James J. Chou简介
JamesJChouisaProfessorinBiologicalChemistryandMolecularPharmacologyatHarvardMedicalSchoolHereceivedhisBSinPhysicsfromUniversityofMichiganatAnnArbor;PhDinBiophysicsfromHarvardUniversity;andpostdoctoraltrainingfromNIHSince2002,hejoinedthefacultyatHarvardMedicalSchoolProfessorChou’sgroupatHarvardpioneeredtheuseofsolutionNMRspectroscopytoobtainstructuresofmembraneionchannels,receptorsandtransportersThebiologycommunityneverthoughtthiswaspossiblebuttheirworkchangedourviewHisgroup’sfirstbreakthroughwasdenovostructuredeterminationofthe30kDapentamericassemblyofphosphoplamban,ahelicalmembraneproteinthatregulatesheartmusclecontractility(PNAS2005,102,10870-10875)ThisworkdemonstratedforthefirsttimethatsolutionNMRiscapableofgeneratinganewstructureofanintacthelicalmembraneproteinInanotherapplication,hislaboratoryrevealedthestructuraldetailsofthemembrane-associatedregionoftheTcellreceptor,whichhaveimportantconsequencesforhowweenvisionimmunesignalstobepropagatedacrossthecellmembrane(Cell2006,127,355-368;Cell2008,135,702-713;NatureImmunology,2010,11,1023-1029)ProfChouandhisgroupalsobroughtNMRtotheageofnanotechnology,bydevelopinganewliquidcrystalmadeofDNAnanotubesforprovidingglobalstructuralrestraintsinNMRstudiesofmembraneproteins(PNAS2007,104,6644-6648)Forquitealongperiodinhistory,manyintenseeffortshavebeenmadetodeterminethe3DstructureoftheM2protonchannelbecauseitisthekeytargetforfindingeffectivedrugsagainstinfluenzaAvirusIn2008,heandhispostdocshavesuccessfullydeterminedthelong-soughtstructureMeanwhile,theyalsodiscoveredanovelallostericmechanismofdruginhibitionanddrugresistanceoftheprotonchannel(Nature2008,451,591-595;PNAS2009,106,7379-7384)ThesediscoverieshaveprovidednewinsightsandstimulatednewstrategiestoovercomethedrugresistanceproblemoffluRecently,JamesChouhasmadeyetanotherbreakthrough;hislabdevelopedanewNMRmethodthatenabledstructuredeterminationofUCP2,a300-residueprotontranslocatorintheinnermembraneofmitochondriathatresistedyearsofcrystallizationeffortsThenewdevelopment,whichincludesfabricationofDNAnanotubesandRDC-basedmolecularfragmentreplacement,overcamemanytechnicalchallengesinvolvedinsolvinglargemembraneproteinsbyconventionalNMRmethods(Nature2011,476,109-113)ThisNMRmethodwillhavestrongimpactonprobingconformationalswitchesofmembranetransportersProfessorChouhasreceivedmanyprestigiousawardssuchasthePewScholarAwardinBiomedicalSciences,theSmithFamilyAward,andtheGenzymeOutstandingAchievementinBiomedicalScienceAward