PROFILE

Scientist, manager, early stage drug discovery, anti-cancer and anti-inflammator

y pharmacology, biomarkers and translational medicine
Protein folding, unfolded protein response, UPR, endoplasmatic reticulum stress,
proteasome inhibitor, mitigation of UPR, IRE1-alpha, XBP1, x-box binding protei
n, biomarkers, gene-expression analysis, high-throughput cytotoxicity assay, non
-steroid anti-inflammatory drugs, NSAID, COX2 inhibitors, kinase inhibitors, str
atification of disease, translational medicine, FDA standards for in vitro diagn
ostic devices, CLSI standards, Title 21 part 820, expression profiling, GEO data
sets, cancer, autoimmune disease
Action-oriented scientist and inventor possessing wealth of experience in biotec
hnology and academic settings. Very strong management and leadership skills wit
h the ability to build data and human systems to achieve organizational goals. H
ighly organized. Very strong communication skills, both written and verbal. Mul
ti-lingual.
* Expert in drug discovery targeting protein folding pathways
* Skilled in managing new technology development
* Experienced in project management, and building international R&D teams
* Highly knowledgeable about bioinformatics and data-mining for novel biomarkers
* Expert in troubleshooting puzzling experimental inconsistencies
* Successful at writing peer-review papers, winning grants, and conference prese
ntations
* Strong at translating experimental medicine into clinical context
* Strong at FDA Tilte 21 Part 820
EXPERIENCE
Protobios OU Estonia, EU 2009-2010
Lead Scientist, Diagnostics & Biomarkers
Reports to the CEO and CSO. Responsible for the design and execution of the com
pany?s molecular diagnostics strategies. Summarized progress reports for execut
ive management. Drafted and executed quarterly plans. Determined the clinical ne
ed for planned molecular diagnostics products. Contributed to small business gra
nt writing efforts. Managed a group of 7 research scientists and built a strong
R& D team spirit. Implemented standardized workflow and quality controls for R&
D diagnostics.
* Enhanced existing technology of diagnostic biomarker discovery and personalize
d medicine; Result: Designed and implemented an ultra-high throughput technology
platform
* Coordinated proof-of-principle experiments for Global Mimotype Mapping (GMM) t
echnology; Result: Provisional Patent that governs Global Mimotope Mapping
* Delivered standardized workflow for diagnostic serum autoantibody discovery by
phage display; Result: novel diagnostic markers for type 1 diabetes.
MannKind Corporation, Valencia, CA 2007-2009
Senior Scientist
Member of the IRE1-alpha project team. Reported to the R&D director. Managed res
earch associates. Validated IRE1alpha inhibitors targeting unfolded protein resp
onse (UPR). Made presentations to company?s management and consultants.
* Designed and implemented high-throughput cytotoxicity assays to test anti-canc
er activity of IRE1alpha inhibitors; Result: Determined that inhibition of unfol
ded protein response and proteasome inhibitors possess additive anti-cancer effe
ct. Constructed lentiviral system for genetic inhibition of IRE1alpha.
* Stratified multiple myeloma bone marrow cancer relative to it?s sensitivity to
anti-cancer activity of proteasome inhibitors; Result: identified the non-IGG m
ultiple myeloma as most proteasome inhibition-sensitive sub-type of multiple mye
loma.
* Built a cancer gene-expression database containing 11,000 breast cancer, multi
ple myeloma, and lymphoma expression profiles; Result: Acquired a tool that prov
ided an additional rational element to the company?s drug design efforts.

CeMines, Inc., La Jolla, CA 2004-2006

Director of Development, Molecular Medicine
Reported to the Chief Scientific Officer. Responsible for managing 5 scientists
and research associates. Designed multivariate cancer diagnostics strategy. Ma
de presentation at World Biomarker Congress.
* Developed CeMines CellCorrect Lung Cancer kit under FDA Title 21, Part 820; Re
sult: 510K application for CeMines CellCorrect Lung Cancer Kit.
* Wrote patents; coordinated with patent attorneys; Result: Won International pa
tent: Mehis Pold & Toomas Neuman: Composition and Methodology for Classifying Bi
ological Samples, International Patent #WO 2006/091734 A2.
* Worked on image analysis software design, diagnostic trial statistical design
and 510K applications; Result: Custom software for automated immunoassay image a
nalysis, and 510K application ?CeMines CellCorrect Lung Cancer Autoantibody Dete
ction Kit?
* Established a collaboration with UCLA Lung Cancer SPORE program. Result: Condu
cted presentation at 13th Annual NIH SPORE Investigators? Workshop;

UCLA, Division of Pulmonary and Critical Care Medicine, Los Angeles, CA 2000-2
004
Leading academic institution. Jonson Comprehensive Cancer Center Pulmonary Immun
ology Laboratory.
Assistant Researcher / Junior Faculty
Reported to the Chief of Pulmonary Medicine Division. Responsible for writing a
nd applying for grants to fund the research at Pulmonary Immunology Lab of UCLA.
Conducted experiments on lung cancer biology and anti-cancer pharmacology. Su
pervised research assistants. Made presentations at seminars and national cance
r conferences. Published in scientific journals. Assisted in peer-review of man
uscripts submitted for review to the faculty of Pulmonary medicine.
* Introduced whole-genome analysis gene-expression analysis at Pulmonary Immunol
ogy lab; Result: Identified new oncology targets for R&D; won a grant from the A
merican Lung Association.
* Wrote and submitted materials for a grant; Result: Won peer-review grant ?Iden
tification of biomarkers by mass spectroscopy and peptide arrays for early diagn
osis of lung cancer? from UCLA Lung Cancer SPORE.
* Authorship of 13 peer-review papers; Result: Published in highly-ranked peer r
eview journals, including Cancer Research, The Journal of Biochemistry, FASEB Jo
urnals.

Department of Veterans Affairs, Div. Hem-Oncology, West Los Angeles, CA 1995-

2000
Division specialized in medical services and biomedical research.
Fellow of The Lymphoma Research Foundation of America, 1999-2000
Reported to the Chief of Hematology and Oncology Division.
* Demonstrated that (1) MAGE-family tumor antigens evolved from an ancestral MAG
E-gene first found in fruit fly Drosophila melanogaster.
* Co-authored a study in Science magazine about the role of Kaposi?s sarcoma vir
us (HHV8) in pathogenesis of multiple myeloma.
* Wrote a fellowship; Result: Won fellowship from The Lymphoma Research Foundati
on of American ?The Role of BCL-1 and Immunoglobulin Heavy Chain Loci in B-Cell
Transformation.?
Postdoctoral Researcher, 1995-1999
Responsible for the study of chromosomal abnormalities of bone marrow cancer mul
tiple myeloma, as well as the role of Kaposis? sarcoma virus in pathogenesis of
multiple myeloma. Presented research at cancer conferences. Designed and execu
ted experimental research on multiple myeloma.
* Authorship on a paper published in the foremost science journal, Science.
* Cloned multiple myeloma breakpoint on chromosome 11q13; Result: Won Fellowship
from The Lymphoma Research Foundation of America.
* Presentations at the national cancer conferences: American Society of Hematol
ogy, 1997 and 1998.
* Chance discovery of HIV in a bone marrow of a volunteer donor.

EDUCATION
M.D., University of Tartu, Estonia, EU
* Medicine

TECHNICAL EXPERTISE

Autoimmune Disease & Cancer bioinformatics and multivariate diagnostics

* Autoimmune disease epitope patterns using Immune Epitope Data base (IEDB). Aut
oantibody, epitope and mimotope discovery using random-peptide phage M13 library
. Pre-printing and on-array phage and autoantibody binding quantification by mid
-density M13-phage nitrocellulose microarrays.
* Treatment response prediction and pathway analysis using clinically annotated
datasets from Gene Expression Omnibus (GEO, NCBI), and Array Express (EMBL): cli
nically supervised learning, Kaplan-Meyer survival analysis, chi-square statisti
cs, GenMAPP pathway analysis, T- and Z-tests.
* Cancer kinase-expression profiling in B- and T-cell malignancies.
* Mathematical modeling of high-throughput cancer gene-expression data: cross-va
lidation of data from independent sources and unrelated technology platforms.
* CeMines peptide array for cancer serum autoantibody detection, image and patte
rn recognition software development: supervised and unsupervised learning in can
cer diagnostics.
* Affymetrix GeneChip expression profiling on nano- and microgram quantity RNA f
rom mouse CD8+ T-cells
.
Cell and molecular biology:
* Cytotoxicity assays (MTS, Cell-Titer Glow); single- and double-color flow cyto
metry by FACSCalibur (Annexin V, PI, DCF, Hoechst, SNARF-1, FITC); fluorescent m
icroscopy (GFP, RFP, JC-1); hypoxia, oxygen consumption and mitochondrial potent
ial (JC-1); luminometry of free radicals, siRNA design and transfection; miRNA d
esign, expression vectors and short and long term in vitro knockdown experiments
; lenti- and retroviral vectors; transfection by liposomes, electroporation.
* DNA and RNA purification from minute amounts of cells including mouse CD8+ T-c
ells; Nanodrop-technology; Southern, Western and Northern blots, immunoprecipita
tion, ELISA, mass-spectrometry (MALDI), PCR; site-directed mutagenesis, differen
tial display, RACE and cDNA libraries, *DNA libraries, DNA sequencing, yeast one
- and two-hybrid system.

PUBLICATIONS
1. Heuze?-Vourc?h N, Liu M, Dalwadi H, Baratelli F, Zhu L, Goodglick L, P?M, Sha
rma S, Ramirez R, Shay J, Minna JD, Strieter RM, Dubinett SM. IL-20, an anti-ang
iogenic cytokine that inhibits COX-2 expression. Biochem & Biophys Res Comm 2005
; 333:470?475
2. P?M, Krysan K, P?A, Dohadwala M, Heuze-Vourc?h N, Mao JT, Riedl KL, Sharma S,
M. Dubinett SM. Cyclooxygenase-2 (COX-2) Modulates The Insulin-like Growth Fact
or (IGF)-axis in Non-SmallCell Lung Cancer (NSCLC). Cancer Res. 2004; 64:6549-55
3. Krysan K, Dalwadi H, Sharma S, P?M, Dubinett S. COX-2-dependent expression of
survivin is critical for apoptosis resistance in NSCLC. Cancer Res. 2004; 64:63
59-62
4. Riedl KL, Krysan K, P?M, Dalwadi H, Heuze-Vourch N, Dohodwala M, Liu M, Cui X
, Figlin R, Sharma S, Dubinett SM. Update on Cyclooxygenase-2 in Lung Cancer. Dr
ug Resistance Updates 2004; 7:169-84. Review
5. Krysan K, Dohadwala M, Luo J, Lin Y, Zhu L, Heuze-Vourch N, Goodglick L, Merc
hant F, Seligson D, P?M, Strieter R, Sharma S, Dubinett S. Cyclooxygenase-2-depe
ndent expression of survivin in non-small cell lung cancer. Chest. 2004;125:140S
6. P?M, Zhu LX, Sharma S, Burdick MD, Lin Y, Lee PP, Pold A, Luo J, Krysan K, Do
hadwala M, Mao JT, Batra RK, Strieter RM, Dubinett SM. Cyclooxygenase-2-dependen
t expression of angiogenic CXC chemokines ENA-78/CXC Ligand (CXCL) 5 and interle
ukin-8/CXCL8 in human non-small cell lung cancer. Cancer Res. 2004;64:1853-60
7. Krysan K, Merchant FH, Zhu L, Dohadwala M, Luo J, Lin Y, Heuze-Vourch N, P?M,
Seligson D, Chia D, Goodglick L, Wang H, Strieter R, Sharma S, Dubinett S. COX-
2-dependent stabilization of survivin in non-small cell lung cancer. FASEB J. 20
04;18:206-8
8. Dubinett SM, Sharma S, Huang M, Dohadwala M, P?M, Mao JT. Cyclooxygenase-2 in
lung cancer. Prog Exp Tumor Res. 2003;37:138-62
9. Batra RK, Lin Y, Sharma S, Dohadwala M, Luo J, P?M, Dubinett SM. Non-small ce
ll lung cancer-derived soluble mediators enhance apoptosis in activated T lympho
cytes through an I kappa B kinase-dependent mechanism. Cancer Res. 2003;63:642-6
10. Sharma S, Huang M, Dohadwala M, P?M, Batra RK, Dubinett SM. Cyclooxygenase
2-dependent regulation of antitumor immunity in lung cancer. Methods Mol Med. 20
03;75:723-36
11. Dohadwala M, Batra RK, Luo J, Lin Y, Krysan K, P?M, Sharma S, Dubinett SM. A
utocrine/paracrine prostaglandin E2 production by non-small cell lung cancer cel
ls regulates matrix metalloproteinase-2 and CD44 in cyclooxygenase-2-dependent i
nvasion. J Biol Chem. 2002;277:50828-33
12. P?M, Dohadwala M, Luo J, Lin Y, Dubinett S. Microarray identifies cyclo-oxyg
enase-2-dependent modulation of insulin-like growth factor binding protein-3 in
non-small cell lung cancer cells. Chest. 2002;121:29S
13. Dohadwala M, Luo J, Zhu L, Lin Y, Dougherty GJ, Sharma S, Huang M, P?M, Batr
a RK, Dubinett SM. Non-small cell lung cancer cyclooxygenase-2-dependent invasio
n is mediated by CD44. J Biol Chem. 2001;276:20809-12
14. Ma HJ, Sjak-Shie NN, Vescio RA, Kaminsky M, Mikail A, P?M, Parker K, Beksac
M, Belson D, Moss TJ, Wu CH, Zhou J, Zhang L, Chen G, Said JW, Berenson JR. Huma
n herpesvirus 8 open reading frame 26 and open reading frame 65 sequences from m
ultiple myeloma patients: a shared pattern not found in Kaposis sarcoma or prima
ry effusion lymphoma. Clin Cancer Res. 2000;6:4226-33
15. P?M, Pold A, Ma HJ, Sjak-Shie NN, Vescio RA, Berenson JR. Cloning of the fir
st invertebrate MAGE paralogue: an epitope that activates T-cells in humans is h
ighly conserved in evolution. Dev Comp Immunol. 2000;24:719-31
16. P?M, Zhou J, Chen GL, Hall JM, Vescio RA, Berenson JR. Identification of a n
ew, unorthodox member of the MAGE gene family. Genomics. 1999;59:161-7
17. Rettig MB, Ma HJ, Vescio RA, P?M, Schiller G, Belson D, Savage A, Nishikubo
C, Wu C, Fraser J, Said JW, Berenson JR. Kaposis sarcoma-associated herpesvirus
infection of bone marrow dendritic cells from multiple myeloma patients. Science
. 1997;276:1851-4