范祖森研究员
ZusenFan,Professor

专家类别:杰出青年，百人计划，研究员
简历&研究组工作摘要：范祖森，博士，研究员，创新课题组长，博士生导师，任中科院感染与免疫重点实验室副主任。1998年获上海交通大学医学院免疫学博士学位，之后到美国哈佛大学医学院从事博士后研究，于2003年晋升为哈佛大学医学院讲师。2004年入选中国科学院“百人计划”研究员回国工作，2005年国家“杰出青年”科学基金获得者，2006年入选“新世纪百千万人才工程”国家级人才。2008年院“百人计划”终期考核优秀。2010年享受“国务院特殊津贴”专家。范祖森课题组从事免疫细胞发育分化、肿瘤干细胞、肿瘤靶标发现与肿瘤个体化治疗等领域的研究，主要研究方向为免疫细胞谱系建立的信号转导、抗肿瘤免疫机制、肿瘤干细胞鉴定及干预机制、肿瘤新靶标的鉴定与肿瘤靶向药物研发等，课题组经过多年的研究积累业已形成优秀的研究平台和良好的科研文化氛围，在肿瘤免疫与肿瘤治疗领域培养出一支优秀的科研团队。以第一及通讯作者在Cell、NatureImmunology、CurrOpinImmunol、Blood、CellDeathDiffer、MCB、JImmunol、JBC等国际优秀学术期刊发表论文近30篇。课题组主要研究方向如下：1.免疫细胞清除肿瘤的免疫效应机制免疫系统在肿瘤的发生、发展及排斥过程中发挥着极其重要的作用。探讨在肿瘤发生早期固有免疫对适应性免疫的激活作用，研究固有免疫和适应性免疫细胞的活化和抗肿瘤作用，探明免疫活性细胞NK/CTL抗肿瘤的分子机制，揭示固有免疫耐受与肿瘤逃逸机制。从而为研发有效的肿瘤疫苗和设计特效的免疫治疗方法提供理论基础。2.免疫细胞的活化和谱系建立的时相遗传调控机制NK细胞是机体固有免疫重要的效应细胞，通过细胞毒活性与释放细胞因子，在机体抗感染、抗肿瘤、免疫调节等方面发挥重要的免疫功能。NK细胞发育分化的不同时相，主要是由于基因的差异表达引起的。通过比较不同发育阶段的基因表达差异，可以分析细胞发育分化过程的时相基因组学及其调控信息基础。以期阐明NK细胞的谱系建立和定向分化调控机理，作为对临床控制NK细胞的成熟活化提高机体固有免疫达到抗感染与抗肿瘤的目的。3.肿瘤干细胞、肿瘤标志物、肿瘤的个体化药物研发肿瘤干细胞具有自我更新能力和可塑性的潜能，对化疗药物具有耐药性。现有的治疗措施尚无法针对肿瘤干细胞发挥作用，成为肿瘤治疗失败和肿瘤复发的主要原因。我们实验室以肝癌和膀胱癌为重要研究对象，筛选发现新的肿瘤干细胞的标志物，研究肿瘤干细胞的自我更新机制，进行肿瘤的分子分型和干预机制研究，研发肿瘤的个体化药物，以期实现肿瘤的个体化治疗，提高用药效率，普惠肿瘤患者。
Biography&IntroductionDr.ZusenFan，Ph.D，Professor,Ph.Dsupervisor,PrincipalInvestigator,DeputyDirectoroftheCASKeyLabforInfectionandImmunity.Dr.FangothisPh.DdegreeofImmunologyatShanghaiJiaotongUniversitySchoolofMedicinein1998.ThenheobtainedpostdoctoraltrainingatHarvardMedicalSchoolandwaspromotedInstructorofHarvardUniversityin2003.HewasrecruitedtotheInstituteofBiophysicsofCASas“HundredTalentsProject”professorin2004.Dr.Fanreceived“theNationalOutstandingYouthGrant”ofNSFCin2005.Hewasawardedfor“theNewCenturyNationalTalentProject”in2006.FanLabfocusesonthesemajorresearchfields:1)NK/CTL-mediatedkillingmechanismsagainstcancersandviruses;2)GeneticandsignalingregulationfordirecteddevelopmentanddifferentiationofNKcells；3)Cancerstemcell,biomarkeridentification,immunotherapyandpersonalizedtherapyforcancers.
SelectedPublications：1.LiuS,ZhangH,LiM,HuD,LiC,GeB,JinB,FanZ*,RecruitmentofGrb2andSHIP1bytheITT-likemotifofTIGITsuppressesgranulepolarizationandcytotoxicityofNKcells.CellDeathDiffer.,2013;20(3):456-464.2.WangL,LiQ,WuL,LiuS,ZhangY,YangX,ZhuP,ZhangH,ZhangK,LouJ,LiuP,TongL,SunF,FanZ*,IdentificationofSERPINB1AsaPhysiologicalInhibitorofHumanGranzymeH,J.Immunol.,,2013;190(3):1319-1330.(Highlightedbythesameissue:keepinggranzymeHincheck)3.WangS,XiaP,ShiL,FanZ*,FADDcleavagebyNKcellgranzymeMenhancesitsself-associationtofacilitateprocaspase-8recruitmentforauto-processingleadingtocaspasecascade,CellDeathDiffer,2012;19(4):605-615,.4.ZhongC,LiC,WangX,ToyodaT,GaoG,FanZ*,GranzymeKinhibitsreplicationofinfluenzavirusthroughcleavingthenucleartransportcompleximportinalpha1/betadimerofinfectedhostcells,CellDeathDiffer,2012;19(5),882-890.5.TangH,LiC,WangL,ZhangH,FanZ*,GranzymeHofcytotoxiclymphocytesisrequiredforclearanceofthehepatitisBvirusthroughcleavageofthehepatitisBvirusXprotein,JImmunol.,2012;188(2):824-831.(RecommendedbyFaculty1000)6.WangL,ZhangK,WuL,LiuS,ZhangH,ZhouQ,TongL,SunF,FanZ*,StructuralinsightsintothesubstratespecificityofhumangranzymeH:thefunctionalrolesofanovelRKRmotif,JImmunol,2012;188(2):765-773.7.GuoY,ChenJ,ShiL,FanZ*.VCPcleavagebygranzymeKdisruptsendoplasmicreticulumassociatedproteindegradationtoforcetumortargetcelldeath.JournalofImmunology2010,185(9):5348–53598.HuD,LiuS,ShiL,LiC,WuL,FanZ.CleavageofsurvivinbyGranzymeMtriggersdegradationofthesurvivin-X-linkedinhibitorofapoptosisprotein(XIAP)complextofreecaspaseactivityleadingtocytolysisoftargettumorcells.JBiolChem.2010;285(24):18326-35.9.HuaG,WangS,ZhongC，XueP,FanZ*.Ignitionofp53bombbygranzymeKsensitizestumorcellstoNKcell-mediatedcytolysis.JournalofImmunology2009;182(4):2152-59.10.ZhangH,ZhongC,ShiL,GuoY,FanZ*.GranulysininducescathepsinBreleaseoflysosomesoftargettumorcellstotargetmitochondriathroughprocessingofBid.JournalofImmunology2009;182(11):6993-7000.11.WuL,WangL,HuaG,LiuK,YangX,ZhaiY,BartlamM,SunF,FanZ*.StructuralBasisforProteolyticSpecificityoftheHumanApoptosis-InducingGranzymeM.JournalofImmunology2009;183(11):421-429.12.ShiL,WuL,WangS,FanZ*.GranzymeFinducesanoveldeathpathwaycharacterizedbyBid-independentcytochromecreleasewithoutcaspaseactivation.CellDeathandDifferentiation2009;16:1694-1076.13.HouQ,ZhaoT,ZhangH,LuH,ZhangQ,SunL,FanZ*.GranzymeHinducesapoptosisoftargettumorcellscharacterizedbyDNAfragmentationandBid-dependentmitochondrialdamage.MolecularImmunology2008;45(4):1044-55.14.GuoY,ChenJ,ZhaoT,FanZ*.GranzymeKdegradestheredox/DNArepairenzymeApe1totriggeroxidativestressoftargetcellsleadingtocytotoxicity.MolecularImmunology2008;45(8):2225-35.15.HuaG,ZhangQ,FanZ*.Heatshockprotein75(TRAP1)antagonizesreactiveoxygenspeciesgenerationandprotectscellsfromgranzymeM-mediatedapoptosis.JBiolChem.2007;282(28):20553-60.16.ZhaoT,ZhangH,GuoY,FanZ*.GranzymeKdirectlyprocessesBidtoreleasecytochromecandendonucleaseGleadingtomitochondria-dependentcelldeath.JBiolChem.2007;282(16):12104-1117.ZhaoT,ZhangH,GuoY,ZhangQ,LuH,HouQ,HuaG,FanZ*.GranzymeKInducesrapidcaspase-independentcelldeathwithapoptoticnuclearmorphologyandsingle-strandedDNAnicks.CellDeathandDifferentiation2007;14:489-499.18.FanZ*,YuP,WangY,LeeY,WangY,FuM,LiuW,SunY,FuYX.NKactivationbyLIGHTprimestumorspecificCD8+Tcellimmunitytorejectestablishedtumors.Blood2006;107:1342-135119.LuH,HouQ,ZhaoT,ZhangH,ZhangQ,FanZ*.GranzymeMdirectlycleavesICADtounleashcaspase-activatedDNaseleadingtoDNAfragmentation.JournalofImmunology2006;177:1171-1178.20.FanZ*,ZhangH,ZhangQ.Tumorsuppressorpp32repressescellgrowthbyinhibitingtranscriptionbyblockingacetylationandphosphorylationofhostoneH3andinitiatingitsproapoptoticactivity.CellDeathandDifferentiation2006;13:1485-1494.21.FanZ*,ZhangQ.Molecularmechanismsoflymphocyte-mediatedcytotoxicity.CellMolImmunol.2005Aug;2(4):259-64.(invitedreview).22.*FanZ.CTL-mediatedkillingmechanismagainstcancers.J.MocriobiolImmmunol2004;2:155-160(invitedreview)23.FanZ,BeresfordPJ,OhDY,ZhangD,LiebermanJ*.ThetumormetastasissuppressorNM23-H1isagranzymeA-activatedDNasethatnicksDNAduringCTL-mediatedapoptosisandthenucleosomeassemblyproteinSETisitsinhibitor.　Cell2003;112:659-672　(WithFirstPreviews:SET-tingthestageforlifeanddeath)24.FanZ,BeresfordPJ,ZhangD,XuZ,NovinaCD,YoshidaA,PommierY,LiebermanJ*.CleavingtheoxidativerepairproteinApe1enhancescelldeathmediatedbygranzymeA.NatureImmunology2003;4:145-153(WiththeNEWSandVIEWS:GranzymeA:theloadlesstraveled;ANDhighlightedinSCIENCE:CompletingtheSET)25.LiebermanJ*,FanZ*.Nuclearwar:theGranzymeA-bomb.CurrOpinImmunology.2003;15:553-559.(invitedreview)26.FanZ,BeresfordPJ,ZhangD,LiebermanJ*.HMG2interactswiththenucleosomeassemblyproteinSETandisatargetofthecytotoxicT-lymphocyteproteasegranzymeA.MolCellBiol.2002;22:2810-20.27.BeresfordPJ,ZhangD,OhDY,FanZ,GreerEL,RussoML,JajuM,LiebermanJ.GranzymeAactivatesanendoplasmicreticulum-associatedcasCaspase-independentnucleasetoinducesingle-strandedDNA.JBiolChem.2001;276,43285-93
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