Na Li, 14+ Years Biotech/Pharma Experience

Cardiff by the Sea, San Diego County, CA 92007

858-405-2597 cell, 858-549-9326 home
lllinali616@gmail.com
PROFILE SUMMARY
aAn integrative (hybrid) molecular cell biologist, biochemist and pharmacologist
with strong background in identifying novel molecules that modulate G-protein c
oupled receptor (GPCR) function or regulate enzyme activities, utilizing analyti
cal pharmacology techniques such as quantitative biochemical assays, organ- or c
ell-based functional assays, ex-vivo and in-vivo animal models;
aGood understanding of drug action at the molecular, cellular, organ system and
intact organism (animal) levels, knowledgeable in receptor pharmacology and enzy
me kinetics, proven achievement via a track record of peer-reviewed publications
and contributions to identification of new molecular entities (NMEs);
aIn-depth knowledge in disease biology of infection & immunity, metabolic disord
ers and cancer; familiar with pharmacological characterization of enzyme inhibit
ors, peptide analogs and antibody based therapeutics, aided discovery of recepto
r agonists & antagonists, enzyme inhibitors, peptide- and protein-based drugs;
aExtensive lab-experience in triage compounds utilizing in vivo disease models a
nd verify mechanism of action ex vivo and in vitro; routine use of liquid handli
ng systems and laboratory automation equipment, familiar with various bio-analyt
ical platforms;
aSupported the creation of novel and robust automation assays via molecular gene
tic approaches such as cDNA cloning, reporter gene construction and siRNA silenc
ing of genes, played critical roles in establishment of novel methodology, analy
tical bioassay development & validation, aided to high throughput screening (HTS
), hit-to-lead, lead optimization and preclinical evaluation of new molecular en
tities (NMEs), supported the delivery of multiple NMEs from the early discovery
to clinical trials;
aWorking knowledge of GLP/ISO regulations, good leadership and managerial skills
, a clear ability to work effectively across different functional teams, comfort
able working in a fast-paced, dynamic environment, nimble minded and adapting to
change quickly.
LABORATORY RESEARCH SKILLS
(including, but not limited to, the listed below)
Protein Biochemistry: protein chemical conjugation and modification (reducing an
d oxidizing, folding, cleavage, labeling etc.), protein analysis (SDS-PAGE, West
ern analysis, microfluidic electrophoresis LabChip GXII), purification and chara
cterization of proteins/peptides utilizing chromatography (size exclusion, ion e
xchange & affinity), reverse-phase HPLC, isoelectric focusing (IEF), TLC, protei
n labeling with radioisotope (125I) and fluorescent dyes
Pharmacology: development of ligand-receptor binding assays, cell- and organ-bas
ed functional assays, enzyme kinetics, pharmacological characterization of recep
tors agonists & antagonists, potency determination (EC50 & IC50, Kd, Bmax & Vmax
) at in vitro assays, biomarker measurement and quantitative analysis, cytotoxic
ity assessment of drugs, PKPD, surgery and animal models
Molecular and Cell Biology: cDNA cloning and expression, transfection and genera
ting stable recombinant cell clones, reporter gene assays, qPCR, real-time RT-PC
R, RNAi silencing of target genes or siRNA knock-downs in cell lines, site-direc
t mutagenesis, DNA hybridization (Southern and Northern), DNA sequencing (Sanger
as method), deriving primary cells from organ tissues, metabolic cell culture an
d peptide hormone release assays
Immunology/Immunochemistry: purification and characterization of proteins & anti
bodies, isolation of immune cells from peripheral blood/spleen/bone marrow, FACS
 analysis, flow cytometry, fluorescence microscopy, ELISA-based multiplexing (MS
D, EnVision, Luminex), antibody neutralization and titration
COMPUTER & INSTRUMENT EXPERIENCE
Google Apps, Microsoft Office (Word, Excel, Power Point, Outlook), Graph Pad/Pri
sm, Chart View 4.1, SciFinder, radiometric (TopCount, beta-counter, r-counter),
FLIPR Tetra, Caliper LS LabChip, multiplexing (MSD, EnVision, Luminex), FACScan
with software Lysis II, FACS vantage with CellQuest, spectrofluorometry, spectro
photometry, automated DNA sequencing
PROFESSIONAL EXPERIENCE
Johnson & Johnson PRD, LLC. 2001 a" 2010
Internal Medicine Team
aInitiated literature review and searches in support of ongoing research activit
ies, generated oral and written reports in summarizing activities and projects,
Initiated communication with related staff and coordinated inter-disciplinary ac
tivities effectively, supported assay transfer to QC and HTS, aided the delivery
of multiple NMEs from early discovery to clinical trials;
aConducted exploratory investigations of aorgan peptidesa derived from Stanford-
J&J PRD collaboration, in an effort of afishing for the potential targetsa and a
validating the relevant biological functionsa of the unknown peptides, identifie
d biologically relevant peptides and generated new lead series that improve card
io output without consuming more O2;
aDesigned and established peptide hormone release assays, such as insulin-secret
ion and GLP-1 secretion assays, identified agonists and antagonists to free fatt
y acid receptors, confirmed receptor-selectivity of leads, aided to the generati
on of new lead series to type 2 diabetes and obesity;
aConducted the measurement and quantitative analyses of PD markers and biomarker
s utilizing ELISA-based multiplexing (MSD, EnVision, Luminex), FACS, qNMR (miniS
PEC), high throughput clinical chemistry and hematology analyzers, aided to the
assessment of NMEs and the effectiveness of disease models;
aDeveloped radioligand binding assays, enzymatic assays, cell-or organ-based fun
ctional assays, determined potency (EC50, IC50, Kd, Bmax, Vmax) of therapeutics
in diverse biochemical and cell-based functional assays;
aConducted pharmacological (PD) studies of ligand to GPCR interactions, e. g. li
gand binding affinity, intracellular cAMP and [Ca++]i release assays, intracellu
lar phosphor-protein detection and quantification, enzyme kinetics, peptide horm
one release assays, supported target validation, lead-optimization and SAR studi
es;
aIsolated and enriched immune cells, reticulocytes from peripheral blood utilizi
ng magnetic-bead based method, monitored hemoglobin biosynthesis in the enriched
cells and in pro-erythroid cell line (G1E-ER4), supported the development of th
erapeutics stimulating hemoglobin biosynthesis;
aValidated free fatty acid receptors (GPCRs) as novel drug targets, confirmed hi
ts from HTS, supported hit-to-lead, identified leads of insulin secretogogue and
incretin secretogogue, aided generation of new lead serials and novel projects;
aPerformed quantitative immunoassays for the measurement of macromolecules in bi
omatrices, supported PK studies of macromolecular therapeutics utilizing MSD pla
tform and immunoanalytical assays, aided the delivery of multiple NMEs from earl
y discovery to clinical trials;
aConducted gene silencing studies in mammalian cell culture utilizing siRNA or R
NAi and subsequent real time RT-PCR analysis, supported molecular pharmacologica
l investigations;
UCLA School of Medicine 1998-2000
Supervisor, Staff Research Associate
aExplored the anti-cancer effects of human monoclonal antibody (Herceptin) in ce
ll-based assays such as CTL (LDH), apoptosis assay (caspase3/7), and antibody-de
pendent cell-mediated cytotoxicity (ADCC) S35-methionine release assay;
aConducted quantitative analyses of effector genes that were affected by the ups
tream regulatory genes such as her-2 and TGF-1, utilizing Northern blotting and
RT-PCR amplification;
aSupported anti-tumor target (HER2) identification and analyses of gene expressi
on patterns of breast cancer utilizing neu/HER-2 over-expressing cell lines and
animal models (xenografts of human primary tumor models);
aAnalyzed the transcript profile and biological significance of candidate genes
obtained from cDNA microarray screens of cancer cell lines and tumor tissues; Pe
rformed transcript imaging experiments which were designed to address 3 major ar
eas of breast cancer biology:
(1) Identification of potential anti-tumor antibody targets, such as HER-2, EGFR
, VEGFR and RTKs;
(2) Oncogenic signal transduction pathways and
(3) Mechanisms of anti-estrogen resistance in breast cancer;
aOptimized and performed Northern, Western analysis of gene products, performed
the tissue culture and in vitro assays measuring cell proliferation, tumorigenic
ity and invasive potential; some of the findings were presented in Keystone Canc
er Symposium 2000;
aStudied the role of endogenous anti-microbial peptides in innate immunity, work
ed on purification and characterization of native peptide (defencin) from biomat
rices, including body fluid such as tears, seminal fluid, and epithelial tissue
of intestine; in parallel, performed the structural and functional analysis of s
ynthetic analogues utilizing the means of reversed-phase HPLC, mass spectrometry
, electrophoresis and chemical modifications such as reduction, alkylation, refo
lding, conjugation, chemical and enzymatic cleavages;
aPerformed anti-microbial activity assays, such as radio diffusion assay, colony
count assay and micro-broth dilution assay, in determination of potency (IC50)
of anti-microbial peptides, aided the discovery of antibiotic peptides.
Molecular Probes, Inc. 1997 - 1998
Scientist, bio-conjugation
aCultivated algae culture and extracted fluorescence proteins from the algae cul
tures, performed native protein purification and characterization utilizing a va
riety of chromatographic platforms (affinity, size exclusion, ion-exchange), dia
lysis, immunoprecipitation, HPLC, FPLC.
aPerformed the bio-conjugation of fluorescence dyes to proteins or antibodies al
ike such as anti-EGFR, anti-IL-2, anti-CD31, actin, lectins, nitro-avidin, avidi
n or streptavidin, biotin and phycobiliproteins in order to produce the fluoresc
ence labelled protein probes;
aTested new fluorescence probes in various cancer cell lines using immuno-conjug
ation assays and fluorescence microscopy; conducted flow cytometry analyses of l
ive cells labelled with novel fluorescence probes; performed immunocytological a
nalyses of fixed cells labelled with fluorescence compounds using fluorescence m
icroscopy;
aConjugated fluorescent protein conjugates with long wavelength (620-670nm) spec
trum utilizing proprietary technology (FRET of the energy-resonance-transferring
of molecules conjugated in tandem). This fruitful research generated new produc
ts that filled in the void of long wavelength protein probes in the reagent mark
et. It was one of many innovations created in Molecular Probes Inc. Patent of
this work was filed by Molecular Probes, Inc.
The University of British Columbia 1994 - 1995
Department of Pathology & Laboratory Medicine
Senior Research Associate
aPerformed detection and identification of RNA viruses such as Hepatitis C Virus
(HCV) and Hantavirus in human serum utilizing RT-PCR amplification method.
aIsolated viral RNA from human blood, performed PCR amplification of conserved r
egion of viral RNA, conducted genotypic analysis of HCV genomic RNA isolated fro
m human blood.
aMolecular detection of drug resistance strains of Mycobacterial Tuberculosis Co
mplex (TB), Staphylococcal aureus, and Streptococcus in human specimens.
aDeveloped microplate hybridization assay for quantification of DNA for applicat
ion in identifying drug resistance Mycobacterial Tuberculosis Complex (TB) in hu
man specimens.
aWorked on development of the cycling probe technology for detection of Mycobact
erial Tuberculosis and Hepatitis C Virus at low cost.
The University of British Columbia 1990 - 1994
Vancouver General Hospital
PhD Graduate Research
aSet-up disease models of Staphylococcal Toxic Shock Syndrome (TSS) in rabbits,
performed PK/PD studies, investigated the molecular pathogenesis of Staph. aureu
s induced toxic shock syndrome in rabbit model.
aCultivated Staphylococcal aureus culture in liters, purified toxic shock protei
n from the culture supernatant, characterized the toxic protein in terms of path
ogenicity, immunogenicity and immunochemical properties.
aImmunized rabbits with TSST-1 toxoid, raised antiserum to TSST-1, isolated IgG
from the pool of antiserum, performed immunogenicity assays including determinat
ion of antibody titer, neutralization, isotyping and total immunoglobulin.
aWorked on purification and characterization of polyclonal antibody to TSST-1 pr
otein.
aWorked on development and characterization of toxic shock syndrome toxin-1 (TSS
T-1) toxoid as vaccine candidate for Staphylococcal Toxic Shock Syndrome.
aStudied receptor-ligand interaction of Staphylococcal Toxic Shock Protein (TSST
-1) with peripheral blood mononuclearcytes (PBMNC).
Tongji Medical University 1983 - 1986
Dept. of Microbiology and Immunology
Faculty Member
aDeveloped detection assays (ELISA, Immunochemical assays) for identification an
d characterization of various microbes or pathogens.
aConducted purification and characterization of recombinant proteins and antibod
ies (Ab), performed immunogenicity and neutralization assays, Ab tiration, Ab ty
ping & sub-typing.
aPurified and characterized polyclonal antibodies from sera by affinity chromato
graphy and immune-precipitation.
aPerformed detection and measurement of cytokines in patient specimens using ELI
SA assay and radioimmunol assay (RIA).
aTaught Medical Microbiology and Immunology in Tongji medical school.
LANGUAGE SKILLS
afluent in English and Chinese (Mandarin)
ELIGIBILITY TO WORK IN AMERICA & CANADA
aauthorized to work in America as a legal permanent resident
aCanadian citizenship
EDUCATION & CREDENTIAL
aMSc Biochemistry, Dalhousie University, Halifax, Nova Scotia, Canada, 1991
aMD Medical Sciences, Tongji Medical University, Wuhan, Hubei, China, 1986
aPhD Molecular Microbiology, the University of British Columbia, Vancouver, Can
ada, 1994
P.S. My PhD advisor left country during my PhD studies. As a result, I went to w
ork for biotech/pharmaceutical industry directly without defending thesis. Howev
er, I passed both oral and written qualification exams of PhD program. J&J evalu
ated all my credentials and rated them as doctoral equivalent (official document
is available for reference).
PROFESSIONAL MEMBERSHIPS
aAmerican Society of Pharmacology and Experimental Therapeutics (ASPET) 2008-201
0
aSigma Xi Scientific Research Society 2007-2010
aNational Association of Professional Women (NAPW) 2007-2008
aAmerican Society for Microbiology (ASM) 1999-2001
aAmerican Association For The Advancement of Science 2000-2001
aCanadian Society of Microbiology (CSM) 1992-1995
aCanadian Bacteria Diseases Network (CBDN) 1992-1995
aCanadian Society for Clinical Investigation (CSCI) 1992-1995
BIBLIOGRAPHY
15. Magda F. Morton, Terrance D. Barrett1, Jamie Freedman, Lina Li, Michele Rizz
olio, Clodagh E. Prendergast, Xiaodong Wu, Veronica Moreno, Jayashree Pyati, Kat
herine Figueroa, Laurence Cagnon, Guy Lagaud, Luc Ver Donck2, Etienne Ghoos2, Br
ett Allison, Michael H. Rabinowitz & Nigel P. Shankley JNJ-26070109 [(R) 4-Brom
o-N-[1-(2, 4-difluoro-phenyl)-ethyl]-2-(quinoxaline-5-sulfonylamino)-benzamide]:
A novel, potent and selective cholecystokinin 2 receptor antagonist with good
bioavailability in rats and dogs. J. Pharmacol. Exp. Ther. (2009), In press
14. Kimon C. Kanelakis, Heather L. Palomino, Lina Li, Jiejun Wu, Wen Yan, Mark D
. Rosen, Michele C. Rizzolio, Meghana Trivedi, Magda F. Monton, Young Yang, Hari
haran Venkatesan, Michael H. Rabinowitz, Nigel P. Shankley and Terrance D. Barre
tt, Characterization of a Robust Enzymatic Assay for Inhibitors of 2-Oxyglutarat
e-Dependent Hydroxylases, J Biomol Screen (2009). 14(6): 627-635 Aug 2009
13. Marna Pippel, Brett D. Allison, Victor K. Phuong, Lina Li, Magda F. Morton,
Clodagh Prendergast, Xiaodong Wu, Nigel P. Shankely, Michael H. Rabinowitz, Anth
ranilic Sulfonamide CCK1/CCK2 Dual Receptor Antagonists I: Discovery of CCKR1 Se
lectivity in a Previously CCK2-Selective Lead Series, Bioorganic & Medicinal Che
mistry Letters (2008), In press
12. Mark D. Rosen *, Michael D. Hack , Brett D. Allison , Victor K. Phuong , Cra
ig R. Woods , Magda F. Morton , Clodagh E. Prendergast , Terrance D. Barrett ,
Carsten Schubert , Lina Li , Xiaodong Wu , Jiejun Wu , Jamie M. Freedman , Nigel
P. Shankley , and Michael H. Rabinowitz . Discovery of potent cholecystokinin-
2 receptor antagonists: Elucidation of key pharmacophore elements by X-ray cryst
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11. Laurent Gomez, Michael D. Hack, Kelly Mclure, Clark Sehon, Liming Huang, Mag
da Morton, Lina Li, Terrance D. Barrett, Nigel Shankley, J. Guy Breitenbucher.
SAR studies of 1,5-diarylpyrazole-based CCK1 receptor antagonists, Bioorganic &
Medicinal Chemistry Letters (2007), doi: 10.1016/j.bmcl.2007.09.093
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dagh E Prendergast, Veronica Moreno, Jayashree Pyati, Katherine Figueroa, Lina L
i, Xiaodong Wu, Michele Rizzolio, James G Breitenbucher, Kelly McClure, and Nige
l P Shankley JNJ-17156516 (3-[5-(3,4-dichloro-phenyl)-1-(4-methoxy-phenyl)-1H-p
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endergast, Mark Rosen, Terry Barrett, Guy Lagaud, Jamie Freedman, Mich*le C. Riz
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ent filed by Molecular Probes Inc.
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occal toxic shock syndrome toxin-1 in immunized rabbits. Abstract for the 1994 C
SM'CBDN joint conference.
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oxic shock syndrome toxin-1. Abstract for 1993 Annual Meeting of Canadian Societ
y of Clinical Investigation, Clini Invest Med Sppl 16:B78, 1993
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1. F. K. Ying, N. Li, H. T. Xu, X.Z. Chen and R. L. Deng, Alpha-interferon inhib
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KEY WORDS
GPCR, lipid receptor, incretin, islet -cells, toxicology, drug safety, enzyme in
hibitor, agonist, antagonist, signal modulator, cell-based assay, receptor bindi
ng, PD end-points, biomarker, translational biology, PKPD model, mTOR, metabolis
m, inflammation, immunity, oncology, therapeutic vaccine, cancer biology, epigen
etic