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- 1. SHENG JIAN CAI, PH.D
(908)-740-7859 (office) shengjian_cai@merck.com
(908)-625-9665 (Mobile) shengjianc@yahoo.com
LinkedInprofile www.linkedin.com/in/sheng-jian
PHARMACEUTICAL RESEARCH SCIENTIST
Highlymotivatedandinnovative seniorscientistwithadvanced knowledgeinpreclinical drugdiscoveryand
developmentrelatedtocardiovasculardiseases,diabetesand oncology(breastcancerand uteruscancer) areas
and withextensiveexperiencein cell biology,molecularbiology,enzymology,immunologyandmicrobiology.
Recognizedproblemsolverwithexceptional abilitytolead invitro,ex vivoassaysdevelopmentandto
coordinate andorganize crossfunctionsstudiesina well-organizedandefficientway.
EXPERIMENTAL EXPERIENCE
Molecularbiology: Genomicand cDNA libraryconstruction, Gene cloning, DNA sequencing,RT-PCR,
Southernblot,NorthernblotandWesternblotanalyses; Expressionvectorconstruction,Site-directed
mutagenesis;Designinganddevelopingtransgenicmouse
Cell Biology: MammalianCellculture,transienttransfectionandstable clone isolation.Protein
expressionwithplasmidandviral vectors(Lenti,Adenoassociated virus,etc.) Isolationof ratprimary
smoothmuscle cellsandprimarycardiomyocyte cellsandassays development
ProteinChemistrytechniques: Proteinpurificationbygel filtration,ionexchange andHPLC;SDS-PAGE.
Isolationof membrane/cytosolicproteins.GST-,MBP-fusion,His-tagProteinexpressioninE.coli and
affinitypurification
Assayand assaydevelopment: Proteinbase, cell base andtissue base (bloodvesselcontractionand
relaxation assay) assay development; ELISA, HTRF assay, Cell-baseactivatorandinhibitorassays,
reportergene assay,Mesoplatformassay,LC/MS
Animal worktechniques: Maintainingmouse,ratandrabbitcoloniesandcollectingblood,tissue
samplesforisolationof RNA, DNA;Gavage,intravenous,intraperitoneal andsubcutaneousdosing.Rat
hyperglycemic,hypoglycemicandeuglycemicclampstudies
PROFESSIONAL EXPERIENCE
Merck & Co. Kenilworth, NJ
Senior Scientist 2012 - Present
Lead invitroassaydevelopmenteffortsandprovide biologysupport forprograms inpulmonary hypertensionand
Diabetes groups
DevelopedCHO/NPRA/PED5cell line tocounterscreen PDE5activityof sGC activators
CoordinatedInvitroandinvivogroupsto collect and processwhole bloodorplasmasamples and
measure cGMP as biomarkerusingLC/MS
Ran glucagon,insulin HTRFassaysand performedrat hyperglycemic,hypoglycemicandeuglycemic
clampstudies
Senior Research Biologist 2002-2012
- 2. Supportprogramsin HypertensionandEndocrinologygroupsforcompounds leadidentification and
optimization
Lead vasoreactivity(bloodvesselscontraction-relaxation)assayusingDMT myograph to measure
efficaciesof compoundsinvasculature andtode-riskpotential cardiovascularadverseeffects for
compoundsbyworkingwithprogramleadsfrom differentfranchisesacrossthe company.
Developedrataorticsmooth muscle primarycell assayand neonatal cardiomyocyteprimarycell assaysto
supportheartfailure andhypertensionprograms
Developed nuclearreceptor-coactivators protein(HTRF) andcell base assaystosupportprogramsrelated
to women’shealthsuchasbreastand uteruscancers -
DevelopedandcharacterizedTPH-1promoter-lacZtransgenicmouse tostudyTPH-1expressionregulated
by estrogen receptors.
PREVIOUS EXPERIENCE
Developedandran cell base assaysto screen compounds forsomatostatinsubtype 2andsubtype 5
receptors
MaintainSst5 Knock-outmice line
Characterizationof structure andfunctionsof polyketide synthase,methyltransferase andhydroxylase
genesinvolvedinthe biosynthesisof the immunosuppressant FK506
Cloningandsequencingof apolipoproteinB-48.Humangenomiclibrary construction, cloningand
sequencinghumanhepaticlipase gene
EDUCATION
Degree: Field Institution
Ph.D. Cell anddevelopmental Biology Graduate School inNew Brunswick,
RutgersUniversity,New Jersey
M. Med. Biochemistry Shanghai secondMedical University Shanghai,China
B.Sc. Microbiology WuhanUniversity,Wuhan,China
AFFILIATIONS
AmericanDiabetesAssociation (2014 - 2016)
Heart Failure societyof America (2014 - 2016)
AmericanHeartAssociation (2007 - 2014)
- 3. PUBLICATIONS
PUBLICATIONS
Motamedi,H.,Shafiee,A.,and Cai,S.J. (1995). Integrative vectorsforheterologousgeneexpressionin
Streptomycessp.Gene 160, 25-31.
Motamedi,H.,Shafiee,A., Cai,S.J.,Streicher,S.L.,Arison,B.H.,andMiller,R.R.(1996). Characterizationof
methyltransferaseandhydroxylase genesinvolvedinthe biosynthesisof the immunosuppressantsFK506and
FK520. J Bacteriol 178, 5243-5248.
Motamedi,H., Cai, S.J., Shafiee,A.,andElliston,K.O.(1997).Structural organizationof amultifunctional
polyketide synthase involved in the biosynthesis of the macrolide immunosuppressant FK506. Eur J Biochem 244,
74-80.
Rohrer,S.P.,Birzin,E.T.,Mosley,R.T.,Berk,S.C.,Hutchins,S.M.,Shen,D.M.,Xiong,Y.,Hayes,E.C.,Parmar, R.M.,
Foor,F., Mitra, S.W.,Degrado,S.J.,Shu,M., Klopp,J.M., Cai,S.J., Blake,A.,Chan,W.W.,Pasternak,A.,Yang,L.,
Patchett,A.A.,Smith,R.G.,Chapman,K.T.,andSchaeffer,J.M.(1998). Rapididentificationof subtype-selective
agonistsof the somatostatinreceptorthroughcombinatorialchemistry.Science 282,737-740.
Wilkinson,H.A., Dahllund,J.,Liu,H.,Yudkovitz,J., Cai,S.J.,Nilsson,S.,Schaeffer,J.M.,andMitra,S.W. (2002).
Identification andcharacterizationof afunctionallydistinctformof humanestrogenreceptorbeta.
Endocrinology 143, 1558-1561.
Cai, S.J., and Inouye,M. (2002). EnvZ-OmpRinteractionandosmoregulationinEscherichiacoli.JBiol Chem 277,
24155-24161.
Yoshida,T., Cai, S.J. and Inouye,M.(2002). Interactionof EnvZ,a sensoryhistidine kinase,withphosphorylated
OmpR,the cognate response regulator.Mol Microbiol 46, 1283-1294.
QinL, Cai,S, Zhu Y, Inouye M. (2003). Cysteine-scanninganalysisof the dimerization domainof EnvZ,an
osmosensinghistidinekinase. JBacterol. 185, 3429-3435.
Cai, S.J., Khorchid,A.,Ikura,M., and Inouye,M.(2003). ProbingCatalyticallyEssential DomainOrientationin
Histidine Kinase EnvZbyTargetedDisulfide Crosslinking.JMol Biol 328, 409-418.
Cai, S.J., and Inouye,M. (2003). Spontaneoussubunitexchange andbiochemical evidence fortrans-
autophosphorylationinadimerof Escherichiacoli histidinekinase(EnvZ). JMol Biol 329, 495-503.
WilkeningRR,Ratcliffe RW,TyneborEC,WildongerKJ,FriedAK,HammondML,MosleyRT, FitzgeraldPM,
Sharma N,McKeeverBM, NilssonS,CarlquistM,Thorsell A,LoccoL, KatzR, FrischK, BirzinET, WilkinsonHA,
Mitra S, Cai S, HayesEC, SchaefferJM,RohrerSP.(2006) The discoveryof tetrahydrofluorenonesas anewclass
of estrogenreceptorbeta-subtype selectiveligands.BioorgMedChemLett.16(13):3489-94.
Chisamore MJ,Mosley RT, Cai SJ, BirzinET, O'Donnell G,ZuckP, FloresO,SchaefferJ,RohrerSP,ChenJD,and
WilkinsonHA. (2008) Identificationof small molecule estrogen- -specificantagonistand
- 4. Dev.Res.69, 203-218.
.
ABSTRACTS PRESENTATION
Cai, S.J., Mitra, S., Rohrer,S.,and Wilkinson,H.(2004) Characterization of ERR interactionwithGrip1orAIBa by
Fluorescence EnergyTransfer.Keystone Symposia,NuclearReceptors:OrphanBrothers.Keystone,Colorado.
February 28- March 4.
Motamedi,H.and Cai, S.J. (1995). Functional replacementof the yeastregulatorysubunit,CNB1,withhuman
counterpartina Fks1mutant. ASMMeeting,WashingtonD.C.May25-30.
Motamedi,H.;Cai, S.J; Shafiee A.andStreicher,S.L.(1994). FK506 polyketide synthase isalarge multifunctional
polypeptide with19FAS-likedomains. Geneticsof Industrial Microorganism(GIM),Montreal,Canada.
Motamedi,H.;Cai, S.J and Shafiee A.(1992).Cloning,sequencingandheterologousgene expressionof 31-
desmethyl immunomycin-O-MethyltransferasefromStreptomyceshygroscopicusvariantascomyceticus
MA6475. 5th
ASMconf.Geneticsof Industrial Microorganism, Bloomington,IN,A19.
Motamedi,H.;Shafiee A and Cai, S.J. (1992). Cloning,andsequence analysisof the gene encoding31-desmethyl
FK506-O-methyltransferase fromStreptomycessp.MA6558 and itsuse as hybridizationprobe.5th
ASMconf.
Geneticsof Industrial Microorganism, Bloomington,IN,C19.
Motamedi,H.;and Cai, S.J. (1992). Constructionof a two componentexpressionvectorforStreptomyces.5th
ASMconf.Geneticsof Industrial Microorganism, Bloomington,IN,B15.
Motamedi,H.;Cai, S.J and Shafiee A.(1992).Early Genesinvolvedinthe biosynthesisof Macrolactone ringof
immunosuppressivedrugFK506 fromStreptomycessp.MA6548. 5th
ASMconf.Geneticsof Industrial
Microorganism,Bloomington,IN,C17.
Cai, S.J.,Mitra, S.,Rohrer,S., and Wilkinson,H.(2004) Charaterizationof ERRinteractionwithGrip1or AIBaby
Fluorescence EnergyTransfer.Keystone Symposia,NuclearReceptors:OrphanBrothers.Keystone,Colorado.
Feburary28- March 4.
NO-ARBPosterforChemistryCouncil LaSapiniere 2007 NO-ARB
for the Treatment ofHypertension
Michael M.-C.Loa, Roxanne Atienzaa,ChristopherL.Franklina,AmjadAlia,Iyassu K.Sebhata,Ravi P.Nargunda,
MatthewJ. Wyvratta,ZheshengChena,TomG. Holte, GinoM. Salituroa,MelbaHernandezb,KarenOrtegaj,
SoniaLevesquej,AmberY.Zhub,MagdalenaAlonso-Galiciab,LinLuob, Sheng-JianCai,DenisY.Streltsovb,Annie
- 5. Zhaob,JisongCuib,Sophie Royb,Shu-YuSunc,Michael J.Forrestc,DanYaod,ShiyaoXud,RandyR. Millerd,Stella
H. Vincentd,BrianT.Farrerf,JingjunYing,DeborahL.Millerh,Dennis Salottih,andRhondaKaufmanh
Departmentof Medicinal Chemistrya,Departmentof CardiovascularDiseasesb,Departmentof Pharmacologyc,
Deparmentof Drug Metabolismd,Departmentof ResearchOperationse, Departmentof Pharmaceutical
Research,Departmentof ProcessResearch,Departmentof Experimental Medicine,MerckResearch
Laboratories,Rahway,NewJersey07065, USA Departmentof Comparative Medicine,MerckFrosstCentre for
TherapeuticResearch,Kirkland,QuebecH9H3L1, Canada
Site reviewposter 2014
Soluble Guanylate Cyclase (sGC) Activatorsfor the Treatment of Hypertension
1
Linda Brockunier, 1
Subharekha Raghavan, 1
Keith Rosauer, 1
Tracey Spencer, 1
John Stelmach, 2
Julia Aguirre,
2
Sheng-Jian Cai, 2
Valdeci da Cunha, 2
Jacqueline Dillon, 3
Michael Forrest, 2
Helen Fu, 2
Qifeng Yang 5
Sonia
Levesque, 2
Lin Luo, 3
Xiuying Ma, 6
Christopher Mortko, 5
Karen Ortega, 3
Lee-Yuh Pai, 3
Cherrie Shepherd, 4
John
Cummings, 4
Gino Salituro, 4
Jackie Shang, 4
Shiyao Xu, 3
Jun Yao, 2
Sophie Roy, 1
James Tata, 2
Jisong Cui and 1
Emma
Parmee
Departments of: 1
Medicinal Chemistry, Rahway; 2
Cardiovascular Diseases, Rahway; 3
Pharmacology, Rahway;
4
Drug Metabolism, Rahway; 5
Comparative Medicine, Merck Frosst; 6
Materials Characterization and Tech.
Assessment,Rahway.
Merck ResearchlaboratoriesSummerPostersection2015
GPR119 Agonist,a Potential Treatment for T1D HypoglycemiaUnawareness
Sheng-JianCai;Yue Feng;Margaret Wu; XiaolanShenandNinaLi
Departmentof Cardiorenal MetabolicDiseases,Diabetes&NASHLate Discovery