鄭銘

鄭銘，北京大學醫學部生理學與病理生理學系研究員，博士生導師。主要研究興趣為心血管系統線粒體質量控制及其病理生理意義，尤其是線粒體融合/分裂、線粒體ROS信號、線粒體自噬、線粒體通訊與功能網路在心肌中的作用及作用機制。承擔多項國家重點基礎研究發展計劃項目課題（973）及國家自然科學基金項目。2007年入選教育部“新世紀優秀人才支持計劃”。在PNAS,JBiolChem,HumMolGenet等雜誌發表SCI論文30餘篇。

1993年獲西安醫科大學醫學學士學位，1999年-2001年作為首屆美國國立衛生研究院（NIH）聯合培養博士研究生，在NIH從事心肌細胞腎上腺素受體信號轉導研究，2001年獲北京大學醫學博士學位。承擔多項國家重點基礎研究發展計劃項目課題（973）及國家自然科學基金項目。

目前主要研究興趣為心血管系統線粒體質量控制及其病理生理意義，尤其是線粒體融合/分裂、線粒體ROS信號、線粒體自噬、線粒體通訊與功能網路在心肌中的作用及作用機制。主要研究方向包括線粒體功能網路調控機制與心肌疾病，以及心肌線粒體自噬機制。

線粒體質量控制與心血管疾病

主要研究內容：

1．線粒體功能網路調控機制與心肌疾病：不斷運動及融合/分裂的線粒體形成涵蓋整個細胞的線粒體功能網路，實現線粒體間物質以及信號的交換，從而對細胞的能量需求和信號轉導進行調控。心肌細胞是高度特化、線粒體含量豐富的細胞，線粒體運動和融合/分裂並不活躍，線粒體間的交互作用尚不清楚。我們目前主要研究心肌細胞線粒體間是否及如何進行交互作用、線粒體間交互作用的關鍵調控分子及調控機制；心肌肥厚及心衰等病理狀況時，線粒體間交互作用及其調控分子的改變及變化規律；

2．心肌線粒體自噬機制：線粒體通過對其自身的調節來滿足不同情況下心肌細胞的能量需求。線粒體自噬是細胞對損傷線粒體的自我清除過程，是保持健康線粒體群體和正常線粒體功能的重要環節。心肌細胞線粒體自噬在心臟生理及病理生理狀態下均發揮重要作用。我們主要探討心肌細胞中介導線粒體自噬的分子機制及其病理生理意義。

近5年發表論文：

Huang X, Sun L, Ji S, Zhao T, Zhang W, Xu J, Zhang J, Wang Y, Wang X, Franzini-Armstrong C*, Zheng M*, Cheng H. Kissing and nanotunneling mediate intermitochondrial communication in the heart. Proc Natl Acad Sci U S A. 2013; 110(8):2846-2851. (*correspondence author)

ZhangH,GomezAM,WangX,YanY,ZhengM,ChengH.ROSregulationofmicrodomainCa2+signalingatthedyads.CardiovasRes2013;doi:10.1093/cvr/cvt050(inpress)

HouT,ZhangX,XuJ,JianC,HuangZ,YeT,HuK,ZhengM,GaoF,WangX,ChengH.SynergistictriggeringofsuperoxideflashesbymitochondrialCa2+uniportandBasalreactiveoxygenspecieselevation.JBiolChem.2013;288(7):4602-12.

DengJ,LiuW,WangY,DongM,ZhengM,LiuJ.PolydatinmodulatesCa(2+)handling,excitation-contractioncouplingandβ-adrenergicsignalinginratventricularmyocytes.JMolCellCardiol.2012;53(5):646-56.

ZhaoT,HuangX,HanL,WangX,ChengH,ZhaoY,ChenQ,ChenJ,ChengH,XiaoR,ZhengM*.CentralRoleofMitofusin2inAutophagosome-LysosomeFusioninCardiomyocytes.JBiolChem.2012;287(28):23615-25(*correspondenceauthor)

WangX,JianC,ZhangX,HuangZ,XuJ,HouT,ShangW,DingY,ZhangW,OuyangM,WangY,YangZ,ZhengM,ChengH.Superoxideflashes:elementaleventsofmitochondrialROSsignalingintheheart.JMolCellCardiol.2012;52:940-8

LiK,ZhangW,FangH,XieW,LiuJ,ZhengM,WangX,WangW,TanW,ChengH.Superoxideflashesrevealnovelpropertiesofmitochondrialreactiveoxygenspeciesexcitabilityincardiomyocytes.BiophysJ.2012;102(5):1011-21.

WeiC,WangX,ZhengM,ChengH.Calciumgradientsunderlyingcellmigration.CurrOpinCellBiol.2012;24:254-61

HuangZ,ZhangW,FangH,ZhengM,WangX,XuJ,ChengH,GongG,WangW,DirksenRT,SheuSS.Responseto"AcriticalevaluationofcpYFPasaprobeforsuperoxide".FreeRadicBiolMed.2011;51:1937-40.

MaQ,FangH,ShangW,LiuL,XuZ,YeT,WangX,ZhengM*,ChenQ*,ChengH.Superoxideflashes:earlymitochondrialsignalsforoxidativestress-inducedapoptosis.JBiolChem.2011;286:27573-81(*Correspondenceauthor)

FangH,ChenM,DingY,ShangW,XuJ,ZhangX,ZhangW,LiK,XiaoY,GaoF,ShangS,LiJC,TianXL,WangSQ,ZhouJ,WeislederN,MaJ,OuyangK,ChenJ,WangX,ZhengM,WangW,ZhangX,ChengH.Imagingsuperoxideflashandmetabolism-coupledmitochondrialpermeabilitytransitioninlivinganimals.CellRes.2011;21(9):1295-304

ChengH*,ZhengM*,PeterAK,KimuraK,LiX,OuyangK,ShenT,CuiL,FrankD,DaltonND,GuY,FreyN,PetersonKL,EvansSM,KnowltonKU,SheikhF,ChenJ.SelectiveDeletionofLongbutnotShortCypherIsoformsLeadstoLateOnsetDilatedCardiomyopathy.HumMolGenet.2011;20:1751-62.(Co-firstauthor)

ZhengM,XiaoRP.Roleofmitofusin2incardiovascularoxidativeinjury.JMolMed.2010;88:987-91

WangX,XieW,ZhangY,LinP,HanL,HanP,WangY,ChenZ,JiG,ZhengM,WeislederN,XiaoRP,TakeshimaH,MaJ,ChengH.CardioprotectionofIschemia/ReperfusionInjurybyCholesterol-DependentMG53-MediatedMembraneRepair.CircRes.2010;107:76-83

LiQ,LiG,LanX,ZhengM,ChenKH,CaoCM,XiaoRP.Receptorinteractingprotein3suppressesvascularsmoothmusclecellgrowthbyinhibitionofthephosphoinositide3-kinase-Aktaxis.JBiolChem.2010;285:9535-44

ZhengM,ChengH,BanerjeeI,ChenJ.ALP/EnigmaPDZ-LIMdomainproteinsintheheart.JMolCellBiol.2010;2:96-102

PengW,ZhangY,ZhengM,ChengH,ZhuW,CaoCM,XiaoRP.CardioprotectionbyCaMKIIdBIsMediatedbyPhosphorylationofHeatShockFactor1andSubsequentExpressionofInducibleHeatShockProtein70.CircRes.2010;106:102-10

WeiC,WangX,ChenM,OuyangK,ZhengM,ChengH.Flickeringcalciumsignalsturningofmigratingcells.CanJPhysiolPharm2010;88:105-10

ZhengM,ChengH,LiX,ZhangJ,CuiL,OuyangK,HanL,ZhaoT,GuY,DaltonND,BangML,PetersonKL,ChenJ.Cardiac-specificablationofcypherleadstoasevereformofdilatedcardiomyopathywithprematuredeath.HumMolGenet.2009;18:701-13

SheikhF,RaskinA,ChuPH,LangeS,DomenighettiAA,ZhengM,LiangX,ZhangT,YajimaT,GuY,DaltonND,MahataSK,DornGW,Heller-BrownJ,PetersonKL,OmensJH,McCullochAD,ChenJ.AnFHL1-containingcomplexwithinthecardiomyocytesarcomeremediateshypertrophicbiomechanicalstressresponsesinmice.JClinInvest.2008;118:3870-80

WangW,FangH,GroomL,ChengA,ZhangW,LiuJ,WangX,LiK,HanP,ZhengM,YinJ,WangW,MattsonMP,KaoJP.Y,LakattaEG,SheuS-S,OuyangK,ChenJ,DirksenRT,ChengH.SuperoxideFlashesinSingleMitochondria.Cell.2008;134:279-290

ShenT*,ZhengM*,CaoC,ChenC,TangJ,ZhangR,ChengP,ChenKH,XiaoRP.Mitofusin2isamajordeterminantofoxidativestress-mediatedheartmusclecellapoptosis.J.Biol.Chem.2007;282:23354-61(*Co-firstauthor)

1.

Huang X, Sun L, Ji S, Zhao T, Zhang W, Xu J, Zhang J, Wang Y, Wang X, Franzini-Armstrong C*, Zheng M*, Cheng H. Kissing and nanotunneling mediate intermitochondrial communication in the heart. Proc Natl Acad Sci U S A. 2013; 110(8):2846-2851. (*correspondence author)

2.

ZhangH,GomezAM,WangX,YanY,ZhengM,ChengH.ROSregulationofmicrodomainCa2+signalingatthedyads.CardiovasRes2013;doi:10.1093/cvr/cvt050(inpress)

3.

HouT,ZhangX,XuJ,JianC,HuangZ,YeT,HuK,ZhengM,GaoF,WangX,ChengH.SynergistictriggeringofsuperoxideflashesbymitochondrialCa2+uniportandBasalreactiveoxygenspecieselevation.JBiolChem.2013;288(7):4602-12.

4.

DengJ,LiuW,WangY,DongM,ZhengM,LiuJ.PolydatinmodulatesCa(2+)handling,excitation-contractioncouplingandβ-adrenergicsignalinginratventricularmyocytes.JMolCellCardiol.2012;53(5):646-56.

5.

ZhaoT,HuangX,HanL,WangX,ChengH,ZhaoY,ChenQ,ChenJ,ChengH,XiaoR,ZhengM*.CentralRoleofMitofusin2inAutophagosome-LysosomeFusioninCardiomyocytes.JBiolChem.2012;287(28):23615-25(*correspondenceauthor)

6.

WangX,JianC,ZhangX,HuangZ,XuJ,HouT,ShangW,DingY,ZhangW,OuyangM,WangY,YangZ,ZhengM,ChengH.Superoxideflashes:elementaleventsofmitochondrialROSsignalingintheheart.JMolCellCardiol.2012;52:940-8

7.

LiK,ZhangW,FangH,XieW,LiuJ,ZhengM,WangX,WangW,TanW,ChengH.Superoxideflashesrevealnovelpropertiesofmitochondrialreactiveoxygenspeciesexcitabilityincardiomyocytes.BiophysJ.2012;102(5):1011-21.

8.

WeiC,WangX,ZhengM,ChengH.Calciumgradientsunderlyingcellmigration.CurrOpinCellBiol.2012;24:254-61

9.

HuangZ,ZhangW,FangH,ZhengM,WangX,XuJ,ChengH,GongG,WangW,DirksenRT,SheuSS.Responseto"AcriticalevaluationofcpYFPasaprobeforsuperoxide".FreeRadicBiolMed.2011;51:1937-40.

10.

MaQ,FangH,ShangW,LiuL,XuZ,YeT,WangX,ZhengM*,ChenQ*,ChengH.Superoxideflashes:earlymitochondrialsignalsforoxidativestress-inducedapoptosis.JBiolChem.2011;286:27573-81(*Correspondenceauthor)

11.

FangH,ChenM,DingY,ShangW,XuJ,ZhangX,ZhangW,LiK,XiaoY,GaoF,ShangS,LiJC,TianXL,WangSQ,ZhouJ,WeislederN,MaJ,OuyangK,ChenJ,WangX,ZhengM,WangW,ZhangX,ChengH.Imagingsuperoxideflashandmetabolism-coupledmitochondrialpermeabilitytransitioninlivinganimals.CellRes.2011;21(9):1295-304

12.

ChengH*,ZhengM*,PeterAK,KimuraK,LiX,OuyangK,ShenT,CuiL,FrankD,DaltonND,GuY,FreyN,PetersonKL,EvansSM,KnowltonKU,SheikhF,ChenJ.SelectiveDeletionofLongbutnotShortCypherIsoformsLeadstoLateOnsetDilatedCardiomyopathy.HumMolGenet.2011;20:1751-62.(Co-firstauthor)

13.

ZhengM,XiaoRP.Roleofmitofusin2incardiovascularoxidativeinjury.JMolMed.2010;88:987-91

14.

WangX,XieW,ZhangY,LinP,HanL,HanP,WangY,ChenZ,JiG,ZhengM,WeislederN,XiaoRP,TakeshimaH,MaJ,ChengH.CardioprotectionofIschemia/ReperfusionInjurybyCholesterol-DependentMG53-MediatedMembraneRepair.CircRes.2010;107:76-83

15.

LiQ,LiG,LanX,ZhengM,ChenKH,CaoCM,XiaoRP.Receptorinteractingprotein3suppressesvascularsmoothmusclecellgrowthbyinhibitionofthephosphoinositide3-kinase-Aktaxis.JBiolChem.2010;285:9535-44

16.

ZhengM,ChengH,BanerjeeI,ChenJ.ALP/EnigmaPDZ-LIMdomainproteinsintheheart.JMolCellBiol.2010;2:96-102

17.

PengW,ZhangY,ZhengM,ChengH,ZhuW,CaoCM,XiaoRP.CardioprotectionbyCaMKIIdBIsMediatedbyPhosphorylationofHeatShockFactor1andSubsequentExpressionofInducibleHeatShockProtein70.CircRes.2010;106:102-10

18.

WeiC,WangX,ChenM,OuyangK,ZhengM,ChengH.Flickeringcalciumsignalsturningofmigratingcells.CanJPhysiolPharm2010;88:105-10

19.

ZhengM,ChengH,LiX,ZhangJ,CuiL,OuyangK,HanL,ZhaoT,GuY,DaltonND,BangML,PetersonKL,ChenJ.Cardiac-specificablationofcypherleadstoasevereformofdilatedcardiomyopathywithprematuredeath.HumMolGenet.2009;18:701-13

20.

SheikhF,RaskinA,ChuPH,LangeS,DomenighettiAA,ZhengM,LiangX,ZhangT,YajimaT,GuY,DaltonND,MahataSK,DornGW,Heller-BrownJ,PetersonKL,OmensJH,McCullochAD,ChenJ.AnFHL1-containingcomplexwithinthecardiomyocytesarcomeremediateshypertrophicbiomechanicalstressresponsesinmice.JClinInvest.2008;118:3870-80

21.

WangW,FangH,GroomL,ChengA,ZhangW,LiuJ,WangX,LiK,HanP,ZhengM,YinJ,WangW,MattsonMP,KaoJP.Y,LakattaEG,SheuS-S,OuyangK,ChenJ,DirksenRT,ChengH.SuperoxideFlashesinSingleMitochondria.Cell.2008;134:279-290

22.

ShenT*,ZhengM*,CaoC,ChenC,TangJ,ZhangR,ChengP,ChenKH,XiaoRP.Mitofusin2isamajordeterminantofoxidativestress-mediatedheartmusclecellapoptosis.J.Biol.Chem.2007;282:23354-61(*Co-firstauthor)

實驗室成員：

鄭銘（研究員，負責人）

王剛（科研助理）

研究生：丁彥紅，高瀚，林青松，賈石，喬雪，葉菁菁，曹陽坡，徐春玲