Neurogenetic InstituteZilkha20

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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

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“Thehumanbrainisthemostcomplicatedbiologicalstructureintheknownuniverse.

We’veonlyjustscratchedthesurfaceinunderstandinghowitworksor,unfortunately,

doesn’tquiteworkwhendisordersanddiseaseoccur.”

—FrancisS.CollinsMDPhD,Director,NationalInstitutesofHealth(NIH)

2

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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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

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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

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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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Robert Chow, cont’d

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

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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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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%

45

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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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.

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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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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]

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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