
ultrasound Doppler technique.
We have been interested in multimodality blood flow imaging of cardiovascular system. 2D blood flow vector was obtained
by Echodynamography in which some fluid dynamics theories are applied to conventional color Doppler data set and by
two-directional observation of the blood flow by very high frame rate ultrasound imaging. These methods are confirmed by
particle image velocimetry of phantom flow in lucent carotid artery model based on 3D CT data.
Figure 1. Imaging of vulnerable plaque with optical and ultrasound microscopy Figure 2. Imaging of finger with ultrasound and photoacoustic imaging
Recent Publications
- Kumagai K et al. High-resolution ultrasound imaging of human skin in vivo by using three-dimensional ultrasound microscopy. Ultrasound Med Biol. 38(10), 1833-8, 2012.
- Le Floc'h S et al. A four-criterion selection procedure for atherosclerotic plaque elasticity reconstruction based on in vivo coronary intravascular ultrasound radial strain sequences. Ultrasound Med Biol.
38(12), 2084-97, 2012.
- Nagaoka R et al. Ultrasonic measurement of microdisplacement induced by acoustic radiation force. Jpn J Appl Phys. 52(7S), 07HF21, 2013.
- Keshavarz-Motamed Z et al. Coronary artery atherectomy reduces plaque shear strains: an endovascular elastography imaging study. Atherosclerosis. 235(1), 140-9, 2014.
- Kobayashi K et al. Acoustic impedance microscopy for biological tissue characterization. Ultrasonics. 54(7), 1922-8, 2014.
Biomedical Imaging 131

Establishment of Disaster Resilient Medical and Public Health Service
International Cooperation for Medical Sciences Course

Disaster Medicine Master / Doctoral Degree
URL:
http://www.irides-icdm.med.tohoku.ac.jp/
EGAWA, Shinichi english/index.html
Contact:
E-Mail egawas@surg1.med.tohoku.ac.jp
Research Theme
Standardization of disaster medicine and public health
Support receiving capacity of the hospitals
Medical and public health needs in disaster
Research Keywords: medical and public health needs, disaster medical and public health coordinator,
education of disaster medicine, support receiving capacity, international medicine and public health
Technical Keywords: database, ICT, teleconference, robot, cluster approach
IRIDeS was established in 2012 after Great East Japan Earthquake and promoting the applied disaster mitigation science including Disaster
Medical Science. Our division is solely unique in the world and enjoy the liberty of research everything related to disaster medicine and public
health. Disaster medical response system in Japan was established after Great Hanshin Awaji Earthquake and is leading the world. The hazard
itself and medical and public health needs, however, are changing continuously and multi-hazard approach is required. Our team are analyzing
the medical and public health needs in disaster and seeking to establish the efficient help relief and support receiving as well as standardization
of international medical response according to the disaster cycle.
We are doing research on the database of medical and public health needs and rapid assessment system of evacuation shelter, nation-wide
survey of disaster medical and public health coordinator, survey of support receiving plan of the hospitals in the GEJE affected area and
possible hazard area of Great Nankai Trough Earthquake, robots in disaster response, application of geographical spatial information to medical
and public health response, as well as organizing international conferences about the standardization of international disaster medicine.
Figure 1. Standardization of disaster medical and public health coordinator is Figure 2. Support receiving capacity of the hospitals should be raized
necessary
Recent Publications
- Aitsi-Selmi A, et al. The Sendai Framework for Disaster Risk Reduction: Renewing the Global Commitment to Peoples Resilience, Health, and Well-being. Int J Disaster Risk Sci 6(2): 164-176, 2015.
- Ashino Y, et al. Ebola Virus Disease: Preparedness in Japan. Disaster Med Public Health Prep. 9(1): 74-78, 2015
- Egawa S, et al. International Symposium on Disaster Medicine and Public Health Management: review of the Hyogo framework for action. Disaster Med Public Health Prep. 8(4):357-358, 2014.
- Usuzawa M, et al. Awareness of disaster reduction frameworks and risk perception of natural disaster: a questionnaire survey among Philippine and Indonesian health care personnel and public health
students. Tohoku J Exp Med. 233(1):43-8, 2014.
- Burkle FM, et al. The 2015 Hyogo Framework for Action: Cautious Optimism. Disaster Medicine and Public Health Preparedness 8 (3): 191-192, 2014.
132 International Cooperation for Disaster Medicine

Identification of Bio-Markers that Lead to Resilience
Disaster-related Infecious Medical Sciences Course

Disease Master / Doctoral Degree
URL:
http://www.irides-drid.med.tohoku.ac.jp/index.html
HATTORI, Toshio
Contact:
E-Mail toshatto@med.tohoku.ac.jp
Research Theme
Roles of matricellular protein in infectious diseases
Develpoment of diagnostic and theraputic agents for dengue infection
Studies on multi-drug-resistant tuberculosis
Research Keywords: human immunodeficiency virus, dengue fever, hemorragic fever, tuberculosis, galectin 9,
zoonosis
Technical Keywords: luminex, flow cytometry, elispot, quantitative PCR, LAMP
Both macro and micro mechanisms of infectious diseases that occur after a large-scale disaster will be studied. By
macroscopic studies, we will disclose which disaster generates which infectious diseases and propose the methods for
prevention. Microscopic studies would produce the novel point-of-care testing and pathological
features. These studies would promise the early diagnosis of infectious diseases. In addition, luminex that can simultaneously
measure the 100 species of biomarkers using a small quantity of plasma will be used to understand and characterize the
inflammatory conditions of each infectious diseases. These studies are supported
by clinical activities such as the practice of HIV infection in the Graduate School of Medicine and the total number of
patients now becomes the 60. We also collaborate with the researchers from Southeast Asia to study dengue, malaria,
leptospirosis
and tuberculosis. We are also interested in developing diagnostic kit, and identifying the resilience factors for infectious
diseases. The functional roles of matricellular proteins in infectious diseases have been studied.
Figure 1. Inflammatory profiles of dengue virus infection Figure 2. Detection of immunological responses to various antigens of tuberculosis
Recent Publications
- http://www.ncbi.nlm.nih.gov/pubmed/24239423
Disaster-related Infecious Disease 133

Radiation Protection and Dosimetry
Disaster Medical Radiology Health Sciences Course

URL:
CHIDA, Koichi http://irides.tohoku.ac.jp/eng/organization/
Professor, Ph.D. medicine/03.html
Contact:
TEL +81-22-717-8010
E-Mail chida@med.tohoku.ac.jp
Research Theme
Radiation safety management and radiological protection in medicine
QC and QA for radiation equipment and optimization of radiation dose and Image performance
Radiation disaster medicine
Research Keywords: patient and occupational radiation exposure, radiation safety management and Quality
assurance and quality control (QA, QC), optimization of radiation dose and radiation image
quality, Interventional radiology, deterministic and stochastic effects
Technical Keywords: radiation dosimetry, energy and beam quality, phantom and Image performance, effective
dose and equivalent dose, radioactivity
The Division of Radiological Examinations and Technology, Tohoku University Graduate School of Medicine, has provided a course
in radiological technology since 2009. Our division researches management of the radiation dose and quality control/assurance of
the radiation equipment used in radiological examinations, including interventional radiology (IVR). In particular, our main fields of
education and research are: 1. Radiation safety and risk management during radiological examinations (patients and staff). 2. Quality
control and quality assurance of medical X-ray systems and radiographic images. 3. Optimization of the radiation dose and X-ray image
quality. 4. Development of dosimeters and evaluation methods for radiation exposure in radiological examinations. 5. Radiation protection
for pediatric patients. 6. Avoidance of radiation-induced injury (deterministic and stochastic effects) in radiological examinations. 7.
Optimization of medical radiation exposure and radiation protection. 8. Justification of radiological procedures. Our laboratory evaluates
radiation doses and radiation effects in humans, analyzes the management of radiation exposure from nuclear hazards, and develops
diagnostic imaging systems for use in disasters. Specifically, our main areas of research and education are: 1. Radiation safety and risk
management; 2. Evaluation/measurement of radiation doses and radiation effects in humans; 3. Development of diagnostic imaging
systems for use in disasters; 4. Public education regarding radiation and radioactivity. Educating students in the technologies of radiology
and medical physics is also an important aspect of our division.
Figure 1. New real-time patient radiation dosimeter (multichannel sensors) Figure 2. Glass dosimeter system measuring the direct patient entrance dose
Recent Publications
- Nakamura M, Chida K. Red emission phosphor for real-time skin dosimeter for fluoroscopy and interventional radiology. Med Phys. 2014;41(10):101913. 1-5.
- Chida, K. et al, Occupational dose in interventional radiology procedures. Am J Roentgenol. (AJR) 200, 138-41 (2013)
- Chida, K. et al, Clarifying and visualizing sources of staff-received scattered radiation in interventional procedures. Am J Roentgenol. (AJR). 197, 900-3 (2011)
- Chida, K. et al, Radiation dose to the pediatric cardiac catheterization and intervention patient. Am J Roentgenol. (AJR). 195, 1175-9 (2010)
- Chida, K. et al, Radiation dose of interventional radiology system using a flat-panel detector. Am J Roentgenol. (AJR). 193, 1680-5 (2009)
134 Disaster Medical Radiology

Join Us to Establish the Basis of Disaster Psychiatry
Disaster Psychiatry Medical Sciences Course

URL:
TOMITA, Hiroaki http://www.irides-dpsy.med.tohoku.ac.jp/english/
Contact:
TEL +81-22-717-7897
E-Mail htomita@med.tohoku.ac.jp
Research Theme
To develop strategies for improve disaster response and psychosocial interventions
Cohort studies and psychosocial support for people affected by disasters
To elucidate molecular basis of disaster stress and related psychiatric conditions
Research Keywords: disaster psychiatry, PTSD, mood disorders, psychosocial interventions, biomarker
Technical Keywords: data archiving, cohort study, omics study, animal model, cell sorting
Our laboratory conducts health surveys and supporting activities of people affected by Great East Japan Earthquake, and
investigate impact of the disaster on mental health condition of the affected people, as well as on mental health care systems
in the affected communities to extract information useful for supporting recovery of affected people and preparing for future
disasters. Our research also focus on the investigation of the pathogeneses of mental disorders, such as mood disorders
and post-traumatic stress disorder, which needs more cautions in medical settings in communities affected by disasters, by
integrating basic and clinical medical researches. Our goal is to develop useful tools for prevention, assessment, diagnosis
and treatment of mental disorders. Furthermore, based on what we learnt from the Great East Japan Earthquake, we
cooperate with domestic and international organizations to direct our study towards reforming of mental health care system
in more efficient ways, to develop education system for disaster mental health, and to establish international collaboration
on disaster psychiatry.
Figure 1. Bio-psycho-social approach into disaster stress and psychiatric disorders Figure 2. Information archive for disaster mental health response and preparedness
Recent Publications
- Tomita H, Ursano RJ. Breakout session 3 summary: psychosocial/mental health concerns and building community resilience. Disaster Med Public Health Prep. 8(4):363-365, 2014
- Yu Z, Ono C, Aiba S, Kikuchi Y, Sora I, Matsuoka H, Tomita H. Therapeutic concentration of lithium stimulates complement C3 production in dendritic cells and microglia via GSK-3 inhibition. Glia, 63(2):
257-270, 2015
- Ono C, Yu Z, Kasahara Y, Kikuchi Y, Ishii N, Tomita H. Fluorescently activated cell sorting followed by microarray profiling of helper T cell subtypes from human peripheral blood. Plos One,9(11):
e111405. 2014
- Moriya Y, Kasahara Y, Hall S, Sakakibara Y, Uhl G, Tomita H, Sora I. Sex differences in the effects of adolescent social deprivation on alcohol consumption in -opioid receptor knockout mice.
Psychopharmacology, 2014 [Epub ahead of print]
- Tomita H, Ziegler ME, Kim HB, Evans SJ, Choudary PV, Li JZ, Meng F, Dai M, Myers RM, Neal CR, Speed TP, Barchas JD, Schatzberg AF, Watson SJ, Akil H, Jones EG, Bunney WE, Vawter MP. G
protein-linked signaling pathways in bipolar and major depressive disorders. Frontiers in Genetics, 23(4): 297. 1-12. 2013
Disaster Psychiatry 135

Scientifically Researching Disaster-related Stress and Gynecological Disorders from the Multifaceted
Perspectives of Epidemiology, Clinical Medicine, and Basic Biology
Disaster Obstetrics and Medical Sciences Course

Gynecology Master / Doctoral Degree
URL:
http://dogtohoku.wix.com/gyne
ITO, Kiyoshi
Contact:
E-Mail Ito@irides.tohoku.ac.jp
Research Theme
Analysis of the effects of disaster-related stress and subsequent changes to the living environment on
gynecological conditions
Establishing prediction markers for gynecological conditions from disaster-related stress
Strategy to recover the Miyagi cancer consultation rate and verification of conditions women are susceptible to
after disasters
Research Keywords: gynecological disease, disaster stress, cancer screening, endometrial cancer,
stress hormone
Technical Keywords: protein analysis, comprehensive gene expression analysis, cell culture (in vitro),
animal experiments (in vivo), questionnaire survey
In the field of disaster-related gynecology, in addition to a multifaceted analysis of the effects of disasters on mothers and children
and establishing international standards in response, the objective is to conduct diverse and long-term research into the effects
of disasters on patients with gynecological conditions. Until now, the effects of stress on female reproductive organs (especially
the womb) have been analyzed using pathology and molecular-biology methods and animal testing. It was found that the stress
hormone in the bloodstream is harmlessly metabolized in the womb, but that cancer may destroy this mechanism for rendering
the hormone harmless. Also, the functions of female reproductive organs are adjusted by the female hormones of estrogen and
progesterone. It is thought that the stress hormone has some disturbing effect on female hormones, but the mechanism is unclear.
The above problems are being clarified by epidemiology and basic biology. In this field, the Hormones and Cancer Study
Meeting is being held with experts in fields like gynecology, pathology, endocrinology, molecular biology, immunology, and
laboratory animal studies. By scientifically researching the effects of disaster-related stress on womens health, the objective is a
research style that can contribute to disaster-affected regions and also widely across society.
Figure 1. Cortisol signal: S100P and GR in endometrial carcinoma Figure 2. Research of disaster-related stress on women's health
Recent Publications
- Tanaka S, et al. The role of 5-reductase type 1 associated with intratumoral dihydrotestosterone concentrations in human endometrial carcinoma. Mol Cell Endocrinol. 2014 Dec 2;401C:56-64.
- Sato N, Takagi K, Suzuki T, Miki Y, Tanaka S, Nagase S, Warita H, Fukudo S, Sato F, Sasano H, Ito K. Immunolocalization of corticotropin-releasing hormone (CRH) and its receptors (CRHR1 and
CRHR2) in human endometrial carcinoma: CRHR1 as a potent prognostic factor. Int J Gynecol Cancer. 2014 Nov;24(9):1549-57.
- Ito K. Miki YWhat is disaster obstetrics and gynecology? Igaku no Ayumi Vol.242 No.12 TOPICS, pp. 949-950, 2012 [Jpn]
- Miki YStress hormone and endometrial cancer: Cortisol signal as a targeted molecular therapy. Miyagi Cancer Society, KUROKAWA CANCER RESEARCH FOUNDATION. 2013 [Research Grant]
- Miki Y. Journal of Steroid Biochemistry and Molecular Biology 2013 Excellence in Reviewing. 2014 [Award]
136 Disaster Obstetrics and Gynecology

To solve medical problems after Mega-Disaster
Disaster Public Health Medical Sciences Course

KURIYAMA, Shinichi URL:

http://www.med.tohoku.ac.jp/english/org/sph/241/index.html
Professor, M.D. Ph.D. http://irides.tohoku.ac.jp/eng/organization/medicine/06.html
Contact:
TEL +81-22-717-8104
E-Mail kuriyama@med.tohoku.ac.jp
Research Theme
To Monitor the persons health after Mega-Disaster
Care for the persons health after Mega-Disaster
To Minimize health problems in the next-coming Mega-Disaster
Research Keywords: Mega-Disaster, health problems, public health, intervention study, next-coming disaster
Technical Keywords: cohort study, monitoring health status, questionnaire, Nation-wide survey, intervention
We conduct cohort studies to monitor and improve persons health in the affected area after the great east Japan Earthquake.
1.Our division has collaboration with Tohoku Medical Megabank Organization. We conduct Three-Generation cohort study
and the long-term community child health survey in Miyagi Prefecture.
2.We have developed brochures which indicates the importance of receiving medical services to patients, especially
children, with allergic diseases.
3.We assess the developmental curves of children in the affected area using data of health check-ups conducted by local
governments.
4.We assess mold and mite in temporary dwelling and investigate the association between these status and allergic
symptoms.
5.We aim to minimize the health problems in the next-coming Mega-Disaster.
http://www.kakegawastudy.jp/
1500
1 2
Figure 1.Nationwide Nursery School Survey on Child Health Figure 2.The Kakegawa Cohort Study
Recent Publications
- Ohuchi N, et al. Sensitivity and specificity of mammography and adjunctive ultrasonography to screen for breast cancer in the Japan Strategic Anti-cancer Randomized Trial (J-START): a randomized
controlled trial. Lancet 2015. pii: S0140-6736(15)00774-6.
- Nagasaki M, et al. ToMMo Japanese Reference Panel Project, Yamamoto M. Rare variant discovery by deep whole-genome sequencing of 1,070 Japanese individuals. Nat Commun. 2015;6:8018.
- Kikuya M, et al. Protocol and Research Perspectives of the ToMMo Child Health Study after the 2011 Great East Japan Earthquake. Tohoku J Exp Med. 2015;236:123-30.
- Nishigori H, et al. Correlation Between the Great East Japan Earthquake and Postpartum Depression: A Study in Miyako, Iwate, Japan. Disaster Med Public Health Prep. 2015;9:307-12.
- Hasegawa J, et al. Change in and long-term investigation of neuro-otologic disorders in disaster-stricken Fukushima prefecture: retrospective cohort study before and after the Great East Japan Earthquake.
PLoS One. 2015;10:e0122631.
Disaster Medical Informatics 137

Be Prepared. Be Productive. Be Practical.
Disaster Medical Informatics Medical Sciences Course

URL:
NAKAYAMA, Masaharu http://www.med.tohoku.ac.jp/english/org/
Professor, M.D. Ph.D. cooperate/228/index.html
Contact:
TEL +81-22-717-7572
E-Mail irides-dmi@med.tohoku.ac.jp
Research Theme
To develop information systems for disaster medicine
To produce useful applications for hospital information systems
To build a clinical database for secondary use
Research Keywords: database, standardization, cardiovascular medicine, electronic medical (health) record,
disaster
Technical Keywords: SS-MIX2, mobile assessment, EKG on QR code, MMWIN, SEAMAT
1.Developing medical information systems for disaster medicine

The disaster management cycle is divided into four phases: response,
recovery, mitigation, and preparedness. Information systems for disaster medicine should be built to meet the specific requirements
and challenges of each phase, from the setting up of adequate information infrastructure and collection of essential information for triage,
to the provision of critical clinical support and efficient management of patients and staff members. Besides developing disaster-ready
medical information systems, we are helping others to develop such systems as co-researchers.
2.Promoting backup systems for hospital clinical data
We aim to promote efficient backup systems for clinical data using SS-MIX (Standard Structured Medical Information Exchange). The
projects we are involved in are: The Gemini Project (to back up clinical data in national university hospitals), Miyagi Medical and Welfare
Information Network (to back up clinical information shared among hospitals in Miyagi Prefecture), and the Japanese Sentinel Project (to
develop a large clinical database for preventing adverse events). In cooperation with the Japanese Circulation Society (JCS) and IHE-J, we
have also formulated a guideline, Standard Export datA forMAT(SEAMAT).
3. Improving hospital information systems
We are currently developing applications that will further improve the hospital information system in Tohoku University Hospital.
Developing excellent information systems that take into consideration each member of the medical staff would contribute to efficient
clinical activity and enhancement of medical safety in hospitals.
4. Formulating IT guidelines
Information technology has been advancing rapidly in the field of medical informatics, and we deal with the situation by formulating
practical guidelines. We also participate in a study meeting held in the Ministry of Internal Affairs and Communications on communication
systems, which medical activities during disasters increasingly depend on.
Figure 1. Developing medical information system for disaster medicine

Recent Publications
- Nakayama M, et al. The need for standardization of allergy information in electronic medical record among Japanese hospitals. Stud Health Technol Inform. 205:1257, 2014
- Nakayama M, Takeda M, Asaumi Y, Shimokawa H. Identification and visualization of stimulus-specific transcriptional activity in cardiac hypertrophy in mice. Int J Cardiovasc Imaging. Jan 30(1):211-9, 2014
- Hao K, Takahashi J, Ito K, Miyata S, Sakata Y, Nihei T, Tsuburaya R, Shiroto T, Ito Y, Matsumoto Y, Nakayama M, Yasuda S, Shimokawa H; Miyagi AMI Registry Study Investigators. Emergency care of
acute myocardial infarction and the great East Japan earthquake disaster. Circ J. 78(3):634-43, 2014
- Nakayama M, Shimokawa H. Evaluation of an electrocardiogram on QR code. Stud Health Technol Inform. 192: 1020, 2013
- Nakayama M, Osaki S, Shimokawa H. Validation of mortality risk stratification models for cardiovascular disease. Am J Cardiol. Aug 1; 108(3):391-6, 2011
138 Disaster Public Health

Conducting Multidisciplinary Research on Medical Application of Cyclotron Technology through
Collaboration with Pharmaceutical Sciences, Engineering and Phsycis
Cyclotron Nuclear Medicine Medical Sciences Course

TASHIRO, Manabu URL:

http://kakuigaku.cyric.tohoku.ac.jp/index-e.html
Contact:
TEL +81-22-795-7802
E-Mail mtashiro@m.tohoku.ac.jp
Research Theme
Functional and molecular imaging research using positron emission tomography (PET)
Multidisciplinary imaging research using other modalities such as MRI and NIRS
Scientific visualization
Research Keywords: clinical pharmacology, regional brain activity, exercise medicine, integrative medicine,
health sciences
Technical Keywords: positron emission tomography (PET), infrared spectroscopy (NIRS), molecular imaging,
functional imaging, scientific visualization
Molecular imaging is a new multidisciplinary field that enables the visualization of the cellular function and disease
processes at molecular level in living organisms without perturbing them. The research outputs are applicable to diagnosis of
diseases such as cancer, neurological and cardiovascular diseases. We are running a special educational course for molecular
imaging in collaboration with National Institute of Radiological Science (NIRS), Chiba, Japan, and you can get a masters
degree and a doctoral degree for medical sciences through this course.
We have been running a variety of research projects such as development and clinical evaluation of new tracers, elucidation
of the pathological mechanism of various neurological diseases and stress disorders, as well as new studies for health-
promotion sciences, mainly using the facilities of the Cyclotron and Radioisotope Center (CYRIC) in Aobayama campus.
In addition, we have also started research and education on scientific visualization, covering all fields (imaging, computer
graphics, illustration, etc.) associated with visual information in scientific activities.
We hope many people are interested in molecular imaging and scientific visualization. Lets start learning it in Sendai, shall
we?
Figure 1. Whole-body energy consumption map during exercise (running) Figure 2. Image of the Year Award at SNMMI2014 (Prof. Okamura, collaborator)
Recent Publications
- Hiraoka K, Tashiro M, Grobosch T, Maurer M, Oda K, Toyohara J, Ishii K,Ishiwata K, Yanai K. Brain histamine H1 receptor occupancy measured by PET after oral administration of levocetirizine, a non-
sedating antihistamine. Expert Opin Drug Saf. 2015;14(2):199-206.
- Kurokawa D, Sano H, Nagamoto H, Omi R, Shinozaki N, Watanuki S, Kishimoto KN, Yamamoto N, Hiraoka K, Tashiro M, Itoi E. Muscle activity pattern of the shoulderexternal rotators differs in
adduction and abduction: an analysis using positron emission tomography. J Shoulder Elbow Surg. 2014;23(5):658-64.
- Sato H, Ito C, Tashiro M, Hiraoka K, Shibuya K, Funaki Y, Iwata R, Matsuoka H,Yanai K. Histamine H receptor occupancy by the new-generation antidepressantsfluvoxamine and mirtazapine: a
positron emission tomography study in healthy volunteers. Psychopharmacology (Berl). 2013;230(2):227-34.
- Shidahara M, Tashiro M, Okamura N, Furumoto S, Furukawa K, Watanuki S,Hiraoka K, Miyake M, Iwata R, Tamura H, Arai H, Kudo Y, Yanai K. Evaluation of the biodistribution and radiation dosimetry
of the 18F-labelled amyloid imaging probe [18F]FACT in humans. EJNMMI Res. 2013;3(1):32.
- Ogura T, Tashiro M, Masud M, Watanuki S, Shibuya K, Yamaguchi K, Itoh M, Fukuda H, Yanai K. Cerebral metabolic changes in men after chiropractic spinal manipulation for neck pain. Altern Ther
Health Med. 2011;17(6):12-7.
Cyclotron Nuclear Medicine 139

Shedding Light in the Blackbox of Neuroscience
Molecular and Cellular Medical Sciences Course

Neuroscience Master / Doctoral Degree
URL:
http://www.med.tohoku.ac.jp/nsgcoe/en/eng/
YAWO, Hiromu member/yawo/index.html
Contact:
E-Mail hiromu.yawo.c7@tohoku.ac.jp
Research Theme
Understanding the mechanisms which govern synapse formation and reconstruction
Manipulating cellular function using optogenetics
Understanding the neural interpretation of tactile patterns
Research Keywords: optogenetics, channelrhodopsin, synapse, tactile pattern, network reorganization

Technical Keywords: optogenetics, Ca2+ imaging, molecular biology, electrophysiology, patch clamp
We developed the first technology in the world able to control the activity of nerve cells using light by genetically
engineering the nerve cells to express channelrhodopsin, an algal photoreceptive molecule from Chlamydomonas (patent
application no. 2005-34529: submitted Feb. 10, 2005). We are researching the structure of channelrhodopsin and elucidated
the structure which are involved in membrane expression, absorption wavelength, and channel characteristics (J Biol
Chem 2009; Photochem Photobiol Sci, 2009; PLoS ONE, 2010; Neurosci Res, 2012; PLoS ONE, 2015; Nature, 2015). We
created transgenic rats able to perceive light hitting their skin as a tactile sensation (PLoS ONE, 2009; 2012). We improved
a method of electroporation and established a technique for expressing a combination of various gene products in the calyx
presynaptic terminals in chicken embryos (PLoS ONE, 2013).
We are elucidating at the molecular level the mechanisms underlying nerve cell network changes caused by the environment
and experience during development and adulthood of organisms. In addition, we are striving to understand the neural
expression of tactile patterns using transgenic rats able to perceive light hitting their skin as a tactile sensation. By applying
the results of such fundamental research, we will be able to produce Brain-Machine Interface (BMI) technology which can
communicate information directly with the brain using light. Let us challenge this uncharted and stimulating world!
Figure 1. ChR2-expressing neurons (green) in dorsal root ganglion (DRG) Figure 2. Brainbow imaging of presynaptic axons in the developing ciliary ganglion
Recent Publications
- Yawo, H., Asano, T., Sakai, S., Ishizuka, T. Optogenetic manipulation of neural and non-neural functions. Dev Growth Differ. 55(4):474-490 (2013). doi: 10.1111/dgd.12053
- Kato, H. E., Inoue, K., Abe-Yoshizumi, R., Kato, Y., Ono, H., Konno, M., Ishizuka, T., Hoque, M. R., Hososhima, S., Kunitomo, H., Ito, J., Yoshizawa, S.,Kato, HE., et al. (2015) Structural basis for Na+
transport mechanism by a light-driven Na+ pump. Nature (in press)
- Asano, T., et al. (2015) Optogenetic induction of contractile ability in immature C2C12 myotubes. Sci Reports 5:8317 doi: 10.1038/srep08317
- Honjoh, T., et al. (2014) Optogenetic patterning of whisker-barrel cortical system in transgenic rat expressing channelrhodopsin-2. PLoS One 9(4), e93706. doi: 10.1371/journal.pone.0093706
- Egawa, R., et al. (2013) Optogenetic probing and manipulation of the calyx-type presynaptic terminal in the embryonic chick ciliary ganglion. PLoS One 8(3), e59179. doi: 10.1371/journal.pone.0059179
140 Molecular and Cellular Neuroscience

To Elucidate How Hypothalamic Endocrine Centers are Regulated by the Central
Stress-Responsive Circuitries
Neuroendocrinology Medical Sciences Course

ITOI, Keiichi URL:

http://www.http://www.bio.is.tohoku.ac.jp/
Contact:
TEL +81-22-795-4741
E-Mail itoik@m.tohoku.ac.jp
Research Theme
Identification of neurotransmitters and humoral factors which regulate CRF neurons
Elucidation of the physiological roles of the central noradrenergic systems in conveying stress responses
Development of mouse lines in which CRF neurons are visualized by fluorescent proteins
Research Keywords: hypothalamus, glucocorticoids, catecholamines, mouse, gene

Technical Keywords: genetically engineered mice, immunohistochemistry, immunofluorescence, patch-clamp,
brain surgery
A living organism is equipped with basic biological systems for maintaining its life. These systems work for maintaining
blood pressure, body temperature, electrolytes and metabolic balance, as well as for defense from stressors and sexual
behaviors. The regulatory centers for the basic life maintenance reside in the hypothalamus and brainstem.
Experimental research works are carried out in Itoi Lab to elucidate the functional mechanisms of the hypothalamus and
brainstem. By visualizing particular neurons in the brain, its morphological structures can be made clear, and in addition,
functional characteristics of these neurons can be elucidated by analyzing their electrophysiological properties.
Recently, we developed a mouse model in which corticotropin-releasing factor (CRF) neurons are visualized by Venus
(modified yellow fluorescent protein), so the electrical signals can be recorded directly from CRF neurons. Using these
animal models, we are now studying the physiological implications of neural inputs and humoral factors that control
hypothalamic CRF neurons.
Figure 1. Venus-labeled CRF neurons in the mouse hypothalamus Figure 2. Ablation of locus ceruleus noradrenergic neurons in mice
Recent Publications
- Itoi K, Talukder AF, Fuse T, Kaneko T, Ozawa R, Sato T, Sugaya T, Uchida K, Yamazaki M, Abe M, Natsume R, Sakimura K. Visualization of corticotropin-releasing factor neurons by fluorescent proteins
in the mouse brain and characterization of labeled neurons in the paraventricular nucleus of the hypothalamus. Endocrinology 155:4054-4060, 2014
- Itoi K, Ohara S, Kobayashi K. Selective ablation of dopamine b-hydroxylase neurons in the brain by immunotoxin-mediated neuronal targeting: new insights into brain catecholaminergic circuitry and
catecholamine-related diseases. Advances in Pharmacology 68:155-166, 2013
- Itoi K, Sugimoto N, Suzuki S, Sawada K, Das G, Uchida K, Fuse T, Ohara S, Kobayashi K. Targeting of locus ceruleus noradrenergic neurons expressing human interleukin-2 receptor a-subunit in transgenic
mice by a recombinant immunotoxin anti-Tac(Fv)-PE38: a study for exploring noradrenergic influence upon anxiety-like and depression-like behaviors. J Neurosci 31:6132-6139, 2011
- Uchida K, Kobayashi D, Das G, Onaka T, Inoue K, Itoi K. Participation of the prolactin-releasing peptide-containing neurons in the caudal medulla in conveying hemorrhagic stress-induced signals to the
paraventricular nucleus of the hypothalamus. J Neuroendocrinol 22:33-42, 2010
- Das G, Uchida K, Kageyama K, Iwasaki Y, Suda T, Itoi K. Glucocorticoid dependency of surgical stress-induced FosB/DFosB expression in the paraventricular and supraoptic nuclei of rat hypothalamus. J
Neuroendocrinol 21:822-831, 2009
Neuroendocrinology 141
To Elucidate Etiology, Pathphysiology of Lifestyle-related Diseases and to Develop New
Biomarkers and Treatment for the Diseases
Informatics on Medical Sciences Course

Pathophysiology Doctoral Degree
URL:
http://www.health.he.tohoku.ac.jp/
KINOUCHI, Yoshitaka ?num=70228130607
Contact:
Research Theme
To unravel an etiology/pathophysiology of inflammatory bowel disease
To develop new biomarkers and treatment for inflammatory bowel disease
To unravel a pathophysiology of common diseases and its clinical application
Research Keywords: inflammatory bowel disease, susceptibility gene, lifestyle-related disease, epigenome
Technical Keywords: genome wide association study, epigenome wide association study, pyrosequencing
The regulatory systems categorized into three types, neural, humoral and behavioral mechanisms play an important role
in maintenance of the homeostasis of the body. These control systems response and compensate by the second, by the
minute, by the hour, by the day or by the year to the internal or external stress. Thus, we can preserve and promote our
health. The worse lifestyle could induce a breakdown in these regulatory systems, and cause lifestyle-related diseases such
as inflammatory bowel disease (IBD), diabetes mellitus, hypertension, ischemic heart disease or obesity. Furthermore, an
impairment of regulatory systems involves changes in physical or mental functions.
This laboratory is now working on the following main projects: unraveling the pathogenesis of IBD, the pathogenesis of
diabetic nephropathy, the pathogenesis of atherosclerosis, and the psychophysiology of psychobehavior control mechanism
in psychiatric disorders.
IBD refers to two chronic diseases that cause inflammation of the intestines: ulcerative colitis and Crohn's disease. The
cause of IBD remains to be elucidated, but there is much evidence that genetic factors affect the susceptibility to IBD. We
aim to clarify the genetic backgrounds of IBD, to determine susceptibility genes in Japanese IBD and to show how the genes
affect the susceptibility to IBD.
Figure 1. Abnormal distribution of DNA methylation in Crohns disease Figure 2. Resistance to apoptosis can be reversed by 5-AZA
Recent Publications
- Shimodaira Y, et al. Modulation of endoplasmic reticulum (ER) stress-induced autophagy by C/EBP homologous protein (CHOP) and inositol-requiring enzyme 1 (IRE1) in human colon cancer cells.
Biochem Biophys Res Commun 445(2):524-33, 2014.
- Moroi R, et al.. FCGR3A-158 polymorphism influences the biological response to infliximab in Crohn's disease through affecting the ADCC activity. Immunogenetics. 65(4):265-71, 2013.
- Asano K, et al. A genome-wide association study identifies three new susceptibility loci for ulcerative colitis in the Japanese population. Nature Genetics 41:1325-1329, 2009.
- Kakuta Y, et al. TNFSF15 transcripts from risk haplotype for Crohns disease are overexpressed in stimulated T cells. Hum molecular Genetics 18(6):1089-1098, 2009.
- Negoro K, et al. Crohn's disease is associated with novel polymorphisms in the 5'-flanking region of the tumor necrosis factor gene. Gastroenterology 117: 1062-1068, 1999.
142 Informatics on Pathophysiology

To Practice Mental Health Cares: Development of Diagnostic Methods and Therapeutic
Agents for Mental Disorders
Mental Health Science Medical Sciences Course

Doctoral Degree
ITO, Chihiro URL:

http://www.ihe.tohoku.ac.jp/index_eng.html
Contact:
TEL +81-22-795-7835
E-Mail citou-thk@umin.net
Research Theme
Mental health cares of students
Elucidation of roles of the central histamine neuron system in mental disorders
Search of candidate gene markers of mental disorders
Research Keywords: mental health care, brain histamine, candidate gene marker
Technical Keywords: clinical observational study, positron emission tomography, gene analysis
Many people have much stress in the present. Mental health cares of students are most important, because student days
are overlapping the predilection ages of various psychiatric disorders. We research to develop diagnostic methods and
therapeutic agents that lead to the prevention and early treatment of mental illness, such as the central histamine that has
been deeply involved in the sleep-wake rhythm and the candidate gene markers of diseases.
Figure 1. Diagnosis of mental health consultation newcomers Figure 2. Histamine H1 receptor occupancy by new antidepressants
Recent Publications
- Sato H, et al. Histamine H1 receptor occupancy by the new generation antidepressants fluvoxamine and mirtazapine: a positron emission tomography study in healthy volunteers. Psychopharmacology
230(2): 227-234, 2013.
- Saito A, et al. An association studyof the Hermansky-Pudlak syndrome type 4 gene in schizophrenic patients. Psychiat Genet. 23(4): 163-173, 2013.
- Saito A, et al. An association study on polymorphisms in the PEA15, ENTPD4 and GAS2L1 genes and schizophrenia. Psychiat Res. 185: 9-15, 2011.
- Ito C. Histamine H3 inverse agonists as novel antipsychotics. Cent Nerv Syst Agents Med Chem. 9(2): 132-136, 2009.
- Saito A, et al. Association study of putative promoter polymorphisms in the neuroplastin gene and schizophrenia. Neurosci Lett. 411: 168-173, 2007.
Mental Health Science 143

To Provide Advanced Personalized Medicine
Oncology, Pharmacy Practice Medical Sciences Course

and Sciences Doctoral Degree
URL:
http://www.pharm.tohoku.ac.jp/~gankagak/
TOMIOKA, Yoshihisa index-e.shtml
Contact:
E-Mail ytomioka@m.tohoku.ac.jp
Research Theme
Proteomics and metabolomics for the personalized pharmacotherapy
Research Keywords: metabolomics, LC/MS/MS, personalized medicine

Technical Keywords: mass spectrometry, chromatography, molecular biology, cell biology
The medical professional is strongly urged to provide safe, trust-worthy and high level medical care on the patients. The
field of medicine is getting more advanced with increasing complexity. The aim of our laboratory is to create a training and
education program for medical professionals with the ability to guide advanced personalized medicine using metabolome-
based individual information.
Figure 1. Inter-individual difference of chromatograms (LC/MS) acquired from urine Figure 2. Prediction and discovery of new biomarker candidate
samples
Recent Publications
- Tsuji M., et al. A validated quantitative liquid chromatography-tandem quadrupole mass spectrometry method for monitoring isotopologues to evaluate global modified cytosine ratios in genomic DNA.J
Chromatogr B Analyt Technol Biomed Life Sci. 953-954:38-47, 2014
- Abe T., et al. SLC10A4 is a protease-activated transporter that transports bile acids. J Biochem. 154(1):93-101, 2013
- Saigusa D., et al. Simultaneous quantitation of sphingoid bases and their phosphates in biological samples by liquid chromatography/electrospray ionization tandem mass spectrometry. Anal Bioanal Chem.
403(7):1897-905, 2012
- Tomioka Y., et al. Education for six-years graduate school of pharmaceutical sciences: a case of Tohoku University.Yakugaku Zasshi. 131(6):933-938, 2011
- Saigusa D., et al. Simultaneous determination of guanidinosuccinic acid and guanidinoacetic acid in urine using high performance liquid chromatography/tandem mass spectrometry. Anal Chim Acta.
677(2):169-75, 2010
144 Oncology, Pharmacy Practice and Sciences

Investigation into the Exacerbation of Allergy by Environmental Factors, and Promotion of
Personalized Medicine by Pharmacogenomics
Pharmacotherapy Medical Sciences Course

Doctoral Degree
HIRASAWA, Noriyasu URL:
Professor, Ph.D.
Contact:
TEL +81-22-795-5915
E-Mail hirasawa@m.tohoku.ac.jp
Research Theme
Pathophysiological analysis of allergy/metal allergy
Development of novel anti-allergic drugs
Pharmacogenomics for personalized medicine
Research Keywords: allergic dermatitis, metal allergy, anti-allergic drugs, personalized medicine,
estimation of pharmacokinetics
Technical Keywords: TSLP-producing cell, quantitation of metal ions, pharmacogenomics, CYP variants
1. Chemicals in environment affect immune responses and worse allergic diseases.

Metal allergies are easily and frequently induced by putting on accessories containing metals and implanting biomedical
devices. Our objectives are to clarify the molecular mechanisms by which environmental chemicals and metal ions
exacerbate allergic dermatitis and to develop novel anti-allergic drugs.
2. The responsiveness of drugs is varied one by one. The most of variation between individuals is caused mainly by genetic
variation of drug-metabolizing enzymes. To promote personalized medicine, we have carried out pharmacogenomics
analysis and tried to develop genetic diagnostic drugs. In addition, we have established about 400 kinds of human
recombinant CYP variant enzymes and are studying their functional differences to various drugs to estimate variation of
pharmacokinetics due to genetic variations.
Figure 1. Allergic inflammation induced by environment/accessories Figure 2. Promotion of personalized medicine by pharmacogenomics
Recent Publications
- Asakawa S, et al. Nickel ions selectively inhibit lipopolysaccharide-induced interleukin-6 production by decreasing its mRNA stability. PLoS One 10:e0119428, 2015
- Segawa R, et al. Identification of a cell line producing high levels of TSLP: Advantages for screening of anti-allergic drugs. J Immunol Methods. 402:9-14, 2014
- Hiratsuka M, et al. Genetic polymorphisms of dihydropyrimidinase gene in a Japanese patient with capecitabine-induced toxicity. PLoS One. 10:e0124818, 2015
- Niinuma Y, et al. Functional characterization of 32 CYP2C9 allelic variants. Pharmacogenomics J. 14:107-114, 2014
- Ohsawa Y, Hirasawa, N. The antagonism of histamine H1 and H4 receptors ameliorates chronic allergic dermatitis via anti-pruritic and anti-inflammatory effects in Nc/Nga mice. Allergy. 67:1014-1022,
2012
Pharmacotherapy 145
To Planning the Integrated Renal Replacement Therapies with Telemedicine and Narrative
Based Medicine
Integrated Nephrology and Medical Sciences Course

Telemedicine Master / Doctoral Degree
URL:
KIYOMOTO, Hideyasu cooperate/197/index.html
Contact:
E-Mail kiyo@megabank.tohoku.ac.jp
Research Theme
Personalized medicine with native based medicine
Bioonfomatics and telemedicine
Integreated renal replacement therapy
Research Keywords: chronic kidney disease (CKD), acute kidney injury (AKI), personalized medicine,
renal transplantation, telemedicine
Technical Keywords: patient support by monitering in long distance, daily home hemodialysis,
information and communications technology, genomic analysis, blood purification
The kidney is very important to contribute homeostasis of circulation, metabolism and endocrinology as well as disposal
the uremic wastes in the living body. The structure of kidney is complicated and composed by many of well differentiated
cells. Chronic kidney disease (CKD) is led by not only specific nephritis but also common lifestyle-related diseases such
as hypertension and diabetes mellitus. Acute kidney injury (AKI) induced by drugs and surgery is also important because
it will be critical and links with death directly. The patients with severe renal insufficiency via either end stage of CKD and
AKI require to survive the suitable renal replacement therapy (RRT) based on clinical evidences. The aim of integrated
nephrology is to escort and advise better medical treatments for patients suffering with CKD and renal insufficiency. In
addition, we try to develop the personalized medicine with collaborators engaged in whole genome analysis. Moreover, we
also support the patients and medical stuffs by integrated ICT and telemedicine in order to promote the renal transplantation
and home hemodialysis. Our policy is simply implicated that the distance to hospital is never associated with mortality of
the patients even though they live in the disaster stricken area after the East Japan Earthquake.
The supporting systems of patients' oriented home care unit

and self-monitoring in remote and rural areas
The evaluation of self-monitoring and the medical advice

Home care Tohoku Univ.
Hospital

the dispatch system of Drs. on

rotation basis
Remote medical support
Sharing of electronic data base
Disease prevention
and treatments in
accordance with the
individuals
Community support hosp.

Cohort participation
Regional Medical
Support Center
Incidental findings and medical consultation
Figure 1. Personalized renal therapy Figure 2. Community medical supports by telemedicine
Recent Publications
- Association between hemoglobin variability, serum ferritin levels, and adverse events/mortality in maintenance hemodialysis patients. Kuragano T, Matsumura O, Matsuda A, Hara T, Kiyomoto H, Murata T,
Kitamura K, Fujimoto S, Hase H, Joki N, Fukatsu A, Inoue T, Itakura I, Nakanishi T. Kidney Int. 2014 Apr 23.
- Beneficial role of tolvaptan in the control of body fluids without reductions in residual renal function in patients undergoing peritoneal dialysis. Mori T, Oba I, Koizumi K, Kodama M, Shimanuki M, Tanno M,
Chida M, Saito M, Kiyomoto H, Miyazaki M, Ogawa S, Sato H, Ito S. Adv Perit Dial. 29:33-7, 2013.
- Plasticity of renal erythropoietin-producing cells governs fibrosis. Souma T, Yamazaki S, Moriguchi T, Suzuki N, Hirano I, Pan X, Minegishi N, Abe M, Kiyomoto H, Ito S, Yamamoto M. J Am Soc
Nephrol.24(10):1599-616, 2013.
- A small molecule inhibitor to plasminogen activator inhibitor 1 inhibits macrophage migration. Ichimura A, Matsumoto S, Suzuki S, Dan T, Yamaki S, Sato Y, Kiyomoto H, Ishii N, Okada K, Matsuo O, Hou
FF, Vaughan DE, van Ypersele de Strihou C, Miyata T. Arterioscler Thromb Vasc Biol. 33(5):935-42, 2013.
- A rare case among hypertensive patients: how do we handle reninomas? Okuda H, Abe M, Kiyomoto H. Intern Med. 52(17):1853, 2013.
146 Integrated Nephrology and Telemedicine

Establishment of personalized perinatal medicine by integrative analysis of gene-
environment Interaction.
Feto-Maternal Medical Medical Sciences Course

URL:
under construction
SUGAWARA, Junichi Contact:
TEL +81-22-73-6283
Professor, MD, PhD E-Mail jsugawara@med.tohoku.ac.jp
Research Theme
Genome analysis for perinatal diseases (e.g. pregnancy induced hypertension)
Multi-omics analysis for pregnancy related disorders
Establishment of network systems and educations of obstetric providers for the support of community perinatal
medicine
Research Keywords: Pregnancy induced hypertension, Genome, Omics, Obstetrics and gynecology,
Community medicine
Technical Keywords: Genome analysis, GWAS, Omics analysis
1. ToMMo Birth and Three Generation Cohort Study

Though this cohort project, we have started multi-omics analysis to clarify pathophysiology of perinatal disorders. Particularly,
genetic analysis with family tree genomic information would be powerful tools to elucidate undetermined mechanisms of
maternal-fetal disorders.
2. Early Prediction by Bioinformatics for Pregnancy Related Disorders

In the MLOG (Maternity Life Log) project, participants will collect daily health parameters, such as body weight, duration of
sleep, activity amount, blood pressure and body temperature using health care devices. With the multilayer integration of these
life log information, lifestyle habits and omics analysis, we try to establish mobile healthcare programs for the prediction of
pregnancy related disorders, including pregnancy induced hypertension, gestational diabetes and premature labor. MLOG project
is the collaborative research with NTT DOCOMO with a widely accepted commercial service of mobile health service in Japan.
3. Establishment of Biomarkers for the diagnosis of feto-maternal disorders.

Using newly developed in silico technology, proteome analysis by the project team with Prof. Terasaki has been just started. This
study would reveal new biomarkers for the early prediction of perinatal disease (e.g. preeclampsia). Development of clinical
diagnostic systems for personalized prevention would be strongly expected.
Recent Publications
- Nagasaki M, et al. Rare variant discovery by deep whole-genome sequencing of 1,070 Japanese individuals. Nat Commun. 2015 Aug 21;6:8018.
- Tadakawa M, et al. Fertility and pregnancy outcomes following B-Lynch sutures for post-partum hemorrhage. J Obstet Gynaecol Res. 41(4):559-64, 2015
- Sugawara J, Yeskey K. Breakout session 2 summary: health planning for all phases of a disaster including risk assessment with concern for vulnerable populations. Disaster Med Public Health Prep.
8(4):361-2, 2014
- Nishigori H,et al. Surveys of postpartum depression in Miyagi, Japan, after the Great East Japan Earthquake. Arch Womens Ment Health. 17(6):579-81, 2014
- Suenaga K, et al. Role of the vasohibin family in the regulation of fetoplacental vascularization and syncytiotrophoblast formation. PLoS One. 9(9):e104728, 2014
Feto-Maternal Medical Science 147

New Health Support System Leading from Oral Genomic Information
Community Oral Health Medical Sciences Course

URL:
http://www.dent.tohoku.ac.jp/english/field/
TSUBOI, Akito megabank/01/index.html
Contact:
E-Mail tsuboi@m.tohoku.ac.jp
Research Theme
Elucidation of oral health factors related to general health maintenance and promotion
Construction of health support system containing oral genomic information provided from prospective large scale
cohort study
Research Keywords: oral health, prospective large scale cohort study, oral metagenomics,
lifestyle-related diseases
Technical Keywords: anaerobic culture, statistical analysis, metagenomic analysis
Progress of low fertility, high life expectancies and nuclear family tendency facilitates to reduce connectivity between members
in a local community and family, and then to bring about a deterioration of functions for community. This weakened community
function leads us to construct a sustainable health support system.
Our division supports the dental part of the long scale genome cohort study conducted by The Tohoku Medical Megabank
project, accumulating and analyzing the lifestyle, health, medical and genomic information including oral microbiome. Most
of oral microbiota has been thought to be non-pathogenic commensals or act as opportunistic pathogens, whereas some are
implicated in oral diseases such as dental caries and periodontitis, which are among the most common infections in humans.
They are also associated with systemic complications. We are focused on the interaction of oral and general disease in terms of
oral microbiome.
Additionally, dental caries, periodontitis and some systematic disease, such as infective endocarditis, diabetes, premature birth,
are related to lifestyle. Our division is going at clarifying a factor influencing to maintain and promote the oral and general health
based on the findings of its analysis and to construct advanced health support system.
Figure 1. Colony formation after anaerobic culture of dental plaque Figure 2. A severe periodontally compromised patient with cardiovascular disease
and diabetes
Recent Publications
- Kawashima J, et al. Fluoride-sensitivity of growth and acid production of oral Actinomyces: comparison with oral Streptococcus. Microbiol Immunol 57(12):797-804, 2013
- Tsuboi A, et al. Difference in water accumulation patterns between solid and closed hollow obturators under a thermal cycle. J Craniofac Surg. 23(5):1535-9, 2012
- Suzuki O, et al. Response properties of temporomandibular joint mechanosensitive neurons in the trigeminal sensory complex of the rabbit. Exp Brain Res. 222(1-2):113-23, 2012
- Kawashima J, et al. Actinomyces acid production: Effects on bicarbonate and fluoride at neural and acid pH, p.189-191. In Sasaki K(ed), Interface Oral Health Science 2011, Springer, New York, 2012
- Shiraishi N, et al. Preparation and characterization of porous alginate scaffolds containing various amounts of octacalcium phosphate (OCP) crystals. J Mater Sci Mater Med.21(3):907-14, 2010
148 Community Oral Health Science

We are Investigating the Relationship between Combination of Genetic and Environmental
Factors and Diseases to Protect Community Health
Personalized Prevention and Medical Sciences Course

Epidemiology Master / Doctoral Degree
URL:
http://www.pprevention.megabank.tohoku.ac.jp/
HOZAWA, Atsushi
Contact:
E-Mail hozawa-thk@umin.ac.jp
Research Theme
Tohoku Medical Megabank Community-Based Cohort Study
Health impact of the Great East Japan Earthquake in community
Gene-environment interaction with lifestyle-related diseases
Research Keywords: community based cohort study, health impact of the Great Eastern Japan Earthquake,
gene, life-style, gene-environment interaction
Technical Keywords: cohort studies, epidemiology, statistics
Main work of the division of personalized prevention and epidemiology is collecting information on community health
after East-Japan Earthquake. We are now establishing Tohoku Medical Megabank Community-Based Cohort Study. Our
objectives are to clarify the health impact of the Great East Japan Earthquake in community, and to clarify gene-environment
interaction with lifestyle-related diseases.
Figure 1. Scene of Community Based Cohort Study recruitment
Recent Publications
- Hozawa A. Attributable fractions of risk factors for cardiovascular diseases. J Epidemiol. 2011;21(2):81-6.
- Miyagawa N(1st) , Hozawa A (9th),et zl; NIPPON DATA80 Research Group. Long-chain n-3 polyunsaturated fatty acids intake and cardiovascular disease mortality risk in Japanese: a 24-year follow-up of
NIPPON DATA80. Atherosclerosis. 2014 Feb;232(2):384-9
- Nakaya N. Effect of psychosocial factors on cancer risk and survival. J Epidemiol. 2014;24(1):1-6.
- Shibata K, Hozawa A2nd, Nakamura T(5th),et al. Yamagata University Genomic Cohort Consortiuma.The confounding effect of cryptic relatedness for environmental risks of systolic blood pressure
on cohort studies.Mol Genet Genomic Med. 2013; 1(1):45-53
- Tsuchiya N, et al. Incidence and predictors of regimen-modification from first-line antiretroviral therapy in Thailand: a cohort study. BMC Infect Dis. 2014 Oct 30;14(1):565
Personalized Prevention and Epidemiology 149

To Establish Comprehensive Biobank Science for Progression of Personalized Medicine
and Health Care
Biobank Life Science Medical Sciences Course

MINEGISHI, Naoko URL:

Contact:
TEL +81-22-272-3103
E-Mail nmine@med.tohoku.ac.jp
Research Theme
Quality improvement of biobank specimens
Innovation of management system of data and biospecimens
Effect of genetic polymorphism on characteristics of human cells
Research Keywords: biobank, biospecimen, preanalytical factor, human genome,

personalized medicine and health care
Technical Keywords: quality management of biological specimens, cell-based research, genetic polymorphism
and cellular characteristics, cryopreservation of biospecimen, laboratory information
management system
The biobank of Tohoku Medical Megabank Organization (ToMMo) was established for storing biological specimens and
health data from participants of cohort studies in Miyagi and Iwate prefectures as a part of the recovery plan from the Great
East Japan Earthquake and Tsunami in 2011. Our Biobank will collect biospecimens from 150,000 participants of prospective
community-based and family-based (three generation) cohort studies until 2017. We stored plasma, serum, urine, buffy coat
cells and mononuclear cells from peripheral blood and cord blood. We automatically extracted genomic DNA from blood
buffy coat cells and saliva. We equipped advanced Laboratory information management system and automatic system to deal
with a lot of de-identified specimens with IDs linked to de-identified health data of participants. Currently, more than 2,100,000
specimens from 120,000 participants (December, 2015) have been accumulated in our biobank. These specimens will be
used as resources to develop personalized medicine and health care. In order to improve the quality of biospecimens in our
biobank, we are investigating for the improvement of management system of specimens and data. We are also searching for
cell-based methods to explore the impact of genetic polymorphism on the risk to develop certain diseases.
Figure 1. Precise sample preparation system with barcoding and automation Figure 2. Liquid nitrogen system for long term storage of biospecimen
Recent Publications
- Minegishi N et al. Biobank Construction after Earthquake and Tsunami Disaster in Japan, Biopreserv Biobank 12:A-21, 2014
- Motoike IN et al. Validation of multiple single nucleotide variation calls by additional exome analysis with a semiconductor sequencer to supplement data of whole-genome sequencing of a human
population. BMC Genomics 15:673, 2014
- Suzuki N et al. Erythropoietin production in neuroepithelial and neural crest cells during primitive erythropoiesis Nat Commun 4:2902, 2013
- Yamazaki S et al. A mouse model of adult-onset anaemia due to erythropoietin deficiency. Nat Commun 4:1950, 2013
- Kon S et al. Smap1 deficiency perturbs receptor trafficking and predisposes mice to myelodysplasia. M. J Clin Invest 123:1123-1137, 2013
150 Biobank Life Science

Providing Total Solution to the Whole Human Genome Analyses
Molecular Network Analysis Medical Sciences Course

YASUDA, Jun URL:

Contact:
TEL +81-22-272-3102
E-Mail jyasuda@megabank.tohoku.ac.jp
Research Theme
Construction of Japanese genome reference panels
Exploring the disease causing variants by population genetics
Findings cancer specific genomic alterations
Research Keywords: genome structures, population genetics, cancer genomics

Technical Keywords: next generation sequencers, SNP arrays, long-read sequencers
Our mission is to develop an infrastructure for realization of personalized prevention and medicine in the devastated areas
by the great east Japan earthquake. To do so, we use genetic and omics information of the participants of prospective cohort
in the damaged area to identify the susceptible loci for the common disease which is aggravating in the area. We have
successfully sequenced the genomes of thousands of healthy participants and have constructed the whole-genome reference
panel of Japanese population. Now we move to the analyses of relationship between genomic alterations and disease
susceptibility and elucidation of molecular networks associated with disease mechanisms. We are expecting several millions
of single nucleotide variants in an individuals genome and some of them might be associated with disease onset. By means
of integration of omics analyses, we will try to narrow down the candidate genes. Finally, we will try to identify disease
susceptible genes for the cohort participants and give them the appropriate information for their health care.
Figure 1. The multi-omics approach to disease research Figure 2. Next-generation sequencing platforms
Recent Publications
- Nagasaki M, et al. Rare variant discovery by deep whole-genome sequencing of 1070 Japanese Individuals. Nat Commun. 6:8018, 2015.
- Yamaguchi-Kabata Y, et al. iJGVD: an integrative Japanese genome variation database based on whole-genome sequencing. Hum Genome Var 2:15050, 2015
- Kawai Y, et al. Japonica Array: Improved genotype imputation by designing a population-specific SNP array with 1,070 Japanese individuals. J Hum Genet. 60(10):581-7, 2015.
- Katsuoka F, et al. An efficient quantitation method of next-generation sequencing libraries by using MiSeq sequencer. Anal Biochem. 466:27-29, 2014.
- Motoike IN, et al. Validation of multiple single nucleotide variation calls by additional exome analysis with a semiconductor sequencer to supplement data of whole-genome sequencing of a human
population. BMC Genomics 15:673, 2014.
Molecular Network Analysis 151

Analysis of Whole-genome, Multi-omics, and/or Meta-genomic Data for Biomedical Science
on High Performance Computer
Biomedical Information Medical Sciences Course

Analysis Master / Doctoral Degree
URL:
http://nagasakilab.csml.org/en/
NAGASAKI, Masao
Contact:
E-Mail ig-nagalab-jimu@ml.megabank.tohoku.ac.jp
Research Theme
Huge scale data analysis of human genome, multi-omics and/or metagenomics data on high performance
computer
Analysis of whole-genome, multi-omics and/or metagenomics data for association study with disease and
phenotype
Data processing, statistical methods and software development for high performance sequencer, SNP array and
other new high-throughput technology
Research Keywords: bioinformatics, data-driven science, high performance computing,

high performance sequence, human genome
Technical Keywords: whole genome sequencing, genome-wide association study, multi dimensional omics analysis,
metagenomics, machine learning
Our research is aiming to make distinct contributions in both methodological and practical aspects of the present-day Big Data science,
particurally biomedical science. We analyze diverse and heterogeneous types of genomic and biomedical data to find new knowledge and
insight. Analysis are conducted utilizing supercomputing resources, informatics, and statistical approaches.
Over a decade ago, the representative human genome was sequenced relying on the efforts of many researchers worldwide and cost more than
one billion dollars. Nowadays, however, personal genomes are being sequenced more easily and faster at lower cost. This situation means
that novel methodological advances are absolutely required for the integration and analysis of individual genomes, omics, and biomedical
information (e.g., physiological and clinical information). On the basis of this view, faculty staff specializing in bioinformatics, statistical
mathematics, population genetics, and molecular evolutionary biology are actively conducting research in our laboratory. Graduate students
can conduct their research in advanced computer science, massive data analysis, statistical modeling, and algorithm/software development with
our laboratory members. We turn out fine students who can solve the flood of biomedical information from a data-driven science point of view.
Currently our lab has constructed the 1070 Japanese whole-genome reference panel from high-performance sequencers on our super-computer
system and have partially opened them to the public (http://ijgvd.megabank.tohoku.ac.jp/). We have also developed a SNP array optimized for
the Japanese population called Japonica array.
Figure 1. Large-scale data analysis of individual genomes towards personalized Figure 2. Big data analysis with data-driven science
healthcare
Recent Publications
- Yamaguchi-Kabata Y et al. iJGVD: an integrative Japanese genome variation database based on whole-genome sequencing. Human Genome Variation. 2:15050, 2015
- Nagasaki M et al. Rare variant discovery by deep whole-genome sequencing of 1,070 Japanese individuals. Nat Commun. 6:8018, 2015
- Kawai Y et al. Japonica array: improved genotype imputation by designing a population-specific SNP array with 1070 Japanese individuals. J Hum Genet. 60:581587, 2015
- Sato Y et al. Inter-individual differences in the oral bacteriome are greater than intra-day fluctuations in individuals. PLoS One. 10(6): e0131607, 2015
- Kojima K et al. HapMonster: a statistically unified approach for variant calling and haplotyping based on phase-informative reads. Lecture Notes in Bioinformatics. 8542, 107-118, 2014
152 Biomedical Information Analysis

To Open New Avenues for Sustainable Medicine and Future of Humanity: Theoretical and
Statistical Genetics for Genomic and Personalized Medicine
Statistical Genomics and Medical Sciences Course

Genetics Master / Doctoral Degree
URL:
http://www.genetix-h.com/~SGG
TAMIYA, Gen
Contact:
E-Mail gtamiya@genetix-h.com
Research Theme
Revealing disease etiologies by analyzing genomic big data using theoretical and statistical genetics
Achieving disease risk prediction using risk factors
Addressing problems in future of humanity by exploiting genetic properties of human populations
Research Keywords: statistical genetics, population genetics, quantitative genetics, genomic medicine,
genomic cohort
Technical Keywords: neutral theory, big data in genomics, gene-by-environment interaction,
big data with high dimension and low sample size, large p small n problem
Human common complex diseases, such as diabetes, hypertension and mental illness, can be contributed by multiple etiologies
involving environmental and/or genetic factors. As far, traditional epidemiological researches revealed a lot of environmental
risk factors, whereas genomic researches identified risk genes for such diseases. However, these risk factors could explain only
small fraction of any complex disease prevalence. This is probably due to underpowered research designs, limited genomic
data and/or poor genetic theories so on. Recently, to overcome this situation, both research communities together make efforts
to decipher comprehensively complex disease etiologies including genes, environments and their interactions by so-called
national-wide genomic cohort study. Although this design seems excellent and promising, there are some radical problems;
one is the lack of appropriate models for the genetic architectures of common complex diseases, and the other is that we have
no effective statistical methods for such big data with high dimension/small sample size. The former is often called missing
heritability problem in the field of genetics and the later p>>n problem in that of statistics. Our department aims to resolve
such radical problems using the most advanced statistical genetics based on traditional population/quantitative genetic theories.
Our studies will open the way for sustainable genomic/personalized medicine as well as the future of humanity.
Figure 1. Genomic/Personalized medicine
Recent Publications
- Tamiya G, et al. A mutation of COX6A1 causes a recessive axonal or mixed form of Charcot-Marie-Tooth disease. Am J Hum Genet. 95(3):294-300, 2014
- Yamagata University Genomic Cohort Consortium. Pleiotropic Effect of Common Variants at ABO Glycosyltranferase Locus in 9q32 on Plasma Levels of Pancreatic Lipase and Angiotensin Converting
Enzyme. PLoS ONE 9(2):e55903, 2014
- Ueki M and Tamiya G. Ultrahigh-dimensional variable selection method for whole-genome gene-gene interaction analysis. BMC Bioinformatics 13(1):72, 2012
- Tamiya G. Transcriptional dysregulation: a cause of dystonia? Lancet Neurol. 8(5):416-8, 2009
- Makino S, et al. Reduced neuron-specific expression of the TAF1 gene is associated with X-linked dystonia-parkinsonism. Am J Hum Genet. 80(3):393-406, 2007
Statistical Genomics and Genetics 153

Evidence-Based Genetic Counseling
Genomic Medicine Support School of Public Health Course

and Genetic Counseling Master Degree
URL:
http://www.clin-gc.megabank.tohoku.ac.jp/
KAWAME, Hiroshi index.html [Jpn]
Contact:
E-Mail hkawame@megabank.tohoku.ac.jp
Research Theme
Delineation of natural history and genetic counseling issues of genetic syndromes
Identification of genetic counseling issues in genome-wide genetic testing
Development of resources and methods of genetic and genomic literacy
Research Keywords: genetic counseling, birth defects, natural history, personalized medicine,
genetic and genomic literacy
Technical Keywords: genetic counseling program, systematic review, role play
Division of Genomic Medicine Support and Genetic Counseling was incorporated of Department of Education and Training,
Tohoku Medical Megabank Organization (ToMMo) in April 2013. Our division conducts clinical research regarding genetic
counseling in pediatrics and personalized medicine, and runs Masters Program in Genetic Counseling, Tohoku University
School of Medicine. Our program in Genetic Counseling, the only genetic counseling program in the Tohoku region, has
been accredited by the Japanese Board of Genetic Counseling, and provides the development of the next generation of
genetic counselors. The mission of our program is train genetic counselors that have the ability to communicate the update
information fully and effectively and can work closely with the clients.
We accept only just for becoming certified genetic counselors who work in Japan.
Figure 1. Genetic counseling program class
Recent Publications
- Shimizu K et al. Microarray and FISH-based genotype-phenotype analysis of 22 Japanese patients with Wolf-Hirschhorn syndrome. Am J Med Genet A. 164A:597-609, 2014
- Nishi E et al. Surgical intervention for esophageal atresia in patients with trisomy 18. Am J Med Genet A. 164A:324-30, 2014
- Kaneko K et al. Diagnosis of balanced translocation carriers and genetic counseling. J Jpn Pediatr Soc 117:1781-1787, 2013 [Jpn]
- Yotsumoto J et al. Attitudes toward non-invasive prenatal diagnosis among pregnant women and health professionals in Japan. Prenat Diagn. 32:674-9 2012
- Bassett AS et al. Practical guidelines for managing patients with 22q11.2 deletion syndrome. J Pediatr 159:332-9 2011
154 Genomic Medicine Support and Genetic Counseling

Challenge for Developing Disease Prevention and Therapy that Use Personal Genetic
Information
Genetic Epidemiology Medical Sciences Course

Research Support Master / Doctoral Degree
URL:
http://www.genepi.megabank.tohoku.ac.jp/
SUZUKI, Yoichi
Contact:
E-Mail ysuzuki@megabank.tohoku.ac.jp
Research Theme
Education of genomic medicine and promotion of individualized medicine
Genetic epidemiology of allergic diseases
Molecular and genetic dissection of allergic diseases
Research Keywords: genomic medicine, allergic disease, genetic epidemiology, molecular genetics,
asthma model mice
Technical Keywords: genetic analysis, genetic epidemiology, molecular genetics, disease model mouse
The followings are our research theme:

"Development of tools for education of human genetics, clinical genetics, and genomic medicine"
Creating textbook for human genetics
Creating visual materials to help understanding human and clinical genetics
Creating video drama to understand genetic counseling and genetic diseases
Developing toys and games for education of genetics
"Genetic epidemiology of allergic diseases"
Genetic variation and risk for allergic diseases
Molecular analysis of airway epithelial cells
Investigation of asthma psychopathology using mouse models
"Molecular analysis of biotin related disorders"
"Developing a strategy for informing large-cohort participants of their genetic variations"
Figure 1. MMP12 gene variations and asthma Figure 2. TBXA2R haplotype and lung function
Recent Publications
- Functional variants in the thromboxane A2 receptor gene are associated with lung function in childhood-onset asthma. CEA 43, 413, 2013
- Association study of matrix metalloproteinase-12 gene polymorphisms and asthma in a Japanese population. Int Arch Allergy Immunol 160, 287, 2012
Genetic Epidemiology Research Support 155

The Challenge to Elucidate the Pathogenesis of Neuropsychiatric Disorders by Utilizing a
Molecular Neuroimaging Technologies with a Focus on PET
Molecular Neuroimaging Medical Sciences Course

(National Institute of Master / Doctoral Degree
Radiological Sciences)
URL:
http://www.nirs.go.jp/seika/brain/english/index.html
Contact:
SUHARA, Tetsuya TEL +81-43-206-3194
Professor, M.D. Ph.D. E-Mail suhara@nirs.go.jp
Research Theme
Clinical study on pathologic condition and therapy evaluation of brain function, mental disease and neurologic
disorder
Basic research of the molecular mechanism on the mental and neurological disorders using model animals
Translational research of the molecular mechanism organizing the cognitive systems and the localization of brain
function
Research Keywords: molecular neuroimaging, translational research, schizophrenia, mood disorder, dementia
Technical Keywords: PET, in vivo imaging, animal disease model, biochemistry, neuropathology
The onset and progression of neuropsychiatric disorders such as depression, schizophrenia, and Alzheimer's disease are not well
understood. The elucidation of the mechanism has become an urgent task in the development of the diagnosis and therapeutics. In
vivo imaging is one of the best technologies as well as gene analysis for brain research. Especially positron emission tomography
(PET) which enables direct visualization of brain molecules is expected to play a crucial role for drug development.
The department of molecular neuroimaging in NIRS is challenging to reveal the brain function by utilizing a variety of imaging
technologies with a focus on PET. Our mission is to elucidate the cause of symptoms such as reduced motivation, delusions or
memory impairment of neuropsychiatric disorders, and to contribute to the development of the diagnosis and therapeutics by
translational research between human and animal disease model of mice or monkey by combination of imaging, biochemical and
pathological analyses.
Figure 1. Regulation of behavior by designer receptor-drug system Figure 2. Relationship between striatal functional connectivity and superiority illusion
Recent Publications
- Takano H, Arakawa R, Nogami T, Suzuki M, Nagashima T, Fujiwara H, Kimura Y, Kodaka F, Takahata K, Shimada H, Murakami Y, Tateno A, Yamada M, Ito H, Kawamura K, Zhang MR, Takahashi H, Kato M,
Okubo Y, Suhara T. Norepinephrine transporter occupancy by nortriptyline in patients with depression: a positron emission tomography study with (S,S)-[F]FMeNER-D., Int J Neuropsychopharmacol
17(4):553-560 (2014)
- Maruyama M., Shimada H., Suhara T., Shinotoh H., Ji B., Maeda J., Zhang MR., Trojanowski JQ., Lee VM., Ono M., Masamoto K., Takano H., Sahara N., Iwata N., Okamura N., Furumoto S., Kudo Y.,
Chang Q., Saido TC., Takashima A., Lewis J., Jang MK., Aoki I., Ito H., Higuchi M., Imaging of tau pathology in a tauopathy mouse model and in Alzheimer patients compared to normal controls., Neuron,
79(6):1094-1108 (2013)
- Yamada M., Uddin LQ., Takahashi H., Kimura Y., Takahata K., Kousa R., Ikoma Y., Eguchi Y., Takano H., Ito H., Higuchi M., Suhara T., Superiority illusion arises from resting-state brain networks
modulated by dopamine., Proc Natl Acad Sci U S A., 110(11):4363-4367 (2013)
- Nagai Y, Minamimoto T, Ando K, Obayashi S, Ito H, Ito N, Suhara T. Correlation between decreased motor activity and dopaminergic degeneration in the ventrolateral putamen in monkeys received
repeated MPTP administrations: a positron emission tomography study., Neurosci Res 73(1):61-67 (2012)
- Maeda J., Zhang MR., Okauchi T., Ji B., Ono M., Hattori S., Kumata K., Iwata N., Saido TC., Trojanowski JQ., Lee VM., Staufenbiel M., Tomiyama T., Mori H., Fukumura T., Suhara T., Higuchi M., In
vivo positron emission tomographic imaging of glial responses to amyloid-beta and tau pathologies in mouse models of Alzheimer's disease and related disorders., J Neurosci., 31(12):4720-4730 (2011)
156 Molecular Neuroimaging (National Institute of Radiological Sciences)

Diagnostic and Therapeutic Approaches by Targeting the Inherent Nature of Cancer Cells
Cancer Molecular Biology Medical Sciences Course

(Miyagi Cancer Center) Master / Doctoral Degree
URL:
SHIMA, Hiroshi
Contact:
E-Mail shima@med.tohoku.ac.jp
Research Theme
Development of diagnostic and therapeutic approaches by targeting the metabolic disorder of cancer cells
Development of diagnostic and therapeutic modalities for cancer by targeting kinases and phosphatases
Research Keywords: Warburg effect, protein phosphatase, genetic instability

Technical Keywords: genetically engineered mice, live imaging, metabolic analysis
(1) There are fundamental differences in the metabolic pathways operating in malignant tissue. Cancer cells preferentially
convert glucose into lactate even when oxygen level are not limiting, a process termed aerobic glycolysis or the Warburg
Effect. Our project is that to develop therapy by targeting the metabolic disorder of cancer cells.
(2) The phosphorylation status of proteins is regulated by the balance of kinase and phosphatase activities. Studies into the
causes of abnormal phosphorylation have, until now, mainly been focused on kinases. Many kinase inhibitors have been
applied as a molecular targeted therapy. At the same time, numerous mechanisms which regulate phosphatase activities have
been identified, and their dysfunction to be related to various diseases. We are trying to develop diagnostic and therapeutic
modalities for cancer by targeting kinases and phosphatases.
PP6 KO is predisposed to skin carcinogenesis

Control skin
DMBA 16 w
TPA/OA
DMBA Repetitive treatment
Ppp6c deleted skin
5w
DMBA
DMBA
Hayashi et al. Oncogene2015
Figure 1 Figure 2
Recent Publications
- Matsuda S, et al. Nuclear pyruvate kinase M2 complex serves as a transcriptional coactivator of arylhydrocarbon receptor. Nucleic Acids Res in press
- Hayashi K, et al. Abrogation of protein phosphatase 6 promotes skin carcinogenesis induced by DMBA. Oncogene 34(35):4647-75, 2015
- Kato H, et al. Loss of protein phosphatase 6 in mouse keratinocytes increases susceptibility to ultraviolet-B-induced carcinogenesis. Cancer Lett. 365(2):223-8, 2015
- Takahashi K et al. Sialidase NEU3 contributes neoplastic potential on colon cancer cells as a key modulator of gangliosides by regulating Wnt signaling. Int J Cancer 137(7):1560-73, 2015
- Hamabe A, et al. Role of pyruvate kinase M2 in transcriptional regulation leading to epithelial-mesenchymal transition. Proc Natl Acad Sci U S A. 111(43):15526-15531, 2014
- Nakahata S, et al. Loss of NDRG2 expression activates PI3K-AKT signalling via PTEN phosphorylation in ATLL and other cancers. Nat Commun. 5:3393, 2014.
Cancer Molecular Biology (Miyagi Cancer Center) 157

To Explore the Mechanisms Underlying the Cancer Development and Challenge the Origin
of Cancer Cells
Cancer Stem Cell Research Medical Sciences Course

(Miyagi Cancer Center) Master / Doctoral Degree
URL:
SATOH, Kennichi related/176/index.html
Contact:
E-Mail ksatoh-gi@umin.ac.jp
Research Theme
Characterization of cancer stem cells and the development of therapeutic strategy for cancer stem cells
Identification of the factors promoting cancer invasion and metastasis and the development of its therapeutic
strategy
Exploration of biomarkers for various tumors
Research Keywords: cancer stem cells, cancer development, biomarker

Technical Keywords: cell isolation, cell culture, molecular biology, animal experiment, pathology
Recent studies suggested the presence of subpopulation of cancer stem cells (CSC) which initiate metastasis and resistance
to therapy. CSCs may generate tumors through the stem cell processes of self-renewal and differentiation into multiple
cell types. Increasing evidence suggests that epithelial to mesenchymal transition (EMT)-type cells share many biological
characteristics with CSCs. Therefore, CSCs and/or EMT-type cells are likely to be the most effective targets for cancer
therapy. On the other hand, CSC like cells have distinct metabolic profile. Cancer cells generally produce the energy by
their anabolic metabolism (Warbrug effect). However, CSC like cells are shown to be less glycolytic and more dependent
on mitochondrial respiration. Based upon these findings, we are studying about the correlation between the expression of
molecules related with EMT or metabolism and cancer cell development in order to reveal the characteristics of CSCs of
various origins.
We have tissue bank in which more than 2,000 matched pairs of frozen normal and cancer tissues from various organs
were stored. We explore the molecules responsible for the enhancement of malignant phenotype of cancer cells by analyzing
the expression levels of candidate molecules between cancer cells and their corresponding normal cells.
Figure 1. Characteristics of cancer stem cells Figure 2. HOTAIR promotes anchorage-independent growth of gastric cancer cells
Recent Publications
- Abue M, et al. Circulating miR-483-3p and miR-21 is highly expressed in plasma of pancreatic cancer. Int J Oncol. 46 (2): 539-47, 2015.
- Satoh K, et al. Involvement of epithelial to mesenchymal transition in the development of pancreatic ductal adenocarcinoma. J Gastroenterol. 50 (2): 140-6, 2015
- Endo H, et al. Enhanced expression of long non-coding RNA HOTAIR is associated with the development of gastric cancer. PLoS ONE 8: e77070, 2013.
- Nakagawa T, et al. Large noncoding RNA HOTAIR enhances aggressive biological behavior and is associated with short disease-free survival in human non-small cell lung cancer. Biochem Biophys Res
Commun 436(2): 319-24, 2013.
- Hamada S, et al. MiR-197 induces epithelial-mesenchymal transition in pancreatic cancer cells by targeting p120 catenin. J Cell Physiol. 228 (6):1255-63, 2013.
158 Cancer stem cell research (Miyagi Cancer Center)

Clinical Study about Gynecologic Malignancies
Gynecologic Oncology Medical Sciences Course

(Miyagi Cancer Center) Doctoral Degree
URL:
http://www.ob-gy.med.tohoku.ac.jp/laboratory/
YAMADA, Hidekazu h-yamada.html
Contact:
E-Mail h-yamada@med.tohoku.ac.jp
Research Theme
Studies of operations to gynecologic malingnancies
Studies of therapy for the patients of recurrent ovarian cancer
Studies of fertility preservation for youg cancer patients
Research Keywords: gynecologic malignancies, ovarian cancer, young cancer patients, recurrent cancer
Technical Keywords: epidemiology, functional preservation, fertility preservation
1. First, I want to establish the functional preservation operations for gynecologic malignancies. Also I aim at establishing
the methods of reduction of patients complications after gynecologic operations. Specifically as follows
1) radical hysterectomy preserving urinary function.
2) optimal surgery of ovarian cancer patients.
3) introduction of laparoscopic surgery for the uterine body cancer patients.
4) study about reduction of a complications after an gynecologic operation(thrombosis, lymphedema).
2. Studies about the therapies for the recurrent ovarian cancer patients.
1) chemotherapy:establishment of the most effective chemotherapy preserving QOL for the recurrent ovarian cancer
patients.
2) operation and radiotherapy: I want to clarify the indication of operation and radiotherapy for the recurrent ovarian cancer
patients.
3. Fertility preservation for the young cancer patients.
Recent Publications
- Production of IL1-beta by ovarian cancer cells induces mesothelial cell beta1-integrin expression facilitating peritoneal disseminationTakafumi Watanabe, Toshihiro Hashimoto, Takashi Sugino, Shu Soeda,
Hiroshi Nishiyama1, Yutaka Morimura2, Hidekazu Yamada1, Steve Goodison and Keiya Fujimori J Ovarian Res. 2012 Feb 1;5(1):7. doi: 10.1186/1757-2215-5-7.
- Soeda S, Mathuda N, Hashimoto Y, Yamada H, Fujmori K.Nonbacterial Thrombotic Endocarditis with Systemic Embolic Events caused by Adenomyosis . J. Obstet. Gynecol.. Res. 37(12), 1838-1841, 2011.
Gynecologic Oncology (Miyagi Cancer Center) 159

To Foster Urologists with a Balance of Experiences in Both Basic and Clinical Domains
Urologic Oncology Medical Sciences Course

URL:
KAWAMURA, Sadafumi
Contact:
E-Mail kawamura-sa889@miyagi-pho.jp
Research Theme
Diagnosis and treatment of malignant urogenital tumors
Developement of the optimal mass screening for prostate cancer
QOL investigation in cancer patients
Research Keywords: prostate cancer, bladder cancer, renal cancer, testicular tumor, mass screening
Technical Keywords: prostatectomy, radiation, chemotherapy, sialidase, QOL
The Division of Urologic Oncology, established at Miyagi Cancer Center Research Institute, is a collaborative chair with
Tohoku University Graduate School of Medicine. We focus mainly on clinical research in the field of malignant urogenital
tumors (prostate, kidney, bladder, testicular, renal pelvis and ureter, adrenal, and penile cancers). By taking advantage of
its extensive dataset obtained from numerous cases, the Division of Urologic Oncology is dedicated to medical practice,
research, and education regarding surgical therapy, for the most part, along with chemotherapy and radiation therapy, as well
as other areas such as quality of life (QOL) investigations. We also emphasize preventive medicine, and have been working
on mass screening for prostate cancer since early on. Through utilization of the admission system for working adults offered
by Tohoku University Graduate School, it is possible to accumulate clinical learning experiences as a full-time doctor or
resident at Miyagi Cancer Center, while working towards a doctorate degree by conducting basic research at its research
institute. In this way, the Division of Urologic Oncology aims at fostering urologists with a balance of experiences in both
basic and clinical domains.
Recent Publications
- Mitsuzuka K, et al. Lymphovascular invasion is significantly associated with biochemical relapse after radical prostatectomy even in patients with pT2N0 negative resection margin. Prostate Cancer Prostatic
Dis. Oct 21,2014 [Epub ahead of print]
- Ito A, et al. Prospective randomized phase II trial of a single early intravesical instillation of pirarubicin (THP) in the prevention of bladder recurrence after nephroureterectomy for upper urinary tract
urothelial carcinoma: the THP Monotherapy Study Group Trial. J Clin Oncol. 31(11):1422-1427, 2013
- Mitsuzuka K, et al. Pathological and biochemical outcomes after radical prostatectomy in men with low-risk prostate cancer meeting the Prostate Cancer International: Active Surveillance criteria. BJU Int.
111(6):914-920, 2013
- Tochigi T, et al. The intravesical recurrence after 3-day consecutive intravesical instillation of pirarubicine hydrochloride (THP) following transurethral resection of bladder tumor (TURBT) for non-muscle-
invasive bladder cancer. Nihon Hinyokika Gakkai Zasshi.103(4):610-616, 2012[Jpn]
- Kawamura S, et al. Plasma membrane-associated sialidase (NEU3) regulates progression of prostate cancer to androgen-independent growth through modulation of androgen receptor signaling. Cell Death
Differ. 19(1):170-179, 2012
160 Urologic Oncology (Miyagi Cancer Center)

To Bring Up Good Head and Neck Surgeon Having a High Clinical Skill and the Quality of
the Basic Research
Head and Neck Oncology Medical Sciences Course

URL:
MATSUURA, Kazuto related/229/index.html
Contact:
E-Mail matsuura-ka447@miyagi-pho.jp
Research Theme
Development of the functional preservation treatment for the head and neck cancer
Development of the supportive care in the chemo-radiotherapy for the head and neck cancer
Search of the cancer stem cell marker in the head and neck cancer
Research Keywords: functional preservation treatment, supportive therapy in the chemo-radiotherapy,

cancer stem cell marker
Technical Keywords: endoscopic laryngo-pharyngeal surgery, skin care, nutritional therapy, CD271
Head and neck region has many functions including the "chewing" "swallowing" "phonation". We perform the
multidisciplinary therapy using a surgery, radiation and the anticancer drug. The first aim of the treatment is improvement of
the overall survival, and the second is functional preservation Therefore, the themes of our department are as follows.
(1) Development of the functional preservation treatment for the head and neck cancer
(2) Development of the supportive therapy in the chemoradiotherapy for the head and neck cancer
(3) Search of the cancer stem cell marker in the head and neck cancer
The ongoing research contents are as follows.
(1) We develop the instrument of the endoscopic laryngopharyngeal surgery to extend the indication of the laryngeal
preservation surgery.
(2) We develop the nutritional therapy to reduce radiation dermatitis.
(3) We found that CD271 was a new cancer stem cells marker in hypopharyngeal squamous cell carcinoma. Therefore we
aim at the development of an antibody and the micromolecule compound which make CD271 a target.
We utilize the admission system for working adults offered by Tohoku University Graduate School. Therefore you make
fundamental research in Miyagi cancer center research institute while doing clinical training as a resident and can acquire a
doctorate. Our department aims for bringing up good head and neck surgeon having a high clinical skill and the quality of
the basic research.
Figure 1. The strategy and tactics in head and neck cancer treatment Figure 2. In vivo tumorigenicity and differentiation capacity of CD271+ cells
Recent Publications
- Imai T, et al. Effect of HMB/Arg/Gln on the prevention of radiation dermatitis in head and neck cancer patients treated with concurrent chemoradiotherapy. Jpn J Clin Oncol 44(5):422-7, 2014
- Imai T, et al. CD271 defines a stem cell-like population 1 in hypopharyngeal cancer. PLoS One. 2013 Apr 23;8(4):e62002. doi: 10.1371/journal.pone.0062002. Print 2013.
Head and Neck Oncology (Miyagi Cancer Center) 161

Sick Children Teach Us on Diseases, We Return the Favor for Them
Pediatric Hematology and Medical Sciences Course

Oncology Master / Doctoral Degree
(Miyagi Children's Hospital) URL:

related/151/index.html
IMAIZUMI, Masue Contact:
TEL +81-22-391-5111
Professor, M.D. Ph.D. E-Mail imaizumi@miyagi-children.or.jp
Research Theme
Clinical research of hematological malignancies in children
Study on pathogenesis of inherited bone marrow failure syndrome
Pathological and epidemiological study of thrombocytopenia in children
Research Keywords: childhood leukemia, inherited bone marrow failure, childhood thrombocyotopenia,
childhood cancer, blood cell transplantation
Technical Keywords: pathological analysis, cytogenetic analysis, genome analysis
In the course of this pediatric hematology and oncology, we study the pathogenesis of childhood leukemia and blood
disorders in the Department of Hematology and Oncology, Miyagi Childrens Hospital (MCH) through cooperation
with Tohoku University School of Medicine. MCH has annually experienced 20 or more new patients with leukemia or
blood disorders. We have diagnosed and treated children with inherited disorders such as congenital immunodeficiency
and inherited bone marrow failure syndrome. Pathogenesis of childhood cancer and blood disorders is often involved in
particular genetic predispositions or mutations in the germline or somatic cells. The understanding of those abnormalities at
cellular or molecular levels may help the development of novel approaches in therapy and diagnosis for childhood cancer
and blood disorders.
Figure 1 Figure 2
Recent Publications
- Niihori T et al. Mutations in MECOM, encoding oncoprotein EVI1, cause radioulnar synostosis with amegakaryocytic thrombocytopenia. Am J Hum Genet. 97:848-54, 2015
- Ouchi-Uchiyama M et al. Analyses of genetic and clinical parameters for screening patients with inherited thrombocytopenia with small or normal-sized platelets. Pediatr Blood Cancer. 62:2082-8, 2015
- Matsubara K et al. Long-term follow-up of children with refractory immune thrombocytopenia treated with rituximab. Int J Hematol. 99:429-36,2014
- Horino S et al. Selective expansion of donor-derived regulatory T cells after allogeneic bone marrow transplantation in a patient with IPEX syndrome. Pediatr Transplant. 18:E25-30, 2014
- Imaizumi M et al. Prospective study of a therapeutic regimen with all-trans retinoic acid and anthracyclines in combination of cytarabine in children with acute promyelocytic leukaemia: the Japanese
childhood acute myeloid leukaemia cooperative study. Br J Haematol. 152:89-98, 2011
162 Pediatric Hematology and Oncology (Miyagi Children's Hospital)

To Develop New Drug Therapies or Biomarkers for Neoplastic Diseases in Clinical Medical
Oncology
Oncotherapeutic Medicine Medical Sciences Course

(Japanese Foundation for Doctoral Degree
Cancer Research)
URL:
TAKAHASHI, Shunji
Contact:
E-Mail s.takahashi-chemotherapy@jfcr.or.jp
Research Theme
Early clinical development of new cytotoxic and molecular targeting drugs for cancer
Elucidation of molecular mechanisms for resistance to molecular targeting drugs and development of new therapy
Development of new biomarkers using multiplex mutation analysis, circulating tumor cells, and circulating tumor DNA
Research Keywords: new antineoplastic drugs, resistance to molecular target drug, biomarkers of cancer,
bone metastases of cancer
Technical Keywords: phase I trial, next generation sequencing, multiplex gene mutation analysis,
circulating tumor cells, circulating tumor DNA, animal metastasis models
This field consists of Department of Medical Oncology, Cancer Institute Hospital, Japanese Foundation for Cancer Research,
and includes many medical oncologists in various fields (Respiratory, Gastrointestinal, Hematological, Breast, Head and
Neck, Sarcoma, and phase I unit).
1) Cancer Institute Hospital is one of the center hospital for early development of new cytotoxic and molecular target drugs,
and many patients participate in phase I trials. During development of new agents, we will start new investigator-initiated
trials and develop new biomarkers. 2) We analyze gene mutation or develop tumor models from clinical samples of patients
resistant to molecular target drugs, and, investigate new mechanisms of drug resistance, and then develop new therapy to
overcome resistance. 3) From the background of highest patient number treated in Japan, we develop new biomarkers using
multiplex PCR, target sequencing with NGS, circulating tumor cells, and circulating tumor DNA. 4) We have conducted
many clinical trials for bone metastases, and will investigate new mechanisms of bone metastases, and develop new bone
modifying agents.
Recent Publications
- Takahashi S, et al. Phase I study of dasatinib (BMS-354825) in Japanese patients with solid tumors. Cancer Sci. 2011 Nov;102(11):2058-64
- Takahashi S, et al. Efficacy of zoledronic acid in postmenopausal Japanese women with early breast cancer receiving adjuvant letrozole: 12-month results. Breast Cancer Res Treat. 2012 Jun;133(2):685-93.
- Dana Rathkopf, et al. Phase I Dose-Escalation Studies of BMS-641988 in Patients with Castration-Resistant Prostate Cancer. Clin Cancer Res. 2011 Feb 15;17(4):880-7.
- Mukai, H et al. Phase I dose-escalation and pharmacokinetic study (TED 11576) of cabazitaxel in Japanese patients with castration-resistant prostate cancer. Cancer Chemother Pharmacol. 2014
Apr;73(4):703-10
- Kurahashi I, et al. A microarray-based gene expression analysis to identify diagnostic biomarkers for unknown primary cancer. PLoS One. 2013 May 9;8(5):e63249.
Oncotherapeutic Medicine (Japanese Foundation for Cancer Research) 163

World-class Clinical Research
Community Psychiatry Medical Sciences Course

(Miyagi Psychiatric Center) Master / Doctoral Degree
URL:
http://www.med.tohoku.ac.jp/org/related/188/
Contact:
TEL +81-22-384-2236
E-Mail mpc-info@miyagi-pho.jp
Research Theme
Interventions promoting school-based mental health services, early treatment of teens with mental illnesses, and
public awareness of youth mental health
Establishing psycho-social treatment models for first episode psychosis
Exploring the effectiveness of a multi-disciplinary outreach service for people with severe mental illnesses
Research Keywords: community psychiatry, severe mental illness, pathology elucidation, clinical research,
prevention
Technical Keywords: outreach, care management, earthquake, community mental health activities
The Division of Community Psychiatry at the Miyagi Psychiatric Center is a collaboration with the Tohoku University
Graduate School of Medicine. We have focused our clinical research on the following projects.
1. Early interventions focusing on the promotion of public awareness of youth mental health, school-based mental health
services, and early treatment for teens with mental illnesses.
2. Establishing psycho-social treatment models for first episode psychosis.
3. Exploring the effectiveness of a multi-disciplinary outreach service for people with severe mental illnesses.
4. Interventions for the mental health of earthquake victims who are living in temporary dwellings.
These projects are linked with our clinical services, and it is possible to get a doctoral degree while working fulltime at the
Miyagi Psychiatric Center. This is done through the admission system for working adults offered by Tohoku University
Graduate School.
Recent Publications
- Hunakoshi S, et al. Factors Associated with the Psychological impact of the Great East Japan Earthquake on High School Students 1 Year and 4 Months after the Disaster. Psychiatria et Neurologia
Japonica.116:541-554,2014[Jpn]
- Ono T, et al. Natori EI Project : The Early Intervention Project for Psychiatric Disorders by the Miyagi Psychiatric Center. Psychiatria et Neurologia Japonica.115:147-153,2013[Jpn]
- Kodaka A. Individual psychotherapy and psychiatric team. Japanese Journal of Clinical psychiatry.36(11):1419-1422,2007[Jpn]
- Kodaka A. Violence in Psychiatric Hospitals. The Japanese Jornal of Hospital and Community Psychiatry. 47(4):425-430,2004[Jpn]
164 Community Psychiatry (Miyagi Psychiatric Center)

To Promote Basic, Clinical and Translational Research in National Cerebral and
Cardiovascular Center Which Possesses Abundant Patients and Research Institute.
Innovative Cardiovascular Medical Sciences Course

Medicine Master / Doctoral Degree
(National Cerebral and

URL:
Cardiovascular Center) http://www.med.tohoku.ac.jp/org/related/189/
Contact:
YASUDA, Satoshi TEL +81-6-6833-5012
E-Mail yasuda.satoshi.hp@mail.ncvc.go.jp
Professor, MD
Research Theme
Imaging and biomarker technology of high-risk plaque for acute coronary syndrome
Cardiovascular protection in heart diseases
The pathological role of inflammation in the process of left ventricular remodeling
Novel biomarker for heart failure
Research Keywords: ischemic heart diseases, atherosclerosis, heart failure

Technical Keywords: biomarker, imaging, preemptive medicine
National Cerebral and Cardiovascular Center is characterized as 1) abundant patients, 2) highly specialized physician, 3)
modern medical equipment, 4) close collaboration among hospital, research institute and research and development initiative
center and 5) facilitating biobank. In particular, our laboratory focuses on a biomarker study to identify high-risk patients
susceptible to future coronary events and advances preemptive medicine for early intervention.
Figure 1. Preemptive Medicine Targeting Biomarker Figure 2. Translational Research: Bioactive Peptide as a Therapeutic Target
Recent Publications
- Shibata T, Kawakami S, Noguchi T, Tanaka T, Asaumi Y, Kanaya T, Nagai T, NakaoK, Fujino M, Nagatsuka K, Ishibashi-Ueda H, Nishimura K, Miyamoto Y, Kusano K,Anzai T, Goto Y, Ogawa H, Yasuda S.
Prevalence, Clinical Features, and Prognosis of Acute Myocardial Infarction Attributable to Coronary Artery Embolism.Circulation. 2015 Jul 28;132(4):241-50.
- Noguchi T, Tanaka A, Kawasaki T, Goto Y, Morita Y, Asaumi Y, Nakao K, Fujiwara R, Nishimura K, Miyamoto Y, Ishihara M, Ogawa H, Koga N, Narula J, Yasuda S. Effect of Intensive Statin Therapy on
Coronary High-Intensity Plaques Detected by Noncontrast T1-Weighted Imaging: The AQUAMARINE Pilot Study. J Am Coll Cardiol. 2015 Jul 21;66(3):245-56.
- Honda S, Asaumi Y, Yamane T, Nagai T, Miyagi T, Noguchi T, Anzai T, Goto Y, Ishihara M, Nishimura K, Ogawa H, Ishibashi-Ueda H, Yasuda S. Trends in the clinical and pathological characteristics of
cardiac rupture in patients with acute myocardial infarction over 35 years. J Am Heart Assoc. 2014 Oct 20;3(5):e000984.
- Noguchi T, Kawasaki T, Tanaka A, Yasuda S, Goto Y, Ishihara M, Nishimura K, Miyamoto Y, Node K, Koga N. High-intensity signals in coronary plaques on noncontrast T1-weighted magnetic resonance
imaging as a novel determinant of coronary events. J Am Coll Cardiol. 2014 Mar 18;63(10):989-99.
- Kawarada O, Yasuda S, Nishimura K, Sakamoto S, Noguchi M, Takahi Y, Harada K, Ishihara M, Ogawa H. Effect of single tibial artery revascularization on microcirculation in the setting of critical limb
ischemia. Circ Cardiovasc Interv. 2014 Oct;7(5):684-91.
Innovative Cardiovascular Medicine (National Cerebral and Cardiovascular Center) 165

Minimally Invasive Cardiac Surgery for Valvular and Ischemic Heart Disease
Innovative Cardiovascular Medical Sciences Course


URL:
Cardiovascular Center) http://www.ncvc.go.jp/english/hospital/
Contact:
KOBAYASHI, Junjiro TEL +81-6-6833-5012
E-Mail jkobayas@hsp.ncvc.go.jp
Research Theme
Minimally invasive mitral valve repair for mitral regurgitation
Total arterial off-pump coaronary artery revascularization
Robot assisted cardiac surgery
Research Keywords: cardiac surgery, robotic surgery, MICS, valvular heart disease, ischemic heart disease
Technical Keywords: remote operation, small shin incision, beating heart surgery, arterial graft, valve repair
The National Cardiovascular Center (NCVC) was founded in 1977 in order to provide the public with the most advanced
treatment for cardiovascular diseases and to conduct the highest level of basic as well as applied research on the
cardiovascular system and its diseases. During these 30 years, we have developed a number of new ways to treat and care for
patients with cardiovascular problems and have also made considerable contribution towards the progress of cardiovascular
research. NCVC was composed of hospital, research institute, and biotechnology ward dealing with not only heart and
vessels, but also brain.
Our department has aggressively introduced new technology and techniques. Off-pump coronary artery revascularization
was performed in more than 2000 cases. Minimally invasive mitral valve repair and coronary bypass surgery using daVinci
robotic system have been applied. Trancatheter aortic valve implantation has been performed in more than 60 cases.
Simultaneous TAVI and OPCAB program has been also introduced.
Figure 1. Set-up for mitral valve repair with da Vinci robotic system Figure 2. Transcatheter aortic valve implantation in hybrid operation room
Recent Publications
- Nakajima H, et al. A 10-year angiographic follow-up of competitive flow in sequential and composite arterial grafts. Eur J Cardiothorac Surg. 40(2): 399-404, 2011;
- Kobayashi J. Changing srategy for aortic stenosis by transcatheter valve treatment in Japan. Circulation J 77: 309-10, 2013
- Kobayashi J. Changing strategy for aortic stenosis with coronary artery disease by transcatheter aortic valve implantation. Gen Thorac Cardiovasc Surg 61: 663668, 2013
- Fujita H, et al. Off-pump coronary artery bypass grafting for a left main lesion due to cardiac allograft vasculopathy in Japan: first report of a case. Surg Today 44:19491952, 2014
- Fujita T, et al. Initial experience with internal mammary artery harvesting with the da Vinci surgical system fr minimally invasive direct coronary bypass. Surg Today 44:22812286, 2014
166 Innovative Cardiovascular Surgery (National Cerebral and Cardiovascular Center)

Taking Clinical Science to Control Cerebral and Cardiovascular Diseases
Preventive Cardiology and Medical Sciences Course

Epidemiology Master / Doctoral Degree

URL:
Cardiovascular Center)
Contact:
MIYAMOTO, Yoshihiro TEL +81-6-6833-5012
E-Mail miyamoty@ncvc.go.jp
Research Theme
Epidemiology of cardiovascular diseases
Population-based cohort study, disease registry
Big data science
Research Keywords: cardiovascular disease, epidemiology, big data, Suita study

Technical Keywords: cohort, meta-analysis, ICT, registry
We must understand real status of cardiovascular diseases in order to control the diseases. Our laboratory join in so many
research projects, such as population-based cohort studies, development of biomarker, disease registry and bio-resource
application.
Recent Publications
- Nishimura K, Okamura T, Watanabe M, Nakai M, Takegami M, Higashiyama A, Kokubo Y, Okayama A, Miyamoto Y. Predicting coronary heart disease using risk factor categories for a Japanese urban
population, and comparison with the framingham risk score: the suita study. J Atheroscler Thromb. 2014;21(8):784-98.
- Nishimura K, Nakamura F, Takegami M, Fukuhara S, Nakagawara J, Ogasawara K, Ono J, Shiokawa Y, Miyachi S, Nagata I, Toyoda K, Matsuda S, Kataoka H, Miyamoto Y, Kitaoka K, Kada A, Iihara K,
Group JAS. Cross-sectional survey of workload and burnout among Japanese physicians working in stroke care: the nationwide survey of acute stroke care capacity for proper designation of comprehensive
stroke center in Japan (J-ASPECT) study. Circulation Cardiovascular quality and outcomes. 2014;7(3):414-22.
- Yokoyama Y, Nishimura K, Barnard ND, Takegami M, Watanabe M, Sekikawa A, Okamura T, Miyamoto Y. Vegetarian diets and blood pressure: a meta-analysis. JAMA internal medicine. 2014;174(4):577-87.
- Noguchi T, Kawasaki T, Tanaka A, Yasuda S, Goto Y, Ishihara M, Nishimura K, Miyamoto Y, Node K, Koga N. High-intensity signals in coronary plaques on noncontrast T1-weighted magnetic resonance
imaging as a novel determinant of coronary events. J Am Coll Cardiol. 2014;63(10):989-99.
- Kataoka Y, Yasuda S, Miyamoto Y, Sase K, Kosuge M, Kimura K, Yoshimasa Y, Miyazaki S, Investigators DS. Clinical Predictors of Atheroma Progression Despite Optimal Glycemic Control in Early-
Stage Diabetic Patients with Coronary Artery Disease: Insight from the DIANA Study. J Atheroscler Thromb. 2014;21(5):509-18.
Preventive Cardiology and Epidemiology (National Cerebral and Cardiovascular Center) 167
Contribution to the Development of Gastroenterology and Community Medicine
Gastrointestinal and Medical Sciences Course

Community Medicine Doctoral Degree
(Internal Medicine)
URL:
(Iwaki Kyouritsu General Hospital)
Contact:
TAKAHASHI, Seiichi TEL +81-246-26-3151
E-Mail setakahashi-gi@umin.org
Research Theme
Etiological and pathophysiological study of inflammatory bowel disease
Establishment of GI cancer chemotherapy that is appropriate for the elderly
Mechanisms of cancer development in NASH
Research Keywords: IBD, GI cancer, NASH

Technical Keywords: endoscopy, capsule endoscopy, ultrasonography
Based on the trend of gastrointestinal diseases, this course was established for the development of community medicine,
enhancement of resident education and promotion of resional medical science. Therefore, we are focused on four themes: (1)
promotion of multicenter prospective study of gastrointestinal disease, (2) developmnet of novel therapies for inflammatory
bowel disease, (3) establishment of appropriate gastrointestinal disease therapies for the super-elderly, (4) enrichment the
curriculum for resident.
168 Gastrointestinal and Community Medicine (Internal Medicine) (Iwaki Kyouritsu General Hospital)
Let's Learn Infectious Disease Epidemiology and Global Infectious Diseases
Infection and Epidemiology Medical Sciences Course

(National Institute of Infectious Doctoral Degree
Diseases)
URL:
http://www.nih.go.jp/niid/ja/from-idsc.html
Contact:
OISHI, Kazunori TEL +81-3-4582-2786
Professor, M.D. Ph.D. E-Mail oishik@nih.go.jp
Research Theme
Infectious disease epidemiology of emerging and re-emerging diseases
Infectious disease epidemiology of food-borne diseases
Infectious disease epidemiology of vaccine preventable diseases
Research Keywords: infectious disease epidemiology, vaccination, public health

Technical Keywords: field epidemiology training program-japan (FETP-J), national epidemiological surveillance
of infectious diseases (NESID), international health regulations (IHR)
National Institute of Infectious Diseases (NIID) plays an essential role for surveillance and protection of domestic and
global infectious diseases cooperating with overseas organizations. Infectious Disease Surveillance Center (IDSC) makes
technical advices for several infectious disease control policy issues and epidemiological investigation in cluster / outbreak
/ abnormality accumulation of infectious diseases domestically and internationally, and monitor and control vaccine
preventable diseases including immunization. Further, we collect and analyze information about infectious diseases aimed
at feedback/dissemination of that information for infectious disease control and prevention. Trainees of Field Epidemiology
Training Program-Japan (FETP-J) can also participate graduate school courses.
We have recently achieved outbreak investigations regarding measles, rubella, domestic dengue fever, and epidemiological
studies of Enterohemorrhagic E. coli (EHEC), invasive pneumococcal disease, amebiasis, syphilis, severe fever with
thrombocytopenia syndrome (SFTS), and hepatitis E, as well as immunological studies on pneumococcal vaccine and its
development.
Infection and Epidemiology (National Institute of Infectious Diseases) 169

Ward for Pulmonary Tuberculosis
Manegement of Infectious Medical Sciences Course

Diseases Doctoral Degree
(Miyagi Cardiovascular &

URL:
Respiratory Center)
Contact:
HIRAKATA, Yoichi TEL +81-22-717-8010
E-Mail hiraichi@med.tohoku.ac.jp
Research Theme
Diagnosis and treatment of pulmonary tuberculosis
Research Keywords: pulmonary tuberculosis, respiratory infection, anti-tuberculosis drug

Technical Keywords: smear, liquid media, PCR
Miyagi Cardiovascular & Respiratory Center has a special ward for pulmonary tuberculosis. Research on diagnosis and
treatment of pulmonary tuberculosis can be done.
170 Manegement of Infectious Diseases (Miyagi Cardiovascular & Respiratory Center)

Shall We Work on Prevention of the Lifestyle Disease and State-of-the-Art Cancer
Therapy?
Preemptive Medicine in Medical Sciences Course

the Community of the North Doctoral Degree
Miyagi
URL:
(Osaki Citizen Hospital) http://www.h-osaki.jp/
Contact:
NAMIKI, Kenji TEL +81-229-23-3311
E-Mail kensyu-och@h-osaki.jp
Professor, M.D.
Research Theme
To find effective and safe methods in cancer therapy
To find risk factors related to secondary prevention of cerebrovascular disease
Research Keywords: preemptive medicine, community health, lifestyle related disease, cancer therapy
Technical Keywords: clinical statistics, survival curve, regression analysis, case-control study
This is a collaborative course between Osaki citizen hospital (OCH) and Tohoku University School of Medicine. Visiting
professors in OCH and professors in Tohoku University direct students cooperatively. You can see a lot of common diseases
and do clinical research and practice because OCH is a core hospital in northern Miyagi area. For example, there are 4200
ambulance, 4498 general anesthesia, 192 lung cancer , 75 acute myocardial infarction, 65 subarachnoid hemorrhage, and
120 bladder cancer cases in 2014. Basic research can be also done using facilities of Tohoku University since OCH is
located near the University ; it is only 40km (13 minutes by Shinkansen) from Sendai. If you want to learn in the fields that
there are no visiting professor in OCH, we can arrange corresponding professor in Tohoku University. This course is best fit
for doctors who are interested in both residency training and academic medicine.
Figure 1. New hospital building opened in July 2014 Figure 2. Study room in medical office
Preemptive Medicine in the Community of the North Miyagi (Osaki Citizen Hospital) 171
To Establish the Methods of Preventing Various Allergic Diseases Initiated by Atopic
Dermatitis during Infancy.
Advanced Pediatric Medicine URL:

http://www.ncchd.go.jp/en/scholar/research/
section/allergy.html
SAITO, Hirohisa Contact:

TEL +81-3-5494-7027
Professor, M.D. Ph.D. E-Mail saito-hr@ncchd.go.jp
Research Theme
Prevention of Atopic Dermatitis
Prevention of Food Allergy
Allergic Inflammatory Diseases and Innate Immunity
Research Keywords: IL-33, Atopic Dermatitis, Allergy, IgE, Mast cells

Technical Keywords: Microarray, Randomized Controlled Trial, Food Allergen Lymphocyte Stimulation Test
Most of allergic diseases develop during infancy, and they are hardly cured after adulthood. Therefore, to prevent the
development of allergic diseases during infancy is an important strategy to resolve the medical issues of people in the next
generation, especially when medical economy is considered. We have an advantage on this research field by reporting the
study results that the use of emollients for neonates prevented the development of atopic dermatitis (Horimukai K, et al. J
Allergy Clin Immunol 2014). Also, we have lead the world over the study regarding the role of IL-33 on innate inflammation
involved in allergic diseases such as severe asthma (Oboki K, et al. Proc Natl Acad Sci USA 2010, Morita H, et al. Immunity
2015).
Figure 1. Atopic Dermatitis triggers Development of Atopic March Figure 2. Emollient is effective for preventing the development of atopic dermatitis
Recent Publications
- Morita H, et al. An Interleukin-33-Mast Cell-Interleukin-2 Axis Suppresses Papain-Induced Allergic Inflammation by Promoting Regulatory T Cell Numbers. Immunity. 2015;43(1):175-186.
- Endo Y, et al. The interleukin-33-p38 kinase axis confers memory T helper 2 cell pathogenicity in the airway. Immunity. 2015 Feb 17;42(2):294-308.
- Vasanthakumar A, et al. The transcriptional regulators IRF4, BATF and IL-33 orchestrate development and maintenance of adipose tissue-resident regulatory T cells. Nat Immunol. 2015;16(3):276-285.
- Horimukai K, et al. Application of moisturizer to neonates prevents development of atopic dermatitis. J Allergy Clin Immunol. 2014;134(4):824-830.
- Oboki K, et al. IL-33 is a crucial amplifier of innate rather than acquired immunity. Proc Natl Acad Sci U S A. 2010;107(43):18581-18586.
172 Advanced Pediatric Medicine

The Research and Development of Diagnosis, Treatment, and Prevention of Emerging and
Re-emerging Infectious Diseases through medical practice and Epidemiological Study
Emerging and Reemerging URL:

http://dcc-ncgm.jp/
Infectious Diseases
Contact:
TEL +81-3-3202-7181
E-Mail nohmagari@hosp.ncgm.go.jp
OHMAGARI, Norio
Professor, M.D., M.Sc., Ph.D.
Research Theme
Management of emerging and re-emerging infectious diseases
Preparedness for emerging and re-emerging infectious diseases
Healthcare-associated infections and antimicrobial resistance
Research Keywords: Emerging and re-emerging infectious diseases, Risk Management,

Antimicrobial resistance, Healthcare associated infections
Technical Keywords: Genome sequencing, Microbiological diagnosis utilizing multiplex PCR, Healthcare
Epidemiology
Field of infectious disease has spread from individual patient's health problems to the global level. Subjects are extremely diverse, ranging
from diagnosis and treatment of individual patients, to prevention and public health measures. To function as a clinical referral center for
infectious diseases in Japan, Disease Control and Prevention Center at the National Center for Global Health and Medicine put emphasis
on 1) clinical management, 2) focus on human resource development / training of infectious diseases area, 3) networking, 4) research
centers at home and abroad of infection, 5)healthcare epidemiology, and carried out a comprehensive and multi-faceted, innovative
initiatives related to domestic and international infectious diseases.
The main research themes are 1)diagnosis using the genomic approach emerging re-emerging infectious diseases, 2)treatment and
prevention of emerging re-emerging infectious diseases, 3) preparedness for emerging infectious diseases at healthcare facilities, 4)
psychosocial factors and method of risk communication, 5) antibiotic-resistant bacteria infection, 6) imported infectious diseases such as
malaria, dengue fever, typhoid fever.
Figure 1. Giemsa stained image of Plasmodium falciparum Figure 2. Training session for emerging infectious diseases
Recent Publications
- Binh NG, Hayakawa K, Co DX, Tuan ND, Anh NH, Thuy NT, Phuong DM, Huong NT, Thuy PT, Chau NQ, Nhung PH, Gam do TH, Hai DT, Huong TT, Van Anh L, Takeshita N, Ohmagari N. The efficacy
and nephrotoxicity associated with colistin use in an intensive care unit in Vietnam: Use of colistin in a population of lower body weight. Int J Infect Dis. 2015 Jun;35:18-23. doi: 10.1016/j.ijid.2015.03.020.
Epub 2015 Mar 30. PubMed PMID: 25835100.
- Sherchan JB, Hayakawa K, Miyoshi-Akiyama T, Ohmagari N, Kirikae T, Nagamatsu M, Tojo M, Ohara H, Sherchand JB, Tandukar S. Clinical epidemiology and molecular analysis of extended-spectrum--
lactamase-producing Escherichia coli in Nepal: characteristics of sequence types 131 and 648. Antimicrob Agents Chemother. 2015;59(6):3424-32. doi: 10.1128/AAC.00270-15. Epub 2015 Mar 30. PubMed
PMID: 25824221; PubMed Central PMCID: PMC4432170.
- Kutsuna S, Kato Y, Moi ML, Kotaki A, Ota M, Shinohara K, Kobayashi T, Yamamoto K, Fujiya Y, Mawatari M, Sato T, Kunimatsu J, Takeshita N, Hayakawa K, Kanagawa S, Takasaki T, Ohmagari N.
Autochthonous dengue fever, Tokyo, Japan, 2014. Emerg Infect Dis. 2015 Mar;21(3):517-20. doi: 10.3201/eid2103/141662. PubMed PMID: 25695200; PubMed Central PMCID: PMC4344289.
- Hayakawa K, Miyoshi-Akiyama T, Kirikae T, Nagamatsu M, Shimada K, Mezaki K, Sugiki Y, Kuroda E, Kubota S, Takeshita N, Kutsuna S, Tojo M, Ohmagari N. Molecular and epidemiological
characterization of IMP-type metallo--lactamase-producing Enterobacter cloacae in a Large tertiary care hospital in Japan. Antimicrob Agents Chemother. 2014 Jun;58(6):3441-50. doi: 10.1128/AAC.02652-
13. Epub 2014 Apr 7. PubMed PMID: 24709261; PubMed Central PMCID: PMC4068452.
- Kutsuna S, Hayakawa K, Kato Y, Fujiya Y, Mawatari M, Takeshita N, Kanagawa S, Ohmagari N. The usefulness of serum C-reactive protein and total bilirubin levels for distinguishing between dengue
fever and malaria in returned travelers. Am J Trop Med Hyg. 2014 Mar;90(3):444-8. doi: 10.4269/ajtmh.13-0536. Epub 2014 Jan 13. PubMed PMID: 24420780; PubMed Central PMCID: PMC3945689.
Innovative Cardiovascular Medicine 173

Development of Innovative Cardiovascular Medicine
Innovative Cardiovascular URL:

http://www.cardio.med.tohoku.ac.jp/english/
Medicine index.html
Contact:
TEL +81-22-717-7153
E-Mail cswt@cardio.med.tohoku.ac.jp
SHIMOKAWA, Hiroaki
Research Theme
Development of non-invasive therapy using shock wave and ultrasound
Development of new biomarkers
Research Keywords: innovative medical devices, non-invasive therapy, regenerative medicine,

sound (shock wave and ultrasound), biomarkers
Technical Keywords: shock wave, ultrasound, non-invasiveness, catheter ablation, biomarkers
Our department focuses on the development of innovative diagnostic tools and therapeutic devices for cardiovascular
diseases. New technology of biomedical engineering enables us to develop non-invasive therapeutics that is advantageous
for elderly patients. One of our main themes is the development of therapeutic devices using acoustic waves such as shock
wave and ultrasound. We have developed the extracorporeal low-energy shock wave therapy for angina pectoris, which
has been approved as a highly-advanced medical treatment by the Japanese Ministry of Health, Labour and Welfare. We
are also conducting the clinical trial of an ultrasound-induced angiogenic therapy in patients with angina. Furthermore, we
are developing shock wave catheter ablation system for fatal tachyarrhythmias and new biomarkers for early detection of
cardiovascular diseases and assessment of medications.
The goal of our department is to promote cardiovascular medicine by developing new innovative diagnostic tools and
therapeutics for cardiovascular diseases.
Figure 1. Low-energy shock wave therapy for angina pectoris. Figure 2. Shock wave catheter ablation system.
Recent Publications
- Ito K, Shimokawa H. The Future of Non-Invasive Angiogenic Therapy Using Acoustic Waves. Circ J. 79(9):1906-7, 2015.
- Hasebe Y, et al. Development of a novel shock wave catheter ablation system--the first feasibility study in pigs. PLoS One.10(1):e0116017, 2015.
- Hanawa K, et al. Low-intensity pulsed ultrasound induces angiogenesis and ameliorates left ventricular dysfunction in a porcine model of chronic myocardial ischemia. PLoS One. 9(8):e104863, 2014
- Yamaya S, et al. Low-energy extracorporeal shock wave therapy promotes vascular endothelial growth factor expression and improves locomotor recovery after spinal cord injury. J Neurosurg.121(6):1514-25,
2014
- Abe Y, et al. Extracorporeal low-energy shock-wave therapy exerts anti-inflammatory effects in a rat model of acute myocardial infarction. Circ J. 78(12):2915-25, 2014.
174 Innovative Cardiovascular Medicine

To Produce Clinical Evidence in Cardiovascular Medicine in Japan
Evidence-based URL:
http://www.med.tohoku.ac.jp/org/contribute/105/
Cardiovascular Medicine Contact:
TEL +81-22-717-7153
SHIMOKAWA, Hiroaki
Research Theme
Japanese evidence of chronic heart failure
Mechanisms in development of de-novo heart failure in stage B patients
Additive therapies for heart failure to evidence-based medications
Research Keywords: observational study, clinical trial, chronic heart failure, lifestyle disease,
evidence-based medicine
Technical Keywords: data collection/management, follow-up study, statistical analysis
Our research interests are (1) Japanese evidence in characteristics, managements and outcomes of chronic heart failure
(HF), (2) mechanisms and predictors for the development of de-novo HF from asymptomatic subjects with structural and/or
functional heart disease, and (3) novel therapies for the HF patients who are already treated with evidence-based medications.
To address these issues, we have been conducting observational cohort studies and randomized clinical trials, such as the
Chronic Heart Failure Analysis and Registry in the Tohoku District 2 (CHART-2) Study and the Supplemental Benefit of an
Angiotensin Receptor Blocker in Hypertensive Patients with Stable Heart Failure Using Olmesartan (SUPPORT) Trial. In
particular, the CHART-2 Study is one of the largest prospective observational multicenter cohort study for HF in the world
(N=10,219), and have unique characteristics such as enrollment of (1) asymptomatic subjects without a history of HF but at
high risk for de-novo HF (so-called Stage B patients), and (2) patients with HF and preserved left ventricular ejection fraction
(HFpEF). Since the number of patients with HF, particularly that of HFpEF patients, has been increasing worldwide, the
biggest emerging healthcare concerns are now establishment of effective management of HFpEF and prevention of de-novo
HF by elucidating mechanisms of transition from Stage B to symptomatic HF, both of which are our study goals.
Figure 1. The profile of the CHART-2 Study Figure 2. Trends of heart failure etiology and prognosis in Japan
Recent Publications
- Sakata Y, Shimokawa H et al.; on behalf of the SUPPORT Trial Investigators. Clinical impacts of additive use of olmesartan in hypertensive patients with chronic heart failure: the supplemental benefit of an
angiotensin receptor blocker in hypertensive patients with stable heart failure using olmesartan (SUPPORT) trial. Eur Heart J. 2015;36(15):915-23.
- Shimokawa H, et al. Heart failure as a general pandemic in Asia. Eur J Heart Fail. 2015 Sep;17(9):884-92. (Review)
- Ushigome R, Shimokawa H et al.; CHART-2 Investigators. Temporal trends in clinical characteristics, management and prognosis of patients with symptomatic heart failure in Japan - Report from the
CHART Studies. Circ J. 2015;79(11):2396-407.
- Takada T, Shimokawa H et al. Impact of elevated heart rate on clinical outcomes in patients with heart failure with reduced and preserved ejection fraction -A report from the CHART-2 Study-. Eur J Heart
Fail. 2014;16(3):309-16.
- Sakata Y, Shimokawa H. Epidemiology of heart failure in Asia. Circ J. 2013;77(9): 2209-17. (Review)
Evidence-based Cardiovascular Medicine 175

Discovery of Treatment to Prevent Virus Infection-Induced Obstructive Respiratory Disease
Exacerbation and Senile Pneumonia, and Pulmonary Regenerative Therapy
Advanced Preventive Medicine URL:

http://www.apmid.med.tohoku.ac.jp
for Infectious Disease Contact:
TEL +81-22-717-7184
E-Mail apmid@med.tohoku.ac.jp
YAMAYA, Mutsuo
Research Theme
To study the pathogenesis of common cold syndrome induced by respiratory viruses, including pandemic influenza
Development of methods to prevent and treat virus infection-induced exacerbation of chronic obstructive
pulmonary disease and bronchial asthma
Discovering mechanisms for lung repair, and analyzing human lung cells from diseased lungs
Research Keywords: common cold syndrome, respiratory virus infection, chronic obstructive pulmonary
disease, bronchial asthma, lung repair and regeneration
Technical Keywords: airway epithelial cell culture, respiratory virus, oral care, isolating individual cellular
components from adult human lungs, stem cell biology
Common cold syndrome affects social and economic activities and activities in young adults as a result of reducing mental
and movement functions. Common cold syndrome also induces the development of bacterial pneumonia and exacerbation of
chronic obstructive pulmonary disease and bronchial asthma in older adults, which is associated with death and respiratory
failure. Common cold syndrome reduces activity of daily living and quality of life in older adults. Because various species of
viruses cause common cold syndrome, the methods to treat and prevent the syndrome have not been developed. Improvement
of dysphagia and immunocompromised condition is required to prevent pneumonia in older adults. In our department, we
are doing projects to develop the methods 1) to prevent and treat virus infection-induced exacerbation of chronic obstructive
pulmonary disease and bronchial asthma developed in older adults, and 2) to prevent and treat aspiration pneumonia in older
adults. Development of regenerative approaches and cell-based therapies for intractable pulmonary diseases are also ongoing.
Other subjects of our lab are establishing clinical biomarkers and drug screening for lung diseases, including lung cancer.
Figure 1. Reduction of influenza virus receptors on the human tracheal epithelium Figure 2. Cell-based therapy for COPD
Recent Publications
- Yamaya M. et alThe serine protease inhibitor camostat inhibits influenza virus replication and cytokine production in primary cultures of human tracheal epithelial cells. Pulm Pharmacol Ther 33:66-74,2015.
- Yamaya M, et al. Formoterol and budesonide inhibit rhinovirus infection and cytokine production in primary cultures of human tracheal epithelial cells. Respir Invest 52: 251-260, 2014.
- Fujino N, et al. Increased severity of H1N1 pandemic influenza virus infection in alveolar type II cells from patients with pulmonary fibrosis. J Infect Dis 207: 692-693, 2013.
- Yamaya M. Virus Infection-Induced Bronchial Asthma Exacerbation. Pulmonary Medicine Article ID 834826, 2012.
- Takahashi T, et al. Increased circulating endothelial microparticles in COPD patients: a potential biomarker for COPD exacerbation susceptibility. Thorax 67:1067-1074, 2012.
- Kubo H. Clinical prospects for treating COPD with regenerative approaches. Stem Cells Trans Med 1:627-631, 2012.
176 Advanced Preventive Medicine for Infectious Disease

Creation of Imaging with High Accuracy to Clarify the Disease Mechanisms and Develop
Diagnostic Methods
Nano-Medical Science URL:

http://www.nano.med.tohoku.ac.jp/
Contact:
TEL +81-22-717-7579
OHUCHI, Noriaki E-Mail nano@med.tohoku.ac.jp
Research Theme
To investigate detailed mechanism of cancer growing and metastasis
To establish novel diagnostic technique of cancer tissue
To clarify precise mechanism of vascular remodeling in arteriosclerotic disease
Research Keywords: cancer, metastasis, arteriosclerotic disease, vascular remodeling

Technical Keywords: in vivo molecular imaging with high accuracy, image analysis, synthesis of fluorescence
nanoparticle with high luminance
In vivo imaging of the function of proteins related to cancer and/or arteriosclerosis is important especially for elucidation of these disease
mechanisms. However it had been difficult to analyze the molecular behavior and distribution with high accuracy, due to heartbeat and
respiration. Our laboratory try to overcome this problem and developed novel imaging system with 9 nm spatial accuracy. Then, we
found that the tumor cells showed increases in membrane fluidity (over 1000-fold) (J. Biol. Chem. 2010) and the three-fold difference in
VEGF-R distribution on the vascular wall is important for the formation of branched vasculature (Blood, 2011). Moreover, we have been
developing the technique to diagnose efficacy of anticancer drugs with high certainty by imaging of surgical specimens (Biochem Biophys
Res Commun, 2012, Scientific Reports, 2015).
A portion of the work, to investigate molecular mechanism of cancer and developing diagnostic technique, is supported by a Grant in-Aid
for A3 foresight program Nanoscale imaging and tracing of key molecular events in cancer biology using nanobiomaterials from Japan
Society for the Promotion of Science (JSPS). Through seminar and collaboration experiment, we try hard to establish international and
transdisciplinary research center and encourage young scientists.
We conduct the the Japan Strategic Anti-Cancer Randomized Trial (J-START), and the result was published in The Lancet in 2015.
It was the world first large scale randomized controlled trial to investigate the efficacy of adjunctive ultrasonography in breast cancer
screening.
Figure 1. Pattern diagram of original imaging system with high resolution Figure 2. Nano-medicine research to integrate medical science, material and optical
engineering
Recent Publications
- Hamada Y, et al. In vivo imaging of the molecular distribution of the VEGF receptor during angiogenesis in a mouse model of ischemia. Blood 118: 118(13):e93-e100, 2011
- Gonda K, et al. Development of a quantitative diagnostic method of estrogen receptor expression levels by immunohistochemistry using organic fluorescent material-assembled nanoparticles. Biochem.
Biophys. Res. Commun. 426(3):409-414, 2012
- Sakurai Y, et al. Development of silica-coated silver iodide nanoparticles and their biodistribution. Tohoku J. Exp. Med. 228(4): 317-323, 2012
- Gonda K, et al. Predictive diagnosis of the risk of breast cancer recurrence after surgery by single-particle quantum dot imaging. Scientific Reports5, Articlenumber:14322, 2015
- Ohuchi N, Sensitivity and specificity of mammography and adjunctive ultrasonography to screen for breast cancer in the Japan Strategic Anti-cancer Randomized Trial (J-START): a randomised controlled
trial. The Lancet. pii: S0140-6736(15)00774-6, doi: 10.1016/S0140-6736(15)00774-6, 2015
Nano-Medical Science 177

Development and Clinical Application of Neuroprotective Therapy for Intractable Retinal
Neurodegenerative Disease
Advanced Ophthalmic URL:

http://www.oph.med.tohoku.ac.jp/
Medicine Contact:
TEL +81-22-717-7294
E-Mail nishiguchi@oph.med.tohoku.ac.jp
NAKAZAWA, Toru
Research Theme
Development of a new platform for sensitive detection of glaucoma progression through clinical evaluation and
genetic analysis
A clinical trial to test the neuroprotective effect of Brinzolamide on glaucoma
Development of an in vivo imaging method that allows determination of the efficacy of neuroprotective agents
Development of gene therapies for retinal disorders
Research Keywords: glaucoma, neuroprotection, drug development, gene therapy, retinitis pigmentosa
Technical Keywords: genetic analysis, molecular biology, animal experiment, cell culture, AAV virus
With our focus on application of advanced technology related to drug delivery system, gene therapy, or stem cell medicine,
we aim to develop novel therapy for intractable retinal neurodegenerative diseases including glaucoma, retinitis pigmentosa,
and age-related macular degeneration.
Recent Publications
- Yukita M, et al. Molecular, anatomical and functional changes in the retinal ganglion cells after optic nerve crush in mice. Doc Opthalmologica 2015 in press
- Yasuda M, et al. Retinal transcriptome profiling at transcription start sites: a cap analysis of gene expression early after axonal injury. BMC Genomics. 15:982, 2014
- Omodaka K, et al.. Neuroprotective effect against axonal damage-induced retinal ganglion cell death in apolipoprotein E-deficient mice through the suppression of kainate receptor signaling. Brain Res.
1586:203-212, 2014
- Yokoyama Y, et al.. The role of calpain in an in vivo model of oxidative stress-induced retinal ganglion cell damage. Biochem Biophys Res Commun. 451(4):510-515, 2014
- Tanaka Y, et al. Profiles of extracellular miRNAs in the aqueous humor of glaucoma patients assessed with a microarray system. Sci Rep. 4:5089, 2014
178 Advanced Ophthalmic Medicine

Clinical Research of Diagnosis and Therapy for Aortic and Heart Diseas
Research Division of Sciences URL:

http://www.cts.med.tohoku.ac.jp/chair.html
for Aortic Disease Contact:
TEL +81-22-717-7222
SAIKI, Yoshikatsu
Professor, Ph.D.
Research Theme
Clinical research for aortic disease
Clinical research for heart disease
Finite element analysis of thoracic aortic aneurysm
Research Keywords: clinical research, aortic disease, heart disease, prediction of aortic rupture
Technical Keywords: clinical research, aortic disease, heart disease, finite element analysis
Research division of sciences for aortic disease was established to develop new diagnostic tools and therapy for heart
and aortic disease. Several clinical researches are ongoing supported by clinical coordinators, for example, preventive
effect of landiolol on postoperative atrial fiblliration (PELTA study), Stanford type B dissection patients with pitavastatin
treatment trial (STANP trial), Effect of pitavastatin on durability of bovine pericardial valve after replacement of heart valve
(ENDURANCE), and so on. Prevention for rupture risk of thoracic aortic aneurysm was another subject. Finite element
analysis was a useful tool for calculating the stress of aortic aneurysm.
Figure 1. Finite element analysis of ruptured thoracic aortic aneurysm
Research Division of Sciences for Aortic Disease 179

To Elucidate Pathogenesis and Develop a Novel Treatment of Frozen Shoulder
Upper Extremity URL:

http://www.upper-extremity.med.tohoku.ac.jp/
Musculoskeletal Medicine index.html
Contact:
TEL +81-22-717-7245
E-Mail itoi-eiji@med.tohoku.ac.jp
ITOI, Eiji
Research Theme
Pathogenesis of frozen shoulder
Epidemiological study for musculoskeletal system
Epidemiological study for survivors of the Great East Japan Earthquake
Research Keywords: frozen shoulder, medical check-up for musculoskeletal disease, medical check-up for
survivors of the Great East Japan Earthquake, lumbar spinal canal stenosis
Technical Keywords: scanning acoustic microscope, photoacoustic imaging system, DNA microarray analysis
Our department cover wide area of investigation from basic to clinical research. One of our main focuses are as follows;
1.Epidemiological study of musculoskeletal disease, 2. Pathogenesis of frozen shoulder and development of novel therapies
for frozen shoulder.
Frozen shoulder is a very common disease, but its cause is still unknown. Inflammation and fibrosis of the joint capsule
has been considered as one of the main pathology. However, our recent study reveal that chondrogenesis is also the main
factors. Further, chondrogeneis is also revealed in thickened ligamentum fluvum from lumbar canal stenosis
Figure 1. Medical check-up for survivors of the Great East Japan Earthquake Figure 2. Cadaver training in Hawaii
Recent Publications
- Yabe Y et al. Chondrogenic and fibrotic process in the ligamentum flavum of patients with lumbar spinal canal stenosis. Spine. in press, 2015
- Hagiwara Y et al. Simultaneous Evaluation of Articular Cartilage and Subchondral Bone from Immobilized Knee in Rats by Photoacoustic Imaging System. J Orthop Sci. in press, 2015
- Hagiwara Y et al. Effects of Intra-Articular Steroid Injection before Pan-Capsular Release in Patients with Refractory Frozen Shoulder. Knee Surg Sports Traumatol Arthrosc. in press, 2015
- Hagiwara Y et al. Blood Flow Changes of the Anterior Humeral Circumflex Artery Decreases with the Scapula in Internal Rotation Knee Surg Sports Traumatol Arthrosc. in press, 2015
- Onoda Y et al. Joint Hemorrhage Partly Accelerated Immobilization Induced Synovial Adhesions and Capsular Shortening in Rats Knee. Knee Surg Sports Traumatol Arthrosc. Nov;22(11):2874-83, 2014.
180 Upper Extremity Musculoskeletal Medicine

To Contribute to the Progress of Advanced Medicine for Difficult-to-treat Eye Diseases,
with a Focus on Retinal Degeneration
Retinal Disease Control, URL:

Ophthalmology contribute/192/index.html
Contact:
TEL +81-22-717-7294
E-Mail kunikata@oph.med.tohoku.ac.jp
NAKAZAWA, Toru
Research Theme
Development of new evaluation systems for retinal function and pharmaceutical effectiveness
Neuroprotective therapies and new retinal drug therapies
Comprehensive analyses of clinical samples and inventions of new surgical instruments
Research Keywords: retina, vitrectomy, neuro-protection, retinal function, pharmaceutical effectiveness

Technical Keywords: evaluation systems for retinal function and pharmaceutical effectiveness, neuroprotective therapies, new
retinal drug therapies, comprehensive analyses of clinical samples, vitreoretinal surgical instruments
The purpose of our division is to contribute to the progress of advanced medicine for difficult-to-treat eye diseases, with a
focus on retinal degeneration.
Specifically, we have four main goals. First, to contribute to the development of new evaluation systems for retinal function
and pharmaceutical effectiveness. Second, to assess neuroprotective therapies for photoreceptor cells and search for new
retinal drug therapies with fewer adverse effects. Third, to perform comprehensive analyses of clinical samples, looking
for correlations between the data and clinical visual function. Fourth, to invent new surgical instruments that allow us to
improve the results of ocular surgery, particularly vitreoretinal surgery.
Our purpose, above all, is to find the mechanism of degeneration of photoreceptor cells and retinal ganglion cells and
establish a diagnostic method for the early detection of retinal degeneration. We hope this will let us bring about a
considerable visual improvement for patients worldwide.
Figure 1. Academic field of our division
Recent Publications
- Kunikata H, et al. Relationship of Ocular Microcirculation, measured by Laser Speckle Flowgraphy, and Silent Brain Infarction in Primary Aldosteronis. PloS One. In press.
- Aizawa N, et al. Laser speckle and hydrogen gas clearance measurements of optic nerve circulation in albino and pigmented rabbits with or without optic disc atrophy. Invest Ophthalmol Vis Sci.
55(12):7991-7996, 2014.
- Kunikata H, et al. Experimental application of piezo actuator-driven pulsed water jet in retinal vascular surgery. Transl Vis Sci Technol. In press.
- Tsuda S, et al. Pulse-waveform Analysis of Normal Population using Laser Speckle Flowgraphy. Curr Eye Res. 39(12):1207-1215, 2014.
- Kunikata H, et al. Chemokines in Aqueous Humour before and after Intravitreal Triamcinolone Acetonide in Eyes with Rhegmatogenous Retinal Detachment. Am J Ophthalmol. 155(6):1028-1037, 2013.
Retinal Disease Control, Ophthalmology 181

Construction of Medical Care System Suitable for Lifestyle of Renal Failure Patients
Integrative Renal URL:

http://www.int2.med.tohoku.ac.jp/index-en.html
Replacement Therapy Contact:
TEL +81-22-717-7163
E-Mail ohsaki@med.tohoku.ac.jp
ITO, Sadayoshi
Research Theme
Construction of medical care system suitable for lifestyle of renal failure patients
Development of novel therapeutic strategy for maintaining / increasing peritoneal dialysis efficiency
Physiological analysis of renal function and investigation of mechanism of renoprotective effect
Research Keywords: renal replacement therapy, peritoneal dialysis, renal failure, home care, renal function
Technical Keywords: animal experiment, (primary) cell culture, clinical specimens, histological assessment
End stage renal failure patients require renal replacement therapy, such as hemodialysis, peritoneal dialysis and kidney
transplantation. It is desirable that patient can choose therapy along with their lifestyle and preference. Currently more than
95% of renal replacement therapy patients select in-center hemodialysis. However, it has been shown that residual renal
function could lose within few years in in-center hemodialysis patients. Although the mechanism is not fully investigated,
peritoneal dialysis and home dialysis could maintain residual renal function. Since, self-management based home medicine
is now required in Japan, peritoneal dialysis and home hemodialysis can be focused.
To provide better renal replacement therapy, purpose of this department is;
1) To determine the mechanism of residual renal function using animal model.
2) To build homecare network system between medical doctor, nurse, dietitian and other healthcare stuffs.
3) To extend the limitation of peritoneal dialysis vintage, we are investigating the mechanism of peritoneal injury.
Recent Publications
- Mori T, et. al., Beneficial Role of Tolvaptan in the Control of Body Fluids Without Reductions in Residual Renal Function in Patients Undergoing Peritoneal Dialysis. Advances in Peritoneal Dialysis.
Volume 29 (2013), 33-37
- Oba I, et. al., Icodextrin-Based Continuous Ambulatory Peritoneal Dialysis Therapy Effectively Reduces Left Ventricular Mass Index and Protects Cardiac Function in Patients with End-Stage Renal
Disease. Advances in Peritoneal Dialysis. Volume 29 (2013), 14-18
182 Integrative Renal Replacement Therapy

Challenge to the Evolution such as Drug-Resistant Acquisition in Various Pathogens
Research Division for URL:

http://www.idac.tohoku.ac.jp/en/activities/
Development of Anti-Infectve research/Anti-Infe/index.html
Agents Contact:
TEL +81-22-717-8540
WATANABE, Akira
Research Theme
Leading-edge drug discovery and development in medical and pharmaceutical sciences and development of
human resources
Establishment of appropriate usage of antibiotics based on the drug characteristics, and promotion of clinical
researches
Epidemiological measures for the prevention of chronic infections such as tuberculosis and promotion of the
prospective treatment and prevention
Research Keywords: antimicrobial resistance, MRSA, Pseudomonas aeruginosa, anti-influenza agent,

pneumococcal vaccine
Technical Keywords: probiotics, PK-PD, anti-biofilm drug, plasma irradiation
This research department places the primary focus more on the appropriate implementation of clinical studies than on preclinical studies
among the various stages of anti-infective drug development, attaching weight especially to secure clinical development in a short period.
Our purpose is to actively and voluntarily undertake the development of not only antibiotics and antibiotics, anti-influenza agents, and
various vaccines. We experienced the advent of emerging infections such as AIDS and the resurgence of reemerging infections such as
intractable tuberculosis caused by multidrug-resistant organism in the 1980s and spread of MRSA and multidrug-resistant Pseudomonas
aeruginosa (MDRP) in the 1990s. In the 2000s, the increase in fatalities from AIDS and the emergence of drug-resistant bacteria such as
community associated MRSA (CA-MRSA) and extremely drug-resistant strain of Mycobacterium tuberculosis (XDR-TB) have attracted
social attention. As for infections and resistant bacteria, it is necessary not only to stop the spread from the outbreak location but also to
control the outbreak itself. We place more emphasis on the prevention of the outbreak itself than on the containment of the infections and
resistant bacteria, and aim to foster human resources involved in the development of drugs for treatment and prevention of infections.
Figure 1. Time to illness alleviation in patients included in the full analysis set Figure 2. Bactericidal effect of each multi purpose solution against biofilm-formed
P.aeruginosa on the contact lens (240min)
Recent Publications
- Professor Akira Watanabe, He was awarded Health Culture Prize 2013 ( 65th Hoken-Bunka-Sho ) in October 23, 2013, and was granted the meeting with Emperor and Empress of Japan in October 24, 2013.
- Kashiwagi S, Watanabe A, Ikematsu H, Awamura S, Okamoto T, Uemori M and Ishida K. Laninamivir octanoate for post-exposure prophylaxis of influenza in household contacts: a randomized double blind
placebo controlled trial. J Infect Chemother 19:740-749,2013.
- Kikuchi T, Kobashi Y, Hirano T, Tode N, Santoso A, Tamada T, Fujimura S, Mitsuhashi Y, Honda Y, Nukiwa T, Kaku M, Watanabe A and Ichinose M. Mycobacterium avium genotype is associated with the
therapeutic response to lung infection. Clin Microbiol Infect. 20: 256-62, 2014.
- Naito T, Matsuda N, Tanei M, Watanabe Y and Watanabe A. Relationship between public subsidies and vaccination rates with the 23-valent pneumococcal vaccine in elderly persons, including the influence of
the free vaccination campaign after the great East Japan earthquake. J Infect Chemothr 20:450-453, 2014.
- Watanabe A, Yates PJ, Murayama M, Soutome T and Furukawa H. Evaluation of safety and efficacy of intravenous zanamivir in the treatment of hospitalized Japanese patients with influenza: an open-label,
single arm study. Antiviral Ther 2014, DOI:10.3851/IMP2922
Research Division for Development of Anti-Infectve Agents 183

Revealing Neural Mechanisms behind Development of Mind and Brain as well as
Developmental Disorders through Brain Imaging
Developmental Cognitive URL:

https://www.fbi.idac.tohoku.ac.jp/dcn/index.html
Neuroscience Contact:
TEL +81-22-717-7988
E-Mail ryuta@idac.tohoku.ac.jp
KAWASHIMA, Ryuta
Research Theme
Exploring the neural mechanisms behind healthy development, and developmental diorders such as autism, and
dyslexia
Revealing the neural mechanisms of higher cognitive functions in those children
Revealing the effects of daily habits and genetic polymorphisms on cognitive functions and brain mechanisms in
those children
Research Keywords: brain imaging, development, developmental disorder, daily habit, genetic polymorphism
Technical Keywords: magnetic resonance imaging (MRI) , psychological assessment, genetic polymorphism
We are investigating various research topics in the healthy children and developmental disorders such as autism and dyslexia
using MRI, psychological assessment, and genetic polymorphism.
We have revealed how the childrens development of brains gray matter, white matter, perfusion, brain activity and its
synchronization occurs. Currently, we are investigating how those developments are in the children of developmental
disorders such as autism and dyslexia.
Further, we are investigating the neural mechanisms of intelligence, higher order social cognitive functions and
psychological characteristics related to developmental disorders in those children.
Also, we are investigating how daily habit, environmental factors, and various genetic polymorphisms are affecting
childrens cognitive and neural development. Through these, we are revealing the factors contributing to heathy development
of childrens mind.
Figure 1. Chidren's daily habit and neurocognitive development Figure 2. Concepts of researches of developmental diorders and tasks
Recent Publications
- Takeuchi H, et al. The impact of parentchild interaction on brain structures: Cross-sectional and longitudinal analyses. Journal of Neuroscience, in press.
- Takeuchi H, et al. The impact of television viewing on brain structures: Cross-sectional and longitudinal analyses. Cerebral Cortex, in press.
- Hashizume H, et al. Developmental changes in brain activation involved in the production of novel speech sounds in children. Human Brain Mapping, 35(8):4079-4089, 2014.
- Taki Y, et al. Linear and curvilinear correlations of brain gray matter volume and density with age using voxel-based morphometry with the Akaike information criterion in 291 healthy children. Human
Brain Mapping, 34(8):1857-1871, 2013.
- Taki Y, et al. Linear and curvilinear correlations of brain white matter volume, fractional anisotropy, and mean diffusivity with age using voxel-based and region-of-interest analyses in 246 healthy children.
Human Brain Mapping, 34(8):1842-1856, 2013.
184 Developmental Cognitive Neuroscience

To Discover a Pleiotropic Effect in Already Employed Drugs in Elderly Frail Subjects
Geriatric Pharmacotherapy URL:

http://www.idac.tohoku.ac.jp/ja/activities/
research/geriatric_pharma/index.html
Contact:
OHRUI, Takashi TEL +81-22-717-8480
E-Mail takashi.orui.a5@tohoku.ac.jp
Research Theme
To elucidate a proper use of drugs for older frail patients
To prevent aspiration pneumonia in older subjects
To propose Shelter Acquired Pneumonia and its preventive strategies
Research Keywords: older subjects, aspiration pneumonia, swallowing reflex, adverse drug event, adherence
Technical Keywords: measurement of swallowing latency, measurement of cough reflex, silent aspiration
Pneumonia is the third leading cause of death despite the availability of potent new antimicrobials in Japan. Aspiration of
oropharyngeal bacterial pathogens to the lower respiratory tract is one of the most important risk factors for pneumonia.
Impairments in swallowing and cough reflexes among disabled older persons having cerebrovascular disease or Parkinson
disease increase the risk of pneumonia. Thus, strategies to reduce the volumes and pathogenicity of aspirated material should
be pursued. Since both swallowing and cough reflexes are mediated by endogenous substance P contained in the vagal and
glossopharyngeal nerves, pharmacologic therapy using angiotensin-converting enzyme inhibitors, which decrease substance
P catabolism, can improve both reflexes and result in the lowering the risk for pneumonia. Similarly, since the production
of substance P is regulated by dopaminergic neurons in the cerebral basal ganglia, treatment with dopamine analogs or
potentiating drugs such as amantadine can reduce the incidence of pneumonia. The mission of this division is to elucidate
how pneumonia develops in disabled older people and to propose preventive strategies that may reduce the incidence of
pneumonia among these subjects.
Figure 1. Possible mechanisms for aspiration pneumonia in disabled elderly Figure 2. Pulmonary CT scans of the shelter acquired pneumonia
subjects
Recent Publications
- Asamura T, et al. Low serum 1,25-dihydroxyvitamin D level and risk of respiratory infections in institutionalized older people. Gerontology. 56:542-543, 2010
- Suzuki M, et al. Shelter-acquired pneumonia after a catastrophic earthquake in Japan. J Am Geriatr Soc 59:1968-1970, 2011
- Ohara Y, et al. Exhaled carbon monoxide levels in preschool-age children with episodic asthma. Pediatr Int. 54:227-232, 2012
- Ohrui T, Arai H. Chapter 48:Aspiration pneumonia. Pathys Principles and Practice of Geriatric Medicine. Editors: Alan J. Sinclair, John E. Morley and Bruno Vellas. Fifth Edition Volume 1. Wiley-
Blackwell. p565-572, 2012
- Uwano C, et al. A rivastigmine dermal patch solved eating problems in an advanced stage Alzheimers disease patient. J Am Geriatr Soc 60:1979-1980, 2012
Geriatric Pharmacotherapy 185

To Study the Neuroscience of Dementia and Contribute to the Welfare of Elderly People
Geriatric Behavioral URL:

http://www.cyric.tohoku.ac.jp/kenkyu/kouji.html
Neurology Contact:
TEL +81-22-717-7359
E-Mail k-meg@umin.ac.jp
MEGURO, Kenichi
Research Theme
To establish a method for assessing cognitive functions of older adults and database
To develop a comprehensive model for dementia including medical and welfare management based on the
neurological basis
To improve the level of medical and welfare for dementia and education
Research Keywords: neuroepidemiology, dementia, psychosocial intervention

Technical Keywords: Alzheimer's disease, neuropsychology, psychosocial intervention
Background
Since 1988, Tohoku University and Tajiri have been performed the community-based stroke, dementia, and bed-confinement
prevention in the town of Tajiri (the Tajiri Project). We have reported the prevalence of dementia to be 8.5% among older
adults aged 65 years or over. However, dementia patients in a community do not always receive an adequate medical and
welfare management based on a scientific evidence including diagnosis of dementing diseases, psychosocial intervention,
and caregiver education. Therefore, the Department of Geriatric Behavioral Neurology aims the followings.
Purposes
1. To establish a method for assessing cognitive functions of older adults and database
2. To develop a comprehensive model for dementia including medical and welfare management based on the neurological
basis
3. To improve the level of medical and welfare for dementia and education
Recent Publications
- Akanuma K, et al. Singing can improve speech function in aphasics associated with intact right basal ganglia and preserve right temporal glucose: Implications for singing therapy indication. Int J Neurosc
2016 Jan;126(1):39-45.
- Liu YC, et al. More delusions may be observed in low-proficient multilingual Alzheiemrs disease patients. PLos One 2015 Nov10;10(11):e0140714.
- Nakamura K, Kasai M, et al. The group reminiscence approach can increase self-awareness of memory deficits and evoke a life review in people with mild cognitive impairment: The Kurihara Project data.
J Am Med Direc Assoc 2016 (in press).
- Nakatsuka M, et al. A cluster randomized controlled trial of nonpharmacological interventions for old-old subjects with a Clinical Dementia Rating of 0.5: The Kurihara Project. Dement Geriatr Cogn Disord
Extra 2015 May 30;5(2);221-232.
- Meguro K, et al. Lifetime expectancy and quality-adjusted life-year in Alzheimers disease with and without cerebrovascular disease: Effects of nursing home replacement and donepezil administration A
retrospective analysis in the Tajiri Project. BMC Neurol 2015 Nov 5;15:227.
186 Geriatric Behavioral Neurology

Molecular Pathology
HORII, Akira
Genomic analyses of oncogenes, tumor suppressor genes, and miRNAs in human cancer
DNA mismatch repair error and human cancer
Molecular analyses of DNA repair mechanisms
Elucidation of epigenetic abnormalities in human cancer
Elucidation of genes and molecules associated with treatment of cancer
Elucidation of cancer stem cells
Molecular mechanisms of resistance to anticancer drugs
Analyses of genetic variations for disease susceptibility and therapeutic responses
(http://www.med.tohoku.ac.jp/org/medical/13/index.html)
Histopathology
SASANO, Hironobu
Pathogenic mechanism and genetics of autoimmune diseases
Pathogenic mechanism of lymphoproliferative disorder
Molecular mechanism of allergogenic response
Molecular Endocrinology
Health Sciences Course
SUGAWARA, Akira
Advanced Therapeutics for Metabolic Diseases

KATAGIRI, Hideki
187
Interdisciplinary Medical Science (Center for Oxygen Medicine)
SUZUKI, Norio
Mammalian cells require oxygen for their energy homeostasis. But cells in solid tumors may survive in hypoxic
microenvironment, where oxygen supply is blocked or instable due to abnormalities of the vascular networks.
Such cells adapt to the chronic or intermittent hypoxic conditions through regulation of stress-responsive genes as
well as energy metabolic pathways of the cells.
This project aims to understand molecular mechanisms involved in regulation of gene expression and energy
metabolism in hypoxic cells using gene-modified mouse and biochemical strategies.
Radioisotope Laboratory
Doctoral Degree
YAMAMOTO, Masayuki
Basic research of radiation effect on cell growth
Center for Community Health

TSUJI, Ichiro
Occupational Health
KUROSAWA, Hajime
Approaches for health promotion (quit smoking, physical activity, nutritional support, etc)
Mental health in workplace
Respiratory physiology, respiratory medicine, sleep disordered breathing (http://www.doh.med.tohoku.ac.jp/)
Central Operation Division

Doctoral Degree
SAIKI, Yoshikatsu
Nursing study in operative treatment
Study of infection at operative site
Study of patient care during an operation
Study of risk management in operating room
Study of medical electronics machine
188
Intensive Care Unit
Doctoral Degree
UNNO, Michiaki
Critical care medicine and pathophysiology of artificial respiration
Pathophysiology and treatment of multiple organ failure
Pathology
Doctoral Degree
SASANO, Hironobu
Endocrine pathology and gynecological pathology
Surgical pathology in general, cytopathology, and anatomic pathology
Blood Transfusion
Doctoral Degree
HARIGAE, Hideo
Immunohematology
Transfusion medicine
Hematopoietic stem cell transplantation
Regenerative medicine
Pathology
Conquest and clinical application of drug and radiation resistance of cancer cells
Human pathology (hepatobiliary, oral, ovarian etc)
Molecular mechanisms of human cancers
Quantification of images and morphology and its clinical application
Radiation effects on animals and environments by the Fukushima nuclear plant accident
(http://www.idac.tohoku.ac.jp/ja/activities/research/pathology/)
(http://www.idac.tohoku.ac.jp/dep/path/)
189
Clinical Pharmacology and Therapeutics
Doctoral Degree
SATO, Hiroshi
R ole and mechanism of hypertension-related genes in the metabolic syndrome, diabetic nephropathy,
preeclampsia, etc.
Pathogenesis and development of nephritis and nephrotic syndrome
Clinical epidemiological research relating to chronic kidney disease (CDK)
Bioactive substances relating to the development of cardiac failure and kidney disease
Onset mechanism and therapy of anemia due to antihypertensive medication
Research of clinical evaluation of antihypertensive drug
Regional cohort study of hypertension and atherosclerosis
Medical Neuroimaging Analysis

TAKI, Yasuyuki
Elucidation of brain development and aging using large brain MRI database
Elucidation of effect of lifestyle to brain for maintaining healthy brain
Biomarker Investigation
FUSE, Nobuo
Functional Evaluation of Genomic Polymorphisms

TANABE, Osamu
Identification of genomic polymorphisms and mutations related to disease susceptibility and drug response, and
elucidation of their pathophysiological significances.
Multi-omics analyses to derive disease biomarkers and unravel disease mechanisms.
Elucidation of molecular mechanisms for epigenetic regulation of gene expression.
(http://www.megabank.tohoku.ac.jp/tommo/member/member05)
(http://www.med.tohoku.ac.jp/org/cooperate/204/index.html)
190
Biomedical Informatics
Medical Informatics, Clinical Informatics, Bio Informatics

BioClinical Informational Infrastructure for Future Medicine
Regional Medical and Welfare Information Network
Translational Research Informatics (TRI)
Informational Analysis around BioMedical Informatics
International Standardization and Intellectual Properties in Medical Informatics
Ethics and Law in Medical Informatics
(http://www.med.tohoku.ac.jp/org/medical/54/)
Cancer Pathology (Miyagi Cancer Center)

TANAKA,Nobuyuki
Identification of genes that regulate Cancer Stem Cells
Oncogenesis using model animals
Cancer stem cell maintenance mechanism
http://www.cbt.med.tohoku.ac.jp/english/
(http://www. miyagi-pho.jp/mcc/htdocs/kenkyu/soshiki-renkei.html)
Respiratory Oncology (Miyagi Cancer Center)

Doctoral Degree
MAEMONDO, Makoto
Development of order-made therapy based on gene status in lung cancer cells
Elucidation of mechanism for resistance of molecular targeting therapy and development of therapy to overcome
the resistance.
D
iscovery of factors to predict chemotherapeutic effects by analyses of gene mutation, expression and protein in
tumor.
(http://www. miyagi-pho.jp/mcc/htdocs/shinryou/kokyuki.html)
Cancer Pathology (Miyagi Cancer Center)

SATO, Ikuro
Genetic diagnosis for cancer and molecular targeting therapy
Genetic, geometric, graph-combinatorial approach for cancer bioplogy
(http://www.geocities.jp/ikuro_kotaro/index.htm)
191
Pediatric Neurosurgery (Miyagi Children's Hospital)
SHIRANE, Reizo
Pediatric neurosurgery
Pediatric neuroimaging
Blood flow and metabolism in the developing brain
(http://www.med.tohoku.ac.jp/org/related/152/index.html)
Fetal Medicine (Miyagi Children's Hospital)

MUROTSUKI, Jun
Development and clinical application of fetal surgery
New evaluation of fetal circulation using ultrasonic phase difference tracking method
Pathophysiology of fetal bones and prenatal diagnosis
Analysis of DOHaD theory from epigenetics
(http://www.ob-gy.med.tohoku.ac.jp/laboratory/j-murotsuki.html)
Cellular and Molecular Imaging of Cancer (Japanese Foundation for Cancer Research)
HIROTA, Toru
Elucidating mechanisms of chromosomal instability in cancers based on state-of-art live cell imaging analyses
(http://www.jfcr.or.jp/tci/exppathol/index.html)
Screening for Molecular Target of Cancer (Japanese Foundation for Cancer Research)
NODA, Tetsuo
In order to identify molecular target and important signaling of cancer, we develop advanced cancer animal
models and perform genomic and epigenomic analysis.
(http://www.jfcr.or.jp/english/laboratory/index.html)
192
Oncotherapeutic Surgery (Japanese Foundation for Cancer Research)
Doctoral Degree
SANO, Takeshi
Establishment of treatment strategy for esophageal adenocarcinoma based on genomic subtypes.
Genetic/epigenetic alterations as carcinogenic field of esophageal squamous carcinoma.
Exploratory analysis of predictive blood biomarker for recurrences of colorectal cancer.
Identification of candidate molecules involved in liver metastasis from colorectal cancer using comprehensive
proteomics.
Gastrointestinal and Community Medicine (Surgery) (Iwaki Kyouritsu General Hospital)

Doctoral Degree
YOSHIDA, Hiroshi
Pathogenesis of abdominal emergency
Multidisciplinary therapies for gastrointestinal and hepato-biliary-pancreatic malignancies
Laparoscopic surgery for the treatment of gastrointestinal and hepato-biliary-pancreatic disorders
Surgical treatment and postoperative pathophysiology of inflammatory bowel disease
Promotion of clinical research in surgery
Gastrointestinal and Community Medicine (Preventive Medicine)

(Iwaki Kyouritsu General Hospital)
Primary prevention in gastrointestinal cancer
Great earthquake / nuclear power plant accident and gastrointestinal disorders
Incidence risk of cancer and nuclear power plant accident
Medial decision making
Infection and Pathology (National Institute of Infectious Diseases)

Doctoral Degree
HASEGAWA, Hideki
Pathology of emerging and re-emerging infectious diseases.
Research and development of next generation vaccine for infectious diseases.
Research and development of animal models of infectious diseases.
(http://www.nih.go.jp/niid/pathology/English.html)
193
Infection and Microbiology (National Institute of Infectious Diseases)
Doctoral Degree
OHNISHI, Makoto
Development of diagnostic tools based on the research for genome plasticity
Novel vaccine development based on the research of transcriptional regulation
Research on survival strategies in host cells of Streptococcus pneumoniae
Research on molecular evolution and global spreading of Neisseria gonorrhoeae
Disease for Mycobacterium Tuberculosis Infection

(Miyagi Cardiovascular & Respiratory Center)
Doctoral Degree
1. Medical support and intervention of a regional hospital for patients with severe chronic respiratory diseases or
terminal lung cancer.
2. Influence of smoking cessation on quality of life and prognosis among patients with respiratory diseases.
3. Molecular epidemiologic studies in tuberculosis outbreak.
4. Clinical characteristics and epidemiologic investigation of tuberculosis after the Great East Japan Earthquake.
Pharmaceutical and Medical Device Regulatory Science

(Pharmaceuticals and Medical Devices Agency)
Emerging and Reemerging Infectious Diseases

(National Center for Global Health and Medicine)
OHMAGARI, Norio
194
Multiple Sclerosis Therapeutics
FUJIHARA, Kazuo
Clinical research and immunological analyses of multiple sclerosis, neuromyelitis optica and related disorders
(http://www.ms.med.tohoku.ac.jp/index.html)
Preventive Psychiatry
MATSUMOTO, Kazunori
Neuro-Imaging
KUDO, Yukitsuka
195
Tohoku University Graduate School of Medicine
2-1, Seiryomachi, Aoba-ku, Sendai,
980-8575, Japan
TEL: +81-22-717-8010
FAX: +81-22-717-8021
E-mail: m-daigakuin@grp.tohoku.ac.jp
URL: http://www.med.tohoku.ac.jp

Laboratory Introduction: Tohoku University Graduate School of Medicine

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Tohoku University

Graduate School of Medicine

Graduate School of Medicine

Epileptology  NAKASATO, Nobukazu 50

Laboratory Animal Medicine  MIYOSHI, Ichiro 99

Tohoku University Hospital

Institute of Development, Aging and Cancer

Graduate School of Biomedical Engineering

International Research Institute of Disaster Science

Laboratory Index iii

Disaster Psychiatry  TOMITA, Hiroaki 135

Other Cooperative Departments in Tohoku University

Tohoku Medical Megabank Organization

Extramural Collaborative Departments

Intramural Endowed Departments

Keyword Index vii

viii Keyword Index

xii Keyword Index

Keyword Index xiii

xiv Keyword Index

xvi Keyword Index

Keyword Index xvii

xviii Keyword Index

Keyword Index xix

Radiation Biology Medical Sciences Course

HOSOI, Yoshio URL:

1. Basic research for radiation oncology.

Organ Anatomy Medical Sciences Course

OWADA, Yuji URL:

Professor, M.D. Ph.D.

Stem Cell Biology and Medical Sciences Course

Stem Cell Biology and Histology 3

Molecular Biology and Applied Medical Sciences Course

Research Keywords: heme, melanin, retina, mitf, pigment cell

4 Molecular Biology and Applied Physiology

Biochemistry Medical Sciences Course

IGARASHI, Kazuhiko URL:

Medical Biochemistry Medical Sciences Course

Neurophysiology Medical Sciences Course

MUSHIAKE, Hajime URL:

Cell Physiology Medical Sciences Course

Figure 1. Apparatus for patch-clamping the membrane

Systems Neuroscience Medical Sciences Course

Molecular Pharmacology Medical Sciences Course

Research Keywords: mitochondrialdisease,GPCR-mediatedsignaltransduction,primaryciliarydyskinesia

Pharmacology Medical Sciences Course

Research Keywords: molecular imaging, Alzheimer disease, drug development, histamine,

Anatomic Pathology Medical Sciences Course

SASANO, Hironobu URL:

We have been and are working in the following areas.

Virology Medical Sciences Course

OSHITANI, Hitoshi URL:

Figure 1. Laboratory activities Figure 2. Field activities

Microbiology and Immunology Medical Sciences Course

14 Microbiology and Immunology

Nephrology Endocrinology Medical Sciences Course

Research Keywords: large-scale clinical study, prorenin-renin-angiotensin-aldosterone system,

Nephrology Endocrinology and Vascular Medicine 15

Hematology and Medical Sciences Course

16 Hematology and Rheumatology

Infection Control and Medical Sciences Course

Infection Control and Laboratory Diagnostics 17

Diagnostic Radiology Medical Sciences Course

Epileptology NAKASATO, Nobukazu 50

Laboratory Animal Medicine MIYOSHI, Ichiro 99

Disaster Psychiatry TOMITA, Hiroaki 135

Research Keywords: mitochondrialdisease,GPCR-mediatedsignaltransduction,primaryciliarydyskinesia

Research Keywords: molecular imaging, Alzheimer disease, drug development, histamine,

Research Keywords: large-scale clinical study, prorenin-renin-angiotensin-aldosterone system,

Research Keywords: inter-organmetaboliccommunication,dynamichomeostasisofsystemicmetabolism,

Research Keywords: obstetrics and gynecology, gynecological oncology, reproductive endocrinology,

Research Keywords: cancermicroenvironment,invasionandmetastasis,pancreatobiliarymalignancies,

PalliativeMedicine Medical Sciences Course

Research Keywords: earlypalliativecare,molecular-targetingagents,psycho-socialpain,cachexia

Research Keywords: systemic inflammatory response syndrome, damage-associated molecular patterns,

Research Keywords: MND/ALS,Parkinsonsdiseaseandrelateddisorders,musculardiseases,multiplesclerosis,

Research Keywords: child and adolescent psychiatry, neurodevelopmental disorders,

Research Keywords: satellitecells,hypoxicpathway,sarcopenia,physicalactivity,microbiome