职称职务：教授、院长
Appointment:Professor,Dean
学科专业：生物化学
Department:Biochemistry
研究方向：胆固醇代谢与代谢性疾病
Research:Cholesterolmetabolismandmetabolicdiseases
实验室位置：生命科学学院大楼1134房间
Location:CollegeofLifeSciences,Room1134
Email:blsong@whu.edu.cn


教育经历/Education
1993－1997南京大学生物科学与技术系，学士
　　　　　　B.S.Biology,NanjingUniversity,Nanjing,China
1997－2002中科院上海生命科学研究院生物化学与细胞生物学研究所，博士
　　　　　　Ph.D.InstituteofBiochemistryandCellBiology,ShanghaiInstitutesforBiologicalSciences,ChineseAcademyof
Sciences.

工作经历与任职/ProfessionalExperience
2002－2005美国德克萨斯大学西南医学中心，博士后
　　　　　　Post-doctoralresearchfellow,UTSouthwesternMedicalCenter,Mentors:Drs.MikeBrown,JoeGoldstein,RussellDeBose-
　　　　　　Boyd
2005－2014中科院上海生命科学研究院生物化学与细胞生物学研究所，研究组长，研究员，博士生导师，“百人计划”择优支持，“百人计划”终期评估优
　　　　　　秀。分子生物学国家重点实验室副主任（2012-2014），生化细胞所所长助理（2013-2014）。
　　　　　　PrincipleInvestigator,InstituteofBiochemistryandCellBiology,ShanghaiInstitutesforBiologicalSciences,
　　　　　　ChineseAcademyofSciences.
2014－至今　武汉大学生命科学学院，教授，院长
　　　　　　ProfessorandDean,CollegeofLifeSciences,WuhanUniversity,Wuhan,China

学术兼职：
2009－至今中国生物物理学会理事会理事
2010－至今J.ofMolecularCellBiology,AssociateEditor
2012－至今J.Biol.Chem.,EditorialBoardMember
2014－2016InternationalConferenceontheBioscienceofLipids(ICBL)筹划委员
2014－至今中国生物化学与分子生物学理事会，常务理事

获奖及荣誉：
国家杰出青年科学基金（2009）
国家重大科学研究计划首席科学家（2009）
中科院优秀研究生指导教师（2010）
陈嘉庚青年科学奖（首届，2012）
****科技创新领军人才入选者（2012）
中科院优秀研究生指导教师（2013）
亚太ArthurKornbergMemorialAward（2013）
新世纪百千万人才工程国家级人选（2013）
中国青年科技奖（2013）
谈家桢生命科学创新奖（2014）
****特聘教授（2015）
中国细胞生物学学会-普洛麦格创新奖（2015）


研究概述/ResearchDescription
　　我们主要从事与心脑血管疾病发生密切相关的胆固醇代谢平衡调控的研究。首次提出并证明了小肠细胞对饮食胆固醇吸收的分子模型，发现了该途径中的多个蛋白因子；深入探索了内源胆固醇合成的负反馈调控机制—HMGCR蛋白的受控降解，揭示了肝脏脂质合成与棕色脂肪能量代谢的联系；构建了基于胆固醇合成负反馈调控途径的筛选体系，并获得了能同时降低胆固醇和甘油三酯的活性化合物白桦酯醇。这些原创性成果不仅丰富了胆固醇代谢平衡调控的基础理论，并且对研发新型的降脂药物具有重要意义。
　　主要研究方向包括：1）小肠胆固醇吸收的分子途径；2）细胞内胆固醇动态运输的分子机制；3）胆固醇代谢调控的信号转导途径和机理；4）胆固醇代谢的药靶系统及新药研发。
　　实验室的长期目标是揭示胆固醇代谢的分子机制，发展治疗胆固醇相关疾病的新策略。
　　Dr.Song’slabworksoncholesterolhomeostasisthatiscloselyrelatedtocardiovasculardisease.Hisgrouphasdissectedthemolecularpathwayofintestinalcholesterolabsorptionandidentifiedmostoftheproteininthisprocess.Hehasuncoveredthemechanismofsterol-regulateddegradationofHMG-CoAreductase,whichisamajorfeed-backregulationofdenovocholesterolbiosynthesis.Hisgroupalsoidentifiedbetulin,asmallmolecule,whichcandecreasebothcholesterolandfattyacidlevelsbyinhibitingSREBPpathway.
　　Ongoingprojectsinthislaboratoryinclude:
　　1)Dissectingthemolecularpathwayofdietarycholesterolabsorption.
　　2)Studyingmechanismandfunctionofintracellularcholesteroltrafficking.
　　3)Uncoveringtheregulatorymechanismsofcholesterolmetabolism.
　　4)Screeningforsmallchemicalcompoundscontrollingcholesterolmetabolism.
　　Thelong-termgoalsofthesestudiesaretorevealthemolecularmechanismofcholesterolmetabolismanddevelopnovelstrategiestotreatcholesterol-relateddiseases.

发表文章/Publications
RepresentativePublications:1)ChuBB,LiaoYC,QiW,XieC,DuX,WangJ,YangH,MiaoHH,LiBLandSongBL*.CholesterolTransportthroughLysosome-PeroxisomeMembraneContacts.Cell,161(2):291-306,2015
2)LiPS,FuZY,ZhangYY,XuCQ,MaYT,LiBLandSongBL*.TheclathrinadaptorNumbregulatesintestinalcholesterolabsorptionthroughdynamicinteractionwithNPC1L1.NatureMedicine,20(1):80-86,2014

3)LiuTF,TangJJ,LiPS,ShenY,LiJG,MiaoHH,LiBL*andSongBL*.Ablationofgp78inliverimproveshyperlipidemiaandinsulinresistancebyinhibitingSREBPtodecreaselipidbiosynthesis.CellMetabolism,16:213-225,2012

4)TangJJ,LiJG,QiW,QiuWW,LiPS,LiBLandSongBL*.InhibitionofSREBPbyasmallmolecule,betulin,improveshyperlipidemiaandinsulinresistanceandreducesatheroscleroticplaques.CellMetabolism,13:44-56,2011

5)GeL,WangJ,QiW,MiaoHH,CaoJ,QuYX,LiBLandSongBL*.Thecholesterolabsorptioninhibitorezetimibeactsbyblockingthesterol-inducedinternalizationofNPC1L1.CellMetabolism,7:508-519,2008

6)CaoJ,WangJ,QiW,MiaoHH,DeBose-BoydRA,WangJ,LiBL*andSongBL*.Ufd1isacofactorofgp78andplaysakeyroleincholesterolmetabolism.CellMetabolism,6:115-128,2007

7)GeL,QiW,WangLJ,MiaoHH,QuYX,LiBLandSongBL*.FlotillinsplayanessentialroleinNiemann-PickC1Like1-mediatedcholesteroluptake.PNAS,108(2):551-6,2011

8)SongBL,SeverN,andDeBose-BoydRA.Gp78,amembraneanchoredubiquitinligase,associateswithInsig-1andcouplessterol-regulatedubiquitinationtodegradationofHMGCoAreductase.MolecularCell.19(6):829-840,2005

9)SongBL,JavittNB,andDeBose-BoydRA.Insig-mediateddegradationofHMGCoAreductasestimulatedbylanosterol,anintermediateinthesynthesisofcholesterol.CellMetabolism,1:179-189,2005

10)SeverN^#,SongBL^#,YabeD^#,GoldsteinJL,BrownMS,andDeBose-BoydRA.Insig-dependentubiquitinationanddegradationofmammalian3-Hydroxy-3-methylglutaryl-CoAreductasestimulatedbysterolsandgeranylgeraniol.JBiolChem,278:52479-52490,2003

OtherPublications:
11)WeiJ,FuZY,LiPS,MiaoHH,LiBL,MaYT,SongBL*.TheClathrinAdaptorProteinsARH,Dab2,andNumbPlayDistinctRolesinNiemann-PickC1-Like1VersusLowDensityLipoproteinReceptor-mediatedCholesterolUptake.JBiolChem,289(48):33689-700,2014

12)JiangW,TangJJ,MiaoHH,QuYX,QinJ,XuJ,YangJ,LiBL,SongBL*.ForwardGeneticScreeningforRegulatorsInvolvedinCholesterolSynthesisUsingValidation-BasedInsertionalMutagenesis.PLoSOne,9(11):e112632,2014

13)JiangW,SongBL*.Ubiquitinligasesincholesterolmetabolism.DiabetesMetabJ.38(3):171-80,2014

14)RogersMA,LiuJ,SongBL,LiBL,ChangCC,ChangTY.Acyl-CoA:cholesterolacyltransferases(ACATs/SOATs):Enzymeswithmultiplesterolsassubstratesandasactivators.JSteroidBiochemMolBiol.S0960-0760(14):00207-6,2014

15)XiaoX*,SongBL.SREBP:anoveltherapeutictarget.ActaBiochimBiophysSin(Shanghai).45(1):2-10,2013

16)SongBL*.Aspecialissueon'Metabolism'.ActaBiochimBiophysSin(Shanghai).45(1):1,2013

17)XuJ,HuG,LuM,XiongY,LiQ,ChangCC,SongBL,ChangTY,LiBL.MiR-9reduceshumanacyl-coenzymeA:cholesterolacyltransferase-1todecreaseTHP-1macrophage-derivedfoamcellformation.ActaBiochimBiophysSin(Shanghai).45(11):953-62,2013

18)LuM,HuXH,LiQ,XiongY,HuGJ,XuJJ,ZhaoXN,WeiXX,ChangCC,LiuYK,NanFJ,LiJ,ChangTY,SongBL*,LiBL*.AspecificcholesterolmetabolicpathwayisestablishedinasubsetofHCCsfortumorgrowth.JMolCellBiol.5:404-15,2013

19)HuGJ,ChenJ,ZhaoXN,XuJJ,GuoDQ,LuM,ZhuM,XiongY,LiQ,ChangCC,SongBL,ChangTY,LiBL.ProductionofACAT156-kDaisoforminhumancellsviatrans-splicinginvolvingtheampicillinresistancegene.CellRes.23(8):1007-24,2013

20)LiuY,XuXH,ChenQ,WangT,DengCY,SongBL,DuJL,LuoZG.MyosinVbcontrolsbiogenesisofpost-GolgiRab10carriersduringaxondevelopment.NatCommun.4:2005.2013

21)XieC,ZhouZS,LiN,BianY,WangYJ,WangLJ,LiBL*andSongBL*.EzetimibeblockstheinternalizationofNPC1L1andcholesterolinmousesmallintestine.JLipidRes,53:2092-2101,2012

22)WangLJandSongBL*.Niemann-PickC1-Like1andcholesteroluptake.BiochimBiophysActa,1821(7):964-72,2012

23)XieC,LiN,ChenZJ,LiBL,SongBL*.ThesmallGTPaseCdc42interactswithNiemann-PickC1Like1(NPC1L1)andcontrolsitsmovementfromendocyticrecyclingcompartmenttoplasmamembraneinacholesteroldependentmanner.JBiolChem,286(41):35933-42,2011

24)ZhangJH,GeL,QiW,ZhangL,MiaoHH,LiBL,YangMandSongBL*.TheN-terminaldomainofNPC1L1proteinbindscholesterolandplaysessentialrolesincholesteroluptake.JBiolChem,286(28):25088-97,2011

25)WangLJ,WangJ,LiN,GeL,LiBLandSongBL*.MolecularcharacterizationoftheNPC1L1variantsidentifiedfromcholesterollowabsorbers.JBiolChem,286(9):7397-7408,2011

26)MiaoHH,JiangW,GeL,LiBL,SongBL*.Tetra-glutamicacidresiduesadjacenttoLys248inHMG-CoAreductasearecriticalfortheubiquitinationmediatedbygp78andUBE2G2.ActaBiochimBiophysSin,42(5):303-310,2010

27)ChuBB,GeL,XieC,ZhaoY,MiaoHH,WangJ,LiBLandSongBL*.RequirementofMyosinVb/Rab11a/Rab11-FIP2complexincholesterol-regulatedtranslocationofNiemann-PickC1Like1proteintothecellsurface.JBiolChem,284:22481-90,2009.

28)WangJ,ChuBB,GeL,LiBL,YanY*andSongBL*.MembranetopologyofhumanNPC1L1,akeyproteininenterohepaticcholesterolabsorption.JLipidRes,50:1653-62,2009

29)LeiL,XiongY,ChenJ,YangJB,WangY,YangXY,ChangCCY,SongBL,ChangTYandLiBL*.TNF-alphastimulatestheACAT1expressionindifferentiatingmonocytestopromotetheCE-ladencellformation.JLipidRes,50:1057-67,2009

30)ZhaoXN,ChenJ,LeiL,HuGJ,XiongY,XuJJ,LiQ,YangXY,ChangC,SongBL,ChangTYandLiBL.Theoptionallong5'-untranslatedregionofhumanACAT1mRNAsimpairstheproductionofACAT1proteinbypromotingitsmRNAdecay.ActaBiochimBiophysSin,41:30-41,2009

31)ChenJ,ZhaoXN,YangL,HuGJ,LuM,XiongY,YangXY,ChangCC,SongBL,ChangTY,LiBL.RNAsecondarystructureslocatedintheinterchromosomalregionofhumanACAT1chimericmRNAarerequiredtoproducethe56-kDaisoform.CellRes,18:921-936,2008

32)QiWandSongBL*.DissectingtheNPC1L1-mediatedcholesterolabsorption.FutureLipidology,3:481-484,2008

33)CaoJ,QiWandSongBL*.Tocotrienolsandtheregulationofcholesterolbiosynthesis.Chapter18(p237-256)In:Tocotrienols:BeyondVitaminE,CRCpress,2008

34)LeeJN,SongBL,DeBose-BoydRA,YeJ.Sterol-regulateddegradationofInsig-1mediatedbythemembrane-boundubiquitinligasegp78.JBiolChem,281:39308-39315,2006

35)SongBL*andDebose-BoydRA*.Insig-dependentubiquitinationanddegradationof3-Hydroxy-3-methylglutaryl-CoenzymeAstimulatedby{delta}-and{gamma}-Tocotrienols.JBiolChem,281:25054-25061,2006

36)SongBL,WangCH,YaoXM,YangL,ZhangWJ,WangZZ,ZhaoXN,YangJB,QiW,YangXY,InoueK,LinZX,ZhangHZ,KodamaT,ChangCC,LiuYK,ChangTYandLiBL.Humanacyl-CoA:cholesterolacyltransferase2geneexpressioninintestinalCaco-2cellsandinhepatocellularcarcinoma.BiochemJ,394:617-626,2006

37)YaoXM,WangCH,SongBL,YangXY,WangZZ,QiW,LinZX,ChangCC,ChangTYandLiBL.TwohumanACAT2mRNAvariantsproducedbyalternativesplicingandcodingfornovelisoenzymes.ActaBiochimBiophysSin,37:797-806,2005

38)SeverN,LeePCW,SongBL,RawsonRB,andDeBose-BoydRA.IsolationofmutantcellslackingInsig-1throughselectionwithSR-12813,anagentthatstimulatesdegradationof3-Hydroxy-3-methylglutaryl-CoenzymeAreductase.JBiolChem,279:43136-43147,2004

39)SongBLandDebose-BoydRA.Ubiquitinationof3-Hydroxy-3-methylglutaryl-CoAreductaseinpermeabilizedcellsmediatedbycytosolicE1andaputativemembrane-boundubiquitinligase.JBiolChem,279:28798-28806,2004