AssistantInvestigator,NIBS,Beijing，ChinaPhone：010-80726688-8380
Fax：010-80727511
E-mail：chenliang@nibs.ac.cn
教育经历Education2002年中国科学院上海生物化学和细胞生物学研究所，细胞生物学博士学位
Ph.D.inCellBiology,ShanghaiInstituteofBiochemistryandCellBiology,ChineseAcademyofSciences,China
1996年杭州大学生物系学士学位
B.S.inBiotechnology,DepartmentofBiology,HangzhouUniversity,Zhejiang,China
工作经历ProfessionalExperience2010年-北京生命科学研究所研究员
AssistantInvestigator,NationalInstituteofBiologicalSciences,Beijing,China
2005-2010年哈佛大学医学院Dana-Farber癌症研究所博士后
PostdoctoralFellow，DepartmentofMedicalOncology,Dana-FarberCancerInstitute,HarvardMedicalSchool
2002-2005年耶鲁大学医学院博士后
PostdoctoralFellow，DepartmentofInternalMedicine,YaleUniversitySchoolofMedicine
研究概述肺癌和肝癌是对中国癌症病人威胁最大的两种肿瘤。中国大陆每年分别有六十万和二十三万人死于肺癌和肝癌。本实验室最终目标是控制这两种癌症。我们的研究将具体在以下四个方面进行：1.寻找驱动中国人肺癌和肝癌癌变的关键癌基因。较之于正常细胞，虽然一个癌细胞在遗传水平和表观遗传水平有很多改变，但当关键的癌基因被灭活后，癌细胞的生长和增殖将受到严重的影响。本实验室的一个重要方向是寻找驱动中国人肺癌和肝癌病变的关键癌基因，为靶向治疗奠定基础。
2.探究癌变早期时抑癌基因的变化。正常组织细胞有一套完善的抑瘤机制来防止细胞的癌变。在癌变早期，与癌基因功能获得性突变平行的是抑癌基因的功能紊乱。我们将在细胞水平和动物模型水平上来研究癌变早期抑癌基因的变化。
3.开发肺癌和肝癌的靶向治疗手段。至今，尽管有比较多的癌症治疗手段可供选择，但肺癌和肝癌病人的五年存活率仍然很低。我们将在细胞和动物水平上来探究有特定癌基因驱动的肺癌和肝癌的肿瘤生物学。基于此，我们将设计针对该种肿瘤的靶向疗法，并用小鼠模型来初步确证该治疗手段的有效性。
4.寻找肿瘤早期诊断的标志蛋白。控制肺癌和肝癌最有效的手段是早期诊断，因为此时可以有效地治疗或手术切除。我们将用已鉴定的小鼠模型来寻找血清中的标志蛋白，以便于早期诊断，再在病人血样中确证。
ResearchDescriptionLungcancerandlivercancerarethetwobiggestthreatstoChinesecancerpatients,whichclaimyearly600,000livesand230,000livesrespectivelyinmainlandChina.Theultimategoalofresearchinourlaboratoryistocurebothdiseases.Specifically,researchwillfocusonthefollowingfourareas:1.IdentifyingkeyoncogenesresponsiblefortumorigenesisoflungcancerandlivercancerinChinesecancerpatients.It’sbeenshownthatalthoughacancercellhasmanygeneticandepigeneticalterations,survivalandproliferationofthecancercellisoftenseverelyaffectedbyinactivationofasinglekeyoncogene.OneimportantareaofourlabistoidentifyoncogenesresponsiblefordrivingtumorigenesisinChineselungcancerandlivercancerpatients,whichisthefirststepfordevelopingtargetingtherapies.
2.Decipheringthechangeshappenedtotumorsuppressorgenesintheprocessoftumorigenesis.Inparalleltogain-of-functionmutationinoncogenes,deregulationintumorsuppressorgenesplaysanimportantroleintumorigenesis.Wewillusecellularandmousemodelstostudythegeneticandepigeneticchangeshappenedintumorsuppressorgenesduringtumorigenesis.
3.Developingtargetingtherapiesagainstlungcancerandlivercancer.Despitethemultimodalitytherapiesagainstbothcancers,the5yearsurvivalrateremainsdisappointinglylowforbothlungcancerandlivercancer.Effectivetherapiesaredesperatelyneededinclinic.Bothcellularandmousemodelswillbeutilizedtocharacterizethebiologyofthetumordrivenbyagivenoncogene.Basedonthatinformation,wewilldesignandrunapreclinicaltrialinmousemodelwithsmallchemicals/antibodiesdeveloped.
4.Identifyingserumproteinbiomarkersforearlydiagnosisoflungandlivercancer.Themosteffectivewaytobenefitcancerpatientsisthroughdiagnosecancersatearlystagewhenthetumorcanbesuccessfullytreatedorsurgicallyremoved.Withwell-characterizedmousemodelthatdeveloptumorsafteractivationofoncogenictransgene,wewillcollectserumfrommousewithearlystagetumors.Bycomparingtheserumsamplesfromtumor-bearingmouseandwell-controlledhealthysiblingsthroughmass-spectrometry,weplantolookfortheproteinbiomarkersthatareselectivelypresentinthetumor-bearingmouse.Thepotentialuseofthesebiomarkerswillthenbeconfirmedonthepatients’sera.
发表文章Publications1.ShimamuraT,PereraSA,FoleyKP,SangJ,RodigSJ,InoueT,ChenL,LiD,CarreteroJ,LiYC,SinhaP,CareyCD,BorgmanCL,JimenezJP,MeyersonM,YingW,BarsoumJ,WongKK,ShapiroGIGanetespib(STA-9090),aNongeldanamycinHSP90Inhibitor,HasPotentAntitumorActivityinInVitroandInVivoModelsofNon-SmallCellLungCancer.ClinCancerRes.2012Sep15;18(18):4973-85.Epub2012Jul17.2.StraumeO,ShimamuraT,LampaMJ,CarreteroJ,OyanAM,JiaD,BorgmanCL,SoucherayM,DowningSR,ShortSM,KangSY,WangS,ChenL,CollettK,BachmannI,WongK-K,ShapiroGI,KallandKH,FolkmanJ,WatnickRS,AkslenLA,NaumovGN.Suppressionofheatshockprotein27induceslong-termdormancyinhumanbreastcancer.ProcNatlAcadSciUSA.2012May29;109(22):8699-704.Epub2012May153.LengL,ChenL,FanJ,GrevenD,ArjonaA,DuX,AustinD,KashgarianM,YinZ,HuangXR,LanHY,LolisE,Nikolic-PatersonD,BucalaR.Asmall-moleculemacrophagemigrationinhibitoryfactorantagonistprotectsagainstglomerulonephritisinlupus-proneNZB/NZWF1andMRL/lprmice.JImmunol2011Jan186(1),527-538.4.M-CLiang,JMa,LChen,PKozlowski,WQin,DLi,JGoto,TShimamura1,DNHayes,MMeyerson,DJKwiatkowskiandK-KWong,TSC1losssynergizeswithKRASactivationinlungcancerdevelopmentinthemouseandconfersrapamycinsensitivity,Oncogene,2010Mar18;29(11):1588-975.ZhouW(*),ErcanD(*),ChenL(*),YunC(*),LiD,CapellettiM,ChirieacL,IacobRE,PaderaR,EngenJR,WongKK,EckM,GrayNSandJännePA.,Novelmutant-selectiveEGFRkinaseinhibitorsagainstEGFRT790M,Nature,2009Dec24;462(7276):1070-4,(*equalcontribution)6.PereraSA,LiD,ShimamuraT,RasoMG,JiH,ChenL,BorgmanCL,ZaghlulS,BrandstetterKA,KuboS,TakahashiM,ChirieacLR,PaderaRF,BronsonRT,ShapiroGI,GreulichH,MeyersonM,GuertlerU,ChesaPG,SolcaF,WistubaII,WongKK.,HER2YVMAdrivesrapiddevelopmentofadenosquamouslungtumorsinmicethataresensitivetoBIBW2992andrapamycincombinationtherapy,ProcNatlAcadSciUSA.2009Jan13;106(2):474-9.7.EngelmanJA(*),ChenL(*),TanX,CrosbyK,GuimaraesAR,UpadhyayR,MairaM,McNamaraK,PereraSA,SongY,ChirieacLR,KaurR,LightbownA,SimendingerJ,LiT,PaderaRF,García-EcheverríaC,WeisslederR,MahmoodU,CantleyLC,WongKK.,EffectiveuseofPI3KandMEKinhibitorstotreatmutantKrasG12DandPIK3CAH1047Rmurinelungcancers.NatMed.2008Dec;14(12):1351-6.(*equalcontribution)8GirnunGD(*),ChenL(*),SilvaggiJ,DrapkinR,ChirieacLR,PaderaRF,UpadhyayR,VafaiSB,WeisslederR,MahmoodU,NaseriE,BuckleyS,LiD,ForceJ,McNamaraK,DemetriG,SpiegelmanBM,WongKK.,Regressionofdrug-resistantlungcancerbythecombinationofrosiglitazoneandcarboplatin.ClinCancerRes.2008Oct15;14(20):6478-86.(*equalcontribution)9.PereraSA,MaserRS,XiaH,McNamaraK,ProtopopovA,ChenL,HezelAF,KimCF,BronsonRT,CastrillonDH,ChinL,BardeesyN,DepinhoRA,WongKK.,TelomeredysfunctionpromotesgenomeinstabilityandmetastaticpotentialinaK-rasp53mousemodeloflungcancer.Carcinogenesis.2008Apr;29(4):747-53.10.JiH,RamseyMR,HayesDN,FanC,McNamaraK,KozlowskiP,TorriceC,WuMC,ShimamuraT,PereraSA,LiangMC,CaiD,NaumovGN,BaoL,ContrerasCM,LiD,ChenL,KrishnamurthyJ,KoivunenJ,ChirieacLR,PaderaRF,BronsonRT,LindemanNI,ChristianiDC,LinX,ShapiroGI,JännePA,JohnsonBE,MeyersonM,KwiatkowskiDJ,CastrillonDH,BardeesyN,SharplessNE,WongKK.,LKB1modulateslungcancerdifferentiationandmetastasis.Nature.2007Aug16;448(7155):807-10.11.LiD,ShimamuraT,JiH,ChenL,HaringsmaHJ,McNamaraK,LiangMC,PereraSA,ZaghlulS,BorgmanCL,KuboS,TakahashiM,SunY,ChirieacLR,PaderaRF,LindemanNI,JännePA,ThomasRK,MeyersonML,EckMJ,EngelmanJA,ShapiroGI,WongKK.BronchialandperipheralmurinelungcarcinomasinducedbyT790M-L858RmutantEGFRrespondtoHKI-272andrapamycincombinationtherapy.CancerCell.2007Jul;12(1):81-93.12.JiH,WangZ,PereraSA,LiD,LiangMC,ZaghlulS,McNamaraK,ChenL,AlbertM,SunY,Al-HashemR,ChirieacLR,PaderaR,BronsonRT,ThomasRK,GarrawayLA,JännePA,JohnsonBE,ChinL,WongKK.,MutationsinBRAFandKRASconvergeonactivationofthemitogen-activatedproteinkinasepathwayinlungcancermousemodels.CancerRes.2007May15;67(10):4933-9.13.ChenL(*),HeW(*),KimST,TaoJ,GaoY,ChiH,IntlekoferAM,HarveyB,ReinerSL,YinZ,FlavellRA,CraftJ..EpigeneticandTranscriptionalProgramsLeadtoDefaultIFN-gammaProductionbygamma/deltaTCells.2007Mar;JImmunol.178(5):2730-2736.(*equalcontribution)14.TaoJ,GaoY,LiMO,HeW,ChenL,HarvevB,DavisRJ,FlavellRA,YinZ.JNK2negativelyregulatesCD8(+)Tcelleffectorfunctionandanti-tumorimmuneresponse.EurJImmunol.2007Mar;37(3):818-829.15.JiH,LiD,ChenL,ShimamuraT,KobayashiS,McNamaraK,MahmoodU,MitchellA,SunY,Al-HashemR,ChirieacLR,PaderaR,BronsonRT,KimW,JännePA,ShapiroGI,TenenD,JohnsonBE,WeisslederR,SharplessNE,WongKK.,TheimpactofhumanEGFRkinasedomainmutationsonlungtumorigenesisandinvivosensitivitytoEGFR-targetedtherapies.CancerCell.2006Jun;9(6):485-95.16.WisnewskiAV,StoweMH,CartierA,LiuQ,LiuJ,ChenL,RedlichCA.,Isocyanatevapor-inducedantigenicityofhumanalbumin.JAllergyClinImmunol.2004Jun;113(6):1178-1184.17.WisnewskiAV,HerrickCA,LiuQ,ChenL,BottomlyK,RedlichCA.Humangamma/deltaT-cellproliferationandIFN-gammaproductioninducedbyhexamethylenediisocyanate.JAllergyClinImmunol.2003Sep;112(3):538-546.18.ChenL,LiG,TangL,WangJ,GeXR,TheinhibitionoflungcancercellgrowthbyintracellularimmunizationwithLC-1ScFv.CellRes.2002Mar;12(1):47-54.
