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北京生命科学研究所研究生导师简介-李文辉 博士

北京生命科学研究所 免费考研网/2013-11-15

李文辉博士北京生命科学研究所研究员WenhuiLi,Ph.D.
AssistantInvestigator,NIBS,Beijing,ChinaPhone:010-80726688-8580
Fax:010-80726689
E-mail:liwenhui@nibs.ac.cn


教育经历Education1994兰州医学院医学学士学位
LanzhouMedicalCollege(SchoolofMedicine,LanzhouUniversity)BachelorDegreeofMedicine
1997兰州生物制品研究所免疫学硕士学位
LanzhouInstituteofBiologicalProductsM.S.inImmunology
2001中国协和医科大学中国医学科学院基础医学研究所病原生物学博士学位
InstituteofBasicMedicalSciencesPekingUnionMedicalCollege&ChineseAcademyofMedicalSciencesPh.D.inPathogenicBiology
工作经历ProfessionalExperience2007-北京生命科学研究所研究员
AssistantInvestigator,NationalInstituteofBiologicalSciences,Beijing
2004-2007哈佛大学医学院Instructor
HarvardMedicalSchool,Boston
2001-2004哈佛大学医学院博士后
PostdoctoralFellow,HarvardMedicalSchool,Boston
1997-1998兰州生物制品研究所研究助理
ResearchAssistant,LanzhouInstituteofBiologicalProducts,Lanzhou
研究概述ResearchDescription本实验室的主要研究兴趣为囊膜病毒侵入细胞及相关过程的分子机制。病毒侵入细胞起始于与细胞表面受体的结合。围绕这一过程,我们希望探索:病毒细胞受体分子的识别;病毒受体是如何介导病毒感染的;其它胞内因子是如何参与病毒侵入的;病毒蛋白是如何进行免疫逃逸的;如何有效地抑制病毒的感染等。我们综合运用病毒学,生物化学,化学生物学等多学科方法,以回答上述问题。这些研究将有利于深化对于病毒基本生物学,及病毒与感染宿主相互作用的认识与理解,并且有助于开发有效的抗病毒制剂及新型疫苗。乙型肝炎是危害人类健康的严重传染病,是导致肝硬化、肝癌的重要病因。我们最近成功地发现并确认了人类乙型肝炎病毒,及其密切相关的丁型肝炎病毒感染肝细胞所必需的功能受体分子是肝细胞膜上的钠离子-牛磺胆酸-协同转运蛋白(NTCP)。这一重要发现为进一步深入研究乙肝病毒及相关致病机制打开了新的大门,并为研发新的药物和治疗手段提供了可能。Ourlabtriestounderstandtheentrymechanismsofenvelopedviruses.Regardlessofthetypeofenvelopedvirus,theinitialstepofviralentryalwaysinvolvestheinteractionsbetweentheviralenvelopeprotein(s)andviralreceptor(s)onhostcells.Thequestionsthatwearemostlyinterestedinare:whatisthespecificcellularreceptorforavirus?Howdoesthereceptorcontributetoviralentry?Howdoestheviralentryproteinevadethehostimmuneresponse?Howcanviralinfectionbeinhibitedbyentryinhibitororhostimmunity.Weseektoidentifythereceptorsandelucidatetheentryprocessesofviralpathogensimportanttohumanhealth.Knowledgeofviralentrymechanismswilldeepenourunderstandingofbasicbiologyofvirusesandtheirhostcells,andoffernewopportunitiestodevelopmoreefficientinhibitorsagainsttheinfectionsandnewgenerationofviralvaccines.HepatitisBvirus(HBV)infectionanditsassociatedcirrhosisandhepatocellularcarcinomacauseaboutonemilliondeathsannually.ThemolecularmechanismsbywhichHBVanditssatellitevirusHepatitisDvirus(HDV)infecthumanliverhavebeenelusive.Bytakingstate-of-the-artaffinitypurificationapproach,werecentlyidentifiedsodiumtaurocholatecotransportingpolypeptide(NTCP),aliverbileacidtransporter,asaspecificreceptorforHBVandHDV.NTCPbindstoacriticalreceptorbindingregionofviralenvelopeLproteinandcontributessubstantiallytotheefficiencyofHBVandHDVinfections.ThisfindingadvancesourunderstandingoftheHBVandHDVinfectionandmayleadtonewstrategiesforpreventionandtreatmentoftheseviralinfectionsandassociateddiseases.发表文章Publications1.SodiumtaurocholatecotransportingpolypeptideisafunctionalreceptorforhumanhepatitisBandDvirus.YanH,ZhongG,XuG,HeW,JingZ,GaoZ,HuangY,QiY,PengB,WangH,FuL,SongM,ChenP,GaoW,RenB,SunY,CaiT,FengX,SuiJ,LiW.elife.2012;1:e00049.doi:10.7554/eLife.00049.2.MolecularDeterminantsofEnterovirus71ViralEntry:cleftaroundGln-172onVP1proteininteractswithvariableregiononscavengereceptorB2.ChenP,SongZ,QiY,FengX,XuN,SunY,WuX,YaoX,MaoQ,LiX,DongW,WanX,HuangN,ShenX,LiangZ,LiW.JBiolChem.2012Feb24;287(9):6406-20.3.StructuralbasisforactivationandinhibitionofthesecretedchlamydiaproteaseCPAF.HuangZ,FengY,ChenD,WuX,HuangS,WangX,XiaoX,LiW,HuangN,GuL,ZhongG,ChaiJ.CellHostMicrobe.2008Dec11;4(6):529-42.4.HuangIC,LiW,SuiJ,MarascoW,ChoeH,FarzanM.InfluenzaAvirusneuraminidaselimitsviralsuperinfection.JVirol.2008May;82(10):4834-43.5.LiW,SuiJ,HuangIC,KuhnJH,RadoshitzkySR,MarascoWA,ChoeH,FarzanM.TheSproteinsofhumancoronavirusNL63andsevereacuterespiratorysyndromecoronavirusbindoverlappingregionsofACE2.Virology.2007;doi:10.1016/j.virol.2007.04.0356.RadoshitzkySR,AbrahamJ,SpiropoulouCF,KuhnJH,NguyenD,LiW,NagelJ,SchmidtPJ,NunbergJH,AndrewsNC,FarzanM,ChoeH.Transferrinreceptor1isacellularreceptorforNewWorldhaemorrhagicfeverarenaviruses.Nature.2007;446(7131):92-6.7.HeY,LiJ,LiW,LustigmanS,FarzanM,JiangS.Cross-neutralizationofhumanandpalmcivetsevereacuterespiratorysyndromecoronavirusesbyantibodiestargetingthereceptor-bindingdomainofspikeprotein.JImmunol.2006,176(10):6085-92.8.LiW,WongSK,LiF,KuhnJH,HuangIC,ChoeH,FarzanM.Animaloriginsofthesevereacuterespiratorysyndromecoronavirus:insightfromACE2-S-proteininteractions.JVirol.2006,80(9):4211-9review9.KuhnJH,RadoshitzkySR,GuthAC,WarfieldKL,LiW,VincentMJ,TownerJS,NicholST,BavariS,ChoeH,AmanMJ,FarzanM.Conservedreceptor-bindingdomainsofLakeVictoriamarburgvirusandZaireebolavirusbindacommonreceptor.JBiolChem.2006,281(23):15951-8.10.HuangIC,BoschBJ,LiF,LiW,LeeKH,GhiranS,VasilievaN,DermodyTS,HarrisonSC,DormitzerPR,FarzanM,RottierPJ,ChoeH.SARScoronavirus,butnothumancoronavirusNL63,utilizescathepsinLtoinfectACE2-expressingcells.JBiolChem.2006,281(6):3198-203.11.HuangIC,BoschBJ,LiW,FarzanM,RottierPM,ChoeH.SARS-CoV,butnotHCoV-NL63,utilizescathepsinstoinfectcells:viralentry.AdvExpMedBiol.2006;581:335-8.12.LiW,ChoeH,FarzanM.InsightsfromtheassociationofSARS-CoVS-proteinwithitsreceptor,ACE2.AdvExpMedBiol.2006;581:209-18.Review.13.LiF,LiW,FarzanM,HarrisonSC.StructureofSARScoronavirusspikereceptor-bindingdomaincomplexedwithreceptor.Science.2005,309(5742):1864-8.14.SuiJ,LiW,RobertsA,MatthewsLJ,MurakamiA,VogelL,WongSK,SubbaraoK,FarzanM,MarascoWA.Evaluationofhumanmonoclonalantibody80Rforimmunoprophylaxisofsevereacuterespiratorysyndromebyananimalstudy,epitopemapping,andanalysisofspikevariants.JVirol.2005,79(10):5900-6.15.LiW,ZhangC,SuiJ,KuhnJH,MooreMJ,LuoS,WongSK,HuangIC,XuK,VasilievaN,MurakamiA,HeY,MarascoWA,GuanY,ChoeH,FarzanM.ReceptorandviraldeterminantsofSARS-coronavirusadaptationtohumanACE2.EMBOJ.2005,24(8):1634-43.16.ChoeH,MooreMJ,OwensCM,WrightPL,VasilievaN,LiW,SinghAP,ShakriR,ChitnisCE,FarzanM.SulphatedtyrosinesmediateassociationofchemokinesandPlasmodiumvivaxDuffybindingproteinwiththeDuffyantigen/receptorforchemokines(DARC).MolMicrobiol.2005;55(5):1413-22.17.LiW,GreenoughTC,MooreMJ,VasilievaN,SomasundaranM,SullivanJL,FarzanM,ChoeH.Efficientreplicationofsevereacuterespiratorysyndromecoronavirusinmousecellsislimitedbymurineangiotensin-convertingenzyme2.JVirol.2004,78(20):11429-33.18.SuiJ,LiW,MurakamiA,TaminA,MatthewsLJ,WongSK,MooreMJ,TallaricoAS,OlurindeM,ChoeH,AndersonLJ,BelliniWJ,FarzanM,MarascoWA.Potentneutralizationofsevereacuterespiratorysyndrome(SARS)coronavirusbyahumanmAbtoS1proteinthatblocksreceptorassociation.ProcNatlAcadSciUSA.2004,101(8):2536-41.19.WongSK,LiW,MooreMJ,ChoeH,FarzanM.A193-aminoacidfragmentoftheSARScoronavirusSproteinefficientlybindsangiotensin-convertingenzyme2.JBiolChem.2004,279(5):3197-201.20.MooreMJ,DorfmanT,LiW,WongSK,LiY,KuhnJH,CoderreJ,VasilievaN,HanZ,GreenoughTC,FarzanM,ChoeH.Retrovirusespseudotypedwiththesevereacuterespiratorysyndromecoronavirusspikeproteinefficientlyinfectcellsexpressingangiotensin-convertingenzyme2.JVirol.2004;78(19):10628-35.21.LiW,MooreMJ,VasilievaN,SuiJ,WongSK,BerneMA,SomasundaranM,SullivanJL,LuzuriagaK,GreenoughTC,ChoeH,FarzanM.Angiotensin-convertingenzyme2isafunctionalreceptorfortheSARScoronavirus.Nature.2003,426(6965):450-4.22.ChoeH,LiW,WrightPL,VasilievaN,VenturiM,HuangCC,GrundnerC,DorfmanT,ZwickMB,WangL,RosenbergES,KwongPD,BurtonDR,RobinsonJE,SodroskiJG,FarzanM.TyrosinesulfationofhumanantibodiescontributestorecognitionoftheCCR5bindingregionofHIV-1gp120.Cell.2003,114(2):161-70.23.FarzanM,ChungS,LiW,VasilievaN,WrightPL,SchnitzlerCE,MarchioneRJ,GerardC,GerardNP,SodroskiJ,ChoeH.Tyrosine-sulfatedpeptidesfunctionallyreconstituteaCCR5variantlackingacriticalamino-terminalregion.JBiolChem.2002,277(43):40397-402.24.LiW,ZhangY,SuiJ,WangS.CombinedimmunizationofDNAvaccineandreplication-defectiverecombinantadenovirusbearingrabiesglycoproteingeneinducesimmuneresponseagainstrabiesvirus.ChineseJournalofMicrobiologyandImmunology,2002,22(4):403-40625.SuiJ,LiW,JiangX,HeY,SongZ.HighlyEfficientExpressionandFunctionalStudiesofAnAnti-KG1aCellscFv5C1derivedfromPhageDisplayAntibodyLibrary.ChineseJournalofMicrobiologyandImmunology.2001,21(4):437~44126.LiW,ZhangY,WangS,LiuL.Immuneresponseofmiceagainstreplication-defectiverecombinantadenoviruscontainingglycoproteingeneofrabies3aGstrain.ChineseJournalofExperimentalandClinicalVirology,2001,15(1):35-3927.LiW,WangS,ZhangY,LiuL.ConstructionofclonedrecombinantadenovirusgenomebyhomologousrecombinationinEscherichiacoli.ChineseJournalofBiochemistryandMolecularBiology,2000,16(3):346-351

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