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Neurogenetic InstituteZilkha20
13-2
014
an
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Table of Contents2 Director’sLetter
3 History and Mission
4 ZNI Faculty
8 Faculty Research Programs
12 ScientificAdvancements
23 Collaborations
37 Faculty News
41 FacultyActivities
43 Grants and Contracts
50 Special Lectures
51 4thAnnualZachHallLecture
52 1stAnnualZilkhaSymposiumonAlzheimer’sDisease&RelatedDisorders
54 AcademicActivities
56 NeurodegenerationJournalClub/NRSAGrantTraining
57 LosAngelesBrainBee
58 MusictoRemember-LAOpera/Alzheimer’sAssociation
59 ZNI Graduate Students
62 ZNI Postdoctoral Trainees
64 FY14FacultyPublications
81 ZNIAdministration
83 ZNIDevelopment
1
Dear Friends,
TheWorldHealthOrganizationestimatesthatdevastatingbraindisordersanddiseasesaffectmorethanonebillionpeopleworldwide.Lastyear,PresidentObamalaunchedtheBRAINInitiativeasalarge-scaleefforttoequipresearcherswithfundamentalinsightsnecessaryfortreatingawidevarietyofbraindisorderslikeAlzheimer’s,schizophrenia,autism,epilepsy,andtraumaticbraininjury.
Researchonthebrainissurging.TheUnitedStatesandtheEuropeanUnionhavelaunchednewprogramstobetterunderstandthebrain.Scientistsaremappingpartsofmouse,flyandhumanbrainsatdifferentlevelsofmagnification.Technologyforrecordingandimagingbrainactivityhasbeenimprovingatarevolutionarypace.Yetthegrowingbodyofdata—maps,atlasesandso-calledconnectomesthatshowlinkagesbetweencellsandregionsofthebrain—representsaparadoxofprogress,withtheadvancesalsohighlightinggreatgapsinunderstanding.
Specifically,interpretingthesebrain-wiringmaps,andultimatelyestablishingtheapproachthatphysiciansandscientistswillusetotreatneurologicaldiseases,requiresaclearunderstandingofbraincircuitry,informationthatcanonlybeobtainedthroughbasicresearchlikethefineworkbeingperformedatZNI.
ScientistsatZNIareworkingharderthaneverandachievingstrongrecognitionfordoingso.Iamproudtosaythatofthe148ofpaperspublishedlastyearbyourinvestigators,17.5%wereinhigh-impactjournals,up3.5%fromlastyear.Similarly,despitethedifficultfundingclimate,totalgrantdollarsbroughtinbyZNIresearchersisup8.3%overlastyear.WealsoshowinthefollowingpagesthatZNIinvestigatorscontinuesignificantcollaborationsacrossUSC,theregionandaroundtheworld.Thisisgreatscience.
AsZNIinvestigatorsdeploynovelapproachestoexamineandunderstandtheunderlyingstructureofandrelationshipsbetweenthevariouscomponentsthatcomprisethenervoussystem,wearedrivingtranslationalresearchmoreandmoretowardtransformativemedicine.
Pleasejoinusonthisexcitingroadofdiscovery.
Allthebest,
dire
cto
r’s
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“Thehumanbrainisthemostcomplicatedbiologicalstructureintheknownuniverse.
We’veonlyjustscratchedthesurfaceinunderstandinghowitworksor,unfortunately,
doesn’tquiteworkwhendisordersanddiseaseoccur.”
—FrancisS.CollinsMDPhD,Director,NationalInstitutesofHealth(NIH)
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History and Mission
WiththesupportoftheWMKeckFoundationandagenerousgiftfromMrSelimZilkha,theZilkhaNeurogeneticInstitute(ZNI)brokegroundinmorethanonewayjustover12yearsago.Somequestionedwhyanewinstitutedevotedtonurturingthebestbasicscientistswouldbelocatedonamedicalcampus.ButasentrepreneurslikeMrZilkhaknowalltoowell,cutting-edgeendeavorsfrequentlyreceiveconsiderablescrutinyandheandtheKeckSchoolofMedicineofUSCpersevered.
Now with more than 30 laboratories populated by hundreds of researchers, ZNI is fast becomingthehuboftheUSCneurosciencecommunity.Clinicians,physicianscientistsalongwithresearchersandtraineesatalllevels—fromundergraduatetograduatetopostdoctoral—areforgingcollaborationsacrossdepartments,disciplinesandschools.Andwearebeginningtoseeotheruniversitiesfollowthismodel,aligningtraditionalwetlabresearchspacedirectlyamidtheirclinicaloperations.
Withthefeedbackbetweenphysiciansandscientists,theworkatZNIisaimedtoidentifythoseatrisk,promotepreventivemeasures,developinnovativetherapiesandultimatelydiscoverandtranslatecuresfrombenchtobedside,foraspectrumofdevastatingbraindisordersfromAlzheimer’sdiseasetoschizophrenia.However,despitethemajoradvancesthatscienceismakinginunderstandinghowthehumanbrainworks,someneurodegenerativedisordersandpsychiatricconditionsareontheriseandbecomingmorefrequent,outpacingdiagnosticandtreatmentapproaches.
OnlyifscientistslikethoseworkingatZNIcontinuetodevotetheireffortstowardtheirareasofresearch,iftheyhaveaccesstosignificantfunding,andifrobustcollaborationsonAlzheimer’sandotherbraindiseasesendure,onlythenwilloureffortseventuallyleadtopreventiveapproachesthatcouldreducememorylossandotherserioussymptomsthatoccurasaresultofbraindiseases.
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Alzheimer’sisthesixth-leadingcauseofdeathinthecountryandtheonlycauseofdeathamongthetop10intheUnited
Statesthatcannotbeprevented,curedorevenslowed.
ZNI Faculty
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Alexandre Bonnin PhD AssistantProfessor Cell&Neurobiology
Daniel B. Campbell PhD AssistantProfessor Psychiatry&theBehavorialSciences
Karen Chang PhD AssistantProfessor Cell&Neurobiology
Jeannie Chen PhDProfessorCell&Neurobiology
Robert H. Chow MD, PhDAssociateProfessorPhysiology&Biophysics
Marcelo Coba PhDAssistantProfessorPsychiatry&theBehavioralSciences
David V. Conti PhDProfessorPreventiveMedicine
Zemin Deng PhDAssistantProfessorofResearchPsychiatry&theBehavioralSciences
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Hong-Wei Dong MD, PhDAssociateProfessorNeurology
Oleg Evgrafov PhDAssociateProfessorofResearchPsychiatry&theBehavioralSciences
Greg Field PhDAssistantProfessorCell&Neurobiology
Rick A. Friedman MD, PhDProfessorOtolaryngology
Radha Kalluri PhDAssistantProfessorofResearchOtolaryngology
James A. Knowles MD, PhDProfessorPsychiatry&theBehavioralSciences
Ralf Langen PhDProfessorBiochemistry&MolecularBiology
Le Ma PhDAssistantProfessorofResearchCell&Neurobiology
William Mack MDAssistantProfessorNeurological Surgery
Takahiro Ohyama PhDAssistantProfessorofResearchOtolaryngology
Carlos Pato MD, PhDProfessor&ChairPsychiatry&theBehavioralSciences
Michele Pato MDProfessorPsychiatry&theBehavioralSciences
Janos Peti-Peterdi MD, PhDProfessorPhysiology&Biophysics
Alapakkam Sampath PhDAssociateProfessorPhysiology&Biophysics
Derek Sieburth PhDAssociateProfessorCell&Neurobiology
Ansgar Siemer PhDAssistantProfessorBiochemistry&MolecularBiology
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Huizhong W. Tao PhDAssociateProfessorCell&Neurobiology
Terrence Town PhDProfessorPhysiology&Biophysics
Kai Wang PhDAssistantProfessorPsychiatry&theBehavioralSciences
Tobias S. Ulmer PhDAssociateProfessorBiochemistry&MolecularBiology
Gabriel Zada MDAssistantProfessorNeurological Surgery
Li Zhang PhDAssociateProfessorPhysiology&Biophysics
Berislav V. Zlokovic MD, PhDDirector,ZilkhaNeurogeneticInstituteProfessor&ChairPhysiology&Biophysics
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ZNI Faculty
ScientistsattheZilkhaNeurogeneticInstitutereachacrossboundariestoembracemethodsandtechniquesfrommanyfieldsofstudy.Theyworktoidentifynewapproachesforexaminingnervoussystemfunction,sowemayallbetterunderstandtheunderlyingcausesofneurologicalandpsychiatricdisorders.Areasofresearchoverlapconsiderably(e.g.,visionandcircuits),andeveryPrincipalInvestigator(PI)hasmultipleprojectsongoingatanyonetime.Hereisanoverviewofthecurrenttopicsofstudywith related examples:
Alzheimer and Related DiseasesTheProteinStructuregroup(Drs Ralf Langen, Ansgar Siemer and Tobias Ulmer)investigatethestructureofproteinsinvolvedindebilitatingdiseasessuchasAlzheimer’sdisease(AD)butalsoParkinson’sandHuntington’sdisease.Becausemanydisordersofthenervoussystemarethoughttoarisefromalterationsinthestructureofcellularproteins, these studies aim to help us understand the molecular basis of neural pathology,withalooktowarddevisingnewtreatmentsforthecureandpreventionofthesediseases.
Dr Karen Chang’slabistryingtodeterminetherolenebula/DSCR1playsinamelioratingaxonaltransportdefectsandmemorylossassociatedwithAlzheimer’sdisease;relatedlyhergroupistryingtoidentifythegenotypetophenotypecorrelationsinDownsyndrome.DrJeannie ChenisstudyinghowAnnexinA5modifiesdiseaseprogressioninamousemodelforAlzheimer’sdisease.DrHong-Wei Dong’s lab is studying the organizationalprincipleofthebrainwiringandhowthesecircuitsaredisruptedinmousemodelsofHuntington’sandAlzheimer’sdiseases.DrTerrence Town and his teamaredevelopingnewanimalmodelsofAlzheimer’sdiseaseandrelateddisorderstostudytheroleoftheimmunesystemindementiaandotherdevastatingdisordersofthemind.
Dr Berislav Zlokovic’s laboratory has a long standing interest in understanding the roleofcerebralbloodvesselsandblood-brainbarrier(BBB)inpathogenesisofneurodegenerativedisorderssuchasAlzheimer’sdiseaseandmorerecentlyamytrophiclateralsclerosis,asfoundationsfordevelopmentofnewtherapiesforADandrelatedneurodegenerativedisordersaswellasstroke.Usingexperimentalmodelsandstudyinghumanbrain,hisresearchteamhasidentifiedthecellularandmolecularmechanismsincerebralbloodvesselsandattheBBBthatmaintainnormalneuronalfunctionandstructure.TheyhaveshownthatBBBdysfunctionanddisruptionofcellularcross-talkbetweendifferentcelltypesoftheneurovascularunit(i.e.,endothelialcells,pericytesandastrocytes)caninitiateneuronaldysfunctionandinjury,degenerationandloss,andaccumulationofAlzheimer’stoxinAβandtaupathology.FindingsfromtheZlokoviclaboratorycontributedtoAβclearancetreatmentsinADpatients,andanewtreatmentforstrokewithanAPCanalogcurrentlyinPhase2studiesinstrokepatients.HismostrecentinterestsaredirectedatunderstandingthebiologyofgenesthatinfluencetheriskforAlzheimer’sdiseaseusingtransgenicmodels,humaniPSCsmodelofneurologicaldisorders,andstudyingimagingandmolecularbiomarkersofvascularinjuryinthelivinghumanbrainwithmildcognitiveimpairmentandAD.
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Faculty Research Programs
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Psychiatric Genetics TheCenterforGenomicPsychiatryinvestigatestherolegenesplayindisordersofthemind.DrMarcelo Cobaisinvestigatinghowcandidateriskfactorsassociatedtoschizophreniaandotherpsychiatricdisorders,workstogetherincommonsignalingpathways,combiningstate-of-the-artmassspectrometry,proteomics,bioinformatics,mousegeneticsandhumanstemcellmethods.Thisstrategyhelpsdeterminecoresignalingmechanismsandproteincomplexes,alteredthroughdevelopmentinschizophrenia,providingnewmoleculartargetsfortreatment.DrDan Campbell discoveredthatalongnon-codingRNA,anoveltypeofgene,contributestoautismrisk.Heseekstounderstandthecontributionsoffunctionalnon-codingRNAstothealteredbraindevelopmentofindividualswithautismandschizophrenia.DrAlex Bonnin is investigatinghowplacentalfunctionaffectsfetalbraindevelopment,specificallylookingattheimpactofmaternalinfectionsinpregnancyandseparately,theeffectsofmaternalstressandantidepressanttreatment.Thisresearchuncoversnewmolecularpathwaysforthedevelopmentaloriginsofmentaldisorders.
Considerableprogresshasbeeninmadeinthefieldofpsychiatricgeneticsoverthelastyear.Drs.Michele Pato, Carlos Pato and Jim KnowlesparticipatedinalargeGenome-WideAssociationStudyof(GWAS)ofschizophreniathatwaspublishedthispastsummeranddiscovered108geneticlocithatincreasetheriskofthedisorder,makingschizophreniaonethebeststudiedhumandiseasesatthegeneticlevel.Together,thesethreeinvestigatorsaremakingprogressonseveralotherpsychiatricdisorders,suchas,ObsessiveCompulsiveDisorder,majordepressionandsuicide,bipolardepression,aswellasdevelopingthelaboratoryandsoftwaretoolstoenablefutureinnovativeresearch.
GenomicsDr Kai Wangisworkingoncreatinganautomatedpipelineforwholeexome/genomesequencinganalysisonMendeliandiseasesandcancer,andforRNA-Seqanalysisofsingleneuronalcells.HislabalsoinvestigatesDNAmethylation,geneexpressionandsomaticmutationsinthemalignanttransformationofmeningiomas.Dr David Contifocusesondevelopingnovelstatisticalmethodstoanalyzenext-generationsequencingdatatodiscoverygeneticvariantsinvolvedindisease.Thisworkisheavilyintegratedintohisappliedcollaborationsexaminingthegeneticcontributiontosmokingprogressionandcessation,multiplesclerosis,colonandprostatecancer,asthma,lymphoma,andpsychiatricdisorders.DrGabriel Zadautilizesnext-generationgenomicandepigenomicprofiling(i.e.DNAMethylationanalysis)tostudythebehaviorofvariousbraintumors.Inparticular,heisinterestedinstudyingtheprocessoflocaltumorinvasionanddevelopingmolecularclassificationsystemsforvariousskullbasetumors,includingpituitarytumorsandmeningiomas.Heisalsoworkingtodevelopnoveltreatmentstrategiesforskullbasetumorsusingintranasaltherapysystems.
CircuitsThe aim of Dr Robert Chow’slaboratoryistoadvanceourunderstandingofhowneuronalandhormonesecretion(exocytosis)iscontrolledinnormalandpathologicalstates;partofthelabfocusesonfundamentalmechanisms(SNARE-mediatedsecretion),andtheotherondiseaseprocesses(diabetes,retinalandneuro-degeneration)orhowtotreatdiseases(retinaldegeneration).TheDerek Sieburthlabcombinesbehavioral,genetic,RNAinterference,andliveimagingtechniquestodissectsynapticfunctionatasystemsandmolecularlevelintheC.elegansmodel.DrLi Zhang’s research is focused on understandingthestructureandfunctionofneuralcircuitssoastodecipherthebrain,whichincludesfouraspects:1)howneuralcircuitsassembleandoperate,2)howcircuitstructuredeterminesbehavioralfunction,3)howcircuitfunctionsaremodulated,aswellas4)howcircuitdisordersleadtobraindisorders.DrHuizhong Tao’sworkalsoexploresestablishmentanddevelopmentoffunctionalvisualcircuits(pleaseseeVision/Eyebelow).
VascularDr William Mackdeploysanexperimentalstrategytodeterminetheeffectsofairpollutiononacutestroke,whichisaleadingcauseofdeathanddisabilityworldwide.Heisfurtherinvestigatinginnovativetreatmentplatformsforrapiddeliveryofneuroprotectiveagentstootherwiseinaccessiblecorticalterritoriesinthesettingofacutestroke.Thebroadinterestofthe Janos Peti-Peterdilabisrenal(patho)physiology,specificallytheintrarenalmechanismsinvolvedinthecontrolofbloodpressureandbodyfluidbalanceundernormalanddiseaseconditions(hypertension,diabetes).DrBerislav Zlokovic’s laboratory has a long standing interest in understanding the role of cerebral bloodvesselsandblood-brainbarrier(BBB)inpathogenesisofneurodegenerativedisorderssuchasAlzheimer’sdisease(AD)andmorerecentlyamytrophiclateralsclerosis(ALS),asfoundationsfordevelopmentofnewtherapiesforADandrelatedneurodegenerativedisordersaswellasstroke.
Vision/EyePhotoreceptorcellsarelightsensitiveneuronsintheretinathatinitiatethefirststepinvision.OneofthemainobjectivesofDrJeannie Chen’s laboratory is to understand how an intracellular signaling cascade is regulated within rod and cone photoreceptor cells,andhowthiscontributestothespecializedabilityofthesecellstodetectdimlightandbrightlight,respectively,andhowmutationswithinthissignalingcascadeleadstoblindness.DrGreg Fieldistryingtounderstandhowneuronsfunctionwithincircuits;currentresearchinhislabiscenteredaroundidentifyingthefunctionalconnectivitybetweenthephotoreceptors(bothrodsandcones)andtheapproximately20distinctretinalganglioncelltypes.DrHuizhong Taoisinterestedinhowfunctionalvisualcircuitsareorganizedtoachievespecificcorticalprocessingfunctionsandhowthesecircuitsareestablishedduringdevelopment.Sheiscurrentlyexamininghowneuralactivityofvariouspatternsleadstomodulationsofsynapticconnectionsandshapestheformationofvisualcircuits.
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Faculty Research Programs
Hearing/EarThe most common sensory abnormality in the world is age-related hearing loss.Thesecondmostcommonformofhearinglossisnoise-induced.DrRick Friedman’s laboratory has demonstrated that both of these traits can betreatedascommondiseasesandcanbeapproachedthroughassociationmapping.TheprimaryobjectiveofDrFriedman’slaboratoryistostudythesecommonformsofhearinglossusingagenome-wideassociationapproachinmice.DrFriedman’slaboratoryhasbeguntodefinethegeneticarchitectureofage-relatedhearinglossinmiceandhasidentifiedseverallocileadingtosusceptibilitytonoise-inducedhearingloss.Thisworkwillprovideimportantinsights into the mechanisms underlying these common forms of hearing loss andstudiesinthemouseprovidethepowertobegintounderstandgeneXenvironmentinteractions.The Takahiro OhyamaLabisinvestigatinghowthecochlea,theauditoryorgan,developsduringembryonicdevelopment.TheydiscoveredBMPsignalingpathwayisimportantforcellfatedecisionbetweensensoryandnon-sensorystructureofmammaliancochlea.TheOhyamalabisalsoanalyzingthemechanismshowmigratingneuralcrestcellsareincorporatedintothenon-sensorystructureofdevelopingcochlea,whichiscrucialforproperhearingfunctions.Theseprojectsaimtounderstanddiseasemechanismsofhearingimpairmentanddeveloptranslationalresearchsuchasregenerationofauditorycells.Recentworkfromthe Radha Kalluri Lab examines how biophysicaldifferencesbetweensubpopulationsofbipolarafferentneuronsintheauditoryandvestibularsystemsinfluencetheirfunctionandtheirsusceptibilitytodamage.
Understandingnervoussystemfunctionanddysfunctionrequiresthecombinedexpertiseofoutstandingscientistsfromavarietyofdisciplines.ItisattheZilkhaNeurogeneticInstitutewheregreatmindscometogether,exploringnewwaystoenhanceourunderstandingofhowthebrainworks,sowemayimprovetheoutlookforfuturepatientcare.
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Photocred
it:Alexand
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ninLab
We share in the following pages some of the notable accomplishments by ZNI faculty over the past year.
Alexandre BonninTheresearchdonebytheBonninLaboverthepastyeardemonstratedthatexposurestobacterialandviral-likeimmunostimulantsinpregnantmicetriggerdifferentmaternalandplacentalinflammatoryresponses,whichinducearapidincreaseoftryptophanmetabolicgeneexpressionandenzymeactivityspecificallyintheplacenta.Mostimportantly,thistranslatesintorapid,differentialalterationsofcriticalneuroactivemolecules,suchasserotonin,inthefetalbrain.Theseeffectsarelikelytoresultincompromisedserotonergicmodulationoffetalbraindevelopmentandhavedirect,long-termconsequencesonfetalbraincircuitformationandpostnatalbrainfunction.Theprogressmadelastyear,soontobereportedinamanuscript,providesstrongsupporttothehypothesisthatalterationofplacentaltryptophanmetabolismbymaternalinflammationduringearlygestationconstitutesanewmolecularpathwayforthefetalprogrammingofneurodevelopmentaldisorderssuchasautismorschizophrenia.Inaddition,thelab’sprenataltoxico-pharmacologicalexposurestudiesrevealunexpected,andpotentiallybeneficial,effectsofantidepressantdrugsonfetalbraindevelopment,inthecontextofunderlyingmaternalgestationalstress.Finally,withDrJenniferKing,LAC+USCmaternal-fetalmedicine fellow, the lab has started to explore a new, long-range, molecular communicationpathwaybetweentheplacentaandthefetalbrain.Preliminaryresultsareencouragingandmayleadtofutureidentificationofnewtargetsandbiomarkersforthefetalprogramingofmentaldisorders.
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ScientificAdvancements
Photocred
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Daniel CampbellTheCampbelllabagainpublishedahighprofilepaperthatproducedwidespreadmediaattention.Inthepasttwoyears,theirworkhasgeneratedmediacoveragefromCNN,Timemagazine,PBS,andAsianNewsInternational.Thisyear,theypublishedthefirststudyshowingagene-environmentinteractionthattriplestheriskofautism.Thelabhadpreviouslydemonstratedthatageneticvariantincreasesautismrisk.TheircollaboratorsintheUSCDepartmentofPreventiveMedicinepreviouslyshowedthatairpollutionincreasestheriskofautism.Puttingheadsanddatatogether,theydiscoveredthatindividualswithboththegeneticriskfactorandexposuretohighlevelsofairpollutionwereatamuchhigherriskforautismthanindividualshavingeitherthegeneticfactorortheairpollutionexposurealone.Thiswasthefirsttimethatanyonehasshownthatacombinationoftwoknownriskfactorsforautismcanmultiplytodramaticallyincreaserisk.TheCampbelllabisnowintheprocessoftryingtounderstandthemechanismsofthisgene-environmentinteraction.Remarkably,amajorcomponentofthemechanismappearstobeanoncodingRNA,whichcouldprovideapotentialtreatmenttargetforautism.
Karen ChangTheChanglabdiscoveredthefollowingthings:1)aproteinupregulatedinbothDownsyndromeandAlzheimer’sdiseaseplaysasurprisinglyroleindelayingneurodegeneration;2)akinasemutatedinautismandupregulatedinDownsyndromeenhancestherateofrecyclingofneurotransmittersrequiredforreliablecommunicationbetweenneurons.Theyarecontinuingtoinvestigatethebiologicalfunctionsofbothoftheseproteinsandtheircontributiontoneurologicaldisorders.
Jeannie ChenExcessivelightexposureisknowntoharmtheretinaandexacerbatesdiseaseprogressioninmanyretinaldisorders,includingage-relatedretinaldegeneration.Howlightexertsitsharmfuleffectontheretinaisnotwellunderstood.Thefirststepinone’snighttimevisionbeginswithphotonabsorptionbyrhodopsin,whichthenactivatesmanytransducinmolecules.Transducin,inturn,stimulatesphosphodiesteraseenzymeactivitytobreakdowncGMP.Attheplasmamembraneoftherodcell,thefallincGMPconcentrationcausescGMP-gatedchannelsclose,whichthenblocktheflowofioncurrentsintothecell.Inthismannerphotonabsorptionultimatelyleadstoachangeincurrentattheplasmamembraneinaprocesscalledthephototransductioncascade.Anover-activephototransductioncascadeisknowntocauseretinaldegeneration.Duringthepastyear,theChenLabshowedthatexcessiveactivationoftransducin,butnotclosureofthecGMP-gatedchannels,causesphotoreceptorcelldeathbyinductionoftheunfoldedproteinresponse.Thesefindingsprovideatargetfortherapeuticinterventionincertainretinaldisorderscausedbyconstitutivephototransduction.
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Robert ChowThe Chow laboratory has started single-cell analysis of human spinal motor neurons offirstandsecondtrimester,correlatingelectrophysiology,morphologyandgenetranscription.Thiswork,inthecontextoftheNIHU01(ChowandKnowlesPIs),haspavedthewayforacollaborationwithDrJustinIchida(Broad/CIRM,KeckSOM)toinvestigategenechangesleadingtospinalmotoratrophy(SMA)andamyotrophiclateralsclerosis(ALS).TheChowlabhasmademajorstridesinunderstandinghowgenesnormallyassociatedwithneuronaldevelopmentalsomayplayamajorroleindeterminingtheinvasionpotentialofcancer.Thepromisingworkmayleadtoareal-timerapidscreenforcancerinvasionpotentialandanoveltreatmentforhighlyinvasivecancers.IncollaborationwiththeLangenlaboratory,theChowlabhasdiscoveredapossiblenewmechanismbywhichplasticizersmayincreasetype2diabetesmellitusandAlzheimersdiseaserisk.Plasticizershadbeenthoughttoactlargelyashormone-disruptors.Ourworksuggeststhatplasticizersmayplayaroleindamagingand/orkillingpancreaticbetacellsandneurons,byacceleratingamyloidproteinmisfolding.
Marcelo CobaManyofthegenesthathavebeenimplicatedasriskfactorsforthepsychiatricdisordersarethoughttoaffectthefunctionofneuronalsynapses.TheCobalabisinterestedtounderstandthemolecularmechanismslinkingpsychiatricdiseasecandidategenestosynapticsignaling.Thisyeartheymadesignificantprogressintheunderstandingofhowsynapticsignalingprocessesrelatestopsychiatricdisease.UsingMassspectrometry,bioinformaticsandmousegenetics,thelabdeterminedthecompositionofdifferentsynapticcomplexes,mappingmorethan2,500in-vivo,proteininteractionsinmousepre-frontalcortex.TheydeterminedthatthesesynapticcomplexeswereenrichedinSchizophreniacandidateriskfactorsandthatdisruptionofcorecomponentsofthesecomplexes,regulatesthecompositionandassociationofproteinsbyimpairmentofprotein-proteininteractions.Theyalsodeterminedthataclusterofproteinsrelatedtopsychiatricdisease,associatesinproteincomplexesthatmodulateshiPSCproliferation,anddifferentiation.Thesecomplexesarenotfunctionallyrelatedtosynapticmoleculesandmightfunctionasanindependentclusterforpsychiatricdiseaserisk.
David ContiTheContilabhasmadeseveraladvancesinstatisticalmethodologyfortheintegrationofbiologicalinformationingeneticassociationstudiesviatheuseofBayesianstochasticsearch.Inparticular,theyhavedevelopedanintegrativeBayesianmodeluncertainty(iBMU)method,whichformallyincorporatesmultiplesourcesofdataviaasecond-stageprobit model on the probability that any predictor is associated with the outcome of interest.Usingsimulations,theydemonstratethatiBMUleadstoanincreaseinpowertodetecttruemarginalassociationsovermorecommonlyusedvariableselectiontechniques,suchasleastabsoluteshrinkageandselectionoperatorandelasticnet.Theincreaseinpowerandefficiencyoftheirmethodbecomesmoresubstantialasthepredictor-levelcovariatesbecomemoreinformative.Inaddition,theContilabhascreatedascalablealgorithmcalledPEAKthatimprovestheefficiencyofMCMCbydividingalargesetofvariablesintorelatedgroupsusingarootedgraph.Theiralgorithmtakesadvantageofparallelcomputingandexistingbiologicaldatabaseswhenavailable.
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Scientific Advancements
Hong-Wei DongTheDonglabmadeasignificantprogressontheNIH-fundedMouseConnectomeProject(MCP,www.MouseConnectome.org),whichproposestogeneratetheconnectivitymapoftheentiremammalianbrainandtosubsequentlyconstructitsneuralnetworksusingcomputationaltechnology.TheMCPhasproducedoneofthefirstonlinedigitalconnectivityatlases,theiConnectome,whichhosts~8,200regularusers.Theteamhastraced600corticalpathwaysandhasgeneratedthemostcomprehensiveconnectivitymatrixofthemammaliancerebralcortex.Theirinteractivecorticalconnectomicmap,whichfeatureshundredsofreconstructedcorticalpathways,isalsoavailableonline.Thedatawerealsosubjectedtographtheoreticalanalyses,whichrevealedthatthecortexisorganizedintoafewrelativelysegregatednetworks.Thisnovelworkwasrecentlypublished(Zinggetal.,Cell156,1096-1111,2014).Becauseofitsbroadscientificrelevance,CellPressandUSCdidapressreleaseonthearticle.AnditwasfeaturedontheNIHdirector’sblog,andwasnationallyrecognizedintherecentInterimreportoftheBRAINinitiative.Theseaccomplishmentswerecontingentuponinnovativedevelopmentsincludingpipelinesforcollecting,presenting,andanalyzinglarge-scaleconnectivity.
Greg FieldTheFieldlabhasbeguntouseengineeredvirusestomanipulatethefunctionofneuronsinthemouseretina.Thesevirusesallowsthelabtoactivateorinactivewithnovelpharmacologicalagentsneuronsintheretina.Thisapproachisallowingthemtodiscovernewcelltypesintheretinaandtheirroleinvisualprocessing.Thelabisalsoinvestigatinghowlightandcircadianrhythmsimpacttheencodingofvisualscenesbytheretina.Finally,theyareinvestigatinghowretinitispigmentschangesretinalfunctionandidentifyingpromisingtherapiesforthisblindingdisorder.
Rick FriedmanTheFriedmanlabhascompletedagenome-wideassociationanalysisofage-relatedhearinglossandnoise-inducedhearinglosssusceptibilitiesinmice.They,inconjunctionwithcollaboratorsfromtheUniversityofAntwerpandTranslationalGenomicsinArizona,haverecentlyshownthecomplexnatureofage-relatedhearinglossinahumanGWAS.Theyhaveidentifiedatleast15novellociforeachdisease.TheyhavedemonstratedthatonelocuscontainingNox3,anNADPH-reductasegene,isimportantforsusceptibilitytonoise-inducedlossandhavecharacterizedthephenotypeinNox3mutantmice.Theyhaveidentifiedanovelage-relatedhearinglossgene,Fhod3,andhavedemonstrateditsexpressioninthehaircellsandspiralganglionofthemouseinnerear.TheyarecurrentlyembarkingoncochlearorgancultureexpressionstudiesandconstructionofatransgenicandCRISPRconditionalknockoutofthegeneinmice.Theyarecurrently50%finishedwithaGWASforstrainvariationinvestibularevokedpotential,ameasureofgravityreceptorfunctioninmiceandhaveacandidategene(Dcc)atagenome-widesignificantlocus.TheyalsohavecompletedthebioinformaticsanalysisandarepreparingamanuscriptonthefirstRNA-seqdataforthehumancochleaandvestibularsystem.Thisanalysishasdemonstratedahostofcochlearspecificgenes,splicevariants,andshortRNAsthatarespecifictotheinnerear.Thiswillserveasaninvaluableresourceforthehearingscientificcommunity.
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Radha KalluriProjectsinthelabarecombininginvitropatchclampexperiments,withanatomy,andcomputationalmodellingtostudythebiophysicalbasisforsensorysignalinginthevestibularandauditorysensorysystems.Inthepastyear,theKallurilabhasbeenworkingondeterminingiftheintrinsicbiophysicalpropertiesofauditoryandvestibularsensoryneuronscontributetofunctionallydistinctsub-classes.They’verecentlyidentifiedgroupsofionchannelsthatmaydifferbetweenfunctionallydistinctgroupsofvestibularandauditoryneurons.They’vedevelopedacomputationalmodelthatteststheimpactoftheseionchannelgroupsonneuronalfunction.
James KnowlesTheKnowleslabareamemberofalargeinternationalconsortiumofresearchersdoingpsychiatricgeneticswhohavediscovered108independentgeneticlociresponsibleforthedevelopmentofschizophrenia.Theyhavecompletedthewholegenomesequencingof~2,000individualswithschizophrenia,bipolardisorderandheathycontrols,andwerejustfundedtosequenceanother10,000samples.Thelabcontinuestodevelopcelllinesofneuralprogentitorsfromindividualswith,andwithout,schizophrenia,andtheywererecentlyfundedtoexaminetheepigeneticsoftheselines.TheycompletedandpublishedthesecondGenome-WideAssociationStudyof(GWAS)ofObsessiveCompulsiveDisorder(OCD),whichfoundevidenceforthegenePTPRD.OneofthebestgenestheyfoundinthefirstOCDGWAS(BTBD3)hasbeendevelopedinamousemodelofthedisease.TheKnowleslabwasalsorecentlyfundedbyNIHtocollectDNAandclinicalinformationfrom5,000individualswithOCD.TheyhavedevelopedanovelandrobustcomputerpipelinetodeterminethelevelofgeneexpressionusingDNAsequencingandappliedittostudiesofgeneexpressioninsinglecells.Theyalsohavepotentiallyidentifiedaregionofthebrainwithdrasticallydifferentgeneexpressionbetweenindividualswhodiedbysuicide,ascomparedtothosewhodidnotsuicide.Additionally,theKnowleslabreceivedtwonewNIHgrants.Thefirstistostudytheepigeneticsofcellsderivedfromindividualswith,andwithout,schizophrenia(Co-PI,PeggyFarnham).ThesecondgrantistocollectanperformaGWASstudyof5,000individualswithOCD(CO-PI,MichelePato).
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Ralf LangenDuringthepastyear,theLangengroupcontinuedtoinvestigatewhatmakesproteinsmisfoldandtakeuptoxicspeciesinAlzheimer’sdisease,Parkinson’sdisease,Huntington’sdiseaseandtype-2diabetes.Towardthisend,theyobtainednovelstructuralinformationofseveraltoxicmisfoldedamyloidogneicstatesandfurtherdevelopedpeptideandprotein-basedmeansforinhibitingthemisfoldingand,thereby,preventingtoxicity.ThestudiesbytheLangengroupalsoprovideinsightintohowenvironmentalfactorsthatcanpromotetheaforementioneddisesasesdosobyaffectingproteinmisfolding.IncollaborationwiththebiotechnologycompanyPROMIDIS,theLangengroupalsoidentifiedanewstructuralstateoftheHuntington’sdiseasecausingproteinhtt,andpreventionofthisstructuralformbypost-translationalmodificationsorsmallmoleculesisthoughttobeatherapeutictarget.Inseparatestudies,theLangengroupidentifiedanewmechanism,bywhichcellscancontroltheshapeofcellularmembranes.Inparticular,itwasfoundthatthesameproteincangeneratedifferenttypesofcurvatureandthatphosphorylationactsasamolecularswitchthatdetermineswhichmembranecurvatureisgenerated.Theinvolvementofthisswitchislikelytobeofrelevanceinseveraldiseases,includingParkinson’sdisease.
William MackTheMacklaboratorywasawardedagranttostudytheeffectsofairpollutionfromvehicularexhaustinthesettingofacutestroke.Pilotstudiesdemonstratedadetrimentaleffectofparticulatematteronstrokeprogression.TheypublishedapapercharacterizingtheroleoftheC5complementcomponentinthesettingofchroniccerebralhypoperfusionsecondarytocarotidarterystenosis.Alongwithourcollaborators,theypublishedseveralstudiesdissectingthegenetic/epigeneticcharacteristicsofmalignantmeningiomas.
Takahiro OhyamaTheOhyamaLabisinvestigatinghowthecochlea,theauditoryorgan,developsduringembryonicdevelopment.TheydiscoveredBMPsignalingpathwayisimportantforcellfatedecisionbetweensensoryandnon-sensorystructureofmammaliancochlea.TheOhyamalabisalsoanalyzingthemechanismshowmigratingneuralcrestcellsareincorporatedintothenon-sensorystructureofdevelopingcochlea,whichiscrucialforproperhearingfunctions.Theseprojectsaimtounderstanddiseasemechanismsofhearingimpairmentanddeveloptranslationalresearchsuchasregenerationofauditorycells.
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Carlos and Michele PatoInthelastyear,thePatolabcontinuedtodeveloptheGenomicPsychiatryCohort(GPC)andmadesignificantprogressinanalyzingthegenotypesofcohortparticipants.Additionally,inMarch2014,theyreceivedanew$3.8milliongranttoexpandtheGPCbeyondSchizophreniaandBipolarDisorderbyaddinganadditional5,000participantswithObsessive-CompulsiveDisorder(OCD).TheGPCisalargeclinicalcohortofpatientswithschizophrenia(n=10,000),patientswithbipolardisorder(n=5,000),familymembers(n=3,000),andcontrolparticipantswithnohistoryorfamilyhistoryofschizophreniaorbipolardisorder(n=15,000)(Patoetal.,2013.Thusfar,theyhaveperformedavarietyofgenotypingandwhole-genomesequencingonover12,000GPCcasesandcontrols.GPCparticipantsgiveverybroadconsents(88%consenttore-contact)sothatdatageneratedcanbeimportantforabroadrangeofphenotypesandgeneralpopulationgenomics.TheGPCresourceincludesanNIMH-managedrepositoryofgenomicsamples,genotypeandsequencedata,anddetailedclinicalanddemographicdataforinvestigationsofmentaldisorders.ThenewgrantexpandstheGPCbyascertaining5,000patientssufferingfromOCDandperformingagenome-wideassociationstudy(GWAS)on5,000OCDpatientsand5,000already-ascertainedandgenotypedOCD-freematchedcontrols.ThePatolabwillmorethandoublethetotalnumberofavailableworld-wideparticipantsforGWASofOCD.
Janos Peti-PeterdiThePeti-Peterdilabinvestigatedthecellularandmolecularmechanismsofglomerularkidneydiseases,andidentifiedseveralnewpotentialtherapeutictargetsforfuturefurtherdevelopment.Themainfocusoftheirstudieslastyearwastheroleofpodocytes,auniquepericyte-likecelltypewithintheglomerulus,inthedevelopmentofglomerulosclerosisandchronickidneydisease.TheyidentifiedpurinergiccalciumsignalingmediatedbytheP2Y2receptor,asthemostsignificantmechanismofpodocytecell-to-cellcommunicationandpropagationofpodocyteinjury.TheyshowedthatmousemodelsdeficientinP2Y2wereprotectedfromthedevelopmentofproteinuria.Thelabalsoshowed,forthefirsttime,directvisualevidenceforthegenerationofnewpodocytesintheintactlivingmousekidney,usinganewtechnicalinnovation,serialmultiphotonmicroscopy.Theytrackedtheoriginandfateofindividuallymarkedpodocytesandresidentrenalmesenchymalstemcellswithinthelivingkidneyusingthistechnology.ThepatternofcellmigrationsgavethePeti-Peterdilabnewvisualcluesonnovelmechanismsofglomerularandrenaltissueremodelingandregeneration.Theyarecurrentlyintheprocessofexploringthesenewmechanismsfurther.
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Ansgar SiemerThemajorgoalofSiemerlabistodescribeonastructurallevelhowsomeamyloidfibrilscanbetoxicandresponsibleforneurodegenerativediseases,whileothershavebeneficialfunctionsasforexampleinlong-termmemory.ThelatterquestionisaddressedintheirresearchontheOrb2functionalamyloid,whichisakeyregulatoroflong-termmemoryinDrosophila.BesidesconsiderableprogressindefiningtheextendandthestructureofOrb2’samyloidcore,theyfoundthatOrb2haspreviouslyundescribedaffinitiestometalions,lipids,andnucleicacids.Theyarefollowinguponthesefindingtounderstandtheimportanceoftheseinteractionsforlong-termmemory.TheirresearchontheoriginoftoxicamyloidsinneurodegenerativediseasesisdoneincollaborationwiththelabofRalfLangenwheretheyareworkingonthestructureoftoxicfibrilsformedbytheproteinhuntingtinimportantinHuntington’sDisease.Withthelab’snewlyinstalledsolid-stateNMRspectrometer,theycoulddetectclearstructuralanddynamicaldifferencesbetweenhighlytoxicamyloidfibrilsandfibrilsthatwereshowntobelesstoxic.Inanextstep,theLangenandSiemerlabswillsolvethestructureofboththetoxicandthebenignhuntingtinfibrils,whichwillgivethemimportantcluesabouthowsomeamyloidfibrilscanbetoxicandothersnot.
Huizhong TaoTheTaolabmadethreemajordiscoveries.First,inlayer4ofthemousevisualcortextheyrevealedsynapticchangesinducedbymonoculardeprivation(MD),whichisapopularexperimentalmodelforstudyingmechanismsandtreatmentsforamblyopia.Whileconfirmingalong-timesuspicionofdecreasedexcitatoryinputsfromthedeprivedeye,theirresultsalsogeneratenovelinsightsintotheexpressionmechanismforMD-inducedcorticalplasticitybydemonstratingthataMD-inducedgeneraldown-regulationofinhibitoryinputscontributestotheincreasedresponsivenessthroughthenon-deprivedeye.Second,bycombiningoptogenetictechniquesinspecifictransgenicmouselineswithintracellularvoltage-clamprecordings,theyfoundthatrecurrentintracorticalexcitatorycircuitsplayanimportantroleinamplifyingtheorientation-tunedsignalrelayedbythevisualthalamus,whilekeeptheoverallorientationtuningpreserved.Thisfindingshedlightontheorganizationofcorticalcircuitstoproducesharporientationselectivityinvisualcortex.Third,theyexaminedsynapticmechanismsunderlyingdirectionselectivityinlayer4oftheprimaryvisualcortex.Theyfoundthatdirectionselectivityoriginatesfromdirection-tunedthalamicinput,butisgreatlysharpenedbyuntunedinhibitoryinputscomingfromnon-direction-selectivefast-spikinginhibitoryneurons,amajorinhibitorycelltype.Interestingly,thedirectiontuningofsynapticinputsishighlycorrelatedwiththeirasymmetryinspatialdistributionofsynapticamplitudes.Ongoingexperimentsareaimedatunderstandinghowspatialasymmetriccanresultsinadirectionalbiasofsynapticresponsestomovingstimuli.
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Scientific Advancements
Derek SieburthTheSieburthlabisinterestedinhowenvironmentalcuesimpactbehaviorbyinfluencinghowneuronscommunicatewitheachotheratspecializedstructurescalledsynapses.Theyusethenematodeasamodelsystemforstudyingsynapsestructureandfunctionbecauseofitssimplenervoussystemandtheabilitytovisualizeproteinsinsynapsesinbehavinganimals.Thisyearthelabdiscoveredanewcellularsignalingpathwaythatcontrolswhenneuronsbecomeactivatedduringarhythmicbehavior.Thelabalsodiscoveredthattheneurotransmitteracetylcholinecanactasamodulatorofneuronalfunctionbyactivatingitsreceptoratsitesfarawayfromsynapses.Finally,thelabshowedthattheamountofthesynapticproteinneuroligin,whichisimplicatedinautism,iscontrolledbyastressresponsepathwaythatfunctionsinneuronstoprotectthemfromdamagefromoxidativestress.
Terrence TownTheTownlab’sfocusistodevelopatreatmentforAlzheimer’sdiseasebytargetingthebody’simmunesystem.Mosttherapiestargetingthediseasearethwartedbytheblood-brainbarrier,a natural mechanism that protects brain cells from entry of peripheral substances, and by thefactthatimmuneresponsesinthebrainaretypicallymuted.However,inlaboratorymiceprogrammedtodevelopAlzheimer’s-likedisease,theTowngrouphasshownthatcertainimmunecellscanbecoaxedintothebrainfromthecirculation,wheretheyattackthedamagingstickyplaquebuildupthatisadefiningfeatureofAlzheimer’sdisease.Theyarecontinuingtopursuethislineofresearchinhopesofdevelopinganext-generationdrugforAlzheimer’sdisease.Thiswork,whichhasbeenfundedbytheNationalInstitutesofHealth,theAlzheimer’sAssociation,andtheAmericanFederationforAgingResearch,hasbeenpublishedinnumeroushigh-impactjournalsincludingScience,NatureNeuroscience,Immunity,PNAS,andTheJournalofNeuroscience.Oftheover100researchpapersthatwehavepublished,halfhavebeenrelatedtoAlzheimer’sdisease.TheTownlabhasrevolutionizedthefieldofAlzheimer’sdiseaseresearchbygeneratingthefirstratmodelofthediseasethatmanifestsalloftheclinico-pathologicalhallmarksofthehumansyndrome.Specifically,theymadetransgenicratsthatover-expresstwomutanthumantransgenesthatareeachindependentlycausativeoffamilialearly-onsetAlzheimer’sdisease:“Swedish”mutantamyloidprecursorproteinanddeltaE9mutantpresenilin-1.Unliketheirtransgenicmousecousinsthatdevelop‘senile’plaquesbutfailtomanifest‘tangles’andfrankneuronalloss,thesetransgenicrats-forthefirsttime-developthefullspectrumofAlzheimerpathologies.ThismakesthemaninvaluabletoolforunderstandingAlzheimer’sdiseaseetiologyandfortestingcutting-edgetherapeuticspre-clinically.UsingthisexcitingnewAlzheimerrat,theyareactivelypursuingcollaborationswithacademicsandwithindustryaroundtheworldtounderstandbasicmechanismsofAlzheimer’sandtodevelopacureforthisdevastatingneurodegenerativedisease.
Tobias UlmerFatalage-dependentneurodegenerativediseasessuchasprevalentParkinsonDisease(PD)encompassthetoxicmisfoldingofthe140-residueproteinα-synuclein(αS).Thesediseaseslimitthelifespanandqualityoflifeofanincreasingandembattlingportionofthehumanpopulation.Toguidetherapeuticcoursesoftreatment,ourlong-termgoalistoobtainvitalunderstandingofthestructure-functionandstructure-dysfunctionrelationshipofαS.TounderstandtherootcauseofαSmisfolding,weperformedcomputationalstudiestosimulatepossiblestartingpointsofmisfolding.TomaintainphysiologicalfunctionofαSupontherapeuticintervention,itsrandomcoiltohelixtransitionuponsynapticvesicleassociationneedstobepreserved,requiringadetailedbiophysicalunderstandingofthisevent.Wehaveusedarangeofbiophysicaltoolstostudythisrandomcoiltohelixtransition.Byprovidingcomprehensive,mechanisticinsightintotheαSfoldingandmisfoldingpathways,itwillbepossibletoidentifynoveltherapeuticavenuestocombatαS-basedneurodegenerationwhilepreservingphysiologicalfunction.
Kai WangTheWanglabhasdevelopedseveralcomputationaltoolsforgenomeanalysis,including(1)Phenolyzer,whichprioritizepotentialdiseasecausalgenesinhumangenomebasedonobservedphenotypepresentations.(2)iCAGES(integratedcancergenomescore),whichidentifiescancerdrivergenesandrelevantdrugsfromwhole-genomesequencingdataontumorsamples.(3)Enlight,asoftwareandwebserverforepigeneticannotationofvariantsidentifiedfromgenome-wideassociationstudiesorwhole-genomesequencingstudies.
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Li ZhangTheZhanglabhasmadetremendouseffortsinmethodologicalinnovation.Inparticular,theyestablishedhigh-qualityinvivowhole-cellvoltage-clamprecordingtechniquestorevealspectrotemporalinterplaysbetweenexcitationandinhibitionindeterminingauditoryprocessingfunctionsofindividualprincipalneurons.Furtherintegratingtwo-photonimagingguided targeted patch-recordings from inhibitory neurons, neural circuit modeling, and optogeneticmanipulationsofneuralactivityofdesiredcellgroups,wewereabletoderivelocalexcitatoryandinhibitorysynapticcircuitsunderlyingspecificauditorycomputation.Theyhavemadesubstantialprogressinunderstandingthesynapticcircuitbasisforauditoryprocessing,alongthefollowingresearchdirections:a)specificandsequentiallaminarprocessingineachlayeroftheprimaryauditorycortex;b)processingofuniquefeaturesofacousticsignalsatseveralmajorsubcorticalauditorynuclei;c)postnataldevelopmentoffunctionalsynapticcircuitsintheauditorycortex.Forexample,oncorticallaminarprocessing,theirseriesofstudiesrevealedthatdifferentialexcitatory/inhibitoryinterplaysintermsofspectral,temporalandamplitopicrelationships,whichareinheritedfromvariationsoflocalcircuitsallrecruitingafeedforwardinhibitorycircuitmodule,leadtodifferentiallaminarprocessing.
Berislav ZlokovicTheZlokoviclab’sprogressinpreclinicalstudiesinrodentmodelsofischemicstrokewith3K3A-APC,a2ndgenerationcytoprotective-selectiveAPCmutantwith>90%lossofanticoagulantactivity,wastranslatedin2014intoPhase2multi-centerclinicaltrialinstrokepatients.Workingwiththeneuroimaginggroup,theyhavedevelopedanewimprovedtesttoevaluatecerebrovascularintegrityandblood-brainbarrierdamageinthelivinghumanbrainduringnormalagingandinindividualswithmildcognitiveimpairmentandmultiplesclerosis.Thelabhasdevelopedanewbatteryofassaystoaccesssimultaneously~30analytesinhumanandrodentbiofluids(CSF,plasma)includingbiomarkersofdifferentcelltypeswithintheneurovascularunit(e.g.,endothelialcells,pericytes,astrocytes,olgo,neurons,inflammatoryresponse,Abetaandtau).Next,theyfoundthatperivascularpericytescontrolprogressionofAlzheimer’sneurodegenerativelikeprocessinmiceincludingaccumulationofAbetaandtauandlossofneuronsusingmodelsofAlzheimer’sdiseasewithacceleratedpericyteloss.Theyalsoshowedthatblood-brainbarrierdisruptionisanearlyeventthatleadstomotorneurondegenerationinamousemodelofamyotrophiclateralsclerosisandthatAPCretardsearlymotorneurondegenerationbypreventingblood-brainbarrierbreakdownandeliminatingneurotoxicmicrovascularlesionsfromtheCNS.Twopatentshavebeenissued:one,foruseofRAGEblockerstoinhibitprogressionofAlzheimer’spathologybyblockingAbeta/RAGEinteractionattheblood-brainbarrier:and,secondforusesofactivatedproteinCanalogswithreducedanticoagulantactivityinneruologicaldisordersandstroke.
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Collaborations
“Science is a collaborative effort. The combined results of several people working together is often much more effective than would be that of an individual scientist working alone.”
—John Bardeen PhD, American Physicist
and the only person to have won the Nobel Prize in Physics twice
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Alexandre BonninIrina Burd of Johns Hopkins University;collaboratingonfetalbrainimagingstudies followingmaternalexposuretostressandantidepressantdrugs.
Anne Andrews of UCLA;collaboratingonfastmicrodialysisstudiestomeasureoffspringneurochemicalactivityfollowingprenatalexposuretostressandantidepressantdrugs.
Gerard Karsenty of Columbia University;collaboratingonastudyrelatedtotheroleofabone-derivedmoleculeinfetalbraindevelopment.
George Anderson of Yale University;collaboratingonfetal,placentalandmaternalmeasuresofbiogenicamines.
Robert Schwarcz of University of Maryland;collaboratingonfetal,placental,andmaternalmeasuresofspecificbiogenicamines.
Brett Lund of USC Neurology;investigatingtheeffectofmaternalinfectiononfetalcytokinelevels.
James Knowles of ZNI;workingonsingle-celltranscriptomeanalysisofhumanplacentalcelltypes.
Skyla Herod of Azusa Pacific College;studyingplacentalandfetalbraindevelopmentinserotonintransporterknockoutmousemodel.
Daniel CampbellWange Lu of USC Broad Institute;studyingtheimpactofautism-relatedgeneticvariantsonneuronaldifferentiation.
James Knowles of ZNI;studyinggeneexpressionchangescausedbynon-codingRNAs.
Kai Wang of ZNI;studyinggeneexpressionchangescausedbynon-codingRNAs.
Gerry Coetzee of USC Department of Urology;studyingstrategiesforfollowingupgenomewideassociationstudyhitsinautism.
Heather Volk of USC Department Preventive Medicine;investigatinggene-environmentinteractionsinautism.
Kevin V. Morris of Scripps Research Institute;studyingthemolecularmechanismsofnon-codingRNAs.
Judy Van de Water of UC Davis;studyingthegeneticbasisofalteredimmunesensitivitiesinautism
Lisa Croen of Kaiser Permanente;studyingthegeneticbasisofalteredimmunesensitivitiesinautism.
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Karen ChangTai Min of UNIST, Korea; investigatingcommonmolecularpathwaysalteredinDownsyndromeandFragileXsyndrome,twoofthemostcommongeneticcausesofmentalretardation.
Dion Dickman of USC Department of Neurobiology; studyingtheroleofanovelsynaptickinaseinregulatingsynapticgrowthandfunction.
Jeannie ChenAmy Lee of USC Department of Biochemistry and Molecular Biology; investigatingtheroleofendoplasmicreticulumstressincertaingeneticmutationsleadingtoblindness.
Ralf Langen of ZNI; investigatingamyloidstructuresineyesaffectedwithmaculardegenerationandexploringtherapeuticagentstodissolvethesestructures.
M. Carter Cornwall of Boston University; collaboratingonthemolecularmechanismsthatregulaterecoveryoflightsensitivityfollowingbrightlightexposure.
King-Wai Yau of Johns Hopkins University School of Medicine; collaboratingontheroleofcalcium-feedbacktotheolfactorysensoryneuronsinsensitivityadjustmentduringodorantadaptation.
Vsevolod Gurevich of Vanderbilt University; studyingfunctionofvisualarrestinsinthephysiologyofthephotoreceptorcell.
Gordon Fain of UCLA; collaboratingonmechanismsthatregulatephototransductioninrodandconephotoreceptors.
Vladimir Kefalov of Washington University; investigatingproteinsthatregulatecalciumconcentrationinrodandconephotoreceptors.
Robert ChowAlan Yu of University of Kansas; evaluatingthestoichiometryofclaudin(tightjunction)proteinsinrenalepithelialcells,usingadvancedmicroscopytechniques.
Cheng-Ming Chuong of USC Department of Pathology; studying to understand the role of calciumchannelsindevelopmentofchickfeatherbudmorphology.
Justin Ichida of USC Department of Stem Cell Biology and Regenerative Medicine; studying tounderstandgenechangesassociatedwiththepathologyofSMAandALS.
Ralf Langen of ZNI; investigatingthepotentiatingeffectoffreefattyacidsinpotentiatingamyloidpeptidecytotoxicity,inthesettingofobesityintype2diabetesandAlzheimer’s.
Janos Peti-Peterdi of ZNI; collaboratingonaprojectaboutthemolecularcontrolofreninsecretion,whichleveragesmyownexpertiseinsynapticproteinbiologyandDr.Peti-Peterdi’sexpertiseinreninbiology.
Jeannie Chen of ZNI; Dr.Chen’slabisusingtheChowlab’snewgeneticallyencodedratiometriccalciumindicatortostudycytoplasmiccalciumofphotoreceptorsinvivoandinvitroinmousemodelsofphotoreceptordegeneration.
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James Knowles of ZNI; studyingtranscriptomevariabilityamongostensiblyidenticalandnon-identicalcells,inordertovalidatethenewestgenerationofRNA-Seqplatforms.TheyarealsocollaboratingtoidentifymiRNAcandidatesregulatingtheswitchingonofglucose-responsegenesinstemcellsbeingdifferentiatedtobeta-likecells.
Mark Humayun and James Weiland of USC Department of Ophthalmology; collaboratingontwoprojects:1)ImprovingperformanceoftheArgusIIretinalprosthesis,and2)Developmentofanovelphotovoltaicnanoswitchforremoteopticalcontrolofneuronactivity.
Koping Kirk Shung of USC Viterbi School of Engineering; collaboratingonaprojecttodistinguishhighlyinvasivebreastcancercellsfromlessinvasivecancercells,usinghigh-frequencyultrasoundstimulationofcytoplasmiccalciumelevation.
Marcelo CobaGuoping Feng of Stanley Center for Psychiatric Research, Broad Institute; collaboratingonthestudyofSHANK3mutationsinpsychiatricdisorders,andtheirroleinpostsynapticsignaling.
Justin Ichida of USC Department of Regenerative Medicine and Stem Cell Research; studying hiPSC cells forthestudyofneurodevelopmentalprocessesinpsychiatricdisease.
James Knowles of ZNI; studyingtheroleofsynapticsignalingcomplexesinObsessivecompulsivedisorderandSchizophrenia.
Ted Abel of University of Pennsylvania; studyingtheroleofShank3andAKAPsignalingmechanismsassociatedtoneurologicaldisease.
Marco Bortolato of Kansas University;collaboratingontheroleofNMDARsignalinginthepathophysiologicalprocessesunderlyingimpulsiveaggressionandrelatedneurodevelopmentaldisorders(autism-spectrumdisorder,ADHD,Tourettesyndrome).
Thomas O’Dell of UCLA;collaboratingontheroleofTNiKandDlgap1signalinginsynapticplasticity,learningandmemory.
Chao Zhang of USC; investigatingthechemicalgenomicsapproachestothestudyofproteinkinasesignaling.
Fengzhu Sun of USC Department of Computational Biology and Bioinformatics; collaboratingontheanalysisofproteindomainsandtheirroleinsynapticsignalingcomplexesassociatedtoSchizophrenia.
Stephanie Dulawa of University of Chicago; studyingtheroleofsynapticsignalingcomplexesinObsessveCompulsiveDisorder.
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David ContiSylvia Richardson and Paul Newcombe of MRC Biostatistics Unit, Cambridge, UK; collaboratingonthedevelopmentofBayesianmodelselectionforfunctionalintegrationingeneticassociationstudies.
Graham Casey, Fred Schumacher, Steve Gruber of USC Department of Preventative Medicine; investigatingtheroleofgeneticvariantsincoloncancerriskusinggeneticassociationstudiesandfunctionalassays.
Chris Haiman, Fred Schumacher, and Brian Henderson of USC Department of Preventative Medicine; investigatingtheroleofgeneticvariantsinprostatecancer.
Marc Tischkowitz of University of Cambridge and Jonine Bernstein of Memorial Sloan Kettering Cancer Center; collaboratingonWECAREStudy(Women’sEnvironmental,Cancer,andRadiationEpidemiology)whichexaminesgeneticsusceptibilityandradiationexposureinbreastcancer. Fred Gilliland and Jim Gauderman of USC Department of Preventative Medicine; examining the role ofgeneticvariationandpollutioninasthmaandlungfunctiondevelopmentinover10,000childrenfollowedforover10yearsinLosAngeles.
James Knowles and Carlos Pato of ZNI; examininggeneticsequencedatatoidentifyvariantsinvolvedinschizophrenia.
Wendy Cozen of USC Department of Preventative Medicine; throughgeneticassociationstudies,theyareinvestigatingtherolegenesplayinmultiplemyelomaandHodgkin’slymphoma.
Neal Benowitz of University of California San Francisco, Rachel Tyndale of University of Toronto, Caryn Lerman of University of Pennsylvania, and Gary Swan and Andrew Bergen of SRI International;aspartofthePharmocogeneticsofNicotineAddictionandTreatment,theyareidentifyinggeneticvariantsinvolvedinsmokingcessationandtreatmentresponse.
Duncan Thomas of USC Department of Preventative Medicine;developingnewstatisticalapproachestotheanalysisofgenesandenvironmentalfactorsthatinteractviabiologicalpathways.
Paul Marjoram, Simon Tavare, Magnus Nordborg and Sergy Nuzhdin of USC Department of Molecular and Computational Biology;aspartofUSCCenterofExcellenceinGenomeSciences,theyareinvestigatinghowpriorbiologicknowledgecanbeusedtoinfluencestatisticalanalysis.
Kiros Berhane of USC Department of Preventative Medicine;developingnewstatisticalmethodsthatincorporatebothageandsexrelatedchangesinthedynamicrelationshipbetweenweight,heightandobesityaswellasthecomplexmulti-levelrelationshipsofdeterminantsofobesity.
Lilyana Amescua of USC Department of Neurology;investigatingtheimpactofgeneticsinMultipleSclerosisusingaHispanicpopulationsampledinLosAngelesandnovelstatisticalmethods.
Collaborations
Hong-Wei DongJames Knowles and Robert Chow of ZNI, USC; initiatedamultidisciplinaryprojecttocharacterizecelltypes in the prefrontal cortexofthemousebrain.
Jean Shih of USC Department of Pharmacology;collaboratingoncharacterizingdisruptionofcortico-striatalpathwaysinthemousemodelsofAutism.
X William Yang of UCLA; collaborating on characterizing connectopathies in the mouse models of Huntington’s disease.
Peyman Golshani of UCLA; collaborating on a project focusing on the optogenetic treatment of social behavior in autism.
Greg FieldAlexander Sher of UC Santa Cruz; collaboratingonthedevelopmentofadvanced,large-scaleneuronalrecordingtechnologies.
Edward Callaway of the Salk Institute and Nicholas Brecha of UCLA;workingtouseengineeredvirusestoinactivateneuronsintheretinatorevealtheirfunction.
E.J. Chichilnisky of Stanford University; investigatingtheeffectsofglaucomaonretinalganglioncellphysiology.
Jeannie Chen of ZNI and Noberto Grzywacz of USC; investigatingtheeffectsofretinitispigmentsonretinalganglioncellphysiology.
Stephanie Dulawa of University of Chicago; studyingtheroleofsynapticsignalingcomplexesinObsessveCompulsiveDisorder.
Rick FriedmanJake Lusis of UCLA;collaboratingontheanalysisoftranscriptomedataandGWASforhearingtraits.
Eleazar Eskin of UCLA; collaboratingontheuseoftheEfficientMixedModelAnalysisofourGWASdata.
Hooman Allayee of USC; collaboratingontheanalysisofGWASforhearingandbalancetraits.
Takahiro Ohyama of ZNI; collaboratingonthedevelopmentofconstructsfortransgenics,knockouts,andorgancultureforFhod3experiments.
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Radha KalluriCarolina Abdala of USC Department of Otolaryngology; usingotoacousticemissionstonon-invasivelyprobethestatusofmechanicaltransductioninhearingimpairedhumans.
Neil Segil of USC Department of Otolaryngology, Takahiro Ohyama of ZNI and Justin Ichida of USC Department of Stem Cell Biology and Regenerative Medicine; studyingthemolecularbasisofneuronaldifferentiationindirectlydifferentiatedneurons.
James KnowlesCarlos and Michele Pato, Oleg Evgrafov, Robert Chow, Derek Sieburth, Kai Wang, Li Zhang, Marcelo Coba, David Conti, Dan Campbell, Chris Haiman, William Mack, and Alexandre Bonnin of ZNI; collaboratingonvariousprojects.
Zemin Deng, Ting Chen, Ewa Deelman, Ann Chervenak, Peter Laird, Ben Berman, Jonathan Buckley, Graham Casey, Colin Dias, Mike Kahn, Carl Kesselman, Helena Mederios, Jerold Shinbane, Justin Ichida, Arthur Toga, Paul Thompson, Gerry Coetzee and Peggy Farnham of USC; collaboratingonvariousprojects.
Dan Stein of University of Capetown, Gerry Nestadt and Jack Samuels of Johns Hopkins University, Abby Fyer of Columbia University, Ben Greenberg and Steve Rasmussen of Brown University, James McCracken and John Piacentini of UCLA, David Pauls, Scott Rauch and Dan Geller of Harvard University, Dennis Murphy and Yin Shugart of NIH, Carol Matthews of UCSF, and Stephanie Dulawa of University of Chicago; studyingObsessivecompulsivedisorder(OCD).
Doug Levinson of Stanford University, Myrna Weissman of Columbia University, James Potash and Bill Coryell of University of Iowa, Bill Scheftner of Rush University, Bill Lawson of Howard University, Peter Holmans of Cardiff University, Ray DePaulo of Johns Hopkins University, Doug Blackwood and Mohammad Ayub of University of Edinburgh, Jim Fallon, Fabio Macciardi and Biff Bunney of UC Irvine; working on Early-onset major depression.
Ayman Fanous of Washington DC, Veterans Administration and Doug Blackwood and Mohammad Ayub of University of Edinburgh; studyingSchizophrenia. Ed Lein and Michael Hawrylycz of Allen Institute for Brain Science , Nenad Sestan and Mark Gerstein of Yale University, Joel Kleinman, Danny Weinberg, Tom Hyde and Richard Straub of NIMH and the Lieber Brain Institute; collaboratingonBrainSpan.
Ned Kalin, Pat Rosebloom, Jonathan Oler, and Drew Fox of the University of Wisconsin, Madison; workingongeneticstudiesofanxietyinprimates.
Ralf LangenHarvey McMahon of Laboratory of Molecular Biology in Cambridge; investigatingmechanismsofmembranecurvatureinductionbyproteins.
Alasdair Steven of the NIH; usingacryoelectronmicroscopytolookatmechanismsofmembranecurvatureandproteinmisfoldinginneurodegenerativediseases.
Tobias Ulmer of ZNI; combiningNMRandEPR-basedapproachestodeterminestructuresofamyloidogenicproteinsinvolvedinneurodegeneration.
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Collaborations
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Ralf Langen, cont’d
Martin Kast of USC Department of Molecular Microbiology & Immunology; investigatingmembrane-boundannexinA2complexesasreceptorsforHPVentry.
Ansgar Siemer of ZNI;combiningsolidstateandNMRandEPR-basedapproachestodeterminestructuresofamyloidogenicproteinsinvolvedinneurodegeneration.
Ian Haworth of USC Department of Pharmacy; combiningEPRandcomputationalmethodsfordeterminingproteinstructures.
Jonah Chan of UC San Francisco;studyingcontrolofmembranecurvatureduringmyelinformationanditsroleinmultiplesclerosis.
Oliver Daumke of University of Berlin; investigatingcontrolofmembranecurvaturebyEHD-2.
Robert Chow of ZNI; investigatingmembrane-mediatedtoxicityofamyloidogenicproteinsinAlzheimer’sdiseaseandtype-2diabetes.
Songi Han of UC Santa Barbara;usingnovelEPRandNMR-basedmethodstomonitorwaterexposureanditsapplicationtoproteinmisfoldingandmembraneinteraction.
Julio Camarero of USC Department of Pharmacy;engineeringcyclotidesinordertomakethemmisfoldinginhibitorsthatcouldbeusedasdrugsagainstAlzheimer’sdisease,Parkinson’sdiseaseandtype-2diabetes
William MackCaleb Finch Of USC School of Gerontology and Constantinos Sioutas of USC Department of Environmental Engineering; collaboratingonstudiesoftheeffectsofparticulatematterexposurefromvehicularexhaustontheprogressionofstrokeandcerebralhypoperfusion.
Kai Wang of ZNI;collaboratingonstudiescharacterizinggeneticandepigeneticsignaturesofMeningiomas.
James Knowles of ZNI;workingonalargestudydesignedtoevaluatecellularheterogeneityoftemporalandcerebellarcellsusingpatchclampandRNA-Seqofsinglecells.
Robert Chow of ZNI;collaboratingonalargestudydesignedtoevaluatecellularhetereogeneityoftemporalandcerebellarcellsusingpatchclampandRNA-Seqofsinglecells.
Takahiro OhyamaNeil Segil of USC Department of Otolaryngology and Justin Ichida of USC Department of Stem Cell Biology and Regenerative Medicine; researchingfactorsthatdirectlytransformsomaticcellsintoauditorysensorycells.
Dean Pinchas Cohen of USC Davis School of Gerontology;testingprotectiveeffectsofmitochondria-derivedpeptidesondrug-inducedhaircelldamage.
Rick Friedman of ZNI; testingmolecularfunctionsofgenesidentifiedthroughgeneticscreeningofmousehearingdiseasemodel.
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Carlos and Michele PatoPamela Sklar of Mt. Sinai, Jordan Smoller of Harvard University, Peter Buckley of Medical College of Georgia, Dolores Malaspina of New York University, Evelyn Bromet of SUNY Stonybrook, Chris Morley of SUNY Upstate, Mark Rapaport of Emory University, Doug Lehrer of Wright State University, Diana Perkins of University of North Carolina, Fabio Macciardi of UC-Irvine, Stephen Marder of UCLA, Humberto Nicolini of Grupo de Estudios Medicos y Familiares Carracci, and Maria Helena Azevedo of University of Coimbra, Portugal; collaboratingonanNIH-fundedprojectcreatingacohortof30,000individualsatUSCforgenomicstudiesandusingnextgenerationsequencinginmultiplelargescalepopulationstudies.
Steve McCarroll of Harvard University and The BROAD Institute; collaboratingonextensivesequencingandgenotypicprojects
Michael Boehnke of University of Michigan; workingonBRIDGESprojectonsequencinginBipolarDisorder Laura Bierut of Washington University; studying substance use and abuse in the Genomic Psychiatry Cohort
Oleg Egrafov of ZNI;studyingolfactoryneuronsinpsychiatricpatients.
Kai Wang of ZNI; usingbioinformaticsandstatisticalgeneticsapproachestoexaminegenenetworksthatareimplicatedinavarietyofconditions.
James Knowles of ZNI; usingnextgenerationsequencinginmultiplelargescalepopulationstudies.
David Conti of USC Department of Preventive Medicine; usingnextgenerationsequencinginmultiplelargescalepopulationstudies.
Janos Peti-PeterdiMichael Caplan of Yale University and Jennifer Pluznick of Johns Hopkins; collaboratingontheroleofolfactoryreceptorsinthekidney.
Andrew McMahon of USC;analysisofthemaculadensacellmolecularfingerprint.
Genevieve Nguyen of College de France, Paris; studying the role of the prorenin receptor in maculadensacells.
Dominique Eladari and Regine Cambrey of INSERM, France; workingnovelelectrolytetransportmechanismsinthedistalnephron.
Paola Romagnani of University of Florence; studyingIntrarenalstemcells.
Andrew Salmon of University of Bristol;studyingtheroleoftheglomerularglycocalyx.
Thomas Benzing of University of Cologne; researchingcalciumimagingofpodocytesinvivo.
Akira Nishiyama of Kagawa University; studyingglomerularfiltrationofreninandprorenin.
Peter Deen of University of Nijmegen;investigatingtheroleofGPR91indistalnephroniontransport.
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Janos Peti-Peterdi, cont’d
Attila Szabo and Agnes Prokai of Semmelweis; studyingmultiphotonimagingoftheeffectsof calcineurininhibitorsinthekidney.
Laura Perin of Children’s Hospital Los Angeles; studyingtheroleofamnioticfluid-derivedstemcellsinkidneyrepair.
Valter Longo of USC; studyingthemechanismofliverregeneration.
Alicia McDonough of USC Department of Neurobiology and Romer Gonzalez-Villalobos of Cedars Sinai Medical Center; studyingtheroleoftheintra-renalrennin-angiotenisnsystem.
Rudy Ortiz of UC Merced; studyingtheroleofmitochondrialfactorsincellandtissuemetabolism.
Stuart Shankland of University of Washington, Seattle; studying the mechanisms of glomerular dysfunctionandrepair.
Katalin Susztak of University of Pennsylvania; studyingpodocytefunctioninhealthanddisease.
Giuseppe Remuzzi of University of Bergamo;collaboratingonaclinicalstudyofanewtherapeuticapproachtokidneyregeneration.
Jochen Reiser of Rush University and Sanja Sever of Harvard University; studyingtheeffectsofsuPARontheglomerularfilter.
Chaim Jacob of USC; studyingtheroleofglomerularimmunecellsinlupusnephritis.
Derek SieburthJames Knowles of ZNI;sequencingentiregenomesofthenematodeC.eleganstoidentifymutationsthatcausedefectsinsynaptictransmission.
Robert Chow of ZNI;examininghowcalciumregulatesthereleaseofneurotransmittersinrealtimefromlivingtissue(usingTotalInternalReflectionFluorescenceMicroscopy)
Ansgar SiemerRalf Langen of ZNI;studyingthestructureanddynamicoftoxichuntingtinfibril.
Kausik Si of Stowers Institute for Medical Research; studyingthestructureofthefunctionalamyloidOrb2responsibleforlong-termmemory.
Ite A Laird-Offringa of USC;workingonthecharacterizationofaggregatesformedbytheHuDprotein.
Collaborations
33
Huizhong TaoChristiaan Levelt of Netherlands Institute for Neuroscience, Royal Academy of Arts and Sciences; studying how monocular deprivedinducesdisruptionofthebalancebetweenexcitatoryandinhibitoryinputs.
Jonah Chan of University of California at San Francisco; studyinghowretinalactivitythroughvisionchangesthematurationstatusofmyelinwrappingonopticnervefibers.
Josh Z. Huang of Cold Spring Harbor; researchingonthefunctionalpropertiesofinhibitoryneurons.
Gage Crump of USC Department of Cell and Neurobiology;studyingagenerationofinhibitoryneuronsspecificzebrafishreporterline.
Li Zhang of ZNI; studyingcommoninhibitorymechanismsunderlyingvisualandauditorycorticalprocessing.
Terrence TownTarek Fahmy of Yale University; collaboratingtodesignanext-generationnanoparticledrugdeliverysystem. Li-Huei Tsai of Harvard University; collaboratingtoinvestigateaberrantcyclin-dependentkinaseactivationinournoveltransgenicAlzheimerratmodel.
Erol Fikrig of Yale University ; interrogatingneuro-immunemechanismsofWestNileencephalitis.
Richard A. Flavell of Yale University;collaboratingondevelopingmousemodelswithhumanimmunesystemsasacriticaltooltoexaminestemcellgrafttolerancevs.rejection.
Pasko Rakic of Yale University
Eliezer Masliah, MD of UCSD; collaborating on developing and characterizing rodent models of Alzheimer’s disease.
Caleb ‘Tuck’ Finch of USC; working together to understand different forms of neuroinflammation.
Helena Chui of USC; began discussions to validate observations that my group has made in mouse models using human Alzheimer patient samples.
Berislav Zlokovic of ZNI; working on a project together to extend his findings with the blood-brain-barrier into our novel Alzheimer transgenic rat model.
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Tobias UlmerMark Ginsberg of UC San Diego; collaboratingontheintegrinreceptorcellbiology.Stanley Opella of UC San Diego;
collaboratingontheintegrinreceptormembraneimmersion.
Kai WangWilliam Mack and Gabriel Zada of ZNI; workingtoperformintegrativeanalysisonDNAmethylation,DNAcopynumberchangeandwhole-genomegeneexpressioninseveraltypesofbraintumors.
Gary Chen of USC Department of Preventive Medicine; workingtodevelopacopynumbervariationcallingalgorithmforwhole-genomesequencingdata.
James Knowles of ZNI; evaluatingbiologicalandtechnicalnoisesofsingle-neuronRNA-Seqdataandbenchmarkingdifferentbioinformaticsalgorithmsonthesedata. Peter Robinson of Charité - Universitätsmedizin Berlin; developingvariantannotationandprioritizationsoftwaretoolsthatincorporatephenotypeinformationandmodelorganisminformation.
Li ZhangPin Wang of USC Department of Engineering; investigatingengineeringofdifferentviralvectors.
Jonah Chan of UC San Francisco; studyingmyelinationofcorticalinhibitoryneuronsduringdevelopment.
Huizhong Whit Tao of ZNI; investigatingimagingprocessinginthevisualcortex.
Le Ma of ZNI; studyingtheroleofaxonalguidancemoleculesintheformationofthespatialandfunctionalorganizationofthecochlear.
Berislav V. Zlokovic of ZNI;investigatingtheimpactofbrainvasculardefectsonthefunctionalcorticalcircuitry.
Berislav ZlokovicArthur Toga of USC Institute of Neuroimaging and Informatics; Paul Thompson, USC Departments of Neurology, Psychiatry & Behavioral Sciences and Engineering; Scott Fraser of USC Departments of Biological Sciences and Biomedical Engineering; Helena Chui of USC Department of Neurology and USC Alzheimer’s Research Disease Center; Lon C. Schneider of USC Alzheimer’s Research Disease Center and Clinical Center and the Pharmacology program of USC NIH Alzheimer’s Disease Research Center; Terrence Town of ZNI; Hong-Wei Dong of ZNI; Roberta Brinton of USC Departments of Pharmacology & Pharmaceutical Science, Biomedical Engineering, and Neurology; and Russell Jacobs of Beckman Institute at Caltech; workingontheUSCCollaborativeInitiativeinAlzheimer’sDisease.
David M. Holtzman of Washington University in St. Louis; workingonamyloid-betametabolismandclearanceinbrainviaLDLRreceptorsandroleofapoEinamyloid-betaclearance.
John Griffin of Scripps Institute; workingonmanufacturingandtestingnewAPCvariantsforstroke.
William Mack of ZNI; collaboratingonhypoperfusioninjurytowhitematter.
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Collaborations
Berislav Zlokovic, cont’d
Meng Law of USC Department of Neuroradiology and Helena Chui of USC Department of Neurology; workingonMRIimagingofblood-brainbarrierpermeabilityconstantsinneurologicallynormalandMSpatientsandpatientsatriskforAlzheimer’sdisease.
Collins Liu and Helena Chui of USC Department of Neurology;studyingcerebrospinalfluidandplasmabiomarkersoftheblood-brainbarrierdamageinindividualsatriskforAlzheimer’sdisease.
Scott Fraser of USC Departments of Biological Sciences and Biomedical Engineering and Andy McMahon of USC Broad CIRM Center; workingontheinstallationofserialtwo-photontomography,cutting-edgeequipmentthatallowsforfullyautomatedbrainimaging.
Scott Fraser of USC Departments of Biological Sciences and Biomedical Engineering and Russell Jacobs of Beckman Institute at Caltech; collaboratingonimagingwhitematterdamageinsmallrodentsduetopericytelossusinghighfieldMRIandblood-brainbarrierpermeabilitylongitudinalstudiesinmousemodelsofstroke.
Li Zhang of ZNI;collaboratingonpericytedegenerationandcorticalinformationprocessing.
Justin Ichida of USC Department of Stem Cell Biology and Regenerative Medicine; workingoniPSCandfibroblastsfromAlzheimer’spatientsconversionintoneuronsandinvitrotrialswith3K3A-APCaswellasonbrainorganoids. Washington University Alzheimer’s Disease Research Center; collaboratingonCSFbiomarkersofblood-brainbarrierdamageinindividualsatriskforAlzheimer’saswellasindividualswithmildcognitiveimpairmentandAlzheimer’swithapoE4allelevs.non-apoE4,aswellasonpostmortembraintissueanalysisandeffectsofapoE4onblood-brainbarrierintegrity.
Nunzio Pomara and Blas Frangione of New York Medical Center; examiningCSFbiomarkersofblood-brainbarrierinjuryincognitivelynormalindividualsatriskforAlzheimer’s.
Antonio Damasio of USC Brain Creativity Institute; studyingthemolecularbasisoffeelings.
Terrence Town of ZNI; studyingpericytesintheratmodelofAlzheimer’sdisease.
Dean Pinchas Cohen of USC, Davis School of Gerontology; workingonMSDbiomarkersofvascularinjury,angiogenesis,immuneresponseandinflammationinpatientsatriskforAlzheimer’sdiseaseandindividualswithmildcognitiveimpairmentandAlzheimer’sdisease.
Pat Lyden of Cedars Sinai; workingonPhase2clinicaltrialforstrokewith3K2A-APC.
Peter Carmeliet of Vesalius Research Center, KU Leuven; studying the role of glucose metabolism in brain endotheliumduringstroke.
Caleb Finch of USC;examiningtheblood-brainbarrierpermeabilityin5FADmiceondifferentapoEgenotype.
Leslie Weiner and Wendy Gilmore of USC;studyingthe3K3APCtreatmentformultiplesclerosis.
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Berislav Zlokovic, cont’d
Jae Jung of USC;workingonbrain-specificTRIpartiteMotifprotein9.
Michael Harrington of Huntington Hospital and USC;collaboratingonimagingblood-brainbarrierintegrityinapoE4individualsandCSFbiomarkers.
Daniel Nation of USC; workingonCSFandimagingbiomarkersinindividualsathighriskforhypertension.
John Morris of Wash University in St, Louis; collaboratingonimagingandCSFbiomarkersandapoEgenotype.
Anne Fagan of Wash University in St. Louis;collaboratingonCSFbiomarkersandapoEgenotype.
Tammie Benzinger of Wash University in St. Louis; workingonmagingvascularbiomarkersinmildcognitiveimpairment.
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Faculty News
37
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Dr.MarcusRaichle,keynotespeakeratthe4thAnnualZachHallLecture(November2013)speakswithDr.LiZhangoutsidethescientificpostersessionattheevent.
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Thesummerof2013broughtnewopportunitiesforpartnershipsintheareasofneuroimagingwhenArthur Toga PhD and Paul ThompsonPhDjoinedUSC,creatingtheInstituteforNeuroimagingandInformatics.ResearchersatZNIareestablishingnewcollaborationswiththisactivegroup,whoareusingmousebraintoprovideaccurateandreliableknowledgeofthenervoussystem’sbasicwiringdiagramatthestructurallevel.Specifically,DrZlokovicisworkingwithPaulThompson’sgrouponClusterinandAlzheimer’sdiseaseandcuprizonmodelofdemyelinationandMRIimaging.DrZlokovic’sgroupisalsoworkingwithDrTogaonvascularimagingandbrainmapping.
Hong-Wei DongMDPhD,movedhislabfromUCLAtoZNI,aspartofalargerrecruitmentofDrToga’sgroup.DrDong,whohasajointappointmentinNeurology,hasanR01whichaimstocreateathree-dimensional,GoogleEarth-like,digitalConnectomeatlasoftheC57Black/6Jmousebraintoprovideaccurateandreliableknowledgeofthenervoussystem’sbasicwiringdiagramatthestructurallevel.DrZlokoviciscollaboratingwithHongweiDongonbrainmapping(tractography)innewanimalmodelsofAlzheimer’sgeneriskfactors.
Inthesummerof2013,ZNIwelcomedthreeinvestigatorsformerlyassociatedwiththeHouseResearchInstitute.Rick FriedmanMDPhD,whoholdsajointappointmentinOtolaryngology,movedhislabtoZNI.HehasanR01whichstudiesnoise-inducedhearinglossusinghigh-resolutionmappingstrategiestocomprehensivelydefinelocithatcontributetostrainvariationinphenotypes. Takahiro Ohyama PhD and Radha Kalluri PhDalsorelocatedtheirlaboratoriesfromHouseResearchInstitutetoZNI.BothholdjointappointmentsinOtolaryngology.DrOhyamahasanR01thatstartedin2014andDrKallurihasanR03thatthatrunsuntil2016.AmajorgoalofresearchintheOhyamalabistounderstandthemolecularmechanismsofinnereardevelopmentattoexplorethepossibilityofregeneratingsensorycellstotreatbalanceandhearingdisorders.DrKalluri’sresearchfocusesonunderstandingthemacro-mechanical,anatomicalandbiophysicalmechanismsthatshapesensorysignalingwithintheauditoryandvestibularsystems.Thelong-termgoaloftheworkistounderstandhowtargeteddysfunctionsinthemacro-mechanicalandcellularmechanismscontributetohearingandbalancedisorders.
Huizhong (Whit) TaoPhDwaspromotedtoAssociateProfessorinCell&Neurobiology.DrTao’slabattemptstounderstandtheprinciplesunderlyingconnectivitybetweenneuronsinthesensorycortex,whichprovidesastructuralbasisfortheinformationprocessingfunctionsthesenervecellsperform.DrTaoisapastrecipientofaKirchgessnerFoundationawardandcurrentlyholdstwograntsfromtheNationalEyeInstitute(NIH).Arecentpublication“Scalingdownofbalancedexcitationandinhibitionbyactivebehavioralstatesinauditorycortex”appearedinAprileditionofNature Neuroscience.
Faculty News
Derek SieburthPhDwaspromotedtoAssociateProfessorinCell&Neurobiology.Dr.Sieburth’sresearchisfocusedonsynapticbiologyusingC. elegansgenetics.HejoinedZNIfollowinghispostdoctoralappointmentatHarvard,whereheidentified,basedonRNAinterferencescreens,over100newgenesinvolvedinsynaptictransmissioninC. elegans.HecurrentlyhasanR01grantfromNationalInstituteofNeurologicalDisordersandStroke,“StressRegulationofSnyapticTransmission”andasatellitefromtheSchoolofGerontology(NationalInstituteofAgingR01),“OxygenRadicalToxicityandProteinDegeneration.”
InOctober2013,Alapakkam SampathPhDrelocatedhislaboratorytotheJulesSteinInstituteatUCLA.DrSampathprobestheconnectionbetweenretinalstructure/functionandvisualsensitivity.Hereceivedhismaster’sandPhDfromUCLAandbecameZNIfacultyin2005.
InJune2014,Le Ma PhDrelocatedhislaboratorytoThomasJeffersonUniversity.DrMastudiesmicrotubuleregulationingrowthcones,linkingthistoCNPsignalinginsensoryaxondevelopment.DrMareceivedhisPhDfromHarvardandjoinedZNIfacultyin2005.
Steve KayPhD,DScwasnamedthefirstDistinguishedAssociate,ZilkhaNeurogeneticInstitute.AccordingtoDrBerislavZlokovic,DirectorofZNI,aDistinguishedAssociatehasachievedahigh-levelofproductivityanddistinction,tobecomeaworldleaderinhisorherfield.DistinguishedAssociatesenjoyallthebenefitsofmembershipatZNI but also act as ambassadors for our mission and assist the Director byengagingindiscussionsregardingstrategicplanningandleadership.
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SteveKayisdeanoftheUSCDornsifeCollegeofLetters,ArtsandSciencesandholderoftheAnnaH.BingDean’sChair.HealsoholdsfacultyappointmentsinmolecularandcomputationalbiologyatUSCDornsifeandinneurology,physiologyandbiophysicsattheKeckSchoolofMedicineofUSC.Oneofthetopexpertsongenesandcircadianrhythms,Dr.Kay’sresearchiscontributingtothedevelopmentofnewdrugsthattreatmetabolicdisorderssuchasType2diabetesaswellastounderstandinghowplantscanbetteradapttoclimatechange.HeisanelectedmemberoftheNationalAcademyofSciencesandin2014wasnamedbyThomsonReutersasoneof“TheWorld’sMostInfluentialScientificMinds.”
WewelcomeDeanKaytoZNI,whereanumberoffacultyareinterestedincollaboratingwithhim.
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AstheUSCAlzheimer’sDiseaseResearchCenter(ADRC)approacheditscompetitiverenewal,ZNIhasbeenworkingwiththeDeptofNeurology(DrsHelenaChui,CollinsLiu)tosupportfuturedirectionsoftheADRC,includingCSFbiomarkerstudiesandimagingbiomarkersofthecerebrovascularsystemandblood-brainbarrierintegrity.Shouldtherenewalbesuccessful,DrsArthurTogaandBerislavZlokovichaveagreedtobepartoftheadministrativecoreofthenewADRC.DrZlokovicwouldalsobeAssociateDirectorofADRC,directoneoftheprojects,andco-directtheCoreforNeuropathologyandBiomarkers.TofurtherstrengthentiesbetweendepartmentsacrosscampusandUSC,ZNIcoordinatedtwomajorcollaborativescientificevents,bothofwhichwillhopefullyleadtofurtherfunding:
Amini-symposiuminAugust2013oncurrentUSCresearchrelatedtoAlzheimer’sdisease,where10USCPIsfrommultiplesschoolsacrossbothcampusespresentedtheirworkbeforetwokeydecision-makersoftheAlzheimer’sAssociationincludingSchoolofpharmacy,Dornsife,andSchoolofGerontology.KeyparticipantsincludedDrsArthurToga,PaulThompson,HelenaChui,PinchasCohen,ScottFraser,RobbieBrinton,andChristianPike.
The1stAnnualZilkhaAlzheimerSymposium,“BreakingthroughBarriers:Neuronal,GlialandVascularContributions”washeldon4April2014,where12nationalandinternationalleadersinthefieldoutsideUSC(PeterCarmelietMDPhD,UnivofLeuven(Belgium);BartDeStrooperMDPhD,FlandersInstituteforBiotechnology(Belgium);ChristianHaasPhD,Ludwig-MaximiliansUniv(Munich);DavidMHoltzmanMD,WashUMedicalSchool;CostantinoIadecolaMD,WeillCornellMedicalCollege;LennartMuckeMD,GladstoneInstitutes,UCSF;MaikenNedergaardMDDMSc,UnivRochesterMedicalCenter;SangramSisodiaPhD,UnivofChicago;RudolphTanziPhD,Harvard;TonyWyss-CorayPhD,Stanford;sessionchairsMariaCarrilloPhD,VP,Medical&ScientificRelations,AlzheimersAssociation;RoderickCorriveauPhD,ProgramDirector,NINDS(NIH);SuzanaPetanceskaPhD,ProgramDirector,NIA(NIH)and5USCleaderssharedtheirunpublishedworkatZNIandtheKeckSchoolofMedicine.Co-organizersforthiseventwithDrZlokovicwereDavidMHoltzmanMD(WashU)andRudiTanziPhD(Harvard).TheeventincludedtheparticipationDrRodCorriveau(NIH/NINDS);DrMariaCarrillo(Alzheimer’sAssociation),andGabriellaStrobel(ALZFORUM).Theday-longeventwasunderwrittenbyagenerousgiftfromEvaandMarcStern.
Faculty News
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Alexandre BonninDr.BonnintaughtintheUSCNeuroscienceGraduateProgramaswellasPharmacologyto1styearUSCmedicalstudents.Additionally,Dr.Bonninwasaninvitedspeakertoseveralnationalandinternalsymposia(includingthoseheldinFrance,Italy,Australia).Dr.BonninisalsoamemberoftheUSCInstitutionalBiosafetyCommittee.
Daniel CampbellDr.Campbell’smanuscriptdescribingagene-environmentinteractionthatcontributesto autismriskwascoveredbydozensofmediaoutlets,includingPBSNewsHour,KABC-TVLosAngeles,LAWeekly,BeverlyHillsCourier,andScienceDaily.Dr.Campbell’scontributionstoourunderstandingoftheroleofnoncodingRNAsinpsychiatricdisorderswasrecognizedbyinvitationstogivelecturesattheHelpGroupSummit,theSocietyforNeurosciencemeeting,theInternationalMeetingForAutismResearch,theUC-Irvine/AllerganAutismUpdateConference,andtheUCLAExtensionSeries:BeyondtheHeadlines.
Jeannie ChenDr.ChenservedontheScientificAdvisoryBoardoftheKarlKirchgessnerFoundation.
Robert ChowDr.Chowservedasamentorforthefollowingprograms:CIRMsummerinternship,CIRM Bridgesinternship,BridgingtheGaps:BenchtoBedsideSummerResearchProgram,EngineeringResearchCenter,andEngineeringHealthAcademy.Additionally,Dr.Chowranaworkshoponpatchclamp,forwhich30peopleacrosstheUSCcampussignedup.
Hong-Wei DongDr.Dongwasinvitedtogiveatalkforthe4thAnnualZachHallLectureandthe1stAnnualZilkhaSymposiumonAlzheimerDisease&RelatedDisordersatZNI.
Radha KalluriDr.KalluriwasappointedasanAssistantEditorofthejournal, Otology Neurotology.
Ralf LangenDr.LangenwasareviewerforNIHstudysections.
William MackDr.MackservedontheSocietyofNeurointerventionalSurgeonsBoardofDirectorsandwasanAssociateScientificadvisorforthejournalScience Translational Medicine.Dr.Mackwas appointed as an associate editor of the Journal of Neurointerventional Surgery and was appointedtotheeditorialboardofWorldNeurosurgeryastheBookreviewsectioneditor.
FacultyActivities
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Carlos PatoDr.Patoistheco-editorof Revista Brasilerira de Psiquiatri andanAssociateEditorofNeuropsychiatric Genetics and American Journal Medical Genetics.Heisalsoontheeditorialboard for Translational Psychiatry.
Michele PatoDr.Patoistheco-editorof Revista Brasilerira de Psiquiatri. She is on the editorial boards of Annals of Clinical Psychiatry and Academic Psychiatry.
Janos Peti-PeterdiDr.Peti-PeterdiservedasthedirectoroftheUSCMultiphotonMicrosopyCore.HealsoestablishedtheinstitutionalresearchbaseforanewkidneyresearchcenterandappliedforNIHfundingforthecenter(P30USCO’BrienKidneyResearchCenter).
Ansgar SiemerDr.SiemercontinuedtoserveonUSC’sPIBBS(ProgramsinBiomedicalandBiologicalSciences)admissioncommittee.
Huizhong TaoDr.TaoservedasthedirectorNeuroscienceGraduateProgramcorecourse.
Kai WangDr.Wangreviewedgrantapplicationsforanumberofagencies,includingMedicalResearchCouncil(MRC)UK,SouthernCaliforniaClinicalandTranslationalScienceInstitute(SC-CTSI),AmericanCancerSociety-InstitutionalResearchGrant(ACS-IRG),TheNationalScienceCentrePoland,NIHGCATStudySection,andA*STARSingapore.
Berislav ZlokovicDrZlokovicwasnamedMaryHayley&SelimZilkhaChairinAlzheimer’sDiseaseResearch.DrZlokovicpresentedtheSocietyforNeurosciencePresidentialLecture:BloodBrain.HewastheCo-ChairfortheAlzheimer’sdisease-realateddementiaworkshop2013(Vascularcontributions),NINDS.Additionally,DrZlokovicworkedcloselywithADRCsteeringcommitteetoreformulatethecompetitiveapplication,formingnewassociationswithadiversegroupofUSCfacultytostrengthentheproposal,currentlyunderreviewbyNIH.DrZlokovicwasselectedtogivetheChancellor’sAwardLectureinNeurosciencesLouisianaStateUniversityHealthSciencesCenter2014.
Dr.ZlokovicbecameaFellowoftheAmericanAssociationforAdvancementofScience.Also,inApril2014,hecoordinatedthe1stAnnualZilkhaSymposiumonAlzheimerDiseaseandRelatedDisorders“BreakingthroughBarriers:Neuronal,GlialandVascularContributions”.Thisday-longeventfeaturedaninternationalgroupincluding10outofthe20topneuroscientistsintheworld,presentingmostlyunpublisheddataaboutexperimentsstillunderway,approachingADfrommultipledisciplines.
DrZlokovic,alongwiththetwoco-organizersoftheaboveconference,DrsDavidHoltzmanandRudolphTanzi,wereallthreenamedasthemostinfluentialscientistsintheworldinthefieldofNeuroscience&BehaviorbyThompsonReuters(July2014).
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Grants and Contracts
43
Total Number of Active Grants for FY14 Federal Grants 40 Federal Fellowships 1Foundation/PrivateGrants 24 Non-Federal Fellowships 3
CaliforniaInstituteforRegenerativeMedicine1
Total 69
2014 Annually Sponsored Awards FederalAwards $16,702,130 PrivateFoundationAwards $3,009,183 Industry $400,000
Total $ 20,111,313
ZNIPIshadabusyFY14.Thenumberofgrantsubmissionswentupfrom6to8permonth,inadditiontoroughly32progressreportseachyear.Wehad69sponsoredproj-ectsduringthereportingperiod,manyfrom11differentNIHinstitutes.Mostsignificantly,despitethedifficultfundingclimate,ZNIinvestigatorsmanagedtoincreasetotalprojectcostsby8.3%overtheprioryear.
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$18,447,570
$20,111,312
$15,000,000
$20,000,000
$25,000,000
Sponsored Projects FY13 to FY14
$‐
$5,000,000
$10,000,000
FY13 FY14
Direct Costs F&A Costs Total Costs
FY13 $12,613,663 $5,833,907 $18,447,570FY14 $13,841,591 $6,269,721 $20,111,312
Number of Awards by NIH Institute/Center FY14
NationalInstituteonDeafnessandOtherCommunicationDisorders(NIDCD) 2NationalCancerInstitute(NCI) 1NationalEyeInstitute(NEI) 4NationalHumanGenomeResearchInstitute(NHGRI) 4NationalHeart,Lung,BloodInstitute(NHLBI) 1NationalInstituteonAging(NIA) 5NationalInstituteofBiomedicalImaging&Bioengineering(NIBIB) 1NationalInstituteofDiabetesandDigestiveandKidneyDiseases(NIDDK) 1NIHBioengineeringResearchPartnership(BRP) 1NationalInstituteofMentalHealth(NIMH) 15NationalInstituteofNeurologicalDisordersandStroke(NINDS) 6
Total Federal 41
NIDCD5%
NCI3% NEI
10%NINDS
2014 ZNI Sponsored Projects by Federal Agency
5%
NHGRI10%
NHLBI2%NIANIMH
15%
2%NIA12%
NIBIBNIDDK
BRP3%
37%
NIBIB3%NIDDK
2%
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Grants and Contracts
46
ZNI Investigator Funding Agency Direct Costs F&A Costs Total Costs Project Title
Bonnin, Alexandre
Children's Hospital of Los Angeles subK (National Institute of Mental Health) $15,123 $9,376 $24,499 Enduring Effects of Early-Life Serotonin Signaling
Bonnin, Alexandre
University of Maryland subK (National Institute of Mental Health) $30,418 $19,582 $50,000 Kynurenic Acid and Cognitive Abnormalities
Bonnin, Alexandre
Autism Science Foundation Fellowship: Nick Goeden $50,000 $0 $50,000
The impact of maternal inflammation during pregnancy on placental tryptophan metabolism, and the downsteam consequences on fetal brain development
Campbell, DanielNational Institute of Mental Health R21 $125,022 $80,343 $205,365 Non-Coding RNAs in Autism
Campbell, DanielNational Institute of Mental Health R01 $264,981 $150,162 $415,143
Biology of Non-Coding RNAs Associated with Psychiatric Disorders
Chang, Karen
National Institute of Neurological Disorders and Stroke R01 $435,312 $279,683 $714,995
Role of DYRK1A/MNB in Synaptic growth and function
Chang, Karen Alzheimer's Association $272,730 $27,270 $300,000Functional Protein Interactions in Alzheimer's Disease and Down Syndrome
Chang, KarenJerome Lejeune Foundation $47,974 $4,796 $52,770
Systematic analysis of genes contributing to synaptic defects in Down syndrome
Chen, Jeannie National Eye Institute R01 $376,557 $242,565 $619,122Phototransduction in dark adaptation and retinal degeneration
Chen, JeannieArnold & Mabel Beckman Initiative $100,000 $0 $100,000
Phenotyping molecular and structural heterogeneity of drusen towards improved AMD classification
Chow, RobertNational Institute of Mental Health U01 $136,079 $87,090 $223,169
Evaluation of Cellular Heterogeneity Using Patchclamp and RNA-Seq of Single Cells
Chow, Robert
National Institute of Biomedical Imaging and Bioengineering P41 (BMES Satellite) $47,486 $30,402 $77,888 A Resource on Medical Ultrasound Transd
Chow, Robert
National Institutes of Health Bioengineering Research Partnerships $126,302 $55,233 $181,535
Experimental and Clinical Investigations of Retinal Stimulation
Chow, Robert
USC Provost Postdoctoral Funds: Reymundo Dominguez $23,958 $0 $23,958
Estradiol-mediated neuronal protection against focal ischemia involves beta-arrestin1
Chow, RobertZumberge Research and Innovation Fund $50,000 $0 $50,000
Evaluating Invasion Potential of Cancer Cells with High-Frequency Ultrasound
Conti, DavidNational Cancer Institute R01 $295,988 $189,556 $485,544
Incorporating Intermediate Biomarkers of folate with colorectal cancer
Evgrafov, Oleg
Strategies for Engineered Negligible Senescence (SENS) Research Foundation $3,200 $0 $3,200
Whole genome sequencing of S.aleutianus: The fish with the highest longevity
Evgrafov, OlegNational Institute of Mental Health R01 $419,097 $259,840 $678,937
Transcriptome sequencing of neuronal cell lines from patients with Schizophrenia
Active Awards ‐ Fiscal Year 2014
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ZNI Investigator Funding Agency Direct Costs F&A Costs Total Costs Project Title
Active Awards ‐ Fiscal Year 2014
Field, GregoryKarl Kirchgessner Foundation $50,000 $0 $50,000 Vision Research Grant
Field, Gregory Whitehall Foundation $206,400 $18,600 $225,000 Mapping the Connectivity on the Mammalian Retina
Friedman, Rick
National Institute on Deafness and other Communicative Disorders R01 $525,618 $313,344 $838,962
High-Resolution Mapping of Susceptibility Genes for NIHL
Knowles, JamesNational Institute of Mental Health R01 $396,000 $245,520 $641,520
Discovery of Genetic Variation influencing Schizophrenia using next Generation DNA sequencing
Knowles, James
University of Wisconsin, Madison subK (National Institute of Mental Health) $54,483 $34,869 $89,352
Brain Mechanisms Mediating Genetic Risk Factors for Anxiety and Depression
Knowles, JamesNational Institute of Mental Health U01 $395,238 $254,765 $650,003 The USC PsychENCODE Project
Knowles, JamesNational Institute of Mental Health U01 $262,240 $164,342 $426,582
Evaluation of Cellular Heterogeneity Using Patchclamp and RNA-Seq of Single Cells
Knowles, James
International Obsessive-Compulsive Disease (OCD) Foundation $43,629 $0 $43,629 Replication of Genome-Wide Association
Knowles, JamesNational Institute of Mental Health R01 $517,920 $322,083 $840,003
Obsessive-Compulsive Disorder (OCD) Collaborative Genetics Association Study
Knowles, James
National Human Genome Research Institute U01 - Satellite $71,104 $43,599 $114,703
Robust and Portable Workflow-Based Tools for mRNA and Genome Re-Sequencing
Langen, RalfCHDI Foundation (Huntington Disease) $413,803 $60,991 $474,794
How structure and dynamics of monomeric huntington are modulated by post-translational modifications and polyQ length
Langen, RalfHereditary Disease Foundation $50,000 $0 $50,000
Molecular Structure of Huntington Fibrils and Oligomers in Huntington's Disease
Langen, Ralf
University of California San Francisco subK / National Multiple Sclerosis Society $96,767 $9,677 $106,444
Initiating Myelination: A Matter of Membrane Curvature
Langen, RalfBatey Family Research Fund $138,312 $0 $138,312
Prevention of Misfolding and Membrane Permeabilization in Parkinson's and Other Neurodegenerative Diseases
Langen, RalfJohn Douglas French Alzheimer's Foundation $42,151 $0 $42,151 Alpha-Synuclein Misfolding in Dementia
Ma, Le
National Institute of Neurological Disorders and Stroke R01 $187,836 $117,620 $305,455
Molecular Mechanisms of Axon Branching Synaptic Development
Mack, WilliamAmerican Heart Association $65,679 $4,321 $70,000
Intra-arterial Magnesium Therapy in Acute Stroke: A Phase II Safety and Feasibility Study
Mack, WilliamBrain Aneurysm Foundation $25,000 $0 $25,000
MRI Perfusion Permeability and Matrix Metalloproteinase-9 Levels Associated with Cerebral Vasospasm following Aneurysmal Subarachnoid Hemmorhage
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ZNI Investigator Funding Agency Direct Costs F&A Costs Total Costs Project Title
Active Awards ‐ Fiscal Year 2014
Pato, CarlosNational Institute of Mental Health R01 $1,797,743 $741,011 $2,538,753 Genetic Psychiatry Cohort
Pato, CarlosNational Institute of Mental Health R01 $350,000 $223,708 $573,708 Genetic Psychiatry Cohort Supplement
Pato, Michele
University of Kansas subK (Tourette Syndrome Association) $36,502 $3,650 $40,152
Role of 5-alpha Reductase 2 and Androgens in Tourette Syndrome
Pato, Michele
Emory University subK (National Institute of Mental Health) $50,000 $32,188 $82,188
1/2 Targeted Sequencing and Functional Evaluation of Mutations in Schizophrenia
Pato, MicheleNational Institute of Mental Health R01 $498,474 $320,685 $819,159 Addition of OCD to the Genomic Psychiatry Cohort
Peti-Peterdi, Janos
National Institute of Diabetes and Digestive and Kidney Diseases R01 $150,950 $97,772 $248,722
Multiphoton Imaging of the Juxtaglomerular Apparatus
Peti-Peterdi, Janos
American Heart Association Fellowship: Anne Riquier-Brison $96,000 $0 $96,000 Tracking the Fate and Function of the Renin Cell
Sampath, Alapakkam National Eye Institute R01 $78,687 $50,459 $129,146Functional Characteristics of Rod Pathways in the Retina
Sieburth, Derek
National Institute of Neurological Disorders and Stroke $206,872 $128,261 $335,133 Stress Regulation of Snyaptic Transmission
Sieburth, Derek
Gerontology Satellite National Inistute on Aging R01 $10,941 $7,025 $17,966 Oxygen Radical Toxicity and Protein Degeneration
Siemer, Ansgar Whitehall Foundation $200,143 $24,857 $225,000The Function of Amyloid Proteins in Long-Term Memory
Siemer, AnsgarZumberge Research Innovatiion Fund $25,000 $0 $25,000
The Structure of a Functional Amyloid in Long-Term Memory
Tao, Huizhong National Eye Institute R01 $288,948 $184,926 $473,874Cortical Synapic Circuitry Underlying Visual Processing
Tao, HuizhongKarl Kirchgessner Foundation $50,000 $0 $50,000 Development of Visual Synaptic Circuitry
Tao, Huizhong National Eye Institute R21 $268,750 $171,750 $440,500Inhibitory Circuitry Mechanisms underlying Visual Cortical Development and Plasticity
Town, Terrence
National Institute of Neurological Disorders and Stroke F31 Fellowship: David Gate $35,832 $0 $35,832
Targeting Abeta phagocytosis by blocking IRAK-M innate immunity in Alzheimer mice
Town, TerrenceNational Institute on Aging R21 $26,848 $17,196 $44,044
An iPS Disease-in-a-Dish Model of Familial Alzheimers
Town, Terrence Alzheimer's Association $137,917 $13,791 $151,708Macrophage TGF-beta-Smad 2/3 Inhibitor Therapy in Transgenic Alzheimer Rats
Town, Terrence
California Institute for Regenerative Medicine (CIRM) $335,073 $18,176 $353,249
Role of HLA in Neural Stem Cell Rejection using Humanized Mice
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ZNI Investigator Funding Agency Direct Costs F&A Costs Total Costs Project Title
Active Awards ‐ Fiscal Year 2014
Town, TerrenceAmerican Federation for Aging Research $311,423 $29,142 $340,565
Re-balancing peripheral TGF-beta signaling in aged Alzheimer's rats
Town, Terrence
National Institute of Neurological Disorders and Stroke R01 $239,425 $153,408 $392,833
Peripheral TGF-beta Pathway Inhibitor Therapy in Alzheimer's Rats
Wang, Kai
Vanderbilt University Medical Center subK (National Human Genome Research Institute) $14,182 $9,077 $23,259
Integrative Statistical Models for Pathway Analysis of GWAS Data
Wang, KaiNational Human Genome Research Institute R01 $215,600 $138,702 $354,302
Integrated variation detection annotation and analysis for high-throughout sequencing
Wang, Kai
University of California San Diego subK (National Human Genome Research Institute) $5,054 $3,235 $8,289
Accelerating Ciration of GWAS Catalog by Automatic Text Mining
Zhang, Li
National Institute on Deafness and other Communicative Disorders R01 $83,397 $132,575 $215,971
Synaptic Circuitry Mechanisms for Auditory Cortical Processing
Zlokovic, Berislav
National Institute of Neurological Disorders and Stroke R01 (Javits) $412,491 $200,909 $613,400
Alzheimer's Abeta. Apoliproteins and Blood-Brain Barrier
Zlokovic, BerislavNational Institute on Aging Fogarty R03 $53,200 $22,414 $75,614
Caloric Restriction and Alzheimers ABeta Clearance Pathway
Zlokovic, Berislav Cure Alzheimer's Fund $250,000 $0 $250,000 Role of PICALM in vascular clearance of amyloid-
Zlokovic, BerislavNational Institute on Aging R37 (Merit) $300,211 $192,386 $492,597
Cebrovascular Beta-Amyloidosis: A-beta CNS Transport Pathways
Zlokovic, Berislav Kaplan Family Foundation $25,500 $0 $25,500 Amyotrophic lateral sclerosis (ALS) Research Fund
Zlokovic, BerislavFidelity Biosciences Research Initiative (FBRI) $400,000 $0 $400,000
Blood-Brain Barrier Pericytes: Safeguards against Amyloid-Beta Brain Degeneration
Zlokovic, Berislav
National Heart, Lung, and Blood Institute (NHLBI) R01 Stroke $330,297 $202,565 $532,862 Regulation of Brain Thrombosis in Stroke Models
Zlokovic, BerislavNational Institute on Aging R01 $193,725 $124,226 $317,951
The Role of Pericytes in the Adult and the Aging Brain
TOTAL $13,841,591 $6,269,721 $20,111,313
Special Lectures
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4th Annual Zach Hall Lecture
OneofZNI’ssignatureevents,the4thAnnualZachHallLecturetookplaceonNovember19,2013intheHerklotzSeminarRoomatZNI.Thelecture,whichisnamedinhonorofZNI’sinauguraldirectorZach W. HallPhD,isaday-longaffair,featuringscientificreports,seminars,postersessionaswellasopportunitiesforgraduatestudentsandpostdoctoralfellowstomixandminglewithestablishedscientistsandseniorfacultyandinformalandinformalways.
TheafternoonbeganwithapresentationbyHong-Wei DongMD,PhD,AssociateProfessorintheDepartmentofNeurologyandZNIfaculty.Histalkwasentitled“AssemblingtheGlobalCortico-CorticalNetworkintheMouseBrain.”DrDongprecededthekeynotelecturedeliveredbyMarcus E. Raichle MD oftheWashingtonUniversityinSt.Louis.Dr.RaichleisProfessorofRadiology,Neurology,Anatomy,andNeurobiology.HeisalsoamemberoftheNationalAcademyofSciences,theInstituteofMedicineandtheAmericanAcademyoftheArts&Sciences.Dr.Raichle,renownedinthefieldofcognitiveneuroscienceformorethan40years,gaveatalkentitled“TheRestlessBrain.”
Theseminarswerefollowedbyascientificpostersessionfeaturingover40displaysacrossmultipledisciplinesfromover25ZNIlaboratories.TherangeofworkspeakstothedepthandbreadthofthetypesofresearchconductedatZNI.ThepostersessionalwaysaffordstimeforspontaneousyetvaluablediscussionsamongthestudentsandresearchersatZNIaswellasvisitingmembersofthescientificcommunityacrosstheSouthland.
The annual Zach Hall lecture shines an important spotlight on the latest research being done at ZNI and acrosstheglobe.
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L to R: Dr.BerislavZlokovic,Dr.Hong-WeiDong,Dr.ZachHall,andDr.MarcusRaichle
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1st Annual Zilkha Symposium on Alzheimer Disease & Related Disorders
MorethanadozenresearchersandpolicymakersfromacrosstheglobegatheredattheZilkhaNeurogeneticInstitute(ZNI)on4April2014,toparticipateinthe1stAnnualZilkhaSymposiumonAlzheimerDisease&RelatedDisordersentitled“BreakingthroughtheBarriers:Neuronal,GlialandVascularContributions.”TheinternationalconferencewasorganizedbyZNIDirector Berislav V. Zlokovic,whoholdstheMaryHayley&SelimZilkhaChairinAlzheimer’sDiseaseResearchattheKeckSchoolofMedicineofUSC,alongwithRudolphTanzi,JosephP.&RoseF.KennedyProfessorofNeurologyatHarvardUniversityandDavidM.Holtzman,AndrewB.&GretchenP.JonesProfessorandChairofNeurologyatWashingtonUniversityinSt.Louis.Theall-daysymposiumfeaturedpresentationsofmostlyunpublishedwork,experimentsstillunderwaythatareapproachingAlzheimerDisease(AD)frommultipledirections.InvestigatorsshareddataaboutthevariedrolesofdifferentinfluencesonAD:genetic,vascular,inflammation,astrocytes,neuronsandendingwithnewandinnovativemethodsformappingchangesinthebrain,usingadvancedimagingtechnologyemployedby Arthur Toga, Paul Thompson and Hong-Wei DongattheKeckSchoolofMedicineofUSC.
Top L to R: Hong-WeiDong,BartDeStrooper,HelenaChiu,TonyWyss-Coray,ArtToga,SangramSisodia,TerrenceTown,LennartMucke,ChristianHaass,PaulThompson,CostantinoIadecola.Bottom, L to R:ScottFraser,RudyTanzi,MaikenNedergaard,BerislavZlokovic,MariaCarrillo,RoderickCorriveau,DavidHoltzman
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Special Lectures
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L to R:Dr.TonyWyss-Coray,Dr.RudyTanzi,andDr.HelenaChuiinbetweentalksatthe1stAnnualZilkhaSymposiumonAlzheimerDisease&RelatedDisorders
Dr.ChristianHaassgiveshistalktoanengagedaudience.
USCExecutiveViceProvostMichaelQuickofferedintroductoryremarksforthesymposium,followedbyZNIfriendandbenefactor,SelimZilkha,whoprovidedaremindertoallattendeesoftheimportanceofcontinuedscientificcollaborationto“arrestandreversethisterribledisease”.FollowingMrZilkha’sremarks,MariaCarrillo,VicePresidentofMedical&ScientificRelationsattheAlzheimer’sAssociation,announcedthatMrZilkhaandMaryHayleywouldbehonoredinJulywiththe2014JeromeH.StonePhilanthropyAwardforAlzheimer’sResearch,aninternationalawardhonoringtheworld’sleadingphilanthropistsandtheirtransformationalimpactontheglobalAlzheimer’sresearchfield.TheawardwaspresentedinJuly,attheAlzheimer’sAssociationInternationalConferenceinCopenhagen,Denmark.MariaCarrillochairedseveralsessionsattheZilkhaSymposium,alongwithRoderickCorriveau,ProgramDirectorofExtramuralResearchProgramsattheNationalInstituteforNeurologicalDisorders&Stroke,NIHandHelenaChui,McCarronProfessor&ChairofNeurologyandDirectoroftheAlzheimer’sDiseaseResearchCenteratUSC.
GabrielleStrobel,ExecutiveEditorofthealzforum.orgwebsite—aweb-basedscientificcommunitydedicatedtofurtheringtheresearchandunderstandingofAlzheimerDiseaseandrelatedneurodegenerativedisorders—attendedtheZilkhaSymposiumandsummarizedthecutting-edgedevelopmentspresentedattheeventinacomprehensivefour-partseriespublishedonthesite:PartI,therelationshipbetweenhypertensionandAlzheimerDiseaseanddementia;PartII,theimportanceofstudyingthebloodbrainbarrier(BBB)inAlzheimerresearch;PartIII,thecontroversialmethodofresearchviaparabiosis(blood-sharingexperiments);andPartIV,theindirectwayinwhichsleepandgeneregulationaffectsneurodegeneration.Toviewtheentireseriesgotohttp://www.alzforum.org>News>ConferenceCoverage.
Ashortvideoabouttheconferenceisavailableathttp://tinyurl.com/AAIC2014ZNI.
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Everyyear,ZNIoffersamultitudeofacademicactivitiesthatrangefromourregularseminarseriestomoreinteractivestudent-ledJournalClubs.Weprideourselvesininvitingsomeofthebestmindsinthefieldtocomeandsharetheirexpertiseandlatestfindingsthroughourseminarseries.Additionally,weencouragein-housecollaborationandcooperationthroughmoreintimateaffairsliketheNeurodegenerationJournalClub,ledbyBrianLeung,agraduatestudentinDr.TerrenceTown’sLab.SomeoftheofferingsfromFY14arebelow.
ZNI Seminar Series
July 2013
“Co-evolutionofBreasttoBrainMetastasisandNeuralProgenitorCells”Josh Neman PhD,BeckmanResearchInstitute,CalTech/CityofHopeCancerCenter
August 2013
“TheTrialsandTribulationsoftheSpinyMouse:ANon-ModelSpeciesforPerinatalResearch”Hayley Dickinson PhD,MonashUniversity
September 2013
“SERTGeneVariants:AComplexCaseforInvolvementinMoodDisordersandTheirTreatment”Anne Andrews PhD,UCLA
“DevelopmentalPatterningoftheInnerEar”Takahiro Ohyama PhD, ZNI
October 2013
“TheOrganizationofSensorySignalsintheInnerEar”Radha Kalluri PhD, ZNI
“TheMolecularBasisofLongLastingMemory”Kausik Si PhD,StowersInstitute/UniversityofKansas
“EPACSignalingLinksmiR-129ExpressioninRegulationofLearningandSocialBehaviors”Youming Lu MD, PhD,LouisianaStateUniv/HuazhongUnivofSciencesandTechnology
December 2013
“MembraneProteinTraffickinginPhotoreceptors”Wolfgang Baehr PhD,UniversityofUtah
AcademicActivities
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January 2014
“MitochondrialPeptidesandtheirRolesinAlzheimer’sandOtherDiseasesofAging”Dean Pinchas Cohen MD,USC,DavisSchoolofGerontology
“Brain-StateDependentMembranePotentialDynamicsinVisualCortex”Peyman Golshani MD, PhD,UCLA
February 2014
“PersonalGenomes&ClanGenomics”James Lupski MD, PhD,BaylorCollege
“VisibleBrain-wideNetworksatSingle-NeuronResolutionwithMicro-OpticalSectioningTomography”Qingming Luo PhD,BrittonChanceCenter/HuazhongUniversityofSciences&Technology
March 2014
“Age-RelatedandNoise-InducedHearingLoss:ComplexTraits”Rick Friedman MD, PhD, ZNI
“BehindtheScenesatNature:InsightsintoSciencePublishing”Magdalena Skipper PhD, Nature
“SynapticandCircuitryMechanismsofPsychiatricDisorders”Guoping Feng PhD, MIT
“RetinalOutputChannels:DistinctNetworksforSynchingtheClockandStabilizingtheVisualWorld”David Berson PhD,BrownUniversity
April 2014
“CapillaryDysfunctioninAlzheimer’sDiseaseandStroke”Leif Ostergaard MD, PhD,AarhusUniversity
“MechanicsofBacterialCellMembranes”Christoph Haselwandter PhD,USC
May 2014
“TheMachineryofNeuronalExocytosis–MolecularMechanismsandDiseaseImplications”Jingshi Shen PhD,UniversityofColoradoatBoulder
“CorticalCircuitsforVision”Massimo Scanziani PhD,UCSanDiego
June 2014
“InVivoOptogeneticManipulationofCellswithintheNeurovascularUnitLeadstoLocalChangesinNeuralActivity”Tyler Brown PhD, BrownUniversity
“NetworkCodingofFearandExtinctioninMouseFrontalCortex”Joshua Trachtenberg PhD,UCLA
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Neurodegeneration Journal Club
January 2014
“Amyloid-βsignalsthroughtautodriveectopicneuronalcellcyclere-entryinAlzheimer’sdisease”M.E.Sewardetal, Cell 2013
“NeuroprotectionthroughExcitabilityandmTORRequiredinALSMotoneuronstoDelayDiseaseandExtendSurvival”S.Saxenaetal,Neuron 2013
February 2014
“IdentificationofnovelmodifiersofAbtoxicitybytranscriptomicanalysisinthefruitfly”G.Favrinetal,Scientific Reports 2013
March 2014
“RegionalNeuronalNetworkFailureandCognitioninLate-OnsetSporadicAlzheimerDisease”S.F.Carteretal,American Journal of Neuroradiology 2014
NRSA Grant Training
InconjunctionwiththeUSCPrograminNeuroscience,ZNIhostedworkshopsforgraduatestudentswhomightbeinterestedinsubmittingproposalsundertheNationalInstituteofHealth(NIH)’sRuthLKirchsteinNationalResearchServiceAwards(NRSA).TheNRSAprogramisafamilyofgrantsprovidedbytheNIHfortrainingresearchersinthebehavioralsciencesandhealthsciences.Theyareahighlyselectiveandveryprestigioussourceoffundingfordoctoralandpostdoctoraltraineesandnotablydifficulttoobtain.Onlyapplicationswithverygoodimpactscoresarefunded,basedonbudgetcutoffsdeterminedbyeachindividualNIHinstitute.
Thetwo-dayworkshops,heldonceeachsemester,areteam-taughtatZNIbyM Carter Cornwall MD PhD, ProfessorofPhysiology&BiophysicsattheUniversityofUtah;andZNIfacultymembersAlapakkam Sampath PhD,AssociateProfessorofPhysiology&BiophysicsandJeannie ChenPhD,ProfessorofCell&Neurobiology.Theworkshopscovertipsandtricks,samplesuccessfulapplications,writingcritiquesbutalsohavestudentssubmittheirdraftapplicationsforanin-depthandcriticalreview.IndividualswhoavailthemselvestothisopportunitydramaticallyincreasetheirsuccessratewhensubmittingfinalNRSAgrantapplications.
Academic Activities
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Los Angeles Brain Bee 2014
AfterZNIhostedthiseventwithUCLAandLosAngelesCityCollege(LACC)theyearprioratUSC,the2014LABrainBeewasheldattheBrainResearchInstituteatUCLA.
OrganizedbyDrsChrisEvans(UCLA)andAmySweetman(LACC)withsignificantcontributionsbytheInteraxongroupsatUCLAandUSC,thedaywasagreatsuccess.Over80highschoolstudentsfromscoresofLAareahighschoolscompetedforthetopprizes.
TheeventwasenhancedbytheassistanceofundergraduateandgraduatevolunteersfromUSCandUCLA.Withtheirhelp,inadditiontothewrittenandoralcompetitions,studentsparticipatedinascavengerhuntlookingthroughdozensofposterdisplaysforkeyfactsaboutneuroscience,research,andcareerinformation.Aguestlecture“EverydayNeuroscience:MigrationandtheAmericanDream”wasgivenbyDrPeterWhybrown,Professor&ExecutiveChairoftheDepartmentofPsychiatryatUCLA.Thedayclosedwiththreeroundsofa“Jeopardy”stylecompetitionresultinginthewinnersparticipatinginatrophyceremony.
Whenalltheresultsweretallied,thewinnerwasShyamChandrasekarajuniorfromTustinDistrictHighSchool.Shyamwentontoplace12thintheNationalBrainBeeheldlaterin2014inBaltimore,Maryland.
ZNIispleasedtobeapartofthisterrificeventthatengageswiththecommunitytoprovidescientificawarenessandeducationforbrightyoungmindsacrossSouthernCalifornia.Welookforwardtothe2015event,tentativelyscheduledtobeheldatUniversityofCalifornia,Irvine.
“It was great to see the many different avenues I can take in terms of my
educational future. I’m definitely going to be a neuro-something!”
–Shyam Chandrasekar
1st place winner of LA Brain Bee
Music to Remember A joint program offered by LA Opera, the Alzheimer’s Association, California Southland Chapter, the Zilkha Neurogenetic Institute (ZNI) and Alzheimer Disease Research Center (ADRC) at the Keck School of Medicine of USC
Whetheritisacouple’sfavoritemelody(“oursong”),anariafromafamousopera,alullaby,ahymnoraholidaycarol,musicevokesmemories.Musicstirsthesoul,butalsoinvolvesthebrain,inwaysneuroscientistsarestillexploring:Listeningtomusicinvolvestheauditorypathways,auditorycortexandsensoryassociationcortex.Registeringemotionlikelyinvolvestheamygdala.Memoryisaccessedviathehippocampus.Theconnectionsamongtheseregionshelpguideandprocessacomplicatedsetofactionswithinthebrain.
Thispastyear,theZilkhaNeurogeneticInstituteformedauniquepartnershipwiththeAlzheimer’sAssociation,CaliforniaSouthlandChapterandLAOpera,tobringmusic—andperhapsmemories—topeoplewhoneeditmost,thoseexperiencingvariousstagesofdementia.ApilotprojectbroughtyoungsingersfromLAOperatoperformforresidents(andworkers)inlong-termcareandassistedlivingfacilitiesthroughoutLosAngeles.
This pilot program was made possible by research funds from the ZNI, as well as the generosity of Alzheimer’sAssociation,CaliforniaSouthlandChapterandLAOpera.Asanaddedbenefit,theperformerswentcarolingontheHealthScienceCampus,surprisingworkersandvisitorsattheKeckSchoolofMedicineofUSC.Wereceivedsuchpositivefeedbackfromthecommunitythatwewillcontinuethisprogramagainin2014.
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YoungsingersfromLAOperaserenadeworkersoutsidetheZilkhaNeurogeneticInstituteattheKeckSchoolofMedicineofUSC.
Residents of an assisted care facility in eastLosAngelessingalongwithLAOpera.
ZNI Graduate Students
The robust graduate student population at ZNI comes from a variety of USC programs and departments: Neuroscience, Preventive Medicine, Biostatistics and Physiology & Biophysics, and PIBBS (Programs in Biomedical and Biological Sciences) , which includes degrees in Cancer Biology & Genomics; Development, Stem Cells & Regenerative Medicine; Medical Biology; and Molecular Structure & Signaling). Each graduate student works with a ZNI faculty mentor for up to 5 years. Below is a current list of students at ZNI and their projects.
Nick Goeden(AlexandreBonnin):PlacentalTryptophanMetabolicDysfunction:APotentialPathwayfortheDevelopmentalProgrammingofMentalDisorders
Juan Velasquez(AlexandreBonnin):“EffectsofMaternalDepressionandAntidepressantTreatmentsonFetalNeurodevelopment
Jessica DeWitt(DanielCampbell):NeurobiologicalImpactofNon-CodingRNAswithGenome-wideSignificantAssociationwithAutism
Brent Wilkinson(DanielCampbell):NeurobiologicalImpactofRareLoss-of-functionMutationsAssociatedwithAutism
Jillian Shaw(KarenChang):ARoleforNebula/DSCR1inAmelioratingAxonalTransportDefectsAssociatedwithAlzheimer’sDisease
Joo Yeun Lee(KarenChang):ANovelDnaJDomainProteinRegulatesSynapticDevelopmentandMaintainsStem Cell Niche in Drosophilia
Syed Qadri(KarenChang):RegulationofSynapticVesicleEndocytosisbytheMinibrainKinase
Kasey Rose (JeannieChen):LiveCellImagingofRetinalPhotoreceptors
Jung Hwa Cho:(RobertChow):CalciumSensitivityofLarge-denseCoreVesicleExocytosisinComplexin2Knock-outMouseChromaffinCells
Jason Lou(RobertChow):ImprovingPerformanceofArgusIIRetinalProsthesis
Steven Walston(RobertChow):ImprovingPerformanceofArgusIIRetinalProsthesis
Victoria Wolseley(RobertChow):PhotovoltaicNanoswitchesforRemoteOpticalControlofNeurons
Lan Yue(RobertChow):PhotovoltaicNanoswitchesforRemoteOpticalControlofNeurons
Madison Zitting (RobertChow):CalciumSensitivityofLarge-denseCoreVesicleExocytosisinComplexin2Knock-outMouseChromaffinCells
Muye Zhou(Hong-WeiDong):MouseConnectomeProject
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Sneha Ravi(GregField):MappingtheCompleteNeuralOutputoftheMouseRetina
Xiaoyang Yao (GregField):LightAdaptationAcrossParallelPathwaysintheMouseRetina
Tingrui Wang(RickFriedman):Fhod3TransgenicandKnockoutMouseModelConstruction
Anthony Myint(RickFriedman):GWASforVestibularVariationinMice
Christopher Ventura(RadhaKalluri):TheroleofHyperpolarization-activatedInwardCurrentsinShapingNeuronalFunctionintheVestibularNerve
Emily Chen(JamesKnowles):InvestigatingMajorDepressiveDisorderbyNext-GenerationSequencingandDifferentialGeneExpressioninBrainsofSuicideCompleters
JaeMun Hugo Kim(JamesKnowles):SingleCellRNASequencing
Edder Lopez(JamesKnowles):DifferentiationofNeuralProgenitorsin2Dand3DCultures
Chris Armoskus(JamesKnowles/KaiWang):StatisticalAnalysisofGeneticVariationPredisposingtoSchizophrenia
Mark Ambroso(RalfLangen):CurvatureDrivenMyelinationbyMyelinBasicProtein
Alan Okada (RalfLangen):UnderstandingandPreventingMisfoldinginNeurodegenerationandDiabetes
Natalie Kegulian(RalfLangen):IdentifyingToxicConformationsinHuntingtin
Trisha Staab(DerekSieburth):RegulationofNeuronalFunctionbytheConservedSKN-1/NrfStressResponsePathwayinCaenorhabditisElegans
Han Wang(DerekSieburth):RegulationofRhythmicBehaviorsinNeuropeptideSignaling
Ninad Agashe(AnsgarSiemer):OligomerFormationoftheFunctionalAmyloidOrb2A
Silvia Cervantes(AnsgarSiemer):StructuralCharacterizationofOrb2AbyEPR
Sandy Falk(AnsgarSiemer):InteractionofOrb2IsoformsAandB”
Maria Conrad(AnsgarSiemer):OligomerFormationandMembraneInteractionofOrb2A
Brian Zingg(HuizhongTao):UsingOptogeneticstoDissectaCircuitforInnateDefenseBehavior
Xiaolin Chou(HuizhongTao:DevelopmentoftheThalacorticalReceptiveFieldsinMice Leena Ibrahim Marosh (HuizhongTao):CrossModelModulationinthePrimaryVisualCortex
Lingyun Li (HuizhongTao):AFeedforwardInhibitoryCircuitMediatesLateralRefinementofAuditoryCorticalProcessing
Brian Leung(TerrenceTown):TREM2/DAP12CerebralInnateImmuneSignalinginVertebratesandInvertebratesandADiseaseinaDishModel:AniPSModelforFamilialAlzheimer’sDisease
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David Gate (TerrenceTown):TargetingAbetaPhagocytosisbyBlockingIRAK-MInnateImmunityinAlzheimerMice
Thomas Schmidt(TobiasUlmer):DualEffectsofTransmembraneProlineResiduesonIntegrinActivity
ChengLiang Dong(KaiWang):ComparisonofFunctionalPredictionMethodsforNonSynonymousSNPsinExomeSequencingStudiesofHumanDisease
Yunfei Guo(KaiWang):“Enlight:AWeb-basedTooltoIntegrateGWASResultswithBiologicalAnnotations&SeqMule:AnAutomatedPipelineforWholeGenome/ExomeAnalysisonMendelianDiseases”
Hui Yang(KaiWang):Phenotype-basedDetectionofCausalSNPsandCNVsfromNext-generationSequencingData
Chao Ling(KaiWang):Genome-ScaleProfilingofDNAMethylationinSporadicPituitaryMacroadenomas
Haiying Jia (KaiWang):TechnicalEvaluationofLong-rangePCRinNext-generationSequencing
Young Joo Kim(LiZhang):MolecularMechanismsfortheDevelopmentofAuditoryCochlearInnervationPattern
Yatang Li(LiZhang):SynapticMechanismsUnderlyingContrast-DependentSharpeningofOrientationSelectivityinMouseVisualCortex
Lukas Mesik (LiZhang):FunctionalCharacterizationofInhibitoryInterneuronsDuringDevelopment
Xiaorui Ray Xiong (LiZhang):DifferentialGainControlandSynapticScalingUnderliesBinauralComputation
Mu Zhou(LiZhang):GenerationofIntensitySelectivityintheCentralAuditoryPathway
Pan Kong(BerislavZlokovic):Glut1andPicalm
Anita Ramanathan(BerislavZlokovic):TheRoleofPericytesinCerebralandVascularMetabolism
Melanie Sweeney(BerislavZlokovic):APOEε4AlleleModulatesRiskforCSFBiomarkersofNeurovascularInjuryinAlzheimer’sDisease
Divna Lazic (BerislavZlokovic):UnderstandingtheroleofMfsd2atransporterinblood-brainbarrierdysfunctioninAlzheimer’sdisease
ZNI Graduate Students
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ZNI Postdoctoral TraineesIndustrious members of any laboratory, postdoctoral trainees continue their training and education by conducting their own experiment under the guidance of an established faculty member. Working on multiple projects provides key support for the faculty member while establishing the postdoctoral research scientist’s interests. Listed below are ZNI’s postdoctoral trainees and the titles of their research projects.
Jennifer King(AlexandreBonnin):InvestigationofaNewCellularCommunicationMechanismBetweenthePlacentaandtheFetalBrain
Yen Chan(AlexandreBonnin):MaternalInfectionEffectsonFetalBrainDevelopment
Tian Wang (JeannieChen):PhototransreductioninDarkAdaptationandRetinalDegeneration
Reymundo Dominguez(RobertChow):Single-cellAnalysis
Nan Lee(RobertChow):InvasionPotentialofCancerCells
Ming-Yi Sonya Lin(RobertChow):Single-CellAnalysis”and“PhotovoltaicNanoswitchesforRemoteOpticalControlofNeurons”
Andrew Weitz(RobertChow):ImagingPlatformforDeterminingTumorInvasiveness
Jing Li (MarceloCoba):SynapticSignalingNetworks
Zhu Chen(DavidConti):UsingQuantileRegressionforPathwayAnalysisinGenome-wide Studies
Lilit Chemenyan(DavidConti):“BayesianModelSelectionforFunctionalIntegrationinGeneticAssociationStudies”
Nicholas Foster(Hong-WeiDong):MouseBrainConnectomeMappingofCorticalandStriatalLong-distanceAxonProjectionDeficitsinHuntington’sDiseaseMouseModels
Michael Bienkowski (Hong-WeiDong):TheMouseConnectomeProject
Juemei Wang(RickFriedman):GWASforNoise-inducedHearingLossinMice
Pezhman Salehi Dermanaki(RickFriedman):NovelgenesInvolvedinAge-relatedandNoise-induced Hearing Loss in Mice
Joel Lavinsky(RickFriedman):Nox3andNoise-inducedHearingLossandaGWASforVestibularVariationinMice
Qingzhong Li (RickFriedman):Fhod3,ANovelCandidateforAge-relatedHearingLossin Mice
Jose Mario Isas(RalfLangen):StructuralStudiesofHuntingtinMisfolding
Toru Miwa(TakahiroOhyama):MolecularAnalysisofDevelopmentalMechanismsofDevelopingMouseInnerEar
Charlotte Buckley(JanosPeti-Peterdi):InteractionsbetweentheReninCellandtheMacula Densa
Anne Riquier-Brison(JanosPeti-Peterdi):TheRoleoftheGPR91/SuccinatePathwayinRenovascularHypertension
Kengo Kidokoro(JanosPeti-Peterdi):TrackingPodocyteFateinNephroticSyndrome
James Burford(JanosPeti-Peterdi):TheRoleofPodocyteCalciuminGlomerularDiseases
Federica Barutta(JanosPeti-Peterdi):TunnelingNanotubulesintheGlomerulus
Rachel Service(AnsgarSiemer):StructuralCharacterizationofFunctionalandDisease-relatedAmyloid
Kevin Doty(TerrenceTown):UsingGenomeWideApproachestoIdentifyandModulateBeneficialNeuroinflammationinAlzheimer’sDisease
Tara Weitz (TerrenceTown):TGF-betaInhibitorTherapyinaTransgenicRatModelofAlzheimer’sDisease
Marie-Victoire Guillot-Sestier(TerrenceTown):ImplicationoftheAnti-InflammatoryCytokineInterleukin-10inInntateImmuneResponsetoAmyloidogenesisinAlzheimer’sDisease
Rodrigo Lopez Leal (TerrenceTown):AniPSDisease-in-a-DishModelofFamilialAlzheimer’sandGenerationofaConditionalRatModelforGeneticAblationofNeuralStem Cell
JiHong Kim (KaiWang):ComparativeAnalysisofMultipleRNA-SeqQuantificationTools&DevelopmentofFullyAutomatedRNA-SeqAnalysisPipelines
Kassandra Kisler Elliott(BerislavZlokovic):PericyteRegulationofNeurovascularCouplingandLocalBrainOxygenSupply
Axel Montagne(BerislavZlokovic):QuantitativeDynamicContrast-EnhancedMagneticResonanceImagingtoEvaluateBlood-BrainBarrierIntegrityinAlzheimer’sDisease and Related Disorders
Amy Nelson (BerislavZlokovic):TheRoleofPericytesinHippocampalFunction
Yaoming Wang(BerislavZlokovic):RegulationofBrainThrombosisinStrokeModels
Gil Carvalho(BerislavZlokovic):CellularBasisofFeelingsandSentience
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FY14FacultyPublications
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One of the most common ways for scientists to formally share their research is to publish an article in a scientific journal focused on a particular area of study. A typical scholarly, scientific journal article is peer-reviewed, discusses the authors’ original research, offers thoughtful analy-sis of the results, and cites relevant papers from other authors that relate to the research. Scien-tists (and editors of these publications) rely on their colleagues, the reviewers, to ensure a critical review of the science is conducted, with all aspects of the approach and techniques described, so that conclusions reached are empirically sound. This process, which takes place as discoveries are made, takes many months of back-and-forth responses between authors and editors and in rare cases, can exceed a year’s time.
A journal’s impact factor is a measure of the frequency with which the average article in a journal has been cited in a particular year. The impact factor is calculated by dividing the number of citations in the current year to articles published in the two previous years by the total number of articles published in the two previous years. While the expectation is that all peer-reviewed publications move science forward, in some areas of study coverage is not as widespread and thus the impact factor of a journal in a highly specialized field will not necessarily have the same impact factor as the broader journals like Science and Nature. How many papers an institution has in high-impact journals is just one of several measures of productivity.
Last year, ZNI faculty published 148 papers, and 17.5% of these were in high impact journals, which represents a 3.5% increase over the prior year. Congratulations to all the ZNI scientists who had their work published in FY14.
OuryF,KhrimianL,DennyCA,GardinA,ChamouniA,GoedenN,HuangYY,LeeH,SrinivasP,GaoXB,SuyamaS,LangerT,MannJJ,HorvathTL,Bonnin A,KarsentyG.Maternalandoffspringpoolsofosteocalcininfluencebraindevelopmentandfunctions.Cell.2013Sep26;155(1):228-41.doi:10.1016/j.cell.2013.08.042.
Goeden N and Bonnin A.(2013)Exvivoperfusionofthemouseplacentaformaternal-fetalinteractionstudiesduringpregnancy;in:Theguideforinvestigationofmousepregnancy(Croy,Yamada,DeMayoandAdamson,Eds.),AcademicPress/Elsevier,pp661-671.
VolkHE,KerinT,LurmannF,Hertz-PicciottoI,McConnellR,Campbell DB.Autismspectrumdisorder:interactionofairpollutionwiththeMETreceptortyrosinekinasegene.Epidemiology.2014Jan;25(1):44-7.
AbrahamsBS,ArkingDE,Campbell DB,MeffordHC,MorrowEM,WeissLA,MenasheI,WadkinsT,Banerjee-BasuS,PackerA.SFARIGene2.0:acommunity-drivenknowledgebasefortheautismspectrumdisorders(ASDs).MolAutism.2013Oct3;4(1):36.doi:10.1186/2040-2392-4-36.
Wilkinson,B.andCampbell, D.B.ContributionoflongnoncodingRNAs(lncRNAs)toautismspectrumdisorderrisk.InternationalReviewofNeurobiology.113:35-59.2013.
DeWitt,J.andCampbell, D.B.TargetingnoncodingRNAfortreatmentofautismspectrumdisorders.In:FrontiersinAutismResearch,DiagnosisandTreatment.(Editor:Hu)2014.
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ChenCK,BregereC,PaluchJ,LuJF,DickmanDK, Chang KT.Activity-dependentfacilitationofSynaptojaninandsynapticvesiclerecyclingbytheMinibrainkinase..NatCommun.2014Jun30;5:4246
ShawJL,Chang KT.Nebula/DSCR1upregulationdelaysneurodegenerationandprotectsagainstAPP-inducedaxonaltransportdefectsbyrestoringcalcineurinandGSK-3βsignaling.PLoSGenet.2013;9(9):e1003792.doi:10.1371/journal.pgen.1003792.Epub2013Sep26.
Chang KT,RoH,WangW,MinKT.Meetingatthecrossroads:commonmechanismsinFragileXandDownsyndrome.TrendsNeurosci.2013Dec;36(12):685-94.doi:10.1016/j.tins.2013.08.007.Epub2013Sep25.Review.
Niescier RF, Chang KT,MinKT.Miro,MCU,andcalcium:bridgingourunderstandingofmitochondrialmovementinaxons.FrontCellNeurosci.2013Sep10;7:148.doi:10.3389/fncel.2013.00148.Review.
Chen J.Thephysiologicalrolesofarrestin-1inrodphotoreceptorcells.HandbExpPharmacol.2014;219:85-99.doi:10.1007/978-3-642-41199-1_4.
SongX,SeoJ,BaameurF,VishnivetskiySA,ChenQ,KookS,KimM,BrooksEK,AltenbachC,HongY,HansonSM,PalazzoMC, Chen J,HubbellWL,GurevichEV,GurevichVV.Rapiddegenerationofrodphotoreceptorsexpressingself-association-deficientarrestin-1mutant.CellSignal.2013Dec;25(12):2613-24.doi:10.1016/j.cellsig.2013.08.022.Epub2013Sep3.
WeitzAC,BehrendMR,AhujaAK,ChristopherP,WeiJ,WuyyuruV,PatelU,GreenbergRJ,HumayunMS,Chow RH, Weiland JD.Interphasegapasameanstoreduceelectricalstimulationthresholdsforepiretinalprostheses.JNeuralEng.2014Feb;11(1):016007.
BortolatoM,GodarSC,TambaroS,LiFG,DevotoP,Coba MP,ChenK,ShihJC.Earlypostnatalinhibitionofserotoninsynthesisresultsinlong-termreductionsofperseverativebehaviors,butnotaggression,inMAOA-deficientmice.Neuropharmacology.2013Dec;75:223-32.doi:10.1016/j.neuropharm.2013.07.003.Epub2013Jul16.
Y.Feng,D.O.Stram,S.K.Rhie,R.C.Millikan,C.B.Ambrosone,E.M.John,L.Bernstein,W.Zheng,A.F.Olshan,J.J.Hu,R.G.Ziegler,S.Nyante,E.V.Bandera,S.A.Ingles,M.F.Press,S.L.Deming,J.L.Rodriguez-Gil,J.R.Palmer,O.I.Olopade,D.Huo,C.A.Adebamowo,T.Ogundiran,G.K.Chen,A.Stram,K.Park,K.A.Rand,S.J.Chanock,L.LeMarchand,L.N.Kolonel,D. V. Conti,D.Easton,B.E.Henderson,andC.A.Haiman,“AcomprehensiveexaminationofbreastcancerrisklociinAfricanAmericanwomen.,”HumMolGen,p.ddu252,May2014.
T.H.T.Cheng,M.Gorman,L.Martin,E.Barclay,G.Casey,P.A.Newcomb,D. V. Conti,F.Schumacher,S.Gallinger,N.M.Lindor,J.Hopper,M.Jenkins,D.J.Hunter,P.Kraft,K.B.Jacobs,D.G.Cox,M.Yeager,S.E.Hankinson,S.Wacholder,Z.Wang,R.Welch,A.Hutchinson,J.Wang,K.Yu,N.Chatterjee,N.Orr,W.C.Willett,G.A.Colditz,R.G.Ziegler,C.D.Berg,S.S.Buys,C.A.McCarty,H.S.Feigelson,E.E.Calle,M.J.Thun,R.B.Hayes,M.Tucker,D.S.Gerhard,J.F.Fraumeni,R.N.Hoover,G.Thomas,S.J.Chanock,J.Ciampa,J.Gonzalez-Bosquet,S.Berndt,L.Amundadottir,W.R.Diver,D.Albanes,J.Virtamo,S.Weinstein,F.R.Schumacher,G.Cancel-Tassin,O.Cussenot,A.Valeri,G.L.Andriole,E.D.Crawford,C.A.Haiman,B.Henderson,L.Kolonel,L.L.Marchand,A.Siddiq,E.Riboli,T.J.Key,R.Kaaks,W.Isaacs,S.Isaacs,K.E.Wiley,H.Gronberg,F.Wiklund,P.Stattin,J.Xu,S.L.Zheng,J.Sun,L.J.Vatten,K.Hveem,M.Kumle,M.Tucker,D.S.Gerhard,M.P.Purdue,M.Johansson,D.Zelenika,J.R.Toro,G.Scelo,L.E.Moore,E.Prokhortchouk,X.Wu,L.A.Kiemeney,V.Gaborieau,W.-H.Chow,D.Zaridze,V.Matveev,J.Lubinski,J.Trubicka,N.Szeszenia-Dabrowska,J.Lissowska,P.Rudnai,E.Fabianova,A.Bucur,V.Bencko,L.Foretova,V.Janout,P.Boffetta,J.S.Colt,F.G.Davis,K.L.Schwartz,R.E.Banks,P.J.Selby,P.Harnden,A.W.Hsing,R.L.GrubbIII,H.Boeing,P.Vineis,F.Clavel-Chapelon,D.Palli,R.Tumino,V.Krogh,S.Panico,E.J.Duell,J.R.Quirós,M.-J.Sanchez,C.Navarro,E.Ardanaz,M.Dorronsoro,K.-T.Khaw,N.E.Allen,H.B.Bueno-de-Mesquita,P.H.M.Peeters,D.Trichopoulos,J.Linseisen,B.Ljungberg,K.Overvad,A.Tjonneland,I.Romieu,A.Mukeria,O.Shangina,V.L.Stevens,S.M.Gapstur,P.D.Pharoah,D.F.Easton,S.J.Weinstein,L.Vatten,I.Njølstad,G.S.Tell,C.Stoltenberg,R.Kumar,K.Koppova,S.Benhamou,E.Oosterwijk,S.H.Vermeulen,K.K.H.Aben,S.L.vanderMarel,Y.Ye,C.G.Wood,X.Pu,A.M.Mazur,E.S.Boulygina,N.N.Chekanov,M.Foglio,D.Lechner,I.Gut,S.Heath,H.Blanche,K.G.Skryabin,J.D.McKay,N.Rothman,M.Lathrop,P.Brennan,B.Saunders,H.Thomas,S.Clark,andI.Tomlinson,“Commoncolorectalcancerriskallelescontributetothemultiplecolorectaladenomaphenotype,butdonotinfluencecolonicpolyposisinFAP,”EurJHumGenet,May2014.
J.D.Figueroa,S.S.Han,M.Garcia-Closas,D.Baris,E.J.Jacobs,M.Kogevinas,M.Schwenn,N.Malats,A.Johnson,M.P.Purdue,N.Caporaso,M.T.Landi,L.Prokunina-Olsson,Z.Wang,A.Hutchinson,L.Burdette,W.Wheeler,P.Vineis,A.Siddiq,V.K.Cortessis,C.Kooperberg,O.Cussenot,S.Benhamou,J.Prescott,S.Porru,H.B.Bueno-de-Mesquita,D.Trichopoulos,B.Ljungberg,F.Clavel-Chapelon,E.Weiderpass,V.Krogh,M.Dorronsoro,R.Travis,A.Tjonneland,P.Brenan,J.Chang-Claude,E.Riboli,D. Conti,M.Gago-Dominguez,M.C.Stern,M.C.Pike,D.VanDenBerg,J.-M.Yuan,C.Hohensee,R.Rodabough,G.Cancel-Tassin,M.Roupret,E.Comperat,C.Chen,I.DeVivo,E.Giovannucci,D.J.Hunter,P.Kraft,S.Lindstrom,A.Carta,S.Pavanello,C.Arici,G.Mastrangelo,M.R.Karagas,A.Schned,K.R.Armenti,G.M.M.Hosain,C.A.Haiman,J.F.Fraumeni,S.J.Chanock,N.Chatterjee,N.Rothman,andD.T.Silverman,“Genome-wideinteractionstudyofsmokingandbladdercancerrisk.,”Carcinogenesis,p.bgu064,May2014.
A.M.Leventhal,W.Lee,A.W.Bergen,G.E.Swan,R.F.Tyndale,C.Lerman,andD. V. Conti,“Nicotinedependenceasamoderatorofgeneticinfluencesonsmokingcessationtreatmentoutcome.,”DrugAlcoholDepend,vol.138,pp.109–117,May2014.
Cheng,J.M.Kocarnik,L.Dumitrescu,N.M.Lindor,Chang-ClaudeJ,C.L.Avery,C.P.Caberto,S.A.Love,M.L.Slattery,A.T.Chan,J.A.Baron,L.A.Hindorff,S.L.Park,F.R.Schumacher,M.Hoffmeister,P.Kraft,A.M.Butler,D.J.Duggan,L.Hou,C.S.Carlson,K.R.Monroe,Y.Lin,C.L.Carty,S.Mann,J.Ma,E.L.Giovannucci,C.S.Fuchs,P.A.Newcomb,M.A.Jenkins,J.L.Hopper,R.W.Haile,D. V. Conti,P.T.Campbell,J.D.Potter,B.J.Caan,R.E.Schoen,R.B.Hayes,S.J.Chanock,S.I.Berndt,S.Kury,S.Bezieau,J.L.Ambite,G.Kumaraguruparan,D.M.Richardson,R.J.Goodloe,H.H.Dilks,P.Baker,B.W.Zanke,M.Lemire,S.Gallinger,L.Hsu,S.Jiao,T.A.Harrison,D.Seminara,C.A.Haiman,C.Kooperberg,L.R.Wilkens,C.M.Hutter,E.White,D.C.Crawford,G.Heiss,T.J.Hudson,H.Brenner,W.S.Bush,G.Casey,L.LeMarchand,andU.Peters,“Pleiotropiceffectsofgeneticriskvariantsforothercancersoncolorectalcancerrisk:PAGE,GECCOandCCFRconsortia.,”Gut,vol.63,no.5,pp.800–807,May2014.
N.Whiffin,F.J.Hosking,S.M.Farrington,C.Palles,S.E.Dobbins,L.Zgaga,A.Lloyd,B.Kinnersley,M.Gorman,A.Tenesa,P.Broderick,Y.Wang,E.Barclay,C.Hayward,L.Martin,D.D.Buchanan,A.KoWin,J.Hopper,M.Jenkins,N.M.Lindor,P.A.Newcomb,S.Gallinger,D. Conti,F.Schumacher,G.Casey,T.Liu,TheSwedishLow-RiskColorectalCancerStudyGroup,H.Campbell,A.Lindblom,R.S.Houlston,I.P.Tomlinson,andM.G.Dunlop,“Identificationofsusceptibilitylociforcolorectalcancerinagenome-widemeta-analysis.,”HumMolGenet,p.ddu177,Apr.2014.
B.Zhang,W.-H.Jia,K.Matsuda,S.-S.Kweon,K.Matsuo,Y.-B.Xiang,A.Shin,S.H.Jee,D.-H.Kim,Q.Cai,J.Long,J.Shi,W.Wen,G.Yang,Y.Zhang,C.Li,B.Li,Y.Guo,Z.Ren,B.-T.Ji,Z.-Z.Pan,A.Takahashi,M.-H.Shin,F.Matsuda,Y.-T.Gao,J.H.Oh,S.Kim,Y.-O.Ahn,J.A.Baron,S.I.Berndt,S.Bézieau,H.Brenner,B.J.Caan,C.S.Carlson,G.Casey,A.T.Chan,J.Chang-Claude,S.J.Chanock,D. V. Conti,K.Curtis,D.Duggan,C.S.Fuchs,S.Gallinger,E.L.Giovannucci,S.B.Gruber,R.W.Haile,T.A.Harrison,R.B.Hayes,M.Hoffmeister,J.L.Hopper,L.Hsu,T.J.Hudson,D.J.Hunter,C.M.Hutter,R.D.Jackson,M.A.Jenkins,S.Jiao,S.Küry,L.LeMarchand,M.Lemire,N.M.Lindor,J.Ma,P.A.Newcomb,U.Peters,J.D.Potter,C.Qu,T.Rohan,R.E.Schoen,F.R.Schumacher,D.Seminara,M.L.Slattery,S.N.Thibodeau,E.White,B.W.Zanke,K.Blalock,P.T.Campbell,C.K.Edlund,J.Figueiredo,W.J.Gauderman,J.Gong,R.C.Green,J.F.Harju,E.J.Jacobs,L.Li,Y.Lin,F.J.Manion,V.Moreno,B.Mukherjee,L.Raskin,G.Severi,S.L.Stenzel,D.C.Thomas,H.-R.Kim,J.-Y.Jeong,J.W.Park,H.-L.Li,S.Hosono,S.-H.Cho,M.Kubo,X.-O.Shu,Y.-X.Zeng,andW.Zheng,“Large-scalegeneticstudyinEastAsiansidentifiessixnewlociassociatedwithcolorectalcancerrisk.,”vol.46,no.6,pp.533–542,Jun.2014.
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FY14 Faculty Publications
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M.Biancolella,B.K.Fortini,S.Tring,S.J.Plummer,G.A.Mendoza-Fandino,J.Hartiala,M.J.Hitchler,C.Yan,F.R.Schumacher,D. V. Conti,C.K.Edlund,H.Noushmehr,S.G.Coetzee,R.S.Bresalier,D.J.Ahnen,E.L.Barry,B.P.Berman,J.C.Rice,G.A.Coetzee,andG.Casey,“Identificationandcharacterizationoffunctionalriskvariantsforcolorectalcancermappingtochromosome11q23.1.,”HumMolGenet,vol.23,no.8,pp.2198–2209,Apr.2014.
H.Ahsan,J.Halpern,M.G.Kibriya,B.L.Pierce,L.Tong,E.Gamazon,V.McGuire,A.Felberg,J.Shi,F.Jasmine,RoyS,R.Brutus,M.Argos,S.Melkonian,Chang-ClaudeJ,I.Andrulis,J.L.Hopper,E.M.John,K.Malone,G.Ursin,M.D.Gammon,D.C.Thomas,D.Seminara,G.Casey,J.A.Knight,M.C.Southey,G.G.Giles,R.M.Santella,E.Lee,D. Conti,D.Duggan,S.Gallinger,R.Haile,M.Jenkins,N.M.Lindor,P.Newcomb,K.Michailidou,C.Apicella,D.J.Park,J.Peto,O.Fletcher,I.dosSantosSilva,M.Lathrop,D.J.Hunter,S.J.Chanock,A.Meindl,R.K.Schmutzler,B.Muller-Myhsok,M.Lochmann,L.Beckmann,R.Hein,E.Makalic,D.F.Schmidt,Q.M.Bui,J.Stone,D.Flesch-Janys,N.Dahmen,H.Nevanlinna,K.Aittomaki,C.Blomqvist,P.Hall,K.Czene,A.Irwanto,J.Liu,N.Rahman,C.Turnbull,fortheFamilialBreastCancerStudy,A.M.Dunning,P.Pharoah,Q.Waisfisz,H.Meijers-Heijboer,A.G.Uitterlinden,F.Rivadeneira,NicolaeD,D.F.Easton,N.J.Cox,andA.S.Whittemore,“Agenome-wideassociationstudyofearly-onsetbreastcanceridentifiesPFKMasanovelbreastcancergeneandsupportsacommongeneticspectrumforbreastcanceratanyage.,”CancerEpidemiolBiomarkersPrev,vol.23,no.4,pp.658–669,Apr.2014.
J.D.Figueroa,Y.Ye,A.Siddiq,M.Garcia-Closas,N.Chatterjee,L.Prokunina-Olsson,V.K.Cortessis,C.Kooperberg,O.Cussenot,S.Benhamou,J.Prescott,S.Porru,C.P.Dinney,N.Malats,D.Baris,M.Purdue,E.J.Jacobs,D.Albanes,Z.Wang,X.Deng,C.C.Chung,W.Tang,H.BasBueno-de-Mesquita,D.Trichopoulos,B.Ljungberg,F.Clavel-Chapelon,E.Weiderpass,V.Krogh,M.Dorronsoro,R.Travis,A.Tjonneland,P.Brenan,Chang-ClaudeJ,E.Riboli,D. Conti, M.Gago-Dominguez,M.C.Stern,M.C.Pike,D.VanDenBerg,J.-M.Yuan,C.Hohensee,R.Rodabough,G.Cancel-Tassin,M.Roupret,E.Comperat,C.Chen,I.DeVivo,E.Giovannucci,D.J.Hunter,P.Kraft,S.Lindstrom,A.Carta,S.Pavanello,C.Arici,G.Mastrangelo,A.M.Kamat,S.P.Lerner,H.BartonGrossman,J.Lin,J.Gu,X.Pu,A.Hutchinson,L.Burdette,W.Wheeler,M.Kogevinas,A.Tardon,C.Serra,A.Carrato,R.Garcia-Closas,J.Lloreta,M.Schwenn,M.R.Karagas,A.Johnson,A.Schned,K.R.Armenti,G.M.Hosain,G.Andriole,R.Grubb,A.Black,W.RyanDiver,S.M.Gapstur,S.J.Weinstein,J.Virtamo,C.A.Haiman,M.T.Landi,N.Caporaso,J.F.Fraumeni,P.Vineis,X.Wu,D.T.Silverman,S.Chanock,andN.Rothman,“Genome-wideassociationstudyidentifiesmultiplelociassociatedwithbladdercancerrisk,”HumMolGenet,vol.23,no.5,pp.1387–1398,Feb.2014.
R.Corral,J.P.Lewinger,D.VanDenBerg,A.D.Joshi,J.-M.Yuan,M.Gago-Dominguez,V.K.Cortessis,M.C.Pike,D. V. Conti,D.C.Thomas,C.K.Edlund,Y.-T.Gao,Y.-B.Xiang,W.Zhang,Y.-C.Su,andM.C.Stern,“ComprehensiveanalysesofDNArepairpathways,smokingandbladdercancerriskinLosAngelesandShanghai,”IntJCancer,vol.135,no.2,pp.335–347,Jan.2014.
W.Cozen,M.N.Timofeeva,D.Li,A.Diepstra,D.Hazelett,M.Delahaye-Sourdeix,C.K.Edlund,L.Franke,K.Rostgaard,D.J.VanDenBerg,V.K.Cortessis,K.E.Smedby,S.L.Glaser,H.-J.Westra,L.L.Robison,T.M.Mack,H.Ghesquieres,A.E.Hwang,A.Nieters,S.deSanjose,T.Lightfoot,N.Becker,M.Maynadie,L.Foretova,E.Roman,Y.Benavente,K.A.Rand,B.N.Nathwani,B.Glimelius,A.Staines,P.Boffetta,B.K.Link,L.Kiemeney,S.M.Ansell,S.Bhatia,L.C.Strong,P.Galan,L.Vatten,T.M.Habermann,E.J.Duell,A.Lake,R.N.Veenstra,L.Visser,Y.Liu,K.Y.Urayama,D.Montgomery,V.Gaborieau,L.M.Weiss,G.Byrnes,M.Lathrop,P.Cocco,T.Best,A.D.Skol,H.-O.Adami,M.Melbye,J.R.Cerhan,A.Gallagher,G.M.Taylor,S.L.Slager,P.Brennan,G.A.Coetzee,D. V. Conti,K.Onel,R.F.Jarrett,H.Hjalgrim,A.vandenBerg,andJ.D.McKay,“Ameta-analysisofHodgkinlymphomareveals19p13.3TCF3asanovelsusceptibilitylocus.,”NatureCommunications,vol.5,p.3856,2014.
B.Young,D. V. Conti,andM.D.Dean,“Sneaker“jack”malesoutcompetedominant‘hooknose’malesunderspermcompetitioninChinooksalmon(Oncorhynchustshawytscha).,”EcolEvol,vol.3,no.15,pp.4987–4997,Dec.2013.
69
N.Whiffin,S.E.Dobbins,F.J.Hosking,C.Palles,A.Tenesa,Y.Wang,S.M.Farrington,A.M.Jones,P.Broderick,H.Campbell,P.A.Newcomb,G.Casey,D. V. Conti,F.Schumacher,S.Gallinger,N.M.Lindor,J.Hopper,M.Jenkins,M.G.Dunlop,I.P.Tomlinson,andR.S.Houlston,“Decipheringthegeneticarchitectureoflow-penetrancesusceptibilitytocolorectalcancer.,”HumMolGenet,vol.22,no.24,pp.5075–5082,Dec.2013.
S.P.David,D.R.Strong,A.M.Leventhal,M.A.Lancaster,J.E.McGeary,M.R.Munafò,A.W.Bergen,G.E.Swan,N.L.Benowitz,R.F.Tyndale,D. V. Conti,R.A.Brown,C.Lerman,andR.Niaura,“Influenceofadopaminepathwayadditivegeneticefficacyscoreonsmokingcessation:resultsfromtworandomizedclinicaltrialsofbupropion.,”Addiction,vol.108,no.12,pp.2202–2211,Dec.2013.
L.T.Hiraki,C.Qu,C.M.Hutter,J.A.Baron,S.I.Berndt,S.Bezieau,H.Brenner,B.J.Caan,G.Casey,Chang-ClaudeJ,S.J.Chanock,D. V. Conti,D.Duggan,C.S.Fuchs,S.Gallinger,E.L.Giovannucci,T.A.Harrison,R.B.Hayes,A.Hazra,B.Henderson,M.Hoffmeister,J.L.Hopper,T.J.Hudson,M.A.Jenkins,S.Kury,L.LeMarchand,M.Lemire,J.Ma,J.E.Manson,H.Nan,P.A.Newcomb,K.Ng,J.D.Potter,R.E.Schoen,F.R.Schumacher,D.Seminara,M.L.Slattery,J.Wactawski-Wende,E.White,K.Wu,B.W.Zanke,P.Kraft,U.Peters,andA.T.Chan,“Geneticpredictorsofcirculating25-hydroxyvitamindandriskofcolorectalcancer.,”CancerEpidemiolBiomarkersPrev,vol.22,no.11,pp.2037–2046,Nov.2013.
J.W.BaurleyandD. V. Conti,“Ascalable,knowledge-basedanalysisframeworkforgeneticassociationstudies.,”BMCBioinformatics,vol.14,no.1,p.312,Oct.2013.
M.A.QuintanaandD. V. Conti,“IntegrativevariableselectionviaBayesianmodeluncertainty.,”StatMed,Jul.2013.
J.P.Lewinger,J.L.Morrison,D.C.Thomas,C.E.Murcray,D. V. Conti,D.Li,andW.J.Gauderman,“Efficienttwo-steptestingofgene-geneinteractionsingenome-wideassociationstudies.,”GenetEpidemiol,vol.37,no.5,pp.440–451,Jul.2013.
X.Jiang,J.E.Castelao,D.Vandenberg,A.Carracedo,C.M.Redondo,D. V. Conti,J.P.ParedesCotoré,J.D.Potter,P.A.Newcomb,M.N.Passarelli,M.A.Jenkins,J.L.Hopper,S.Gallinger,L.LeMarchand,M.E.Martínez,D.J.Ahnen,J.A.Baron,N.M.Lindor,R.W.Haile,andM.Gago-Dominguez,“GeneticVariationsinSMAD7AreAssociatedwithColorectalCancerRiskintheColonCancerFamilyRegistry.,”PLoSONE,vol.8,no.4,p.e60464,2013.
BotaM,TalpalaruS,HintiryanH,Dong HW,SwansonLW.BAMS2workspace:Acomprehensiveandversatileneuroinformaticplatformforcollatingandprocessingneuroanatomicalconnections.JCompNeurol.2014Dec1;522(14):3160-76.doi:10.1002/cne.23592.Epub2014Apr12.
ZinggB,HintiryanH,GouL,SongMY,BayM,BienkowskiMS,FosterNN,YamashitaS,BowmanI,TogaAW,Dong HW.Neuralnetworksofthemouseneocortex.Cell.2014Feb27;156(5):1096-111.doi:10.1016/j.cell.2014.02.023.
GrayM,WangN,LuX-H,CantleJ,GreinerE,GuX,CepedaC,OsmandA,Dong H-W,LevineM,andYangXW.CorticalandStriatalPathogenicSynergyandNon-cell-autonomousAggregateSuppressioninHDMice.NatureMedicine2014.20(5):536-41.
Greschner M, Field GD,LiPH,SchiffML,GauthierJL,AhnD,SherA,LitkeAM,ChichilniskyEJ.Apolyaxonalamacrinecellpopulationintheprimateretina.JNeurosci.2014Mar5;34(10):3597-606.doi:10.1523/JNEUROSCI.3359-13.2014.
Li PH, Field GD,GreschnerM,AhnD,GunningDE,MathiesonK,SherA,LitkeAM,ChichilniskyEJ.Retinalrepresentationoftheelementaryvisualsignal.Neuron.2014Jan8;81(1):130-9.doi:10.1016/j.neuron.2013.10.043.Erratumin:Neuron.2014Apr16;82(2):500.
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FransenE,BonneuxS,CorneveauxJJ,SchrauwenI,DiBerardinoF,WhiteCH,OhmenJD,VandeHeyningP,AmbrosettiU,HuentelmanMJ,VanCampG,Friedman RA.Genome-wideassociationanalysisdemonstratesthehighlypolygeniccharacterofage-relatedhearingimpairment..EurJHumGenet.2014Jun18.doi:10.1038/ejhg.2014.56.[Epubaheadofprint]
HoMK,LiX,WangJ,OhmenJD,Friedman RA.FVB/NJmicedemonstrateayouthfulsensitivitytonoise-inducedhearinglossandprovideausefulgeneticmodelforthestudyofneuralhearingloss.AudiolNeurotolExtra.2014Jan1;4(1):1-11.
OhmenJ,KangEY,LiX,JooJW,HormozdiariF,ZhengQY,DavisRC,LusisAJ,EskinE, Friedman RA.Genome-wideassociationstudyforage-relatedhearingloss(AHL)inthemouse:ameta-analysis.JAssocResOtolaryngol.2014Jun;15(3):335-52.doi:10.1007/s10162-014-0443-2.Epub2014Feb26.
FayadJN,UrsickJ,BrackmannDE,Friedman RA.Totalossiculoplasty:short-andlong-termresultsusingatitaniumprosthesiswithfootplateshoe.OtolNeurotol.2014Jan;35(1):108-13.doi:10.1097/MAO.0b013e3182a475ac.
SchwartzMS,KariE,StricklandBM,BerlinerK,BrackmannDE,HouseJW,Friedman RA.Evaluationoftheincreaseduseofpartialresectionoflargevestibularschwanommas:facialnerveoutcomesandrecurrence/regrowthrates.OtolNeurotol.2013Oct;34(8):1456-64.doi:10.1097/MAO.0b013e3182976552.
OhmenJD,WhiteCH,LiX,WangJ,FisherLM,ZhangH,DereberyMJ, Friedman RA.GeneticevidenceforanethnicdiversityinthesusceptibilitytoMénière’sdisease.OtolNeurotol.2013Sep;34(7):1336-41.doi:10.1097/MAO.0b013e3182868818.
Kalluri R,SheraCA.Measuringstimulus-frequencyotoacousticemissionsusingswepttones.JAcoustSocAm.2013Jul;134(1):356-68.doi:10.1121/1.4807505.
Bigdeli,T.B.,Maher,B.S.,Zhao,Z.,Sun,J.,Medeiros,H.,Akula,N.,McMahon,F.J.,Carvalho,C.,Ferreira,S.R.,Azevedo,M.H.,Knowles, J.A., Pato, M.T.,Pato, C.N.,andFanous,A.H.(2013).Associationstudyof83candidategenesforbipolardisorderinchromosome6qselectedusinganevidence-basedprioritizationalgorithm.AmericanjournalofmedicalgeneticsPartB,Neuropsychiatricgenetics:theofficialpublicationoftheInternationalSocietyofPsychiatricGenetics,PMID:24123842.
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FY14 Faculty Publications
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Cross-DisorderGroupofthePsychiatricGenomics,C.,Lee,S.H.,Ripke,S.,Neale,B.M.,Faraone,S.V.,Purcell,S.M.,Perlis,R.H.,Mowry,B.J.,Thapar,A.,Goddard,M.E.,Witte,J.S.,Absher,D.,Agartz,I.,Akil,H.,Amin,F.,Andreassen,O.A.,Anjorin,A.,Anney,R.,Anttila,V.,Arking,D.E.,Asherson,P.,Azevedo,M.H.,Backlund,L.,Badner,J.A.,Bailey,A.J.,Banaschewski,T.,Barchas,J.D.,Barnes,M.R.,Barrett,T.B.,Bass,N.,Battaglia,A.,Bauer,M.,Bayes,M.,Bellivier,F.,Bergen,S.E.,Berrettini,W.,Betancur,C.,Bettecken,T.,Biederman,J.,Binder,E.B.,Black,D.W.,Blackwood,D.H.,Bloss,C.S.,Boehnke,M.,Boomsma,D.I.,Breen,G.,Breuer,R.,Bruggeman,R.,Cormican,P.,Buccola,N.G.,Buitelaar,J.K.,Bunney,W.E.,Buxbaum,J.D.,Byerley,W.F.,Byrne,E.M.,Caesar,S.,Cahn,W.,Cantor,R.M.,Casas,M.,Chakravarti,A.,Chambert,K.,Choudhury,K.,Cichon,S.,Cloninger,C.R.,Collier,D.A.,Cook,E.H.,Coon,H.,Cormand,B.,Corvin,A.,Coryell,W.H.,Craig,D.W.,Craig,I.W.,Crosbie,J.,Cuccaro,M.L.,Curtis,D.,Czamara,D.,Datta,S.,Dawson,G.,Day,R.,DeGeus,E.J.,Degenhardt,F.,Djurovic,S.,Donohoe,G.J.,Doyle,A.E.,Duan,J.,Dudbridge,F.,Duketis,E.,Ebstein,R.P.,Edenberg,H.J.,Elia,J.,Ennis,S.,Etain,B.,Fanous,A.,Farmer,A.E.,Ferrier,I.N.,Flickinger,M.,Fombonne,E.,Foroud,T.,Frank,J.,Franke,B.,Fraser,C.,Freedman,R.,Freimer,N.B.,Freitag,C.M.,Friedl,M.,Frisen,L.,Gallagher,L.,Gejman,P.V.,Georgieva,L.,Gershon,E.S.,Geschwind,D.H.,Giegling,I.,Gill,M.,Gordon,S.D.,Gordon-Smith,K.,Green,E.K.,Greenwood,T.A.,Grice,D.E.,Gross,M.,Grozeva,D.,Guan,W.,Gurling,H.,DeHaan,L.,Haines,J.L.,Hakonarson,H.,Hallmayer,J.,Hamilton,S.P.,Hamshere,M.L.,Hansen,T.F.,Hartmann,A.M.,Hautzinger,M.,Heath,A.C.,Henders,A.K.,Herms,S.,Hickie,I.B.,Hipolito,M.,Hoefels,S.,Holmans,P.A.,Holsboer,F.,Hoogendijk,W.J.,Hottenga,J.J.,Hultman,C.M.,Hus,V.,Ingason,A.,Ising,M.,Jamain,S.,Jones,E.G.,Jones,I.,Jones,L.,Tzeng,J.Y.,Kahler,A.K.,Kahn,R.S.,Kandaswamy,R.,Keller,M.C.,Kennedy,J.L.,Kenny,E.,Kent,L.,Kim,Y.,Kirov,G.K.,Klauck,S.M.,Klei,L.,Knowles, J.A., Kohli,M.A.,Koller,D.L.,Konte,B.,Korszun,A.,Krabbendam,L.,Krasucki,R.,Kuntsi,J.,Kwan,P.,Landen,M.,Langstrom,N.,Lathrop,M.,Lawrence,J.,Lawson,W.B.,Leboyer,M.,Ledbetter,D.H.,Lee,P.H.,Lencz,T.,Lesch,K.P.,Levinson,D.F.,Lewis,C.M.,Li,J.,Lichtenstein,P.,Lieberman,J.A.,Lin,D.Y.,Linszen,D.H.,Liu,C.,Lohoff,F.W.,Loo,S.K.,Lord,C.,Lowe,J.K.,Lucae,S.,MacIntyre,D.J.,Madden,P.A.,Maestrini,E.,Magnusson,P.K.,Mahon,P.B.,Maier,W.,Malhotra,A.K.,Mane,S.M.,Martin,C.L.,Martin,N.G.,Mattheisen,M.,Matthews,K.,Mattingsdal,M.,McCarroll,S.A.,McGhee,K.A.,McGough,J.J.,McGrath,P.J.,McGuffin,P.,McInnis,M.G.,McIntosh,A.,McKinney,R.,McLean,A.W.,McMahon,F.J.,McMahon,W.M.,McQuillin,A.,Medeiros,H.,Medland,S.E.,Meier,S.,Melle,I.,Meng,F.,Meyer,J.,Middeldorp,C.M.,Middleton,L.,Milanova,V.,Miranda,A.,Monaco,A.P.,Montgomery,G.W.,Moran,J.L.,Moreno-De-Luca,D.,Morken,G.,Morris,D.W.,Morrow,E.M.,Moskvina,V.,Muglia,P.,Muhleisen,T.W.,Muir,W.J.,Muller-Myhsok,B.,Murtha,M.,Myers,R.M.,Myin-Germeys,I.,Neale,M.C.,Nelson,S.F.,Nievergelt,C.M.,Nikolov,I.,Nimgaonkar,V.,Nolen,W.A.,Nothen,M.M.,Nurnberger,J.I.,Nwulia,E.A.,Nyholt,D.R.,O’Dushlaine,C.,Oades,R.D.,Olincy,A.,Oliveira,G.,Olsen,L.,Ophoff,R.A.,Osby,U.,Owen,M.J.,Palotie,A.,Parr,J.R.,Paterson,A.D.,Pato, C.N., Pato, M.T.,Penninx,B.W.,Pergadia,M.L.,Pericak-Vance,M.A.,Pickard,B.S.,Pimm,J.,Piven,J.,Posthuma,D.,Potash,J.B.,Poustka,F.,Propping,P.,Puri,V.,Quested,D.J.,Quinn,E.M.,Ramos-Quiroga,J.A.,Rasmussen,H.B.,Raychaudhuri,S.,Rehnstrom,K.,Reif,A.,Ribases,M.,Rice,J.P.,Rietschel,M.,Roeder,K.,Roeyers,H.,Rossin,L.,Rothenberger,A.,Rouleau,G.,Ruderfer,D.,Rujescu,D.,Sanders,A.R.,Sanders,S.J.,Santangelo,S.L.,Sergeant,J.A.,Schachar,R.,Schalling,M.,Schatzberg,A.F.,Scheftner,W.A.,Schellenberg,G.D.,Scherer,S.W.,Schork,N.J.,Schulze,T.G.,Schumacher,J.,Schwarz,M.,Scolnick,E.,Scott,L.J.,Shi,J.,Shilling,P.D.,Shyn,S.I.,Silverman,J.M.,Slager,S.L.,Smalley,S.L.,Smit,J.H.,Smith,E.N.,Sonuga-Barke,E.J.,StClair,D.,State,M.,Steffens,M.,Steinhausen,H.C.,Strauss,J.S.,Strohmaier,J.,Stroup,T.S.,Sutcliffe,J.S.,Szatmari,P.,Szelinger,S.,Thirumalai,S.,Thompson,R.C.,Todorov,A.A.,Tozzi,F.,Treutlein,J.,Uhr,M.,vandenOord,E.J.,VanGrootheest,G.,VanOs,J.,Vicente,A.M.,Vieland,V.J.,Vincent,J.B.,Visscher,P.M.,Walsh,C.A.,Wassink,T.H.,Watson,S.J.,Weissman,M.M.,Werge,T.,Wienker,T.F.,Wijsman,E.M.,Willemsen,G.,Williams,N.,Willsey,A.J.,Witt,S.H.,Xu,W.,Young,A.H.,Yu,T.W.,Zammit,S.,Zandi,P.P.,Zhang,P.,Zitman,F.G.,Zollner,S.,InternationalInflammatoryBowelDiseaseGenetics,C.,Devlin,B.,Kelsoe,J.R.,Sklar,P.,Daly,M.J.,O’Donovan,M.C.,Craddock,N.,Sullivan,P.F.,Smoller,J.W.,Kendler,K.S.,andWray,N.R.(2013).Geneticrelationshipbetweenfivepsychiatricdisordersestimatedfromgenome-wideSNPs.Naturegenetics45,984-994,PMID:23933821.
Hartz,S.M.,Pato, C.N.,Medeiros,H.,Cavazos-Rehg,P.,Sobell,J.L.,Knowles, J.A.,Bierut,L.J.,Pato, M.T., for the GenomicPsychiatryCohort,C.,Abbott,C.,Azevedo,M.H.,Belliveau,R.,Bevilacqua,E.,Bromet,E.J.,Buckley,P.F.,Dewan,M.J.,Escamilla,M.A.,Fanous,A.H.,Fochtmann,L.J.,Kinkead,R.,Kotov,R.,Lehrer,D.S.,Macciardi,F.,Malaspina,D.,Marder,S.R.,McCarroll,S.A.,Moran,J.,Morley,C.P.,Nicolini,H.,Perkins,D.O.,Potkin,S.G.,Purcell,S.M.,Rakofsky,J.J.,Rapaport,M.H.,Scolnick,E.M.,Sklar,B.,Sklar,P.,Smoller,J.W.,Sullivan,P.F.,andVivar,A.(2014).ComorbidityofSeverePsychoticDisordersWithMeasuresofSubstanceUse.JAMApsychiatry,PMID:24382686.
Guffanti,G.,Torri,F.,Rasmussen,J.,Clark,A.P.,Lakatos,A.,Turner,J.A.,Fallon,J.H.,Saykin,A.J.,Weiner,M.,Initiative,A.t.A.s.D.N.,Vawter,M.P.,Knowles, J.A.,Potkin,S.G.,andMacciardi,F.(2013).IncreasedCNV-regiondeletionsinmildcognitiveimpairment(MCI)andAlzheimer’sdisease(AD)subjectsintheADNIsample.Genomics102,112-122,PMID:23583670.
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Davis,L.K.,Yu,D.,Keenan,C.L.,Gamazon,E.R.,Konkashbaev,A.I.,Derks,E.M.,Neale,B.M.,Yang,J.,Lee,S.H.,Evans,P.,Barr,C.L.,Bellodi,L.,Benarroch,F.,Berrio,G.B.,Bienvenu,O.J.,Bloch,M.H.,Blom,R.M.,Bruun,R.D.,Budman,C.L.,Camarena,B.,Campbell,D.,Cappi,C.,CardonaSilgado,J.C.,Cath,D.C.,Cavallini,M.C.,Chavira,D.A.,Chouinard,S.,Conti,D.V.,Cook,E.H.,Coric,V.,Cullen,B.A.,Deforce,D.,Delorme,R.,Dion,Y.,Edlund,C.K.,Egberts,K.,Falkai,P.,Fernandez,T.V.,Gallagher,P.J.,Garrido,H.,Geller,D.,Girard,S.L.,Grabe,H.J.,Grados,M.A.,Greenberg,B.D.,Gross-Tsur,V.,Haddad,S.,Heiman,G.A.,Hemmings,S.M.,Hounie,A.G.,Illmann,C.,Jankovic,J.,Jenike,M.A.,Kennedy,J.L.,King,R.A.,Kremeyer,B.,Kurlan,R.,Lanzagorta,N.,Leboyer,M.,Leckman,J.F.,Lennertz,L.,Liu,C.,Lochner,C.,Lowe,T.L.,Macciardi,F.,McCracken,J.T.,McGrath,L.M.,MesaRestrepo,S.C.,Moessner,R.,Morgan,J.,Muller,H.,Murphy,D.L.,Naarden,A.L.,Ochoa,W.C.,Ophoff,R.A.,Osiecki,L.,Pakstis,A.J.,Pato,M.T.,Pato,C.N.,Piacentini,J.,Pittenger,C.,Pollak,Y.,Rauch,S.L.,Renner,T.J.,Reus,V.I.,Richter,M.A.,Riddle,M.A.,Robertson,M.M.,Romero,R.,Rosario,M.C.,Rosenberg,D.,Rouleau,G.A.,Ruhrmann,S.,Ruiz-Linares,A.,Sampaio,A.S.,Samuels,J.,Sandor,P.,Sheppard,B.,Singer,H.S.,Smit,J.H.,Stein,D.J.,Strengman,E.,Tischfield,J.A.,ValenciaDuarte,A.V.,Vallada,H.,VanNieuwerburgh,F.,Veenstra-Vanderweele,J.,Walitza,S.,Wang,Y.,Wendland,J.R.,Westenberg,H.G.,Shugart,Y.Y.,Miguel,E.C.,McMahon,W.,Wagner,M.,Nicolini,H.,Posthuma,D.,Hanna,G.L.,Heutink,P.,Denys,D.,Arnold,P.D.,Oostra,B.A.,Nestadt,G.,Freimer,N.B.,Pauls,D.L.,Wray,N.R.,Stewart,S.E.,Mathews,C.A.,Knowles, J.A.,Cox,N.J.,andScharf,J.M.(2013).PartitioningtheheritabilityofTourettesyndromeandobsessivecompulsivedisorderrevealsdifferencesingeneticarchitecture.PLoSgenetics9,e1003864,PMID:24204291.
Hodges,L.M.,Fyer,A.J.,Weissman,M.M.,Logue,M.W.,Haghighi,F.,Evgrafov,O.,Rotondo,A.,Knowles, J.A., andHamilton,S.P.(2014).EvidenceforLinkageandAssociationofGABRB3andGABRA5toPanicDisorder.Neuropsychopharmacology:officialpublicationoftheAmericanCollegeofNeuropsychopharmacology,PMID:24755890.
Mattheisen,M.,Samuels,J.F.,Wang,Y.,Greenberg,B.D.,Fyer,A.J.,McCracken,J.T.,Geller,D.A.,Murphy,D.L.,Knowles, J.A.,Grados,M.A.,Riddle,M.A.,Rasmussen,S.A.,McLaughlin,N.C.,Nurmi,E.L.,Askland,K.D.,Qin,H.D.,Cullen,B.A.,Piacentini,J.,Pauls,D.L.,Bienvenu,O.J.,Stewart,S.E.,Liang,K.Y.,Goes,F.S.,Maher,B.,Pulver,A.E.,Shugart,Y.Y.,Valle,D.,Lange,C.,andNestadt,G.(2014).Genome-wideassociationstudyinobsessive-compulsivedisorder:resultsfromtheOCGAS.Molecularpsychiatry,PMID:24821223.
McGrath,L.M.,Yu,D.,Marshall,C.,Davis,L.K.,Thiruvahindrapuram,B.,Li,B.,Cappi,C.,Gerber,G.,Wolf,A.,Schroeder,F.A.,Osiecki,L.,O’Dushlaine,C.,Kirby,A.,Illmann,C.,Haddad,S.,Gallagher,P.,Fagerness,J.A.,Barr,C.L.,Bellodi,L.,Benarroch,F.,Bienvenu,O.J.,Black,D.W.,Bloch,M.H.,Bruun,R.D.,Budman,C.L.,Camarena,B.,Cath,D.C.,Cavallini,M.C.,Chouinard,S.,Coric,V.,Cullen,B.,Delorme,R.,Denys,D.,Derks,E.M.,Dion,Y.,Rosario,M.C.,Eapen,V.,Evans,P.,Falkai,P.,Fernandez,T.V.,Garrido,H.,Geller,D.,Grabe,H.J.,Grados,M.A.,Greenberg,B.D.,Gross-Tsur,V.,Grunblatt,E.,Heiman,G.A.,Hemmings,S.M.,Herrera,L.D.,Hounie,A.G.,Jankovic,J.,Kennedy,J.L.,King,R.A.,Kurlan,R.,Lanzagorta,N.,Leboyer,M.,Leckman,J.F.,Lennertz,L.,Lochner,C.,Lowe,T.L.,Lyon,G.J.,Macciardi,F.,Maier,W.,McCracken,J.T.,McMahon,W.,Murphy,D.L.,Naarden,A.L.,Neale,B.M.,Nurmi,E.,Pakstis,A.J.,Pato,M.T.,Pato,C.N.,Piacentini,J.,Pittenger,C.,Pollak,Y.,Reus,V.I.,Richter,M.A.,Riddle,M.,Robertson,M.M.,Rosenberg,D.,Rouleau,G.A.,Ruhrmann,S.,Sampaio,A.S.,Samuels,J.,Sandor,P.,Sheppard,B.,Singer,H.S.,Smit,J.H.,Stein,D.J.,Tischfield,J.A.,Vallada,H.,Veenstra-VanderWeele,J.,Walitza,S.,Wang,Y.,Wendland,J.R.,Shugart,Y.Y.,Miguel,E.C.,Nicolini,H.,Oostra,B.A.,Moessner,R.,Wagner,M.,Ruiz-Linares,A.,Heutink,P.,Nestadt,G.,Freimer,N.,Petryshen,T.,Posthuma,D.,Jenike,M.A.,Cox,N.J.,Hanna,G.L.,Brentani,H.,Scherer,S.W.,Arnold,P.D.,Stewart,S.E.,Mathews,C.A.,Knowles J.A.,Cook,E.H.,Pauls,D.L.,Wang,K.,andScharf,J.M.(2014).Copynumbervariationinobsessive-compulsivedisorderandtourettesyndrome:across-disorderstudy.JournaloftheAmericanAcademyofChildandAdolescentPsychiatry53,910-919,PMID:25062598.
Miller,J.A.,Ding,S.L.,Sunkin,S.M.,Smith,K.A.,Ng,L.,Szafer,A.,Ebbert,A.,Riley,Z.L.,Royall,J.J.,Aiona,K.,Arnold,J.M.,Bennet,C.,Bertagnolli,D.,Brouner,K.,Butler,S.,Caldejon,S.,Carey,A.,Cuhaciyan,C.,Dalley,R.A.,Dee,N.,Dolbeare,T.A.,Facer,B.A.,Feng,D.,Fliss,T.P.,Gee,G.,Goldy,J.,Gourley,L.,Gregor,B.W.,Gu,G.,Howard,R.E.,Jochim,J.M.,Kuan,C.L.,Lau,C.,Lee,C.K.,Lee,F.,Lemon,T.A.,Lesnar,P.,McMurray,B.,Mastan,N.,Mosqueda,N.,Naluai-Cecchini,T.,Ngo,N.K.,Nyhus,J.,Oldre,A.,Olson,E.,Parente,J.,Parker,P.D.,Parry,S.E.,Stevens,A.,Pletikos,M.,Reding,M.,Roll,K.,Sandman,D.,Sarreal,M.,Shapouri,S.,Shapovalova,N.V.,Shen,E.H.,Sjoquist,N.,Slaughterbeck,C.R.,Smith,M.,Sodt,A.J.,Williams,D.,Zollei,L.,Fischl,B.,Gerstein,M.B.,Geschwind,D.H.,Glass,I.A.,Hawrylycz,M.J.,Hevner,R.F.,Huang,H.,Jones,A.R.,Knowles, J.A.,Levitt,P.,Phillips,J.W.,Sestan,N.,Wohnoutka,P.,Dang,C.,Bernard,A.,Hohmann,J.G.,andLein,E.S.(2014).Transcriptionallandscapeoftheprenatalhumanbrain.Nature508,199-206,PMID:24695229.
Samuels,J.,Shugart,Y.Y.,Wang,Y.,Grados,M.A.,Bienvenu,O.J.,Pinto,A.,Rauch,S.L.,Greenberg,B.D.,Knowles, J.A.,Fyer,A.J.,Piacentini,J.,Pauls,D.L.,Cullen,B.,Rasmussen,S.A.,Stewart,S.E.,Geller,D.A.,Maher,B.S.,Goes,F.S.,Murphy,D.L.,McCracken,J.T.,Riddle,M.A.,andNestadt,G.(2014).Clinicalcorrelatesandgeneticlinkageofsocialandcommunicationdifficultiesinfamilieswithobsessive-compulsivedisorder:ResultsfromtheOCDCollaborativeGeneticsStudy.AmericanjournalofmedicalgeneticsPartB,Neuropsychiatricgenetics:theofficialpublicationoftheInternationalSocietyofPsychiatricGenetics165,326-336,PMID:24798771.
SchizophreniaWorkingGroupofthePsychiatricGenomics,C.(2014).Biologicalinsightsfrom108schizophrenia-associatedgeneticloci.Nature511,421-427,PMID:25056061.
Staab,T.A.,Evgrafov, O.,Knowles, J.A., and Sieburth, D.(2014).RegulationofSynapticnlg-1/NeuroliginAbundancebytheskn-1/NrfStressResponsePathwayProtectsagainstOxidativeStress.PLoSgenetics10,e1004100,PMID:24453991.
LaiY,KimS,VarkeyJ,LouX,SongJK,DiaoJ,Langen R,ShinYKNonaggregatedα-SynucleinInfluencesSNARE-DependentVesicleDockingviaMembraneBinding..Biochemistry.2014Jun24;53(24):3889-96.doi:10.1021/bi5002536.Epub2014Jun13.
AmbrosoMR,HegdeBG,Langen R.EndophilinA1inducesdifferentmembraneshapesusingaconformationalswitchthatisregulatedbyphosphorylation.ProcNatlAcadSciUSA.2014May13;111(19):6982-7.doi:10.1073/pnas.1402233111.Epub2014Apr28.
ShahC,HegdeBG,MorénB,BehrmannE,MielkeT,MoenkeG,SpahnCM,LundmarkR,DaumkeO, Langen R.Structuralinsightsintomembraneinteractionandcaveolartargetingofdynamin-likeEHD2.Structure.2014Mar4;22(3):409-20.doi:10.1016/j.str.2013.12.015.Epub2014Feb6.
ChengCY,VarkeyJ,AmbrosoMR, Langen R,HanS.Hydrationdynamicsasanintrinsicrulerforrefiningproteinstructureatlipidmembraneinterfaces.ProcNatlAcadSciUSA.2013Oct15;110(42):16838-43.doi:10.1073/pnas.1307678110.Epub2013Sep30.
WenT,HeS,AttenelloF,CenSY,Kim-TenserM,AdamczykP,AmarAP,SanossianN,Mack WJ.Theimpactofpatientageandcomorbiditiesontheoccurrenceof“neverevents”incerebrovascularsurgery:ananalysisoftheNationwideInpatientSample.JNeurosurg.2014Jun27:1-7.[Epubaheadofprint]
73
FY14 Faculty Publications
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ChangJJ,Mack WJ,SaverJL,SanossianNMagnesium:potentialrolesinneurovasculardisease..FrontNeurol.2014Apr15;5:52.doi:10.3389/fneur.2014.00052.eCollection2014.Review.
Tenser MS, Mack WJ.PlaqueMorphologyandEmbolicProtectionStrategiesinCarotidArteryStenting.WorldNeurosurg.2014Feb16.pii:S1878-8750(14)00153-3.doi:10.1016/j.wneu.2014.02.023.[Epubaheadofprint]Noabstractavailable.
LucasJ,Mack WJ.Effectsofionizingradiationoncerebralvasculature.WorldNeurosurg.2014Mar-Apr;81(3-4):490-1.doi:10.1016/j.wneu.2014.01.006.Epub2014Jan18.
FargenKM,BlackburnS,DeshaiesEM,CarpenterJS,JabbourP,Mack WJ,RaiAT,SiddiquiAH,TurnerRD,MoccoJ.Finalresultsofthemulticenter,prospectiveAxiumMicroFXforEndovascularRepairofIntraCranialAneurysmStudy(AMERICA).JNeurointervSurg.2014Jan6.doi:10.1136/neurintsurg-2013-011049.[Epubaheadofprint]
LiuQ,HeS,GroysmanL,ShakedD,RussinJ,CenS,Mack WJ.WhitematterinjuryduetoexperimentalchroniccerebralhypoperfusionisassociatedwithC5deposition.PLoSOne.2013Dec30;8(12):e84802.doi:10.1371/journal.pone.0084802.eCollection2013.
Pease M, Ling C, Mack WJ, Wang K, Zada G.Theroleofepigeneticmodificationintumorigenesisandprogressionofpituitaryadenomas:asystematicreviewoftheliterature.PLoSOne.2013Dec18;8(12):e82619.doi:10.1371/journal.pone.0082619.eCollection2013.
He S, Pham MH, Pease M, Zada G,GiannottaSL,Wang K, Mack WJ.Areviewofepigeneticandgeneexpressionalterationsassociatedwithintracranialmeningiomas.NeurosurgFocus.2013Dec;35(6):E5.doi:10.3171/2013.10.FOCUS13360.Review.
ChangX,ShiL,GaoF,RussinJ,ZengL,HeS,ChenTC,GiannottaSL,WeisenbergerDJ,Zada G, Wang K, Mack WJ.Genomicandtranscriptomeanalysisrevealinganoncogenicfunctionalmoduleinmeningiomas.NeurosurgFocus.2013Dec;35(6):E3.doi:10.3171/2013.10.FOCUS13326.
Zada G,YasharP,RobisonA,WinerJ,KhalessiA,Mack WJ,GiannottaSL.Aproposedgradingsystemforstandardizingtumorconsistencyofintracranialmeningiomas.NeurosurgFocus.2013Dec;35(6):E1.doi:10.3171/2013.8.FOCUS13274.
ChandraRV,MeyersPM,HirschJA,AbruzzoT,EskeyCJ,HussainMS,LeeSK,NarayananS,BulsaraKR,GandhiCD,DoHM,PrestigiacomoCJ,AlbuquerqueFC,FreiD,KellyME,Mack WJ,PrideGL,JayaramanMVVertebralaugmentation:reportoftheStandardsandGuidelinesCommitteeoftheSocietyofNeuroInterventionalSurgery..SocietyofNeuroInterventionalSurgery.JNeurointervSurg.2014Jan;6(1):7-15.doi:10.1136/neurintsurg-2013-011012.Epub2013Nov6.Noabstractavailable.
ISchubergS,SongS,SaverJL,Mack WJ,CenSY,SanossianN.mpactofemergencymedicalservicesstrokeroutingprotocolsonPrimaryStrokeCentercertificationinCalifornia.Stroke.2013Dec;44(12):3584-6.doi:10.1161/STROKEAHA.113.000940.Epub2013Oct8.
GaoF,LinE,FengY,Mack WJ, Shen Y, Wang K.Characterizingimmunoglobulinrepertoirefromwholebloodbyapersonalgenomesequencer.PLoSOne.2013Sep13;8(9):e75294.doi:10.1371/journal.pone.0075294.eCollection2013.
MehtaV,Mack WJ.BalloonTestOcclusionintheSettingofVesselSacrifice:ProceduralRefinementsandAdjunctAssessmentMeasures..WorldNeurosurg.2013Sep11.pii:S1878-8750(13)01067-X.doi:10.1016/j.wneu.2013.08.036.[Epubaheadofprint]
FargenKM,BlackburnS,CarpenterJS,JabbourP,Mack WJ,RaiAT,SiddiquiAH,TurnerRD,MoccoJ.EarlyresultsoftheAxiumMicroFXforEndovascularRepairofIntraCranialAneurysm(AMERICA)study:amulticenterprospectiveobservationalregistry.JNeurointervSurg.2013Sep11.doi:10.1136/neurintsurg-2013-010887.[Epubaheadofprint]FY
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HeS,RussinJJ,AdamczykP,GiannottaSL,AmarAP,Mack WJ.APersistentPrimitiveHypoglossalArteryArisingfromtheExternalCarotidArteryAssociatedwithSubarachnoidHemorrhage.WorldNeurosurg.2013Jul9.pii:S1878-8750(13)00761-4.doi:10.1016/j.wneu.2013.06.015.[Epubaheadofprint]Review.
EdlundRK, Ohyama T,KantarciH,RileyBB,GrovesAK.(2014).FoxitranscriptionfactorspromotepharyngealarchdevelopmentbyregulatingformationofFGFsignalingcenters.Dev.Biol.390:1-13.PMCID:24650709
McGrathLM,YuD,MarshallC,DavisLK,ThiruvahindrapuramB,LiB,CappiC,GerberG,WolfA,SchroederFA,OsieckiL,O’DushlaineC,KirbyA,IllmannC,HaddadS,GallagherP,FagernessJA,BarrCL,BellodiL,BenarrochF,BienvenuOJ,BlackDW,BlochMH,BruunRD,BudmanCL,CamarenaB,CathDC,CavalliniMC,ChouinardS,CoricV,CullenB,DelormeR,DenysD,DerksEM,DionY,RosárioMC,EapenV,EvansP,FalkaiP,FernandezTV,GarridoH,GellerD,GrabeHJ,GradosMA,GreenbergBD,Gross-TsurV,GrünblattE,HeimanGA,HemmingsSM,HerreraLD,HounieAG,JankovicJ,KennedyJL,KingRA,KurlanR,LanzagortaN,LeboyerM,LeckmanJF,LennertzL,LochnerC,LoweTL,LyonGJ,MacciardiF,MaierW,McCrackenJT,McMahonW,MurphyDL,NaardenAL,NealeBM,NurmiE,PakstisAJ,Pato MT, Pato CN,PiacentiniJ,PittengerC,PollakY,ReusVI,RichterMA,RiddleM,RobertsonMM,RosenbergD,RouleauGA,RuhrmannS,SampaioAS,SamuelsJ,SandorP,SheppardB,SingerHS,SmitJH,SteinDJ,TischfieldJA,ValladaH,Veenstra-VanderWeeleJ,WalitzaS,WangY,WendlandJR,ShugartYY,MiguelEC,NicoliniH,OostraBA,MoessnerR,WagnerM,Ruiz-LinaresA,HeutinkP,NestadtG,FreimerN,PetryshenT,PosthumaD,JenikeMA,CoxNJ,HannaGL,BrentaniH,SchererSW,ArnoldPD,StewartSE,MathewsCA,KnowlesJA,CookEH,PaulsDL,WangK,ScharfJM.Copynumbervariationinobsessive-compulsivedisorderandtourettesyndrome:across-disorderstudy.JAmAcadChildAdolescPsychiatry.2014Aug;53(8):910-9.doi:10.1016/j.jaac.2014.04.022.Epub2014Jun24.
TGuffantiG,GaudiS,FallonJH,SobellJ,PotkinSG,Pato C,MacciardiF.ransposableelementsandpsychiatricdisorders.AmJMedGenetBNeuropsychiatrGenet.2014Apr;165B(3):201-16.doi:10.1002/ajmg.b.32225.Epub2014Feb28.
DavisLK,YuD,KeenanCL,GamazonER,KonkashbaevAI,DerksEM,NealeBM,YangJ,LeeSH,EvansP,BarrCL,BellodiL,BenarrochF,BerrioGB,BienvenuOJ,BlochMH,BlomRM,BruunRD,BudmanCL,CamarenaB,CampbellD,CappiC,CardonaSilgadoJC,CathDC,CavalliniMC,ChaviraDA,ChouinardS,Conti DV,CookEH,CoricV,CullenBA,DeforceD,DelormeR,DionY,EdlundCK,EgbertsK,FalkaiP,FernandezTV,GallagherPJ,GarridoH,GellerD,GirardSL,GrabeHJ,GradosMA,GreenbergBD,Gross-TsurV,HaddadS,HeimanGA,HemmingsSM,HounieAG,IllmannC,JankovicJ,JenikeMA,KennedyJL,KingRA,KremeyerB,KurlanR,LanzagortaN,LeboyerM,LeckmanJF,LennertzL,LiuC,LochnerC,LoweTL,MacciardiF,McCrackenJT,McGrathLM,MesaRestrepoSC,MoessnerR,MorganJ,MullerH,MurphyDL,NaardenAL,OchoaWC,OphoffRA,OsieckiL,PakstisAJ,Pato MT, Pato CN,PiacentiniJ,PittengerC,PollakY,RauchSL,RennerTJ,ReusVI,RichterMA,RiddleMA,RobertsonMM,RomeroR,RosàrioMC,RosenbergD,RouleauGA,RuhrmannS,Ruiz-LinaresA,SampaioAS,SamuelsJ,SandorP,SheppardB,SingerHS,SmitJH,SteinDJ,StrengmanE,TischfieldJA,ValenciaDuarteAV,ValladaH,VanNieuwerburghF,Veenstra-VanderweeleJ,WalitzaS,WangY,WendlandJR,WestenbergHG,ShugartYY,MiguelEC,McMahonW,WagnerM,NicoliniH,PosthumaD,HannaGL,HeutinkP,DenysD,ArnoldPD,OostraBA,NestadtG,FreimerNB,PaulsDL,WrayNR,StewartSE,MathewsCA,KnowlesJA,CoxNJ,ScharfJM.PartitioningtheheritabilityofTourettesyndromeandobsessivecompulsivedisorderrevealsdifferencesingeneticarchitecture.PLoSGenet.2013Oct;9(10):e1003864.doi:10.1371/journal.pgen.1003864.Epub2013Oct24.
ReesE,WaltersJT,ChambertKD,O’DushlaineC,SzatkiewiczJ,RichardsAL,GeorgievaL,Mahoney-DaviesG,LeggeSE,MoranJL,GenoveseG,LevinsonD,MorrisDW,CormicanP,KendlerKS,O’NeillFA,RileyB,GillM,CorvinA;WellcomeTrustCaseControlConsortium,SklarP, Hultman C, Pato C, Pato M,SullivanPF,GejmanPV,McCarrollSA,O’DonovanMC,OwenMJ,KirovG.CNVanalysisinalargeschizophreniasampleimplicatesdeletionsat16p12.1andSLC1A1andduplicationsat1p36.33andCGNL1.HumMolGenet.2014Mar15;23(6):1669-76.doi:10.1093/hmg/ddt540.Epub2013Oct26.
deCandiaTR,LeeSH,YangJ,BrowningBL,GejmanPV,LevinsonDF,MowryBJ,HewittJK,GoddardME,O’DonovanMC,PurcellSM,PosthumaD;InternationalSchizophreniaConsortium;MolecularGeneticsofSchizophreniaCollaboration,VisscherPM,WrayNR,KellerMC.AdditivegeneticvariationinschizophreniariskissharedbypopulationsofAfricanandEuropeandescent.AmJHumGenet.2013Sep5;93(3):463-70.doi:10.1016/j.ajhg.2013.07.007.Epub2013Aug15.
AZhaoZ,WebbBT,JiaP,BigdeliTB,MaherBS,vandenOordE,BergenSE,AmdurRL,O’NeillFA,WalshD,ThiseltonDL,ChenX,Pato CN;InternationalSchizophreniaConsortium,RileyBP,KendlerKS,FanousAH.ssociationstudyof167candidategenesforschizophreniaselectedbyamulti-domainevidence-basedprioritizationalgorithmandneurodevelopmentalhypothesis.PLoSOne.2013Jul29;8(7):e67776.doi:10.1371/journal.pone.0067776.Print2013.
GomesJB,VanNoppenB,Pato M,BragaDT,MeyerE,BortoncelloCF,CordioliAV.Patientandfamilyfactorsassociatedwithfamilyaccommodationinobsessive-compulsivedisorder.PsychiatryClinNeurosci.2014Aug;68(8):621-30.doi:10.1111/pcn.12172.Epub2014Apr13.
Peti-Peterdi J,BurfordJL,HacklMJ.Cankidneyregenerationbevisualized?NephronExpNephrol.2014;126(2):86.doi:10.1159/000360673.Epub2014May19.
BurfordJL,VillanuevaK,LamL,Riquier-BrisonA,HacklMJ,PippinJ,ShanklandSJ, Peti-Peterdi J.Intravitalimagingofpodocytecalciuminglomerularinjuryanddisease.JClinInvest.2014May1;124(5):2050-8.doi:10.1172/JCI71702.Epub2014Apr8.
ADaSaccoS,LemleyKV,SedrakyanS,ZanussoI,PetrosyanA,Peti-Peterdi J,BurfordJ,DeFilippoRE,PerinL.novelsourceofculturedpodocytes.PLoSOne.2013Dec12;8(12):e81812.doi:10.1371/journal.pone.0081812.eCollection2013.
HacklMJ,BurfordJL,VillanuevaK,LamL,SusztákK,SchermerB,BenzingT,Peti-Peterdi J.Trackingthefateofglomerularepithelialcellsinvivousingserialmultiphotonimaginginnewmousemodelswithfluorescentlineagetags.NatMed.2013Dec;19(12):1661-6.doi:10.1038/nm.3405.Epub2013Nov24.
SvenningsenP,BurfordJL,Peti-Peterdi J.ATPreleasingconnexin30hemichannelsmediateflow-inducedcalciumsignalinginthecollectingduct.FrontPhysiol.2013Oct16;4:292.doi:10.3389/fphys.2013.00292.eCollection2013.
MiyashitaT,BurfordJL,HongYK,GevorgyanH,LamL,MoriN,Peti-Peterdi J.Localizationandproliferationoflymphaticvesselsinthetympanicmembraneinnormalstateandregeneration.BiochemBiophysResCommun.2013Oct25;440(3):371-3.doi:10.1016/j.bbrc.2013.09.054.Epub2013Sep19.
GueutinV,ValletM,JayatM,Peti-Peterdi J,CornièreN,LevielF,SohetF,WagnerCA,EladariD,ChambreyR.Renalβ-intercalatedcellsmaintainbodyfluidandelectrolytebalance.JClinInvest.2013Oct1;123(10):4219-31.doi:10.1172/JCI63492.Epub2013Sep24.
KishoreBK,ZhangY,GevorgyanH,KohanDE,SchiedelAC,MüllerCE,Peti-Peterdi J.Cellularlocalizationofadeninereceptorsintheratkidneyandtheirfunctionalsignificanceintheinnermedullarycollectingduct.AmJPhysiolRenalPhysiol.2013Nov1;305(9):F1298-305.doi:10.1152/ajprenal.00254.2013.Epub2013Aug28.
76
FY14 Faculty Publications
ShenH,GiordanoF,WuY,ChanJ,ZhuC,MilosevicI,WuX,YaoK,ChenB,BaumgartT,Sieburth D,DeCamilliP.Couplingbetweenendocytosisandsphingosinekinase1recruitment.NatCellBiol.2014Jul;16(7):652-62.doi:10.1038/ncb2987.Epub2014Jun15.
Wang H, Sieburth D.PKAcontrolscalciuminfluxintomotorneuronsduringarhythmicbehavior.PLoSGenet.2013;9(9):e1003831.doi:10.1371/journal.pgen.1003831.Epub2013Sep26.
ChanJP,StaabTA,WangH,MazzasetteC,ButteZ,Sieburth D.ExtrasynapticmuscarinicacetylcholinereceptorsonneuronalcellbodiesregulatepresynapticfunctioninCaenorhabditiselegans.JNeurosci.2013Aug28;33(35):14146-59.doi:10.1523/JNEUROSCI.1359-13.2013.
Siemer AB(2014)AntifreezeProteinsbySolid-stateNMR:MethodsandApplications.eMagRes,3,153–160
Siemer AB (2013)MagicAngleSpinningSolid-StateNMRonProteins.EncyclopediaofBiophysics
ZhouM,LiangF,XiongXR,LiL,LiH,XiaoZ, Tao HW, Zhang LI.Scalingdownofbalancedexcitationandinhibitionbyactivebehavioralstatesinauditorycortex.NatNeurosci.2014Jun;17(6):841-50.doi:10.1038/nn.3701.Epub2014Apr20.
LiYT,LiuBH,ChouXL,Zhang LI, Tao HW.StrengtheningofDirectionSelectivitybyBroadlyTunedandSpatiotemporallySlightlyOffsetInhibitioninMouseVisualCortex.CerebCortex.2014Mar20.[Epubaheadofprint]
LiLY,XiongXR,IbrahimLA,YuanW, Tao HW, Zhang LIDifferentialReceptiveFieldPropertiesofParvalbuminandSomatostatinInhibitoryNeuronsinMouseAuditoryCortex..CerebCortex.2014Jan14.[Epubaheadofprint]
XiongXR,LiangF,LiH,MesikL,ZhangKK,PolleyDB,Tao HW,XiaoZ,Zhang LI.Interauralleveldifference-dependentgaincontrolandsynapticscalingunderlyingbinauralcomputation.Neuron.2013Aug21;79(4):738-53.doi:10.1016/j.neuron.2013.06.012.
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Li LY, Li YT, Zhou M, Tao HW, Zhang LI.Intracorticalmultiplicationofthalamocorticalsignalsinmouseauditorycortex.NatNeurosci.2013Sep;16(9):1179-81.doi:10.1038/nn.3493.Epub2013Aug11.
LiYT,IbrahimLA,LiuBH,Zhang LI, Tao HW.Lineartransformationofthalamocorticalinputbyintracorticalexcitation.NatNeurosci.2013Sep;16(9):1324-30.doi:10.1038/nn.3494.Epub2013Aug11.
WangSZ,IbrahimLA,KimYJ,GibsonDA,LeungHC,YuanW,ZhangKK,Tao HW, Ma L, Zhang LI.Slit/Robosignalingmediatesspatialpositioningofspiralganglionneuronsduringdevelopmentofcochlearinnervation.JNeurosci.2013Jul24;33(30):12242-54.doi:10.1523/JNEUROSCI.5736-12.2013.
Ma WP, Li YT, Tao HW.Downregulationofcorticalinhibitionmediatesoculardominanceplasticityduringthecriticalperiod..JNeurosci.2013Jul3;33(27):11276-80.doi:10.1523/JNEUROSCI.5598-12.2013.
GateD,DanielpourM,RodriguezJr.J,KimG-B,LevyR,BannykhS,BreunigJJ,KaechS,FlavellRA,andTown T.TCellTGF-βSignalingAbrogationRestrictsMedulloblastomaProgression(2014).PNAS,inpress.
WeitzTM,GateD,Rezai-ZadehK,Town T.MyD88isdispensableforcerebralamyloidosisandneuroinflammationinAPP/PS1transgenicmice(2014).AmericanJournalofPathology,inpress.
LokappaSB,SukJE,BalasubramanianA,SamantaS,SituAJ,Ulmer TS.Sequenceandmembranedeterminantsoftherandomcoil-helixtransitionofα-synuclein.JMolBiol.2014May15;426(10):2130-44.doi:10.1016/j.jmb.2014.02.024.Epub2014Mar6.
SamantaS,SituAJ,Ulmer TS.Structuralcharacterizationoftheregulatorydomainofbraincarnitinepalmitoyltransferase1.Biopolymers.2014Apr;101(4):398-405.doi:10.1002/bip.22396.
MazumderP,SukJE,Ulmer TS.Insightintoα-synucleinplasticityandmisfoldingfromdifferentialmicellebinding.JPhysChemB.2013Oct3;117(39):11448-59.doi:10.1021/jp402589x.Epub2013Sep12.
JiaH,GuoY,ZhaoW,Wang K.Long-rangePCRinnext-generationsequencing:comparisonofsixenzymesandevaluationontheMiSeqsequencer.ScientificReports,4:5737,2014(PMID:25034901)
McGrathLM,YuD,MarshallC,DavisLK,ThiruvahindrapuramB,Wang K,ScharfJM.Copynumbervariationinobsessive-compulsivedisorderandTourettesyndrome:Across-disorderanalysisstudy.JournaloftheAmericanAcademyofChildandAdolescentPsychiatry,53:910-919,2014(PMID:25062598)
WeiWH,GuoY,KindtA,MerrimanTR,SempleCA,Wang K,HaleyCS.Abundantlocalinteractionsinthe4p16.1regionsuggestfunctionalmechanismsunderlyingSLC2A9associationswithhumanserumuricacid.HumanMolecularGenetics,pii:ddu227,2014(PMID:24821702)
JagerM,Wang K,BauerS,SmedleyD,KrawitzP,RobinsonPN.Jannovar:AJavaLibraryforExomeAnnotation.HumanMutation,35:548-555,2014(PMID:24677618)
St.PourcainB,SkuseDH,MandyWP,Wang K,HakonarsonH,TimpsonNJ,EvansDM,KempJP,RingSM,McArdleWL,GoldingJ,DaveySmithG.Variabilityinthecommongeneticarchitectureofsocial-communicationspectrumphenotypesduringchildhoodandadolescence.MolecularAutism,5:18,2014(PMID:24564958)
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LingC,PeaseM,ShiL,PunjV,ShiroishiMS,ComminsD,WeisenbergerDJ,Wang K, Zada G.APilotGenome-ScaleProfilingofDNAMethylationinSporadicPituitaryMacroadenomas:AssociationwithTumorInvasionandHistopathologicalSubtype.PLoSONE,9:e96178,2014(PMID:24781529)
WangL,SwierczekSI,HickmanK,WalkerK,Wang K,DrummondJ,DoddapaneniH,MuznyDM,GibbsRA,WheelerDA,PrchalJT.TherelationshipofJAK2V617FandacquiredUPDatchromosome9pinpolycythemiavera.Leukemia,28:938-941,2014(PMID:24463469)
RobinsonP,KöhlerS,OellrichA,SangerMouseGeneticsProject,Wang K,MungallC,LewisSE,WashingtonN,BauerS,SeelowDS,KrawitzP,GilissenC,HaendelM,SmedleyD.Improvedexomeprioritizationofdiseasegenesthroughcrossspeciesphenotypecomparison.GenomeResearch,24:340-348,2014(PMID:24162188)
ChenG,ChangX,CurtisC,Wang K.PreciseinferenceofcopynumberalterationsintumorsamplesfromSNParrays.Bioinformatics,29:2964-2970,2013(PMID:24021380)
St.PourcainB,WhitehouseAJ,AngWQ,WarringtonNM,GlessnerJT,Wang K,TimpsonNJ,EvansDM,KempJP,RingSM,McArdleWL,GoldingJ,HakonarsonH,PennellCE,SmithGD.Commonvariationcontributestothegeneticarchitectureofsocialcommunicationtraits.MolecularAutism,4:34,2013(PMID:24047820)
Gao F, Ling C, Shi L, Commins D, Zada G, Mack W, Wang K.Inversion-mediatedgenefusioninvolvingNAB2-STAT6inanunusualmalignantmeningioma.BritishJournalofCancer,109:1051-1055,2013(PMID:23860521)
ShiM,InnK-S,YangA,ZhaoZ,LiangQ,VersteegGA,Amini-Bavil-OlyeeS,WongL-Y,ChoH,Zlokovic BV,ParkS-H,García-SastreA,JungJ.(2014)NegativeregulationofNF-αBactivitybybrain-specificTRIpartiteMotifprotein9NatureCommunications5:4820(DOI:10.1038/ncomms5820)
WinklerEA,SagareAP,Zlokovic BV(2014)Thepericyte:aforgottencelltypewithimportantimplicationsforAlzheimer’sdisease?BrainPathol24,371-386.
MontineTJ,KoroshetzW,BabcockD,DicksonD,GalpernW,GlymourMM,GreenbergS,HuttonM,KnopmanD,KuzmichevA,ManlyJ,MarderK,MillerB,PhelpsC,SeeleyW,SieberB-A,SilverbergN,SutherlandM,TorborgC,WaddyS, Zlokovic BV,CorriveauRAfortheADRD2014ConferenceCommittee(2014).RecommendationsoftheAlzheimer’sDisease-RelatedDementiasConferenceNeurology83(9):851-60.
Zhao Z, Zlokovic BV.Blood-brainbarrier:aduallifeofMFSD2A?Neuron.2014May21;82(4):728-30.doi:10.1016/j.neuron.2014.05.012.
WinklerEA,SengilloJD,SagareAP,ZhaoZ,MaQ,ZunigaE,WangY,ZhongZ,SullivanJS,GriffinJH,ClevelandDW,Zlokovic BV.Blood-spinalcordbarrierdisruptioncontributestoearlymotor-neurondegenerationinALS-modelmice.ProcNatlAcadSciUSA.2014Mar18;111(11):E1035-42.doi:10.1073/pnas.1401595111.Epub2014Mar3.
SagareAP,BellRD,ZhaoZ,MaQ,WinklerEA,RamanathanA,Zlokovic BV(2013)PericytelossinfluencesAlzheimer-likeneurodegenerationinmiceNatureCommunications4:2932(DOI:10/1038/ncomms3932)
HallidayMR,PomaraN,SagareAP,Mack WJ,FrangioneB,Zlokovic BV(2013)ElevatedcyclophilinAlevelsandmatrixmetalloproteinase-9activityincerebrospinalfluidofcognitivelynormalapolipoproteinE4carrierscorrelatewithblood-brainbarrierbreakdownJAMANeurol70(9),1198-1200.
FY14 Faculty Publications
SagareA,BellR,SrivastavaA,SengilloJ,SinghI,NishidaY,ChowN, Zlokovic, BV(2013)AlipoproteinreceptorclusterIVmutantpreferentiallybindsamyloid-bandregulatesitsclearancefromthemousebrainJBiolChem288,15154-15166. WangY,ZhaoZ,ChowN,RajputPS,GriffinJH,LydenPD, Zlokovic BV.ActivatedproteinCanalogprotectsfromischemicstrokeandextendsthetherapeuticwindowoftissue-typeplasminogenactivatorinagedfemalemiceandhypertensiverats.Stroke.2013Dec;44(12):3529-36.doi:10.1161/STROKEAHA.113.003350.Epub2013Oct24.
HallidayMR,PomaraN,SagareAP,Mack WJ,FrangioneB,Zlokovic BV.Relationshipbetweencyclophilinalevelsandmatrixmetalloproteinase9activityincerebrospinalfluidofcognitivelynormalapolipoproteine4carriersandblood-brainbarrierbreakdown.JAMANeurol.2013Sep1;70(9):1198-200.doi:10.1001/jamaneurol.2013.3841. LydenP,LevyH,WeymerS,PryorK,KramerW,GriffinJH,Zlokovic BV(2013)Phase1,safety,tolerabilityandpharmacokineticsof3K3A-APCinhealthyadultvolunteers.CurrentPharmDesign19,no.42(2013):7479–7485. MosnierLO,FernándezJA,DavisTP,Zlokovic BV,GriffinJH(2013)Influenceofthe3K3A-activatedproteinCvariantontheinvitrofibrinolyticactivityoftPAThrombosisHemostasis(11(11):2059-62.doi:10.1111/jth.12400.PMID:24034518
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FY14 Faculty Publications
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ZNIAdministration
Nearly300peopleworkattheZilkhaNeurogeneticInstitute(ZNI)—faculty,postdoctoralfellows,staff,studentsandvisitors—allofwhomreceivesupportfromateamoftalentedindividualswhohavethecollectivegoalofreducingtheadministrativeburdenasmuchaspossiblesothesciencemaythrive.
ThesenioradministrativeofficerforZNIisDavid Warren whooverseesallday-to-dayactivitiesattheZNI,managingmultiplebudgetsandprovidingfinancialreporting,supervisingtheareasofpayroll/personnel,grantsmanagement,purchasing,facilities,constructionandequipmentacquisition.Davidactivelyparticipatesinfacultyrecruitment,publicrelations,funddevelopmentandsuperintendsZNI’sprogrammaticeventsforallfaculty,staff,studentsandvisitors.DavidworkscloselywithDrZlokovictoestablishstrategiesdesignedtoservethemissionoftheinstitute,aswellassetandenforceprocessestoensureeffectiveandefficientoperations.Thispastyear,amongotherprojects,DavidworkedcloselywithKeckResearchAdvancementandKeckPublicRelationsandMarketingtorevampandredesigntheZNIwebsite,whichisexpectedtore-launchinearly2015.
Davidisgreatlyassistedbyastrongteamofpeoplewhodeploytheirskillsandexpertisetoprovideworld-classsupportforourworld-classresearchers.Barbara Lockley,OfficeManagerandHomeDepartmentCoordinator,managesallaspectsofpayrollandHR.USCrolledoutanewintegratedpayrollsystem,thefirstinover30years,andBarbaraspentmuchof2014becominganexpertinWorkday.BarbaraalsoworkscloselywithMarlen Turcios who monitors graduate student set-ups,submitsvisasandpreparesfacultydossiers.Marlensplitmuchofhertimein2014helpingestablishandtracksubcontractsaswellasprepareandapproveeffortreportingacrosssponsoredprojectsforinternalandexternalcertification.Rusty KingistheFacilitiesManagerforour125,000sqftbuilding,supervisingallservices,construction,remodelsandmoveswhilealsoensuringsmoothandsafeinstallationandoperationofavarietyofspecializedequipment,frommicroscopesandlaserstoNMRs.RustyworkscloselywithcolleaguesinmanycentraldepartmentsandoverseestheglasswareandautoclavecorefortheInstituteaswell.
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FY14 Operating Budget Forward Income From FY13 ExpensesBalance
Program Funds (Endowment) $2,417,995$1,126,514*$3,113,951$430,559
Departmental Funds(KSOM-Provided) Administrative $506,851 N/A $511,469 $(4,618)Facilities $150,000 N/A $156,388 $(6,388) DeansDevelopmentFunds $1,350,402 N/A $1,339,396$11,006 Philanthropy UnrestrictedGifts $674,450 $188,364$665,048$197,766
*includes $976,041 for solid-state NMR encumbered in FY12, expensed in FY14
Gabriela Torresmanagesallpre-andpost-awardgrantsmanagement,providingindividualsupportforeachPI:analyzingguidelinesfrommultiplesources,preparingbudgets,submittinggrantsandadministeringnearly100sponsoredprojectsatanytime,fromproposaltoclose-out.Leslie Ortiz waspromotedin2014toBudget/BusinessAnalyst.LeslieemployseMarketandKualiamongothersystemstoprepareorapprovepurchasingorders;sheanalyzespoliciestomanagethetravelandreimbursementsforpersonnelacross30laboratories.LeslieengagesanetworkofUSCdepartmentstoensurePIsareabletoaccessoftenuniquesuppliesfromavarietyofvendors.Briana Armour recentlyjoinedZNIasaProjectSpecialistforDrZlokovic,assistingwithhiscalendar,meetingsaswellascoordinatingcomplexprograms.
AspecialthankstoJulie Carl,ProjectSpecialistwhocoordinatesZNISeminars,Symposiaandspecialevents.JuliecollectsandassemblesthecontentforZNIpublications,includingprograms,posters,emailblasts,website,promotionalitems,ournewslettersandthisannualreport,frequentlypartneringwithKeckPRonlayoutanddesign.
ZNI Administration
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Photocred
it:SteveCoh
n
MrSelimZilkhawelcomesDrZachHallatthe4thAnnualZachHallLectureatZNIwhileUSCUniversityProfessorJeanShihlookson.
Hazel BreenservesasExecutiveDirectorofDevelopmentattheKeckSchoolofMedicine,undertheKeckMedicineInitiativeforneurosciences.TheZilkhaNeurogeneticInstituteisanintegralpartofabroaderUSCneuroscienceinitiativethatisexploringnewwaystoexaminenervoussystemfunctioninordertobetterunderstandtheunderlyingcausesofneurologicalandpsychiatricdisorders.Atthisworld-classcenterforresearchexcellence,USCfaculty,fellowsandgraduatestudentsarereachingacrossboundariestoembracemethodsandtechniquesfromotherfieldsofstudytodiscoverinnovativecuresandtreatmentforneurogeneticdiseasessuchasAlzheimer’s,Parkinson’s,MultipleSclerosisandmanyotherdevastatingillnesses.
UndertheKeckMedicineInitiative,theZilkhaNeurogeneticInstitutefundraisingprioritiesinclude:• SeedfundingtoallowZNIinvestigatorstopursueinnovativeresearch,leadingtofurtherexternalsponsoredprojectsupport• Graduateandpostdoctoralfellowshipstoassistintherecruitmentofclinicalandresearchleadersofthehighestdistinctionwhoshareourvisionofexcellenceandinnovation• Coreresearchfacilitieswithstate-of-theartequipmentandlaboratories
Giftsandgrantshelpusmeetournation’sgrowingdemandtoimprovethequalityoflifeforindividualsandsocietybypromotinghealth,preventingandcuringdiseaseandadvancingmedicalresearch.Byapplyingemergingtechnologiesandforgingnewpartnershipsandcollaborations,ZNIinvestigatorswillcontinuetoleadKeckMedicineofUSCintotheforefrontofmedicalresearchandtreatment.Wehopeyouwilljoinusincontributingtothefutureoftransformativemedicineandpatientcare.
PleasecontactHazelBreenathbreen@usc.eduorat(323)442-2684ifyouwouldlikemoreinformationregardingselectresearchfundingandcapitalnamingopportunities.
ZNIDevelopment
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ZilkhaNeurogeneticInstitute1501 San Pablo StreetLosAngeles,CA90033
Phone:(323)442-2144Fax:(323)442-2145Email:zni@usc.eduwww.usc.edu/zni
©2014KeckMedicineofUSC
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