fda commissioner's fellowship program class of 2010

FDA Commissioner’s Fellowship Program Class of 2010

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FDACommissioner’sFellowshipProgram

2010Fellows

Ali,Akhtar……………………………………………. 7 Imam,Syed……………………………………...… 26

Bailey,Alexander…………………………………. 8 Karmakar,Sudipan…………………………….. 27

Betz,Martha………………………………………… 9 Kuate,Seraphin…………………………………. 28

Bewernitz,Michael………………………………. 10 Kwegyir‐Afful,Ernest……………………….... 29

Bright,Patricia…………………………………….. 11 Li,Xingfang……………………………………….. 30

Buchholz,Annemarie…………………………… 12 McDowell,Tzu‐Yun……………………………. 31

Chen,Xinrong………………………………………. 13 Mi,Zenghui………………………………………... 32

Conenello,Gina…………………………………….. 14 Mokhtarzadeh,Maryam……………………... 33

Cruz‐Fisher,Maria……………………………….. 15 Nemecek,Julie………………………………….... 34

Damdinsuren,Bazarragchaa…………………. 16 Olumee‐Shabon,Zohra……………………….. 35

Ding,Hongliu……………………………………….. 17 Piao,Yun‐Shang…………………………………. 39

Ge,Yun………………………………………………… 18 Pierce,Sarah……………………………….……... 37

Gerson,Jason……………………………………….. 19 Robinson,Rebecca……………………………... 38

Gokulan,Kuppan………………………………….. 20 Simpson,Natalie………………………………... 39

Grasso,Elizabeth………………………………….. 21 Song,Wei…………………………………………... 40

Gupta,Shikha……………………………………….. 22 Swain,Marla…………………………………...…. 41

Hellberg,Rosalee…………………………………. 23 Zhichkin,Pavel…………………………………… 42

Howard,Kristina………………………………….. 24

Hu,Haijing…………………………………………… 25

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FDACommissioner’sFellowshipProgram

2010Preceptors

Abernethy,Darrell………..………………….….. 44 Luccioli,Stefano…………………………………. 63

Beland,Frederick………………………………… 45 Luke,Markham………………………………….. 64

Binienda,Zbigniew……………………………… 46 Madabushi,Rajanikanth…………………….. 65

Boehmer,Jamie…………………………………… 47 Mallis,Elias……………………………………….. 66

Brynes,Andrew…..………………………………. 48 Martin,William………………………………….. 67

Chen,Tao……………………………………………. 49 Nagaich,Akhilesh………………………………. 68

Chu,Pak‐Sin……………………………………….. 50 Nagaraj,Srinidhi………………………………… 69

Davidson,Maureen…………………………….. 51 Nelson,Robert…………………………………… 70

Durfor,Chalres…………………………………… 52 Pogribny,Igor……………………………………. 71

Foley,Steven………………………………………. 53 Ragheb,Jack……………………………………… 72

Fuscoe,James……………………………………… 54 Resier,Jakob……………………………………… 73

Gardner,John……………………………………… 55 Salminen,William……………………………… 74

Gobburu,Joga……………………………………… 56 Serabian,Mercedes…………………………….. 75

Goering,Peter…………………..………………… 57 Tolnay,Mate………………………………………. 76

Gregori,Luisa……………………………………… 58 Tortorello,MaryLou………………………….. 77

Hart,Mark………………..………………………… 59 Willams‐Hill,Donna…………………………… 78

Jackson,Lauren…………………………………… 60 Xu,Nancy……………..……………………………. 79

Larkin,John………………………………………… 61 Yancy,Haile……………………………………….. 80

Lazarus,Ellen……………………………………… 62

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CBERPreceptor FellowAndrewP.Byrnes GinaConenelloLuisaGregori JulieNemecekEllenF.Lazarus Yun‐shangPiaoJakobReiser SeraphinKuateCDERPreceptor FellowDarrellR.Abernethy PavelZhichkinJogaGobburu MichaelBewernitzRajanikanthMadabushi Tzu‐YunChang‐McDowellAkhileshK.Nagaich SudipanKarmakarJackA.Ragheb KristinaHowardMateTolnay BazarrgchaaDamdinsurenNancyXu ZenghuiMiCDRHPreceptor FellowPeterL.Goering MarthaBetzMarkhamC.Luke MaryamMokhtarzadehSrinidhiNagaraja ShikhaGuptaCFSANPreceptor FellowLaurenS.Jackson ElizabethGrassoJohnW.Larkin HongliuDingStefanoLuccioli ErnestKwegyir‐AffulMaryLouTortorello AnnemarieBuchholz CVMPreceptor FellowJamieL.Boehmer ZohraOlumee‐ShabonPak‐SinChu WeiSongMaureenK.Davidson MariaCruz‐FisherHaileYancy MarlaSwain

FDACommissioner’sFellowshipProgram2010PreceptorsandFellowsbyCenter

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NCTRPreceptor FellowZbigniewBinienda SyedImamTaoChen XinrongChenStevenL.Foley KuppanGokulanJamesC.Fuscoe YunGeMarkHart HaijingHuWilliamSalminen AliAkhtarFrederickA.Belandand NatalieSimpsonIgorP.PogribnyOCPreceptor FellowJohnW.Gardner XingfangLiRobertM.Nelson JasonGerson andPatriciaBright ORAPreceptor FellowWilliamB.Martin SarahPierceDonnaWilliams‐Hill RosaleeHellbergRegenerativeMedicineProjectPreceptor FellowCharlesN.Durfor, AlexanderBaileyEliasMallis,and andRebeccaRobinsonMercedesA.Serabian

FDACommissioner’sFellowshipProgram2010PreceptorsandFellowsbyCenter

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FDACommissioner’sFellowshipProgram2010Fellows

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Scienti icandProfessionalBackground2007‐2010 VisitingAssistantProfessor,UniversityofArkansas:LittleRock2007‐2010 ORISEFellow,NationalCenterforToxicologicalResearch2005‐2006 SeniorScientist,NeoPharm,Inc.2000‐2005 ResearchInstructor,UAMS1997‐2000 ResearchScientist,MedicalCollegeofGeorgia1995‐1997 PostdoctoralResearchAssociate,YaleUniversitySchoolofMedicine1993‐1995 PostdoctoralResearchAssociate,UniversityofNorthCarolina:ChapelHill1990‐1991 PostdoctoralFellow,CreightonUniversitySchoolofMedicine1990 Ph.D.Chemistry,LucknowUniversity ResearchInterestsMyacademicinterestsencompassmajorareasofbiochemistry,cellandmolecularbiology,andtoxicol‐ogy.Researchinterestsincludepharmacokineticandtoxicologicalevaluationsofxenobiotics,therapeu‐ticef icacyandtoxicitydeterminations forpreclinicalassessmentofsyntheticdrugs forosteoporosisandcancertreatments.Lately,myeffortshavebeenfocusedonhealthbene its,andsideeffectsofherb‐al dietary supplements used asweight loss products and alternative products for arthritis.With theabundance of con licting information available about dietary supplements, it is utmost important toevaluate their complete toxicity pro iles and determine safety, ef icacy andmechanism of action ofthesecompounds.Commissioner’sFellowshipProjectOverviewAssessmentofAcetaminopheninducedliverinjuryandin luenceofdietarysupplements:potentialsyner-gisticinteractions.Acetaminophen(APAP),alsocalledasParacetamol(4'‐hydroxyacetanilide,N‐acetylp‐aminophenol),isa widely used over‐the‐counter (OTC) analgesic and antipyretic drug. It is a leading cause of drug‐inducedliverinjury(DILI)intheUS.ArecentFDAAdvisoryCommitteerecommendedloweringthedai‐lytherapeuticdoseofAPAPinordertoreducethehighnumberofDILI.Ithasbeenhypothesizedthatexposure to dietary supplements (DS) contributes to the high number of APAP DILI cases since DScausevariouspharmacologicaland toxicologicaleffects that couldact synergisticallywithAPAP.TheobjectiveofthisstudyistoscreeninvitroandinvivotoxicologicalaffectsofAPAPaloneandincombi‐nationwith ivecommonlyusedDSnamelyblackcohosh,ginkgobiloba,greentea,kavaandusnicacid.Anumberofparameters/pathwayswill be evaluated to identify themechanismsof toxicityofAPAPandDSaloneandincombinationofboth.

AkhtarAli,Ph.D.

NationalCenterforToxicologicalResearch

Preceptor:WilliamSalminen,Ph.D.

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Scienti icandProfessionalBackground2009‐2010 PostdoctoralResearchFellow,FredHutchinsonCancerResearchCenter2008‐2009 PostdoctoralResearchFellow,UniversityofVirginia2004‐2008 Ph.D.BiomedicalEngineering,UniversityofVirginia2000‐2004 B.S.MechanicalEngineering,TuftsUniversityResearchInterestsMyprimary research interestsare in theareasofadult stemcellsand theiruse in regenerativemedicine,aswellasthedevelopmentofmulti‐scalecomputationalmodelstounderstandcomplexbiological phenomena. Primarily, this has focused on identi ication of rate‐limiting steps in thetraf ickingoftherapeuticallydeliveredstemcellstositesofischemicinjury.Otherareasofinterestincludeadipose‐derivedstemcells,micro‐vascularremodeling,andprostatecancermetastasis.Commissioner’sFellowshipProjectOverviewEvaluation of tumorigenicity risk in cell-based regenerativemedicine products:Preclinical reviewpractice,productriskstrati ication,andenhancementofFDAreviewThe ieldofregenerativemedicine israpidlyprogressing,andmanyinnovativecell‐basedthera‐piesarebeingdevelopedforthetreatmentofseriousconditions.However,fortheseinvestigation‐alproductsmanyofthebiologicalpropertiesthatprovidefortheregenerationofmissing,injured,ordiseasedtissues–self‐renewal,plasticity,andhighratesofproliferation–alsoraiseconcernsoftumor formation following administration. Prior to initiation of a irst‐in‐human clinical trial,theseconcernsmustbeaddressed throughacomprehensivesafetyassessment.For theseprod‐uctshowever,thedevelopmentofastandardandprescribedpreclinicalprogramtoevaluatetu‐morigenicpotentialisdif icult.Inpart,thisisduetothevarietyandcomplexityofcell‐basedprod‐ucts,aswellasalackofclearunderstandingofproductcharacteristicsthatmaybepredictiveoftumorigenicity.Asaresult,thedesignandreviewofthesestudiesarecurrentlyconductedusingacase‐by‐case approach. Thismulti‐center project will evaluate current scienti ic and regulatoryknowledgerelatedtothetumorigenicityofcell‐basedproducts,includingrisk‐factorsandthepre‐clinicalmodels,endpoints,andstudydesignsthatareusedintumorigenicitystudiestoassessthisrisk.Theprojectwillreviewdatafrombothscienti icliteratureandregulatorysubmissions.Thereviewandevaluationofthisdatawillthenhelpinformregulatorydecisionsrelatedtotumorigen‐icityriskandtheevaluationoftumorigenicitystudieswithintheagency.Projectdeliverableswillhelptomaximizethesafetyofnewcell‐basedtherapies,ensureregulatoryreviewpracticescon‐tinuetore lectthebestavailablescience,andfosterinnovationbyprovidingamorepredictableandtransparentregulatorypathway.

AlexanderBailey,Ph.D.

CenterforDevicesandRadiologicalHealthandCenterforBiologicsEvaluationandResearch

Preceptors:CharlesDurfor,Ph.D.,EliasMallis,B.S.,and

MercedesA.Serabian,M.S.,D.A.B.T

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Scienti icandProfessionalBackground2009 Ph.D.Bioengineering,UniversityofMaryland2004 B.S.ChemicalEngineering,TuftsUniversityResearchInterestsPreviouslymyresearchhasfocusedontissueengineeringstrategiesfortheregenerationofcraniofacialboneusingnovelhydrogelscaffolds.Injuriestocraniofacialboneareofin‐terestbecausethebodylacksanappropriateresponseforregenerationtypicallyformingscar tissueratherthan load‐bearingbone. Engineereddegradablehydrogelscanhaveasigni icant impactoncellpopulations,speci icallyhavingprofoundeffectsonexpressionandtransportofendogenoussignalingmolecules,proliferation,migration,anddifferentia‐tion. I investigated their use in promoting differentiation of mesenchymal stem cellsthroughincreasedosteogenicsignalinganddemonstratedenhancedboneregenerationinorbital loordefects.Commissioner’sFellowshipProjectOverviewInvitroandinvivotoxicityofnanomaterialsassociatedwithFDA-regulatedproducts

Whilenanotechnologyhasmadegreatprogress in recent yearsdemonstratingdevelop‐mentofnewproducts,thereisarelativelackofinformationrelatingtothesafetyofnano‐materials. The purpose of my fellowship project is to investigate properties of nano‐materials toelucidatewhat role theymayplay inadversehealtheffects. Currently, theFDAdoesnotfollowthestandardde initionofnanotechnologyasmaterialswithatleastonedimensionof1‐100nanometers,andinsteadrecognizesthatlarger(>100nm)parti‐clesmay possess unique properties similar to nano‐sizedmaterials. Therefore,my re‐searchprojectinvolvesinvestigatingthetoxicologicaleffectsofnanotosub‐micronparti‐cleswith speci ic emphasis onneuronal cell toxicity, systemic distribution pro iles, andabilitytocrosstheplacentalbarrier.TheknowledgegainedinthisprojectwillassistFDAreview scientists in assessing the safety of medical products which incorporate engi‐neerednanomaterialsorgenerateparticulateweardebris. Theprojectwillalsocontrib‐ute to thedevelopment of consensus standards and guidancedocuments by identifyingthemostcriticalphysicochemicalpropertiesandrelevanttestmethodsforassessingthesafetyandef icacyofnanomaterialsusedinFDA‐regulatedproducts.

MarthaBetz,Ph.D.

CenterforDevicesandRadiologicalHealth

Preceptor:PeterGoering,Ph.D.

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Scienti icandProfessionalBackground2008‐2010 Post‐DoctoralAssociate,UniversityofFlorida2008 Ph.D.Engineering,UniversityofFlorida2007 M.S.Engineering,UniversityofFlorida2002 B.S.ChemicalEngineering,MichiganStateUniversityResearchInterestsMycurrentresearchinterestsaremodelingofdrugactivity,diseaseprogression,clinicaltrialsorcombinationsthereoftohelpdesignbetterclinicaltrialsandoptimizedosing.Mydoctoralresearchfocusedoncharacterizingtheelectroencephalogrampro ilechangesin‐ducedbyvagusnervestimulationtherapyinpatientswithepilepsy.Mypost‐doctoralre‐searchfocusedonanalyzingtheeffectsofavigilance‐promotingdrugonelectroencepha‐logram recordings in sleep‐deprived healthy volunteers using pharmacokinetic/pharmacodynamicmodeling. I hope tobuild onmy interests andgain experiencewhileconductingpharmacometricanalysesattheFDA.Commissioner’sFellowshipProjectOverviewPharmacometricAnalysisofClinicalDataMy fellowship project focuses on the application of statisticalmodeling and simulationtechniquestoanalyzeclinicaldatainordertoassessdrugsafetyandef icacypro iles.Ex‐amplesincludepopulationpharmacokinetic/pharmacodynamicmodelingandsimulation,thoroughQTprolongation analysis, and exposure‐response analysis of available clinicaldata.Thespeci icaimistoutilizepharmacometricanalysismethodsonclinicaldatainor‐der to further our understanding of this strategy for enhancing the regulatory decisionmakingprocess.

MichaelBewernitz,Ph.D.

CenterforDrugEvaluationandResearch

Preceptor:JogaGobburu,Ph.D.

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Scienti icandProfessionalBackground2006 Faculty,JohnsHopkinsUniversity,SchoolofMedicine2003 ResearchAssociate,JohnsHopkinsUniversity,SchoolofMedicine2003 Ph.D.Epidemiology,UniversityofNorthCarolina,SchoolofPublicHealth2000 B.S.N.Nurse(RN),UniversityofMaryland,SchoolofNursing1993 M.S.P.H.Epidemiology,UniversityofNorthCarolina,SchoolofPublicHealth1986 B.A.Biology,MountHolyokeCollegeResearchInterestsIaminterestedinethicalissuesthatariseduringclinicaltrials,particularlythoseinvolvinginfants,children,andpregnantwomen,andespeciallyininterculturalandinternationalsettings. Myre‐centworkinvolvedcollaboratinginAfricawithUgandanandU.S.investigatorstoorganize,train,supervise, and report adverse events in clinical trials assessing prevention strategies to reducematernal‐to‐childHIVtransmission.Myworkincludedoversightofthe irstpediatricHIVvaccinetrial inAfrica. Formypriordoctoralwork, Ihadcarriedouta longitudinalstudy inaculturallyandeconomicallydiversepopulationofAmericanwomen(includingadolescents). Thisobserva‐tionalstudyinvestigatedpossiblesideeffectsofmedicationsonwomen’shealth.Commissioner’sFellowshipProjectOverviewImplementingPediatricResearchEthicsinResourceLimitedSettingsHistorically, research studies evaluating medication safety and ef icacy did not enroll children.However,manyexpertsnowrecognizetheimportanceofthedatathatpediatricclinicalresearchcan generate concerning the safety and effectiveness of FDA‐regulated products in children ‐‐whentemperedbyacarefulassessmentofethicalconsiderations.Thereareamultitudeofethicalchallenges,however,when implementing suchclinical trials. Often implementershave tomakedif icult judgmentsandweighcomplextrade‐offs. Inresourcelimitedsettings,expertisetosup‐portsuchdecisionmakingmaybeconstrainedandtheclinicaltrialsmayposeadditionalethicalcomplexities.Wewillexplorerisktopediatricparticipantsinforeignclinicalstudies.Wewillalsoexaminetheroleoftheresearchstudyclinicianinthecontextofinadequatelocalcapacity/healthcareinfrastructureandwillfocusontheethicsofancillarycareobligations. Ouranalysiswillbedisseminatedsoastoserveasaresourceforthosedesigning,implementingandoverseeingpedi‐atricresearchinresourcelimitedsettings.

PatriciaBright,Ph.D.

Of iceoftheCommissioner

Preceptor:Robert“Skip”Nelson,M.D.,Ph.D.

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Scienti icandProfessionalBackground2010 Ph.D.FoodScience,MichiganStateUniversity2007 LaboratoryTechnician,EasternRegionalResearchCenter2006 B.S.BiotechnologyandMicrobiology,Rutgers:theStateUniversityofNewJerseyResearchInterestsMycurrentresearchinterestsareintheareaofmicrobialfoodsafety,speci icallyfocusingonthedetection,transferandsurvivaloffoodbornepathogens.Pastprojectshaveincluded:comparingtheef icacyofperoxy‐aceticacidandchlorinetreatmentforthereductionofSalmonellaonalfalfaseed,evaluatingtheeffectofSimulatedGastricFluidandBileSaltsonthegrowthofListeriamono-cytogeneswhengrownonfrankfurtersandReady‐to‐Eatturkey,improvingthetechniqueandtyp‐ingstrainsofStaphylococcusaureusbypulsed‐ ieldgelelectrophoresis(PFGE),studyingtheef ica‐cyofcommercialsanitizersduringleafygreenprocessing,typingListeriamonocytogenesbyPFGEandserotyping,andisolating,identifyinganddeterminingthethermalresistanceofgas‐producingmicroorganismsinmaraschinocherries.MydoctoralworkfocusedonthetransferofEscherichiacoliO157:H7toleafygreensduringsimulatedcommercialprocessing.Commissioner’sFellowshipProjectOverviewIndicatorMethodstoEvaluateProcessControlsforFreshProduceFreshproducehasbeenrecognizedasanimportantvehicleof foodborneillness inrecentyears,andnewapproachesareneededtoensuresafety.Microbiologicalmonitoringofthepre‐orpost‐harvestwatersmaybeausefulcomponentofriskreductionstrategies,butmoredataareneededtoverifyitseffectiveness.Themicrobiologicalqualityofwateriscurrentlyevaluatedforfecalcon‐taminationthroughtheuseofbacterialindicators(fecalcoliforms,totalcoliforms,genericEsche-richiacolietc.)andbacteriophage(somaticcoliphage). Incorporatingmicrobiologicalmonitoringintofoodsafetyprogramsrequiresmuchtime,labor,andexpense.Methodsformicrobialindica‐torsmaybeused,butcanbelengthyanddif iculttoconduct,andtheircorrelationtothepresenceof pathogens is not alwaysupheld. Newautomated, quantitativemethods for indicator testing,havethepotentialtodecreaselaborandtimeofanalysisandimproveprocesscontrol.Anevalua‐tionofhowthesemethodsholdupunderconditionsthataffectthequalityandcharacteristicsofirrigationandproduceprocessingwater,speci icallyhighorganiccontent,backgroundmicro loraandsanitizers,isnecessary.Theobjectiveofthisstudyistoevaluatequantitativemicrobialwaterquality indicatormethods, for example, the bioMerieux TEMPO automatedMPNprocedure andthestandardEPAMPNprocedure, forenumeratingtotalaerobicbacteria,genericE.coli,Entero-bacteriaceaeandcoliphageinproduceirrigationandprocessingwatersforassessingwashingandsanitizationprocesscontrolsforfreshproduce.

AnnemarieBuchholz,Ph.D.

CenterforFoodSafetyandAppliedNutritionSummit‐Argo,IL

Preceptor:MaryLouTortorello,Ph.D.

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Scienti icandProfessionalBackground2009‐2010 Instructor,UniversityofArkansasforMedicalSciences2006‐2009 AssociateResearchAssistant,OklahomaMedicalResearchFoundation2006 Ph.D.Toxicology,OklahomaStateUniversity

ResearchInterestsMydoctoralresearchfocusedonthetranscriptionalregulationofaPhaseIIDrugmetabolismenzymeasso‐ciatedwithxenobioticdetoxi ication.Duringmypostdoctoralwork, I studied thehematopoietic stemcelldifferentiationandlineageinstabilityunderpathologicalconditionssuchasvirusinfection.Forthepast1.5years, Ihavebeeninvestigatingtheimportant functionofBandTlymphocytesinvolvedinestrogende i‐ciency and in lammation induced bone loss (osteoporosis) by using conditional knock‐out and immune‐de icientmousemodels.

Commissioner’sFellowshipProjectOverviewMicroRNA-34aMediateMutagenesisinaP53dependentwayMicroRNAs(miRNAs)aresmallnon‐codingregulatoryRNAmoleculesthatregulategeneexpressionatthepost‐transcriptionallevel.miR‐34aisatumorsuppressormiRNAwhoseexpressionisregulatedbythetu‐mor suppressor gene P53. The P53 gene responds to DNA damage, mutation induction and tumor for‐mation.TK6,WTK1,andNH32arehumanlymphoblastcelllinesderivedfromasameprogenitorwithdif‐ferentP53status:TK6withthewild‐typeP53genes,NH32withnullP53alleles,andWTK1withmutantformofP53.Previous studies showed that the spontaneous andmutagen‐inducedmutant frequencies inTK6andNH32cellsweresimilarwhiletheyweresigni icantlylowerthanthoseinWTK1cells.ItisunclearwhyNH32andWTK1cell lines,bothofwhichhavelostthe functionofP53,havesuchabigdifferenceintheirresponsetomutationinduction.Toelucidatethepossiblemechanismsinvolvedinthedifferentialmu‐tagenicresponsesamongthethreecelllines,wehypothesizethattheP53‐regulatedmiR‐34aisresponsiblefor thehighermutant frequency inWTK1cellsandwillexamine thishypothesisby conducting followingstudies.First,wewillmeasuretheexpressionlevelsofmiR‐34ainTK6,WTK1andNH32cells.Iftheexpres‐sionofmiR‐34ainthethreecelllinescorrelateswellwiththemutantfrequencyintherespectivecellline,wewillchallengethecellsusinggenotoxinsandcheckwhetherthegenotoxicstresswillresultinanychang‐esinmiR‐34aexpression.Second,bytransfectingeithermiR‐34ainhibitorsormiR‐34aprecursorsintothedifferentcells,wewillmanipulateexpressionofmiR‐34a in thecells todetermine theroleofmiR‐34a insuppressingmutationinduction.Finally,tode inethecellularpathwayinvolvedinthefunctionofmiR‐34a,wewill apply computational analysis to search possible target genes regulated bymiR‐34a and con irmthesetargetgenesexperimentally.OncethefunctionsofmiR‐34aiscon irmedtobecloselyrelatedtomuta‐tioninduction,thismolecularwillhavegreatpotentialtobeusedasabiomarkertoassessgenotoxicityofchemicalsandotheragents.

XinrongChen,Ph.D.


Preceptor:TaoChen,Ph.D.,D.A.B.T.

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Scienti icandProfessionalBackground2009‐2010 Postdoctoralresearchfellow,MountSinaiSchoolofMedicine2005‐2009 Ph.D.BiomedicalScience,MountSinaiSchoolofMedicine2003‐2005 Post‐baccalaureatefellow,NewYorkStateDepartmentofHealth1999‐2003 B.S.BiochemistryandCellBiology,BucknellUniversityResearchInterestsMyresearchinterestslieinthe ieldsofvirologyandinfectiousdiseases.Ipursuedthisinterestasa ieldofstudydirectlyoutofcollegewith theNYSDept.ofHealthEmerging InfectiousDiseaseFellowship.ThereIgotmy irstchancetoworkwiththeFDAbyparticipatingintheRetailFoodStudy,whichsampledretailmeatproductsforantibiotic‐resistantbacterialpathogens.ItwasalsoattheNYSDept.ofHealththatIdevelopedandinterestandexpertiseinRNAviruses,particularlyin luenza.DuringmyfellowshipIconductedresearchonavianin luenzaandtheSARSvirus.En‐joyingthecomplexityoftherelativelysmallRNAvirusesImovedontograduateschooltostudyunderDr.PeterPalese.ThePaleselaboratoryhasalonghistoryofexcellenceinthein luenzare‐search ield,fromwhichIbene ittedgreatly.Mygraduateandpost‐doctoralworkfocusedonthePB1‐F2protein,anewlydiscoveredvirulencefactorofin luenzaAvirus.Myinterestscontinuetobeinin luenzavirus,butIameagertobranchoutintootherviralrespiratorypathogens.Mycur‐rentCommissioner’sFellowshipresearchwillfocusonadenovirus,anditsuseasagenetherapyvector.Commissioner’sFellowshipProjectOverviewImprovingadenovirusgenetherapyvectorsforsystemicuseTherearecurrentlyover80clinicaltrialsusingadenovirusvectorsforgenetherapy.Mostclinicaltrialsadministerviruslocally,withonlyahandfuldeliveringvirusintravenously(i.v.)becauseofsafetyandeffectivenessconcerns.Adenovirustargetstheliverwhenadministeredi.v.butmuchofthevirusiseliminatedbycellsintheliver.Manymorediseasescouldbetreatedifwecouldim‐provethesafetyandtargetabilityofadenovirusvectors.Thisworkwillstudyhowadenovirusliv‐ertargetingisaccomplishedandwhatfactorscanbeusedtoretargetthevirus.Adenovirushasahigh‐af initybindingsiteforcoagulationfactorX(FX),andthisisthoughttobeimportantforvirustargetingtotheliver.ThisprojectaimstodeterminethedomainsoftheFXproteinthatareessen‐tial for liver targeting. WewillmutateFXanddeterminehowFXinteractswithadenovirus, thecomplementsystem,andtheliver.Wewillalsodevelopnovelassaystoevaluatethecoatofplas‐maproteins(opsonins)thatimmediatelyattachestoadenovirusafteri.v.injection.Theresultsoftheseexperimentswillallowustodevisenewstrategiestode‐targetadenovirusvectorsfromtheliverandretargetthemtoothertissues.

GinaConenello,Ph.D.

CenterforBiologicsEvaluationandResearch

Preceptor:AndrewByrnes,Ph.D.

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Scienti icandProfessionalBackground2007‐2010 PostdoctoralScholar,UniversityofCalifornia2006 Ph.D.MicrobiologyandMolecularGenetics,RutgersUniversity2000 B.S.IndustrialMicrobiology,UniversityofPuertoRicoResearchInterestsIhavelongbeeninterestedinboththetheoreticalandappliedaspectsofmicrobiology.Thephysi‐calworldweexperienceappearsverydifferentatthemicrobiallevel.Thisisespeciallytrueofpar‐asiticand/orpathogenicorganisms,whomustcontinuouslyovercomehostdefensesforsurvival.Pharmacology provides compounds formicrobial control. However, lateral and horizontal genetransferendowsthesemicrobesanever‐evolvingarrayofbiochemicaltoolsforinactivatingthesecompounds. Althoughantibiotic resistancehadbeen largelystudiedonzoonoticpathogens,mymaingoalasaFDACommissioner’sFellowistostudythemechanismsofresistance,andunder‐standtheirevolutionarygenetransferamongveterinarypathogens.Commissioner’sFellowshipProjectOverviewAntibioticResistanceofCampylobacterspp.fromanimalsContaminationof foodwithCampylobacterspp. isoneof the leadingcausesof food‐borne infec‐tionsinhumansintheUnitedStates,withabout1.4millionclinicalcasesperyear.Inthelastcou‐pleofdecades,therehasbeenanincreaseofreportedantibioticresistance(AR)amongCampylo-bacter spp., especially tomacrolides and luoroquinolones, from human clinical cases and live‐stock. Thishas raisedconcernsbecausesomeof theseantibioticsalsoareused to treathumaninfections.MostoftheinformationaboutthedisseminationofCampylobacterspp.andthemecha‐nismsofARcomesfromstudiesofC.jejuniandC.coli,butlittleisknownabouttheseparametersinanimalhostsorinotherCampylobacterspp.TheCenterforVeterinaryMedicine/Of iceofRe‐search/DivisionofAnimalandFoodMicrobiology(CVM/OR/DAFM)hasrecentlyacquiredalargecollectionofisolatesofCampylobacterspp.whichspanthelast50years.Thiscollectionincludesisolatesfromthetimeperiodbeforeantibioticswerecommonlyusedfortreatmentorgrowthpro‐motioninfoodproductionanimals.Inourstudy,weareinterestedininvestigatingtheprevalenceandtemporalappearanceofAR inCampylobacterspp. toantibioticscommonlyused in the foodproductionanimalsand therelatedantimicrobialagentsused in treatmentofhuman infections.Ourspeci icobjectivesaretoidentifythespeciesandsubspeciesofeachisolateandtoperforminvitro antimicrobial susceptibility testing against a panel of antibiotics that are used in animalsOnceantibioticresistant isolatesare identi ied,wewillusemolecular techniques to identify thegenesresponsibleforARandtodeterminerelatednessoftheisolateswiththegoalofdeterminingwhetherthereisanevolutionarypatternofacquisitionofantibioticresistancethatcorrelateswiththeintroduction,orcommonuse,ofeachantibioticinanimals.

MariaCruz‐Fisher,Ph.D.

CenterforVeterinaryMedicine

Preceptor:MaureenK.Davidson,Ph.D.

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Scienti icandProfessionalBackground2006‐2010 Postdoctoralfellow,NationalInstituteonAging2005‐2006 JSPSPostdoctoralfellow,OsakaUniversity,Japan2005 Ph.D.OsakaUniversity,Japan1999‐2000 Residencyofsurgery,NationalCancerCenter,Mongolia1999 M.D.NationalMedicalUniversity,MongoliaResearchInterestsIhaveacombinationoftrainingasaMedicaldoctorandofresearchinthe ieldsofnormaland cancer cell biology, immunology and experimental oncology. My recent researchaimedtounderstandhowantigenrecognitionchangesBcellphysiology;includingaspectsofsignaltransductionandgeneregulation(includingroleofNF‐κBtranscriptionfactors),which affected B cell survival, differentiation, and interactionwith other immune cells.My graduate work focused on liver cancer biology and effectiveness of immune‐ andchemo‐therapyforthistypeofcancer.Inthefuture,Iaminterestedinworkinginareasofimmune cell biology, oncology or tumor immunology.Also in a broader range, I have alongstandinginterestinimprovingthehumanhealthbyaddressingef icacyandsafetyoftherapeuticagents.Commissioner’sFellowshipProjectOverviewThesignalingandfunctionofFc-receptorlike5proteininBlymphocytes.Many co‐receptors on immune cells deliver competing activating and inhibitory signalsthatareintegratedtobalancecellularresponsestoantigens.TheFcreceptor‐like(FCRL)familyofco‐receptorshasbeenproposedtomodulateantigenreceptorsignalingofBlym‐phocytes.TheaimofmyprojectistostudythefunctionofFCRL5inrelationwithitssig‐nalinginhumanBlymphocytes.Theproject’sspeci ictopicsare:(1)studythesignalingproperties of FCRL5 in interactionwith the antigen receptor andother co‐receptors, inparticularCD22,(2)studytherolesofFCRL5inBcellactivationandcellfatedetermina‐tion.ItishopedthatthesestudieswillexpandourunderstandingofFCRL5biology.Inad‐dition,ourstudiescouldcontributetoestablishingFCRL5asapotentialdiseasemarkeraswellasatherapeutictargetinBcellmalignancies.

BazarragchaaDamdinsuren,M.D.,Ph.D.


Preceptor:MateTolnay,Ph.D.

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Scienti icandProfessionalBackground2008 Ph.D.Clinical&PopulationHealthResearch,U.ofMassachusettsMedical

School2002 M.P.H.Epidemiology,UniversityofMassachusetts1998‐2005 PostdoctoralResearchAssociate,U.ofMassachusettsMedicalSchool1991 M.S.Pharmacology,ShanghaiSecondMedicalUniversity1985‐1988 Resident,TianchangCityHospital1985 M.D.Medicine,AnhuiMedicalUniversityResearchInterestsIamaphysicianandmedicalresearcherwithasystematictraininginbasicandclinicalsciencesaswellasexpertiseinepidemiologyandpublichealthresearch.AsanepidemiologistatBrighamandWomen’sHospital,HarvardMedicalSchool,Ihavebeenconductingclinicalresearchininvestigat‐inggeneticandenvironmentalriskfactorsandidentifyingbiomarkers/predictorsofdiseaserisk,progression,prognosis,andtreatmentef icacyforagingassociateddiseasesinpatients.Iaminter‐estedinexploringfoodanddrugsafetyrelatedresearchandhealthpolicyissuesatFDA.Usingabiostatisticalapproach,Iwillconductquantitativeriskanalysesandbuildassessmentmodelsforriskpredication and reductionbasedondata from laboratory experiments and epidemiologicalstudiesandreports.Commissioner’sFellowshipProjectOverviewEvaluationofriskmanagementoptionstoreducemicrobialhazardsinsproutsthroughquantitativeriskassessmentMicrobialhazardsthatoccurinanystepwithinthefoodsupplychaincanleadtopropagationofthe contamination and causewidespread foodborne illnesses. Sprouted seeds pose a particularconcernasthesameconditionsthatencouragegerminationandgrowthofseedsalsoencouragethegrowthofbacterialpathogens.Toprovidethesproutindustrywithascience‐basedapproachfor theselectionofoptimal riskmanagementprograms toensure foodsafety, this researchwilldevelopquantitativeriskassessmentmodelsthatcanbeusedtoevaluatedifferentriskmanage‐mentoptionsandtodeviseoptimizedsproutsupplychainfoodsafetyprograms.Aseriesofmod‐elswill be developed for assessing the risk associatedwithmicrobial contamination in sproutsandtheextentofriskreductionthatcanbeachievedthroughapplicationsofacombinationofmit‐igationstepsandmicrobialsamplingandtestingprograms.Thesemodelswillbeusedtoprioritizeriskinterventionstrategiesthatcanbeappliedateachstageofsproutproduction.

HongliuDing,M.D.,Ph.D.


Preceptor:JohnLarkin,Ph.D.

18

Scienti icandProfessionalBackground2004 B.S.UniversityofArkansasatLittleRock2003 Ph.D.UniversityofArkansasforMedicalScience1999 M.S.UniversityofArkansasforMedicalScience1991 M.D.BeijingMedicalUniversityResearchInterestsIearnedaPh.D. inpharmacology,amasterdegree inpharmaceuticalscience fromUniversityofArkansas forMedicalScience,andabachelordegree incomputerscience fromUniversityofAr‐kansas.IalsoobtainedmedicinedegreefromBeijingMedicalUniversity,China.Offeringanexcep‐tionaleducationalbackground,over5yearsofpost‐PhDpharmacology/toxicology,statistics,bio‐informatics (including SAS programming), and gene transcriptional research experience, I haveachievedastrongrecordofperformance in researchplanning,goal/objectivedevelopment,andbolsteringresearchsupportthroughnetworking.Commissioner’sFellowshipProjectOverviewSexandagerelatedtranscriptionalnetworksforgenescodingforhepaticphaseIandIImetabolismenzymesinratsSex‐andage‐dependentdrugtoxicitieshavebeenrecognizedbyregulatoryagenciesand,insomecases,havebeenshowntoberelatedtosex‐andage‐dependentexpressionofdrugmetabolizingenzymes (DMEs). Althoughsex‐andage‐dependent transcriptionof genesencodingDMEsmayunderlie these toxicities, themechanism(s)arenotcompletelyunderstood.Functionalgenomicsapproachesintoxicologicalresearchhaveprovidednewandinnovativestrategiestoaddresssex‐andage‐linkeddrugsafetyconcerns. Inthisstudy,wewillusecomputationalbioinformaticsap‐proachestocharacterizehepatictranscriptionalregulationnetworksforDMEgenesbasedonPCRvalidatedgeneexpressionsignaturesinmaleandfemaleratsaged2,5,6,8,15,21,52,78,and104weeks. Computational analysis of the promoter composition of drugmetabolism genes will beusedtodeducetheregulatorytranscriptionalnetworksthatmediatesex‐andage‐relateddiffer‐encesfortheseDMEs.Adetailedcharacterizationoftranscriptionalregulatorynetworksrespon‐siblefortheexpressionofhepaticphaseIandIImetabolismenzymeswillprovideafoundationforsupporting drug safety assessment, guiding the selection of sex‐ and age‐appropriate pharma‐cotherapy,andimprovingFDAregulatoryscience.

YunGe,M.D.,Ph.D.


Preceptor:JamesFuscoe,Ph.D.

19

Scienti icandProfessionalBackground2009 Ph.D.JohnsHopkinsBloombergSchoolofPublicHealth1996 A.B.BrownUniversityResearchInterestsTwointerestshaveledmetotheFDACommissioner’sFellowshipprogram.The irstisaninterestinevaluating thequalityandstrengthofevidence forregulatoryactionandpolicy‐making. I amparticularlyinterestedinquestionsconcerninghowtoincorporateevidenceofbiologicalmecha‐nismintheevaluationofemergingtherapies,orestablishedtherapiesforwhichtheempiricalevi‐denceisweak.Forexample,inpediatricresearch,therapeuticef icacymaydependonatrialbe‐ingconductedatanearlyagewhenpatientscanderivemaximumbene itfromthetherapy,beforediseaseprogressionreduceschancesforpreservingqualityoflife.Howshouldourinterpretationsofrisk–bene itanalysesbeaffectedbyevidenceofage‐relatedmechanisms?Mysecondinterestisintheethicalissuesarisingfrompediatricparticipationinclinicaltrials,particularlyfortreatmentofpediatricobesity.Obesityinterventionsincludeamixoflifestyle,pharmacologicalandsurgicalinterventions with varying degrees of safety and evidentiary support, particularly in pediatricpopulations.Iamespeciallyinterestedincomparativeregulatoryapproachestoobesity,inunder‐standinghowtheFDAanditsinternationalpartnersregulateinthecontextofbothscienti icun‐certaintyanddifferentprevailingculturalnorms.Commissioner’sFellowshipProjectOverviewLinkingRegulatoryScienceandEthicsinPediatricProductDevelopmentThecriticalneedforpediatricresearchondrugs,devices,andbiologicalproductsunderscorestheresponsibility to assure that children are enrolled in clinical research that is both scienti icallynecessaryandethicallysound.Theoverallaimofthisprojectistoproduceaconceptpapercon‐cerningethicalissuesinpediatricproductdevelopment.Indevelopingthisconceptpaper,wewillreviewawiderangeofethicalconsiderationsconcerningtheparticipationofchildren inclinicalresearch,including:themoralstatusofchildrenasavulnerablepopulation;theappropriatebal‐ance of risk and potential bene it in pediatric research; and ethical considerations underlyingstudydesign,includingthechoiceofcontrolgroupandclinicalequipoise.Theconceptpaperwillproposeabasicethical frameworktoguidepediatricresearch,andsuggesthowthis frameworkmightbe operationalized in linking regulatory science and ethics, an effort critical to the FDA’smission.

JasonGerson,Ph.D.


Preceptor:Robert“Skip”Nelson,M.D.,Ph.D.

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Scienti icandProfessionalBackground2000‐2010 SeniorResearchScientist,TexasA&MUniversity 1998‐2000 PostdoctoralResearchAssociate,TexasA&MUniversity1996‐1977 PostdoctoralFellow,UniversityofSaskatchewan1990‐1995 Ph.D.Immunology&Biochemistry,AllIndiaInstituteofMedicalSciencesResearchInterestsMylongtermcareergoalistoidentifyalternativedrugtargetsformulti‐drugresistantandpersistentbacterialpatho‐gensbyemployingastructuralandcomputationalbiologicalapproach.Ihaveauniquecombinationofresearchexperi‐enceinImmunology(developmentofsyntheticvaccineagainstHIV),MolecularBiology(cloningandsitedirectedmuta‐genesisofvirulentgenes),ProteinChemistry(puri icationofenzymes,refoldingandthermalshiftassay),andStructur‐alandComputationalBiology.MycurrentresearchisfocusedonutilizingX‐raycrystallographytechniquestosolvethecrystalstructuresofenzymesthatareinvolvedinfattyacidandaminoacidmetabolisms,andtoidentifyitsroleinthepersistenceofMycobacteriumtuberculosis.Iamalsointerestedinhighthroughputscreeningandidentifyingsmallmol‐eculesthatcouldpotentiallyactasantibacterialagents.Commissioner’sFellowshipProjectOverviewStructuralandFunctionalCharacterizationof(VirB4,VirB11andVirD4)PutativeATPasesoftype-IVSecretionSystemofSalmonellaentericaSerovarHeidelbergSalmonellaentericaisoneof themostcommoncausesof foodborne infectionsintheUnitedStates. Antimicrobialre‐sistanceamongthesebacterialpathogenscontinuestobeamajorpublichealthconcern.Anincreasingnumberofre‐portsofinfectionswithmulti‐drugresistantstrainsofS.entericaoverthelastfewdecadeshavelimitedourcapabilitytotreatinfections. Speci ically,S.entericaserovarHeidelbergisolatesfromhumansandpoultryareoftenresistanttocephalosporinsandotherantimicrobialagents,whichareimportantforthetreatmentofseverecasesofsalmonellosis.Recent studies have shown that S.entericaserovar Heidelbergisolates contains transmissible plasmids that containgenesimportantforvirulence,colonization,persistenceanddrugresistance.TheDNAsequenceanalysisofonesetoftheseplasmidsfromS.entericaserovarHeidelbergstrainsinourlaboratoryrevealedthepresenceofgenesthatencodetype‐IVsecretionsystem(T4SS).OtherbacterialspeciesemployT4SStoinjecttoxinsintothehostcells.MyresearchwillfocusoncharacterizationofT4SS‐containingplasmidsfrommulti‐drugresistantS.entericaserovarHeidelbergiso‐latestodeterminethepotentialroleoftheT4SSincolonization,invasionandthetransferplasmidscontainingantimi‐crobial resistanceand/orvirulencegenes. A furtherunderstandingof the involvementofplasmid‐encodedgenes inantimicrobialresistance,colonization,invasion,andformationofthesecretaryapparatuswillprovideanimprovedun‐derstandingofresistanceandmolecularmechanismofvirulence‐associatedsecretionbytheT4SS.Myprojectsgoalsaretwofold;1)tounderstandtheinvolvementofT4SSencodingplasmidsonthevirulenceofS.entericaserovarHeidel‐bergstrains,2)toresolvethestructureoftheputativeATPasesoftype‐IVsecretarysystem,whicharetheproteinsthatlikelyturnon/offtheabilityoftheT4SStosecretemoleculesfromthebacteriatohostorotherbacterialcells.Theout‐comeofthestudywilladdressseveralunresolvedquestionsofbacterialpathogenesisandtheidenti icationoftheputa‐tiveATPase structurewill help to identifypotential novel structurebaseddrug/inhibitor targets against pathogenicbacteria.

KuppanGokulan,Ph.D.


Preceptor:StevenLFoley,Ph.D.

21

Scienti icandProfessionalBackground2007‐2010 Ph.D.FoodScienceandTechnology,TheOhioStateUniversity2005‐2007 M.S.FoodScienceandNutrition,TheOhioStateUniversity2001‐2005 B.S.FoodScience,PennsylvaniaStateUniversityResearchInterestsMy research background has focused on food safety and foodmicrobiology. DuringmyM.S. Iworkedwithattenuatedtotalre lectanceinfraredspectroscopyasarapiddetectiontechniqueforthedifferentiationofendospore‐formingbacteria.Formydoctoraltraininginemergingfoodsafe‐ty issues I studied threenonthermal interventionstrategies;highpressureprocessing,electron‐beamirradiation,andtheuseofantimicrobialsurfacecoatingstominimizepathogenicfoodbornemicroorganisms.Commissioner’sFellowshipProjectOverviewSanitationandprocessingconditionstoreducetheriskofSalmonellacontaminationandtransferinnutbutterproductsContamination of peanut butter and nut butter products by pathogenic Salmonellaentericaserovarshaveledtoanincreasingnumberofproductrecallsandfoodborneoutbreaks.Postpro‐cessingcontaminationofpeanutbutterwillremainasigni icanthealthrisktoconsumersduetoinherentcharacteristicsofpeanutbutterproductswhichallowpathogenicmicroorganismstore‐mainviablethroughouttheshelflifeoftheproduct.Currentproceduresusedtocleanpeanutpro‐cessingequipmentmaynotbeeffectiveforeradicatingSalmonellapresentonequipmentsurfaces.Inaddition,informationislackingonthemechanismsbywhichpeanutbutterbecomescontami‐natedinthefoodprocessingenvironment.Thisprojectintendsto:1.)Determinethethermalre‐sistancesofSalmonellaculturesgrowninplanktonicandsessileenvironmentsaswellaslyophi‐lizedcellsinoculatedintopeanutbuttersamples;2.)Determinethecontaminationtransferratesbetweenuninoculatedpeanutbutterandfood‐contactmaterialspreviouslycontaminatedviaSal-monellabio ilms;3.)Determinetheef icacyofthepeanutbutter‘push‐through’methodforequip‐mentsanitationcurrentlyusedinthefoodindustryfollowingequipmentcontamination;4.)Evalu‐atecommonlyusedcommercialcleaningmethodsonSalmonellasurvivalusingcommercialpilotplantscaleprocessingequipment.

ElizabethGrasso,Ph.D.


Preceptor:LaurenJackson,Ph.D.

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Scienti icandProfessionalBackground2008‐2010PostdoctoralFellow,StateUniversityofNewYorkatStonyBrook2007‐2008Scienti icConsultant,SidleyAustin,LLP2002‐2008Ph.D.AppliedScienceandTechnology,UniversityofCaliforniaatBerkeley1997‐2001B.S.MaterialsScienceandEngineering,MassachusettsInstituteofTechnologyResearchInterestsAsaninterdisciplinaryscientist,Ihaveawide‐rangeofresearchinterestsattheintersectionofmaterials,mechanics,andmedicaldevices.Mydoctoralresearchfocusedonmicroscalebiomaterialscharacteriza‐tion of both natural and syntheticmaterials used in orthopaedic devices. I developed of experimentaltesting standards for biomaterials microindentation and numerical analysis methods that permit thequanti icationof thenonlinear, time‐dependentbehaviorofsoft,hydratedmaterials. Mypostdoctoraltraininghasalso focusedonorthopaedic tissues ‐ speci ically,howdifferent repetitivepatternsofme‐chanicalunloading(disuse)affectlong‐termboneandmusclequantity,quality,andstrength,howperi‐odsofrecoverybetweencyclesofdisusemayaffecttheseindices,andwhethernon‐pharmacologicinter‐ventionscanbeusedeffectivelytomitigatedisuse‐inducedmusculoskeletalatrophyCommissioner’sFellowshipProjectOverviewTheEffectsofPrestrainontheFatigueLifeofElectropolishedNitinolWiresOverthelastdecade,Nitinol,thenearlyequiatomicmetalalloyofnickelandtitanium,hasbecomeaubiq‐uitousbiomedicaldevicematerialduetoitsuniquematerialproperties.Nitinolhasbeenusedprimarilyincardiovasculardevicestodate,includingstents,endovasculargrafts,andvenacava ilters. Thesein‐travasculardevicesareloadbearing,andmaybesubjectedtomillionsofcyclesofmulti‐axialloadingin-vivo,makingthemsusceptibleto fatiguefailure. Designingagainstfatiguefailurenotonlydemandsanunderstandingofin‐serviceloads,butalsoofthematerial‐levelfatiguebehaviorofNitinolunderdiffer‐entmodesofdeformation.SinceNitinolispresentasthinwireinmanyofthesedevices,anunderstand‐ingofthemechanicalpropertiesinthewiregeometryisrequisite.Manyintravasculardevicesarenowimplanted using minimally invasive surgery in which the device must be crimped, or radially com‐pressed,ontoadeliverydevicesuchasacatheterbeforebeingbeinsertedordeployed.However,littleisknownabouttheeffectsofsuchcrimp‐inducedstrainonthefatigueperformanceoftheNitinol,and,con‐sequently,thedurabilityofthedevicein-vivo.Bendingisthepredominantmodeofdeformationexperi‐encedbythewiresduetocrimpingandpulsatileblood low.Thepresentprojectaimstoelucidatetheeffectsofprestrainonthelowandhigh‐cyclebendingfatiguelifeofNitinolwiresusingrotarybendtest‐ing.BetterknowledgeofthemechanicalbehaviorofNitinolwillinformthedevelopmentofmorerobusttestingstandards,provideinsightintothetypesofbenchtestsrequisiteforprovingthesafetyandef ica‐cyofdifferentNitinoldevices,andaidinidentifyingthemechanismsofpost‐marketfailures.

ShikhaGupta,Ph.D.


Preceptor:SrinidhiNagaraja,Ph.D.

23

Scienti icandProfessionalBackground2010 Post‐doctoralscholar,OregonStateUniversity2006‐2009 Ph.D.FoodScienceandTechnology,OregonStateUniversity 2004‐2006 M.S.FoodScienceandTechnology,OregonStateUniversity 1998‐2002 B.A.Biochemistry,Lewis&ClarkCollege

ResearchInterestsMyresearchinterestsencompassavarietyoftopics,includingfoodsafety,publichealth,andmo‐lecularbiology.ThefocusofmyPh.D.workwastoimproveuponanddevelopnovelmethodsfortheDNA‐basedidenti icationofcommercially‐importantseafoodspecies. Iemployedtechniquessuchaspolymerasechainreaction(PCR)‐restrictionfragmentlengthpolymorphism(RFLP),DNAbarcoding,andreal‐timemultiplexPCRto identifysalmonandtroutspecies incommercial foodproducts.Ihavealsoconductedanumberofstudiesexaminingthelevelsofnutrientsandheavymetalsinseafood.Asapost‐doctoralscholar,Iparticipatedinthedevelopmentofcommunicationmaterialsdesigned to informhealthcareprofessionals and theirpatients about thebene its andrisksofseafood.InmypositionasanFDACommissioner’sFellow,Iwillberesearchingthedetec‐tionofnorovirusandHepatitisAvirusinavarietyoffoodsystems.Commissioner’sFellowshipProjectOverviewDevelopmentofNovelMethodsfortheDetectionandCharacterizationofNorovirusNorovirusesaretheleadingcauseof foodborneillnessworldwide,withanestimated5.5millioncasesannuallyintheUnitedStates.ThecurrentmethodofusingDNAsequencingforcharacteri‐zationofnoroviruses inoutbreaksituationscanbeproblematicand time‐consumingdue to thehighdiversityofthenorovirusgenome.ThisCommissioner’sFellowshipprojectisfocusedonthedevelopmentofanovel,rapidmethodtodetectandcharacterizenorovirusesatthegenotypeandstrainlevel.ThismethodcombinesmultiplexPCRwithelectrosprayionizationmassspectrometrytodeterminetheuniquebasecompositionsoftargetorganisms.The irstphaseoftheprojectin‐volvesthedesignanddevelopmentofanassayplatetoallowfordifferentiationofnorovirusgeno‐typesandstrains,aswellasdetectionofHepatitisAvirus.Followingdevelopment,theassayplatewillundergooptimizationandvalidationtestingwithisolatedvirusstrainsandfoodsamples.Theresultsofthisprojectwillenhancetheabilityofpublichealthof icialstorespondinnorovirusout‐breaksituationsandcontributetoroutinesurveillanceofnorovirusesinfoods.

RosaleeHellberg,Ph.D.

Of iceofRegulatoryAffairsIrvine,CA

Preceptor:DonnaWilliams‐Hill,Ph.D.

24

Scienti icandProfessionalBackground2005‐2010 ResearchAssistantProfessors,NorthCarolinaStateUniversity2001‐2005 Ph.D.Immunology,NorthCarolinaStateUniversity2000‐2001 AssociateVeterinarian,LumsPondAnimalHospital1996‐2000 D.V.M.Virginia‐MarylandRegionalCollegeofVeterinaryMedicineResearchInterestsThe focus ofmy research to date has been vaccine development and host immune re‐sponsetoviralinfection,withemphasisonthemucosalimmunesystem.Myongoingre‐searchinterestsareinunderstandinghowthehostimmunesystemrespondstotherapeu‐ticmodalitiesinthecontextofinfectiousandautoimmunediseases.Iamalsointerestedinthedevelopmentandtestingoftherapeuticbiologiccompoundstotreatpersistentviralinfectionandcancer.Commissioner’sFellowshipProjectOverviewTestingImmunogenicityofTherapeuticProteinsinaHumanizedMouseModelTherapeuticproteinsrepresentan importantandrapidlygrowingsectorofthepharma‐ceuticalindustry.Manyoftheseproteinsactdirectlyoncomponentsoftheimmunesys‐temandpresentnewparadigmsforsafetyandef icacytesting.Inaddition,themanufac‐turingprocessesusedtocreatethesedrugscanresultinparticulates(proteinaggregates)thatcansigni icantlyincreasetheimmunogenicityoftheproduct.Theimmunesystemsofnon‐humanprimates and rodents are suf icientlydifferent fromhumans that studies inthesemodelsmaynotaccuratelypredictoutcomesinhumans.Thus,itisimportanttode‐velop and utilize new animalmodels, such as immunologically humanizedmice, to ad‐vance drug testing. This projectwill utilize immunologically humanizedmice to test anapprovedtherapeuticproteinforwhichclinicaldatainhumansisavailable.Resultsfromthehumanizedmicewillbecomparedwithactualclinicalexperiencetovalidatetheutilityofthisanimalmodel.Theabilitytotesttherapeuticproteinsinananimalmodelthatcanaccuratelypredictimmunogenicityaswellasadverseeventsinhumanswouldaidinthedevelopmentofsaferandmoreef icaciousdrugproducts.

KristinaHoward,D.V.M.,Ph.D.


Preceptor:JackA.Ragheb,M.D.,Ph.D.

25

Scienti icandProfessionalBackground2009‐2010 ResearchScientist,WalterReedArmyInstituteofResearch2006‐2009 ResearchFellow,NationalInstitutesofHealth2003‐2006 Postdoctoraltraining,PurdueUniversity2003 Ph.D. CornellUniversityResearchInterestsI am interested in studying bacterial diseases for the development of effective therapies and vaccines. IstudiedantimicrobialpeptidesduringmyPh.D.studyatCornellUniversity.Aftergraduation,IwenttoPur‐dueUniversitytostudythepathogenesisofBacillusanthracis.Usinginsitu luorescentstaining,wedemon‐stratedthatsporesgerminate inmacrophagesandarerapidly inactivated. Twogerminationsystemsareinvolvedwithinmacrophages.Tofurtherstudythehostresponsestobacterialinfections,IthenworkedatNIAID,NIHwhere I applied FluorescenceResonanceEnergyTransfer (FRET) techniques to visualize theinteractionbetweenthehostimmunesystemandtheanthraxtoxininamousemodel.Throughcollabora‐tion,Iresearchednewtechniquesforanthraxdetectionandpotentialanthraxvaccine.IworkedatWalterReedArmyInstituteofResearchafterwardsdevelopingasubunithumanvaccineforBrucellosis.Commissioner’sFellowshipProjectOverviewExpressionofhyaluronidaseStaphylococcusaureusUAMS-1anditsderivatives

Hyaluronicacid,alsocalledhyaluronan,iswidelydistributedthroughoutconnective,epithelialandneuraltissues.Asamajorcomponentofextracellularmatrix,thiscompoundcontributessigni icantlytocellprolif‐erationandmigration.Staphylococcusaureussecretshyaluronidasewhichhasbeenshowntocontributetosubcutaneousinfectioninmousemodel.ItwasnotedthathigherhyaluronidaseactivitywasdetectedwhensarA,whichencodesaDNAbindingprotein,wasdeleted.Basedonaboveresults,weproposethatSarAreg‐ulateshyaluronidasegeneexpressionbybindingtothepromoterregion.Inthisstudy,weplanto: UseqPCRtocomparetheexpressionofhyaluronidaseinvariousStaphylococcusaureusstrainsincluding

mutantswithregulatordeleted. IdentifytheSarAbindingsiteonthepromoterregionofhyaluronidasegenes. Identifythetranscriptionstartpointandthebindingregion.SarAisanimportantregulatoryproteininStaphylococcusgeneexpression.SeveralSarAbindingsequenceshavebeenidenti ied.TheresultofthisstudywillprovideinformationofSarAbindingsitesandbindingaf‐inity,aswellasprovideaninsightintothedifferentialexpressionoftwohyaluronidasegenes(hysA1andhysA2)inStaphylococcusaureusUAMS‐1.

HaijingHu,Ph.D.


Preceptor:MarkHart,Ph.D.

26

Scienti icandProfessionalBackground2005‐2010 AssistantProfessorofMedicine&Pharmacology,UTHealthScienceCenter2002‐2005 PostdoctoralFellow,NIH/NIA2002 Ph.D.Neurotoxicology,HamdardUniversity&USFDA/NCTR1996 M.S.Toxicology,HamdardUniversityResearchInterestsThemainresearchgoalofmylaboratoryistounderstandthemolecularbasisofneurodegeneration,whichcanbeimplicatedtodeveloptherapeutictrialsforneurodegenerativediseases.Thebroadareasofinvestigationinmylabincludethestudyofthemolecularmecha‐nismsofneuronalcelldeath,novelcelldeathandcellsurvivalpathwaysandtheircorrelationwiththemolecularbasisofParkinson'sdisease(PD),α‐synucleinopathiesandrelatedneurodegenerativedisorders.Westrivetoidentifyregulatabletargetsthatcanbemanipu‐latedbychemicalorgeneticmeansforpharmaceuticalandtherapeuticintervention.Presently,mylaboratoryisfocusedonroleofsig‐nalingkinasesintheregulationofvariouscomponentsofPDasatherapeutictargetinanimalmodelsandinPDpatients.Ournovel ind‐ingthatoxidativestresssensitivetyrosinekinaserendersparkin,anE3ubiquitinligase,non‐functionalhasopenedupvariousnewave‐nuestounderstandprogressionofnigro‐striataldegenerationduringthepathogenesisofPD.Weareinvestigatingtheroleofcellsignal‐ingregulationofα‐synucleinandLRRK2inthepathogenesisofPD.Furthermore,wehaveongoingpre‐clinicalstudiesontheroleofki‐nase inhibitors as a potential therapeutic approach in slowing down the progression of PD. Furthermore,my laboratory has a verystrongbackgroundintheoxidative‐stressmediatedneurotoxicityinducedbysubstitutedamphetaminesaswellasinDNAdamageandrepairinagingbrain.Mylaboratoryhasset‐upextensivecollaborationswithvariousPDresearchandclinicalcentersinUSAandEuropethatincludeMorrisUdallCenterofExcellenceforPDResearchatJohnsHopkinsSchoolofMedicine,DepartmentofNeurologyatUCSD,Hertie Institute of ClinicalBrainResearch atUniversity of Tubingen, Germany andBrainMind Institute of Swiss Federal Institute ofTechnology,Switzerland.Commissioner’sFellowshipProjectOverviewAssessmentofironoxidenanoparticles-inducedneurotoxicity.HYPOTHESIS:Iron‐oxidewillinducemitochondrialdysfunctionanddopaminergicneurotoxicityviareactiveoxygen(ROS)andreactivenitrogenspecies(RNS).SPECIFICAIMS:(1)TodetermineiftreatmentwithdifferentsizesofironoxidenanoparticlestoSHSY‐5YNeu‐roblastomacellswouldresultincytotoxicityviafreeradicalgeneration.(2)Todetermineifacute/chronicexposureofvaryingsizesofironoxidenanoparticleswouldalterneurochemicalreleaseasmeasuredbyinvivomicrodialysis,mitochondrialfunction,inducechangesinanti‐oxidantsystemsandcausecelldeathviagenerationofROSindifferentregionsofratbrain.Engineerednanomaterialsarewidelyusedincosmetics,foodpackaging,drugdeliverysystems,therapeutics,biosensors,etc.Thus,theexposureofthepopulationtonanomaterialscontinuesto increaseastheirapplicationexpands. Dairyproducts,cereals,breadsandbeveragesareforti iedwithvitaminsandmineralssuchasiron,magnesiumorzinc,andprobiotics,bioactivepeptides,antioxidants,etc.Someoftheseingredientsarebeingaddedtofoodsasnanoparticles(NP).Activeingredientsarebeingnano‐encapsulatedandincludevitaminsandfattyacidswhicharesoldcommerciallyforuseinprocessingandpreservationofbeverages,meats,cheeseandotherfoods.NPareintentionallyaddedtomanyfoodstoimprove lowproperties(e.g.,howwelltheypour),colorandstabilityduringprocessing,ortoincreaseshelflife.Forexample:ToddlerHealth’sforti iedchocolateandvanilla‘nutritionaldrinks’include300nmparticlesofSunAc‐tive®iron.Ironoxideisalsoaddedtocosmeticpigments(lipstick)andnano‐ironoxidemagneticparticlesareusedinagrochemicalstodeliverandconcentratedifferentsubstancesonplantsormaybeusedasvectorsfordiagnosticandtherapeuticinterventions(Lietal.,2009).Therefore,theFDAregulatoryinterestinnanomaterialsrangesfromtheiruseinagricultureandforti iedfoodsandunintentionalcontaminationfromfoodprocessingmachinesandthemigrationofmanufacturednanomaterialsfrompackagingintofoods.Thesestud‐iesaredesignedtoprovideneurotoxicitypro ileofironoxidenanoparticlestherebyproducingscienti icinformationregardingtheexpo‐sure limitof theseparticlesandneurochemicalalterations inducedby theexposure to thesenanoparticles.Thedataobtainedwillbehelpfulinsettingaregulatoryguidelineforrisk‐assessmentoftheuseofironoxidenanoparticles.

SyedImam,Ph.D.


Preceptor:ZbigniewBinienda,D.V.M.,Ph.D.

27

Scienti icandProfessionalBackground2009‐2010 ResearchInstructor,BaylorCollegeofMedicine2004‐2009 PostdoctoralAssociate,BaylorCollegeofMedicine1998‐2003 Ph.D.MolecularBiology,IndianInstituteofChemicalBiology1995‐1997 M.S.Biochemistry,KolkataUniversity1992‐1995 B.S.Chemistry,KolkataUniversityResearchInterestsMyresearchinterestsarebroadlyfocusedondifferentaspectsofcancerbiology,startingfromearlycancerinitiatingsig‐nalingprocesstodrugresistance.Mypost‐doctoralresearchmainlyinvolvedstudyingthecomplexregulationoftranscrip‐tionalactivityofestrogenreceptor(ERa)bynuclearreceptorco‐regulators(co‐activatororco‐repressor)inrelationtoen‐docrineresistanceofbreastcancer.Idiscoveredthatawellknownco‐repressorSMRT(SilencingMediatorofRetinoicacidandThyroidhormonereceptor)whichisgenerallyknowntorepressnuclearreceptormediatedtranscription,isinvolvedinactivationofERainagenespeci icandcontextdependentmannerandinsodoingSMRTisactivelyinvolvedinbreastcancercellproliferationandsurvival.IalsofoundthatSMRTexpressesinprimarybreastcancerpatients(n=587)thatre‐ceivednoadjuvanttreatment,which indicatesthatSMRTexpression iscorrelatedwithtumorrecurrence.Duringmyre‐searchtenure,Ialsocametolearnandcharacterizeepigeneticre‐programmingofSMRTthatmaybecrucialinpromotionofbreastcarcinogenesis,tumorrecurrenceandpooroverallsurvival.Iwishtoapplyandextendmyexperiencefurthertodeterminediverseepigeneticcontrolmechanismsofgeneexpressioninrelationtodrugresistanceandtherebyachievemylongtermcareergoaltodiscovernewbio‐markersthatwouldaidindiagnosisandtreatmentdecisions.Commissioner’sFellowshipProjectOverviewRoleofaforkheadboxproteinFOXA1inregulatingglucocorticoidreceptoractivityandglucocorticoidmediatedbreastcancercellproliferationandsurvivalBreastcanceristhemostcommontypeofcanceramongwomenintheUnitedStates.Althoughvarioustreatmentoptions(e.g.endocrine,radio/chemo‐ortargetedtherapy)arenowavailabletocombatthisdisease,breastcancerstillremainsthesecondleadingcauseofdeathinwomeninthiscountry.Glucocorticoidsarewellknownfortheirimmunosuppressantac‐tivityandaregenerallyusedasanantiemeticagenttoreducenauseaandvomitingassociatedwithchemotherapytreat‐ment.Glucocorticoidsarealsogiven tobreastcancerpatients for theirantitumorigenicactivity.However,recentstudiesindicatethatglucocorticoidsarenotequallyeffectiveinalltypesofbreastcancerandhaveantiapoptoticactivityincertaintypesofbreastcancer.Ourpreliminarydataindicatethatglucocorticoidreceptor(GR)activityisdependentonaforkheadboxtranscriptionfactor(FOXA1),thelevelofwhichvariesamongthevariousbreastcancersubtypes(luminaltypebeingthehighestexpresser,lowinbasaltypeandabsentintriplenegative).Inthisfellowshipprogram,IseektoinvestigatetheGRactivityanditseffectonbreastcancercellproliferationandsurvivalinvariousbreastcancercellsubtypes.Theoutcomeofthisstudywoulddeterminetheeffectivenessofglucocorticoidsagainstvarioussubtypesofbreasttumorsandtherefore,establishafoundationfor,a)pursuingglucocorticoidtreatmenttoenhancetheef icacyofendocrine‐therapy,radiotherapyandchemotherapyforbreastcancerpatientsinasaferandeffectivemanner,b)de iningasubpopulationofbreastcancerpatientswhoarelikelytobene itfromorbeadverselyaffectedbyglucocorticoidtreatment,leadingtoamorepersonalizedmedicationforthetreatmentofbreastcancer.

SudipanKarmakar,Ph.D.


Preceptor:AkhileshK.Nagaich,Ph.D.

28

Scienti icandProfessionalBackground2007‐2010 CRTAResearchFellow,NationalInstitutesofHealth2005‐2008 M.S.Epidemiology,UniversityofBielefeld2002‐2007 PostdoctoralResearchFellow,Ruhr‐UniversityofBochum1999‐2002 Ph.D.MolecularVirology/Immunology,Ruhr‐UniversityofBochum1994‐1996 M.S.Biochemistry,UniversityofYaoundeIResearchInterestsMyresearchinterestsincludethedevelopmentandcharacterizationof lentiviral,andadenoviralvectors for gene transfer and genetic vaccinations; the design and characterization of differentclassicandgeneticvaccinationapproachesagainstviralinfections;andtheepidemiologyofinfec‐tiousdiseases.

Commissioner’sFellowshipProjectOverviewDesignandtestingofsafety-improvedlentiviralvectorsGenetherapyholdsgreatpotentialfortreatingavarietyofinheritedandacquireddiseases,someofwhichareasyetincurable.Onestrategyfordeliveringtherapeuticgenesintopatient’scellsistousevirus‐basedvectors.Overthepastdecade,avarietyofinvestigatorshavedevelopedgenether‐apyvectorsbasedonhumanimmunode iciencyvirus(HIV).Thesearereferredtoaslentiviralvec‐tors.Lentiviralvectorshavebeengeneticallymodi iedso that their likelihoodof reproducing intargetcellsasreplication‐competentlentiviruses(RCL)isdiminished.Our goal is to improve the safety of lentiviral vectors by further reducing the risk of RCL for‐mation.Thevectorandpackagingconstructsthatareusedfortheproductionoflentiviralvectorsfor clinical applications contain sequence overlaps that can potentially lead to RCL precursorsthroughhomologousrecombination.My research plans include the following: (1) Development of safety‐improved lentivirus‐basedvectors through reduction of sequence overlaps in order to minimize potential recombinationeventsbetweenvectorandpackagingconstructs;(2)Developmentofasensitivecell‐basedassayfor the detection of recombination intermediates, and (3) Establishment of an assay to test themobilizationofsuchrecombinationintermediatesinvolvingenvelopesfromendogenousretrovi‐ruses.

SeraphinKuate,Ph.D.


Preceptor:JakobReiser,Ph.D.

29

Scienti icandProfessionalBackground2005‐2010 PostdoctoralFellowship,UniversityofPittsburghSchoolofMedicine2005 Ph.D.NeurologyandCognitiveSciences,UniversityofMaryland1999 M.PhilPartI,Biochemistry,UniversityofGhana1997 B.S.BiochemistryandPsychology,UniversityofGhanaResearchInterestsTrainedasaneurophysiologist,mypreviousresearchinvolvedinvestigatingthefunctionofneuralcircuitsthoughttoparticipateinsomatosensoryperception,goal‐directedmotormovements,ab‐senceepilepsyandmemoryconsolidation.Whiletheimmediateactivityofneuralcircuitsisregu‐latedbyneurotransmitters, long‐termmodulatoryeffectsofenvironmental toxins,nutritionandsocio‐economicactivitieshavebeenobserved.Myinterestsincludeunderstandinghownutritionandfoodadditivesmayaffectneuraldevelopmentandhowconsiderationsofsuchfactorsaffectriskestimatesduringtraditionalfoodsafetyriskassessments.Iamalsointerestedinunderstand‐inghowtheresultsfromsuchriskandbene itanalysisareusedtoinformpolicymakingdecisions.Commissioner’sFellowshipProjectOverviewRiskandBene itAnalysisofFoodAllergenThresholdsFoodallergicreactionscanbelife‐threateningandnotonlypresentadiseaseburdenforsocietybutalsohaveanegativeimpactonqualityoflifeofaffectedconsumersandtheirfamilies.Sincenopreventative treatmentsarecurrentlyavailable, the food label is thebest riskmanagement toolusedtomitigatetheriskforreactionsandadversehealthconsequences.However,allergenavoid‐anceisdif icultand indingnutritiousfoodstoeatmaypresentaburdenonconsumers.Moreover,sincelabelinglawsdonotadviseonallergenthresholdsorpotentiallysafelevelsofallergenexpo‐sure,productscontainingpotentiallyinsigni icantamountsofallergencarryalabel,thuscontrib‐utingtolessavailabilityof“safe”nutritiousfoodchoicesforallergicconsumers.Thepurposeofthisprojectistousestatisticalmodelsofavailablefoodchallengedatatoestimatepopulationthresholds forpeanut,milkandsoycontainingproducts.Usingthisdataandcurrentexposureestimates,wewillquantitatetherisksandbene itsassociatedwithimplementingthesethresholdsasriskmanagement tools.Wewillalsoemployananimalmodelofpeanutallergytounderstand dose‐responses associated with increasing threshold concentrations. Knowledge ofthesethresholdsandtheirassociatedrisks/bene itscanbeusedtosetguidelinesforlabelingex‐emptionsandthustoimprovethelabelef icacyofallergenicingredientsbyallowingavailabilityofmorenutritiousfoodchoiceswithlowriskforallergicreaction.

ErnestKwegyir‐Afful,Ph.D.

CenterforFoodSafetyandAppliedNutrition

Preceptor:StefanoLuccioli,M.D.

30

Scienti icandProfessionalBackground2009‐2010 PsychogenicsInc.2002‐2009 P izerInc.2001 M.S.,inBiomedicalInformatics,UMDNJandNJIT1998‐2002 MemoryPharmaceuticals1992‐1998 PostdoctoralResearchFellow,NewYorkUniversity1992 M.S.,inNeurophysiology,PekingUnionMedicalCollege1985 M.D.,WannanMedicalCollegeResearchInterestsMyresearchinterestsarefocusedmainlyonanintegrateddatasystemwithstandardizeddataformats.Notonlycanacentralizeddatasystemmanagedatamoreef icientlytofacil‐itateanFDAreviewprocess,butalsoitcanbene ithealthcareindustrysubmittersforthesubmissionprocessesandeasilygatheringvery important information fromtheFDA. Inadditiontothedatasystem,Iamalsointerestedinpharmacovigilanceandpost‐marketingsurveillanceformedicinalproducts.Commissioner’sFellowshipProjectOverviewInformationTechnologyforPharmacovigilance:FutureDirectionsandChallengesfromReg-ulatoryAgencyPerspectivesInpharmacovigilance,makingtherightdecisionsattherighttimeiscritical.Asinallriskassessment,ajudgmenthastobemadebaseduponavailableinformation.Accesstoup‐to‐dateandaccurateinformationiscrucial.Threekeyinformationmanagementdomainsareneededtoenhanceand integrate: (1)accessto information(data); (2) interface,oruser‐friendly toolssupportedbyarobustarchitecture, toef icientlyconvert information intoknowledge;and(3)datastandards.Thesethreedomainsinteracttoin luencethewaywereceive,manage,andcommunicateinformation.Myprojectworkwillfocusonenhancingandintegratinginformationmanagementtoensurethedataquality.

XingfangLi,M.D.


Preceptor:JohnW.Gardner,M.D.,Ph.D.

31

Scienti icandProfessionalBackground

2010 Ph.D.EpidemiologyandPublicHealth,UniversityofMaryland2007‐2010 ResearchAnalyst/Programmer,UniversityofMaryland2003‐2007 StudyCoordinator/ResearchAnalyst(Full‐Time),UniversityofMaryland2004 M.A.KinesiologicalSciences,UniversityofMaryland,2000 B.S.SchoolofPhysicalTherapy,NationalTaiwanUniversityResearchInterestsMygeneralresearchinterestslieinthe ieldoftranslationalscienceusingepidemiologicalandsta‐tisticaltechniques.MypreviousresearchinvolvedtheinvestigationoftheprognosticfactorsandotherhealthoutcomesamongVeteranswithMultiple Sclerosisusingactive surveillance systemandlargeadministrativedatabases.Myepidemiologicaltrainingalongwithstrongcomputationalbackgroundinprogramming,datamining,andstatisticalanalysishavedrivenmyinteresttowardstheareaofappliedresearchinpublichealth.Speci ically,IamveryexcitedfortheopportunitytoworkasaCommissioner'sFellowtoconductquantitativeresearchandmodelingusingdatafromongoingnationalstudies,establishedclinical trials,andsurveillancesystemstoguideregulatorydecisionsaswellaspromotepublichealth.Commissioner’sFellowshipProjectOverviewImprovePre-MarketSafetyAssessmentofCardiovascularRiskduetoUnintendedElevationsofBloodPressureforNewMolecularEntitiesElevatedbloodpressurehaslongbeenrecognizedasamajorriskfactorforcardiovascularmodal‐ityandmortality.Thereisevidencetoillustratethatevensmallelevationsinbloodpressureareassociatedwithasigni icantincreaseinriskofcardiovasculardiseases(CVD).Druginducedeleva‐tioninbloodpressurehasbeendocumentedforanumberofpharmaceuticalagents.However,inthepre‐marketarena,therearecurrentlynoimplementedregulatorystandardsorcriteriatosys‐temicallyreviewsafetyissuesassociatedwithdruginducedbloodpressureanditspotentiallongtermeffectsonCVDrisk.Asaconsequence,risk‐bene itevaluationforanewmolecularentitycan‐notbeappropriatelyassessed.Thisprojectseekstoimprovepre‐marketsafetyassessmentsofthepotential CVD risk due to unintended elevation of blood pressure for new molecular entitiesthroughacomprehensivequantitativeassessment.

Tzu‐YunChang‐McDowell,Ph.D.

CenterofDrugEvaluationandResearch

Preceptor:RajanikanthMadabushi,Ph.D.

32

Scienti icandProfessionalBackground2002‐2005 CRTAFellow,NationalCancerInstituteatFrederick1999‐2002 PostdoctoralFellow,UTHealthScienceCenteratSanAntonio1999 Ph.D.inPharmacology,StateUniversityofNewYorkatBuffalo1989 M.D.,BeijingMedicalUniversityResearchInterestsMycurrentresearch focusesonclinical trialdatamanagementanddatabasedesignandbuild.Besidesmyclinicalresearch,Ialsohavemanyyearsofexperienceindrugdiscoveryanddevelopment.Mydrugresearchinterestsliepredominatelyintheareasofpharmaco‐kinetics/pharmacodynamics (PK/PD), drugmembrane transport, drugmechanism, pre‐clinicaldrugevaluation,anddrugscreeningstudies,especiallywithbonedensityandcan‐cerdrugs.Commissioner’sFellowshipProjectOverviewRenalfunctionanddrugdosingIn theUS,over twenty‐onemillionpeoplehave impairedkidney functionandareat in‐creased risks of drug related adverse events. Currently, several serum creatinine‐basedequationsarebeingusedfortheestimationofrenalfunctionanddrugdosingadjustmentsinpatientswithrenal impairment.However, theseequationscannotprovideanoptimalapproachtoestimaterenalfunctionacrossweightstratatoenhancedrugsafety.Recently,ourresearchgroupdevelopedanewmodi iedequationforrenalfunctionestimation.Fa‐cilitatedbythisprogress,myresearchwillfocusontesting:1)whetherthenewequationhas better renal function estimation compared with other estimation equations beingused,intermsofaccuracyandbias;2)whetherthenewequationhasthebestcorrelationswithotherpharmacokineticsparameters;3)whetherthenewequationwillgivethebestpredictionsondrugs’safetyandef icacyoutcomesand,therefore,beusedfordoseadjust‐mentintheproductlabel.

ZenghuiMi,M.D.,Ph.D.


Preceptor:NancyXu,M.D.

33

Scienti icandProfessionalBackground2010 Post‐doctoralFellowship,JulesSteinEyeInstitute,UCLA2008 Residency,KresgeEyeInstitute,WayneStateUniversity2005 Internship,SinaiGraceHospital,DetroitMedicalCenter2004 M.D.JohnsHopkinsSchoolofMedicine2000 A.B.Chemistry,PrincetonUniversityResearchInterestsWithexperienceinbothclinicalophthalmology,andophthalmologyrelatedresearch,Iaminter‐ested in the interfacebetweenmedicine,publicpolicy, innovation,andregulation. Mypreviousresearchprojectshaveincludedworkongeneticeyediseases,refractivesurgery,ophthalmicsur‐gicalinnovations,dryeyesyndrome,andcornealtransplanttechniques.Ihopetobuildonmyin‐terestsandexperiencewhileworkinginthedeviceapprovalandregulationsectionoftheCDRH.Commissioner’sFellowshipProjectOverviewRegulatoryClassi icationofFiveUnclassi iedOphthalmicDevicesThe Medical Device Amendments to the Food, Drug, and Cosmetic Act were enacted in 1976.Theseamendmentscategorizeddevicetypesintooneofthreeclasses(ClassI,II,orIII)basedontherisksposedbythedeviceandtheregulatoryoversightneededtoassurethesafetyandeffec‐tiveness of the device before it enters the US market. However, some well characterized, pre‐Amendmentophthalmicdevicesarestillunclassi iedand iveofthesedevicetypeswerepresent‐ed for classi ication recommendations at differentOphthalmicDevicesAdvisoryPanelmeetingsthattookplacebetween1996and2000.Asofyet,thesedevicesareunclassi iedbecausenewreg‐ulations(andinsomecasesspecialcontrolsguidancedocuments)haveyettobecreatedinordertocompletetheclassi icationprocess.Thespeci icobjectiveofthisprojectistowritetheseclassi‐ication documents proposing the promulgation of a rule for inal classi ication and to presentthesedocumentstoothercenterswithintheFDAfor inalreviewandclearance.Thedevicestobeclassi iedinclude:scleralplugs,punctalplugs,lacrimalsystemrepairdevices,cornealstorageandtransportsystems,andeyelidweights.Achievingprogress towardsthe inalizedregulationsandspecialcontrolsnecessarytoclassifythese ivedeviceswillcontributetotheFDA’smissiontopro‐tect thepublichealthby facilitatingavailabilityandaccess todevices through the leastburden‐somepathtoapproval,whilemaintainingassuranceofsafetyandeffectiveness.

MaryamMokhtarzadeh,M.D.


Preceptor:MarkhamLuke,M.D.,Ph.D.

34

Scienti icandProfessionalBackground2006‐2010 IRTAPostdoctoralFellow,NationalInstitutesofHealth2006 Ph.D.,Microbiology,UniversityofWisconsin‐Madison2000 B.A.BiologicalSciences,CornellUniversityResearchInterestsAsapostdoctoral fellowat theNational InstitutesofHealth, IworkedwithReedWickner inthestudyofyeastprions,whichserveasanexcellentmodelforunderstandingpriondiseasesinhu‐mans and animals. Wedesigned a genetic screen for identifying and con irmingnewprions inyeastwhichcanbeusedtoidentifyinfectiousproteinsinotherorganisms.Throughthistechnique,I identi ied aprion formof theS.cerevisiaemetacapaseMca1p—theonly caspaseof yeast. Thisproteinisbelievedtoplayacrucialroleinyeastapoptosis.TheprionformofthiscaspasehasadramaticmutageniceffectonthemitochondrialDNAofyeast.Interestingly,thedamagecausedby[MCA]tothemitochondrialDNAhasaprotectiveeffectundercertaingrowthconditions.Addition‐alworkinvolvsingtheuseofsolid‐stateNMRveri iedthattheMca1pamyloidformisaparallelin‐registerβ‐sheet,asisthecasewithotheryeastprions.Commissioner’sFellowshipProjectOverviewDetectionofPrionsinInfectedBloodviaProteinMisfoldingCyclicAmpli ication(PMCA)Ourworkwillinvestigatewhetherproteinmisfoldingcyclicampli ication(PMCA)isaviabletech‐niqueforampli icationofabnormalprionproteinfromvariantCreutzfeldt‐JakobDisease(vCJD)‐infectedmacaqueblood. vCJD is apriondisease that affectshumans and canbeexperimentallytransmitted tomacaques.Prionsarealtered formsofahostproteinbelievedbymany tobe theinfectiousagentsof transmissiblespongiformencephalopathies(TSEs).PMCAisan invitropro‐tein ampli ication technique analogous to the polymerase chain reaction (PCR) used to amplifyDNA.Bytakingadvantageofprions’ innateabilitytoself‐propagate, theabnormalprionproteinpresent inpotentially infected sampleswillbeampli iedvia cyclesof sonicationand incubationanddetectedviaWesternblotting.Inthisproposal,PMCAwillbeadaptedandoptimizedfordetec‐tionofprionsinblood.Blood,however,isknowntocontainlowlevelsofinfectiousmaterial,com‐pared tobrainorother tissues from infected animals.Compounding this issue, transmissionbybloodishighlyef icientandrequiresonlyverylowlevelsofprionprotein.Ahighlysensitiveandef icientPMCAusingbloodasasubstratewillbedevelopedduringthecourseofthiswork.ThisassaywillbeinvaluableforfurtherdevelopmentofabloodscreeningtesttoidentifyvCJD‐infecteddonorsandthuspreventtransmissionofvCJDbybloodtransfusion.

JulieNemecek,Ph.D.


Preceptor:LuisaGregori,Ph.D.

35

Scienti icandProfessionalBackgroundResearchAssociateChildren’sNationalMedicalCenter2004–2007PostDoctoralFellowNationalInstituteofHealth2000‐2004Ph.D.Chemistry,GeorgeWashingtonUniversity,Washington,D.C.,1999B.Sc.Chemistry,GeorgeMasonUniversity,VA1992ResearchInterestsInthelastfewyears,Ihaveacquiredextensiveexperienceinthedetection,identi ication,andquanti icationofproteinandpeptideexpressionlevels.Myresearchhasbeenfocusedonthedevelopmentofnovelmethodologiestostudyproteins,de iningtheproteomepro‐ile of cellular and sub‐cellular organelle undernormal anddisease states, anddetailedinvestigationofspeci icproteinsandpeptidestodeterminetheirpossiblebiologicalandclinicalimportance.Commissioner’sFellowshipProjectOverviewBiomarkersofIn lammationandEffectsofNon-SteroidalAnti-In lammatoryDrugsFollow-ingExperimentalInductionofMastitiswithLipopolysaccharideinGoatsRecent veterinary biomarker discovery initiatives have focused on the identi ication ofsensitiveandreliableindicatorsforuseinevaluatingtheef icacyofadjunctivetherapiesfaonrimthaelst.reMatymreensteoarfc ihn ilsaimnvmoaltvieodnaapsspolicciaattieodnwoifthmcaosslifsopremctrmomasetittriisc‐inbafsoeoddpprrootdeuocminigcmethod‐ologiestothediscoveryofbiomarkersofin lammationincomplexbiologicalmatricesin‐cludinggoatmilkandplasma.Iinvestigatedifferentialproteinexpressionincaprinemilkduringexperimentallyinducedcoliformmastitisusing2‐dimensionalgelelectrophoresis(2D‐GE)andliquidchromatographyfollowedbytandemmassspectrometry(LC‐MS/MS).Thebiomarkers identi ied in thisresearchwillbevital to thepotentialestablishmentofregulatorycriteriaaimedatassessingtheef icacyofnonsteroidalanti‐in lammatorydrugsfortreatingin lammationinruminantspecies.

ZohraOlumee‐Shabon,Ph.D.


Preceptor:JamieBoehmer,Ph.D.

36

Scienti icandProfessionalBackground2009‐2010 ResearchScientist,NationalInstitutesofHeath2005‐2008 ResearchAssistantProfessor,MontanaStateUniversity2004‐2005 VisitingScientist,UniversityofTexasM.D.AndersonCancerCenter2002‐2004 VisitingScientist,KarolinskaInstitute1997‐2002 TeamLeader,ChineseAcademyofSciences1997 Ph.D.Biochemistry&MolecularBiology,UniversityofOuluResearchInterestsIamaphysiologistwithexpertiseinendocrinology,reproductivemedicine,andoncology.My research interests include reproductive hormones, pregnancy, gynecological disor‐ders,andhormone‐relatedcancers.Commissioner’sFellowshipProjectOverviewAssessment of risks to living donors of human cells, tissues, and cellular and tissue-basedproducts(HCT/Ps)HCT/Ps are increasingly used in medical and cosmetic procedures. While recovery ofHCT/Psfromlivingdonorsisgenerallyperformedaccordingtoestablishedproceduresinamannerthatassurestheirsafety,therearepotentialrisksfromtissuedonation.Forex‐ample,oocytedonorsareexposedtorisksofovarianhyperstimulationsyndrome,surgicalcomplications and theoretically, development of hormone‐related cancers. Peripheralblood stem cell donors face known risks related to growth factor administration andapheresis,andtheoreticallong‐termrisksofleukemiaandotherblooddyscrasias.Infantcordblooddonorsmaybeexposedtorisksresultingfromdeviationsfromstandardperi‐natalcareduringcordbloodrecovery.Alllivingdonorsareexposedtoshort‐termrisksofphlebotomytoobtainsamplesforeligibilitydetermination.Further,theresultsofdonortestingmaydisclosemedicalconditionsorhealthpredispositions.Federalandstateover‐sight of HCT/Ps focus on recipient safety. Voluntary guidelines promulgated by profes‐sionalorganizationsincludesomeprovisionsfordonorsafety.However,theextentofdo‐nor protection afforded under these guidelines is dif icult tomeasure because they arelimitedinscopeandenforcementpower.Inthisstudy,wewillidentifygapsinscienti icknowledgeaboutrisksforlivingdonorsofHCT/Psandevaluatecurrentoversightofdo‐norsafety.

Yun‐shangPiao,Ph.D.


Preceptor:EllenF.Lazarus,M.D.

37

Scienti icandProfessionalBackground2010 Ph.D.Chemistry,UniversityofTexasatAustin2004 B.S.Chemistry,DukeUniversity ResearchInterestsMygraduateresearchfocusedondevelopingmassspectrometricmethodstoinvestigatenucleicacidinteractionswithnoveldrugs.Speci ically,myresearchfocusedonassessingtheeffectivenessofnovelanti‐cancerdrugsdesignedtotargetspeci icnucleicacidsse‐quencesandstructures.Throughmassspectrometrictechniquestherelativebindingaf‐inityandspeci icityofavarietyofanti‐cancerdrugswerescreened.Thesuccessfulanal‐ysisoftheseanti‐cancerdrugsaidedinstructuralre inementandimprovedsequencetar‐getingoffuturedrugstructureiterations.Commissioner’sFellowshipProjectOverviewProjecttitle:Rapid Detection and Identification of Foodborne Bacterial Pathogens via PCR/ESI-MS In order to contain and prevent outbreaks of foodborne bacteria, the source of the pathogen needs to be quickly identified. Current methods of detecting, isolating, and identifying bacteria to an actionable level can take weeks. Epidemiological studies can provide possible culprits, but the isolation of the bacterium involved in the outbreak is necessary to identify the affected products. In a collaborative effort with CFSAN and the North Carolina State Department of Health, this work evaluates a novel technology for the detection and identification of a variety of bacterial pathogens found in food. The method combines PCR amplification of DNA with mass spectrometric detection of the resulting amplicons. The use of mass spectrometry as a de-tection method allows for the identification of bacteria in mixed culture preventing the need for an isolation step. Due to the use of PCR primers covering a range of bacterial species, a variety of bacteria can be identified in one multiplexed assay. This project involves the evaluation of this method for the identification of relevant foodborne pathogenic bacteria. After initial work to expand the limits of the current database by analyzing a large collection of bacteria, the ana-lytical characteristics of the method will be determined. This project is a fundamental step to-wards fast, accurate identification of pathogens and is a part of a larger movement towards im-proving the agency’s response to food emergencies.

SarahPierce,Ph.D.

Of iceofRegulatoryAffairsIrvine,CA

Preceptor:WilliamB.Martin,Ph.D.

38

Scienti icandProfessionalBackground2010 Ph.D.BiomedicalEngineering,YaleUniversity2007 M.S.BiomedicalEngineering,YaleUniversity2003 B.S.BiomedicalEngineering,ColumbiaUniversityResearchInterestsMyresearchinterestsarefocusedoninvestigatingdrugdeliveryandtissueengineeringtherapiesforrepairinthecentralnervoussystemusingsyntheticpolymerscaffolds.Myrecentworkhasfocusedonfabricatingand characterizing degradable polymer constructs to deliver small‐molecule tyrosine kinase inhibitors topromoteopticnerveregenerationfollowinginjury.Speci ically,effortsweremadetodeterminetheutilityofdegradablemicrospheresandnanospheresforsustainedoculardrugdeliveryandtheadvantagesofonecon‐structovertheotherusingarodentopticnerveinjurymodel.Otherareasofinterestinclude,syntheticpoly‐mer,hyaluronicacid,andnatural‐synthetichybridscaffolddevelopmentwiththegoalofcreatingacentralnervoussystemextracellularmatrixmimicforstudyofnervoussystempathologies.

Commissioner’sFellowshipProjectOverviewMeshMash:Past,present,andfuturesurgicalmeshandscaffolddesignandimpactonFDAregulatorypracticesTheprimarypurposeofabsorbable/degradablesyntheticandbiologicsurgicalmeshesistoreinforceweak‐enedsofttissuethroughencouragingtissueremodeling,eitherbytissueingrowthintotheimplantorencap‐sulationoftheimplant.Inthepasttenyearstherehasbeenanincreaseinthecomplexityofmeshdevicede‐signaswell as thenumberof adverseeventsassociatedwith thesedevices—in2008FDA issuedaPublicHealthNoticealertingpatientsandhealthcareproviderstotheseriousadverseeventsassociatedwithuseofsurgicalmeshforurogynecologicrepair.Inaddition,sincethecurrentCDRHsurgicalmeshguidancewasis‐suedourunderstandingof themethodsfor implantingsurgicalmeshdevicesandtheirsubsequentclinicalperformancehas improved.This issue also extends toCBER reviewpractices asmany tissue‐engineered/regenerative‐medicine(TERM)productsinvolveascaffold‐basedapproachwherethedegradablescaffoldisintendedtoencourageorpromotetissueregrowthand/orremodelingyetmaintainitsintegrityduringthisprocess.Giventherecentconcernsregardingadverseeventsandthechangeinpaceofthe ield(i.e.,scaffold/mesh design and implantation techniques), premarket review practices require updating to address newconcernsregardingthesafetyandeffectivenessofsurgicalmeshdevicesandotherscaffold‐basedproducts.Toachievethisgoal,myprojectwillfocusonestablishingadatabasetocatalogpremarketsubmissionsforsurgicalmeshdevicesatCDRHandscaffold‐basedproductsatCBER.Datainputtedintothedatabasewillbeusedtorecommendpreclinicaltestingproceduresandstudiesforsurgicalmeshdevicesandscaffold‐basedproductsthatareexpectedtoremodelorreplacetissue.Theserecommendationswillbeusedtoinformde‐velopmentofnewdraftguidanceforreviewofpremarketsubmissionsforurogynecologicsurgicalmesh.Fi‐nally,theresultsofthisprojectwillbeusedtofacilitatecommunicationandincreasetheknowledgebaseofreviewersofTERMproducts.

RebeccaRobinson,Ph.D.

CenterforBiologicsEvaluationandResearchandCenterforDevicesandRadiologicalHealth

Preceptors:CharlesDurfor,Ph.D.,EliasMallis,B.S.,andMercedesA.

Serabian,M.S.,D.A.B.T

39

Scienti icandProfessionalBackground2002‐2010 Ph.D.BasicMedicalSciences,NewYorkUniversity1995‐1999 B.S.Biology,MaryWashingtonCollegeResearchInterestsDuringmygraduatecareerIbecameinterestedinstudyingthegeneexpressionandepigeneticchangesthatoccurduringbreastcancerprogression.InthelaboratoryofDr.MichaelGarabedianatNYU,Iobservedthathumanbreastcancerpatients,whoexpresshighlevelsoftheHsp90co‐chaperonep23protein,aremorelike‐lytoexhibit lymphnodemetastasesandexperiencediseaserecurrenceandmortality.Geneexpressionandepigeneticchangesmostlikelyunderliethenegativeeffectsassociatedwithhigherp23expressioninbreastcancerpatients,basedonresultsfromextensiveinvitrostudiesobtainedusingahumanbreastadenocarcino‐maMCF‐7celllinewhich,uponp23overexpression,becomesinvasiveanddrugresistant. Forexample,thehistonesatthepromotersofmanygenesupregulatedbyp23overexpressionarehyperacetylated,includingABCC3, an ATP‐dependent cassette transporter responsible for resistance to the chemotherapeutic drugsetoposideanddoxorubicin.Additionally,uponp23overexpressioninMCF‐7cells,manymetabolicpathwaysarealtered themayaffecthistonemodi icationsatgenes regulating invasionanddrug resistance inbreastcancer.ThefocusofmyresearchinthelaboratoryofDr.IgorPogribnyattheNCTRwillbetofurtherexplorethe link between metabolism and histone modi ications in cancer, as well as characterize the epigeneticchanges,includingchangesinDNAandhistonemethylation,thatoccurduringcancerprogression.Theulti‐mategoalofthisworkwillbetoidentifybiomarkerstoimproveearlydiagnosisandpredictbettertherapiesforcancer.Commissioner’sFellowshipProjectOverviewAninvitroinvestigationofmetabolicallysensitivebiomarkersinbreastcancerprogression.My research centers on invitro identi icationofprotein, genetic, andmetabolicbiomarkers that canbeex‐panded to the clinic to predict, for breast cancer patients, disease susceptibility and therapeutic response.Resultsfromrecentinvivoandinvitrostudieshavedemonstratedsubstantialmetabolicdifferencesbetweenbreastcancersofnon‐invasiveepithelialorinvasivemesenchymalorigin.Wehavediscoveredthatthelevelsofmetabolically sensitive epigeneticmarks, including acetylated andmethylated histones, are distinct be‐tweenepithelialandmesenchymalcelllines.Thesigni icanceofthisobservationisnotonlythathistonemod‐i icationsin luencegeneexpression,chromatinassembly,andchromosomestability incancercells,butthatthesemarksmightserveasbiomarkerstodistinguishbetweenlessandmoreaggressivetypesofcancers.Wehavealsoestablishedacorrelationbetweenparticularepigeneticmodi icationsandmetabolitelevels(i.e.glu‐tamineandglutamate)inbreastcancercells.Weareexploring,usingacombinationofmetabolomicandmo‐lecular, chromatin, and cell biology techniques, the effects that metabolism‐associated epigenetic changeshaveondrugresistanceandgeneexpression,aswellastheiroverallimplicationsinbreastcancerdiagnosis,prognosis,andtreatment.

NatalieSimpson,Ph.D.


Preceptor:FrederickBeland,Ph.D.andIgorPogribny,M.D.,Ph.D.

40

Scienti icandProfessionalBackground2004‐2010 Scientist,RicercaBioscience,LLC2008 Ph.D.Clinical‐BioanalyticalChemistry,ClevelandStateUniversity2000‐2004 ResearchAssistant,ClevelandClinicalFoundation1996‐1999 Instructor,BeijingMedicalUniversity1996 B.S.MedicinalChemistry,BeijingMedicalUniversityResearchInterests:Mypreviousresearchinterestslayindevelopmentandapplicationofanalyticalmethodol‐ogiesforthedetectionvariousbiomarkersandpharmaceuticalmoleculesincomplexma‐tricesbyusingGC‐MSorLC‐MS/MS.Comingfromacontractresearchorganization(CRO),ItrulybelievethatthisFDAcommissioner’sfellowshipprovideagreatopportunitytore‐ceiveintensivetraininginbothregulatoryscienceandbasicresearch.Thisfellowshipex‐periencewillfurtherdevelopmyexpertiseinanalyticalchemistryandallowmetosolvetheproblemsthatmayaffectthefoodsafety.Commissioner’sFellowshipProjectOverviewAsensitive,highthroughputanalysisofmultiplehormonesin ishtissuebyLC-MS/MSOverthepastseveraldecades,growthhormoneshavebeenusedinmeat‐producingani‐malstopromoteanimalmuscledevelopment,improvemeatquality,andincreasefeedef‐iciency. Low levelsofhormoneresidues inedibleanimal tissuemayhavea signi icantimpactonhumanpubertyandmaybeassociatedwithcancerdevelopment.In2009,theU.S. importedabout5.2billionpoundsof seafood fromAsia,EuropeandCanada,whichmadeup84%oftotalseafoodconsumption.Toensureimportedseafoodsafety,anana‐lyticalmethodforthedetectionofhormonesinedible ishmuscleatpartsperbillionlev‐elsisneeded. Thisprojectwilladdressthecontroversialquestionregardingtheneedofenzymatichydrolysis fordeterminingconjugatedresidues inmuscle tissue. Inaddition,wewilldevelopandmakeavailableavalidatedanalyticalmethodsuitableformonitoringillegal use of hormones in ish. Such validatedmethod is critical to understanding andmonitoringthesafetyoffoodproductsfromanimalsandwillallowtheAgencytorespondtoemergingdrug residueproblems, topreventunsafe seafood importation, and to sup‐portFDA’sfundamentalmissionofprotectingandpromotingpublichealth.

WeiSong,Ph.D.


Preceptor:Pak‐SinChu,Ph.D.

41

Scienti icandProfessionalBackground2007‐2010 NationalResearchCouncilResearchAssociate,NavalResearchLab2007 Ph.D.Chemistry,WayneStateUniversity2001 B.S.Chemistry,WayneStateUniversity1995 B.S.Physiology,MichiganStateUniversityResearchInterestsMyresearchexperiencehasprimarilyinvolvedtheuseofbiomoleculesasrecognitionelementsinsensorsforthedetectionofsmallproteins,neurotoxinsandexplosives.Mygraduateworkfocusedonthedevel‐opmentofaquantumdot‐aptamerbiosensortodetecttheserineproteasethrombin.Anotherunrelatedprojectinvolvedinvestigatinghowgeometry(i.e.bondanglesandpositionsofaminoacids)playsaroleintheformationofcrosslinkedaminoacidcofactorsthatareformedposttranslationinmetalloenzymes.Mypostdoctoralresearcheffortswereaimedatusingsingledomainantibodiesderivedfromimmunizedlla‐mastodetectbotulinumneurotoxinsAandB,ricinandtheexplosivecompoundsPETNandTNT.Myla‐boratoryexperiencerangesfrommolecularbiologyandproteinchemistrytoinorganicsynthesisanditismygoaltousemytechnicalexperiencetopromotedrugsafetyandeffectiveness.Commissioner’sFellowshipProjectOverviewThe development of alternative in vitro screening methods for the screening of potentially toxic P-glycoproteinsubstratesCertainbreedsofdogs,suchasCollies,havebeenobservedtoexperiencelife‐threateningtoxicityaftertheadministration of drugs such as avermectins, which are P‐glycoprotein (P‐gp) substrates. The alteredpharmacokinetics of P‐gp substrates in the effected dog breeds can be attributed to amutation in theABCB1gene(ABCB1‐1Δ)thatleadstotheexpressionofnon‐functionalP‐gp.AspartoftheInvestigationalNewAnimalDrug(INAD)process,newlyintroducedavermectinsmustundergoadditionalsafetystudies.Thesestudies,whichuseCollieswiththeABCB1‐1Δmutation,arebecomingmoredif iculttoconductasthenumberof ivermectinsensitivecolonies isdecreasing. Toaddress theneed forothermethods thatevaluateP‐gpsubstratetoxicity,wehavedevelopedamousemodelexpressingthemutatedformofthecanineABCB1gene.ThismodelwillbeusedtoassessparallelsbetweenthemousemodelresponsetoP‐gp substrates and the adverse neurotoxic effects observed in ABCB1‐1Δ homozygous recessive Collies.Results from this studywill beused to investigate invitromethodsusing cellsderived from transgenicmice to assess the toxicity of newly introduceddrugs that areP‐gp substrates. These invitromethodshavethepotentialtoprovidetheagencywiththeabilitytopredictthesafetyofnewdrugswithouttheuseofColliecolonies.Furthermore,theobjectivesofthisstudyareinlinewithFDA’sCriticalPathInitiativewhichinvolvesimprovingand/oracceleratingtheapprovalprocesssothatregulatedproductsreachthemarketinatimeliermanner.

MarlaSwain,Ph.D.


Preceptor:HaileF.Yancy,Ph.D.

42

Scienti icandProfessionalBackground2001‐2010 ProjectLeader/AssociateResearchFellow,AlbanyMolecularReasearchInc.1994‐2001 Chemist/SeniorResearchScientist1994 Ph.D.OrganicChemistry.MoscowStateUniversity1989 M.S.Chemistry.MoscowStateUniversityResearchInterestsMyresearchinterestsincludetheprediction,recognitionandreportingonadverseeffects,includingpost‐marketingsurveillance,clinicalandpre‐clinicalpharmacologyandregula‐toryissuesinsmallmoleculesdrugdevelopment.Commissioner’sFellowshipProjectOverviewMechanism-basedPredictionofAdverseEffectsofKinaseInhibitorsThecurrentpharmacovigilanceapproachistopassivelyobservethepostmarketingortri‐alsignalsofexcessadversedrugreactionsforthedrug.Acandidatesignalisthenstudiedfromthepointofstatisticalstrengthandmechanisticplausibility.Thegoalofmyprojectistodevelopapro‐activeapproachinwhichthemechanismofactionofthedrugischarac‐terizedusing state‐of‐the‐art cheminformatics, bioinformatics, network andmechanisticapproacheshelpinginformthesubsequentpharmacovigilancethusimprovingitssensitiv‐ityandspeci icity.Weareplanningtoshowthepossibilityofmechanism‐basedpredictionofadverseeffectsofkinaseinhibitordrugsbasedontheirstructureandavailableinvitrodata (primarily kinase inhibition and other receptor screening pro iles) and to try toquantifytheadvantagesofthemethodascomparedwithrandomandbest‐guess(basedonpreviousexamples)approaches.

PavelZhichkin,Ph.D.


Preceptor:DarrellAbernethy,M.D.,Ph.D.

43

FDACommissioner’sFellowshipProgram2010Preceptors

44

Scienti icandProfessionalBackgroundM.D.,Ph.D.inPharmacologyAcademicTeachingandResearchinClinicalPharmacologyClinicalTraininginInternalMedicineandGeriatricsResearchInterestsUseofpharmacologicalmechanismstopredictdrugsafety.Developmentofsystemsbiol‐ogyapproachestopredictriskfromdrugexposure.Bene it/riskofdruguseinolderpa‐tients(>85years).

DarrellAbernethy,M.D.,Ph.D.

Of iceofClinicalPharmacologyCenterforDrugEvaluationandResearch

Fellow:PavelZhichkin,Ph.D.

45

Scienti icandProfessionalBackgroundB.A.ColoradoCollegeM.S.MontanaStateUniversityPh.D.MontanaStateUniversityFDAexperience—33yearsResearchInterestsTheroleofgeneticandepigeneticchangesintheetiologyofcancer.

FrederickBeland,Ph.D.

DivisionofBiochemicalToxicologyNationalCenterforToxicologicalResearch

Jefferson,AR

Fellow:NatalieSimpson,Ph.D.

46

Scienti icandProfessionalBackgroundD.V.M.Ph.D.FDAexperience—19yearsResearchInterestsMitochondrialdysfunction,brainhypoxia,neurotransmittersystems,nanoparticles,neu‐roimaging,neurotoxicity

ZbigniewBinienda,Ph.D.

Head,NeurophysiologyLaboratoryDivisionofNeurotoxicology

NationalCenterforToxicologicalResearchJefferson,AR

Fellow:SyedImam,Ph.D.

47

Scienti icandProfessionalBackgroundB.S.UniversityofMarylandM.S.VirginiaPolytechnicInstituteandStateUniversityPh.D.UniversityofMarylandFDAexperience—6yearsResearchInterestsDr.Boehmer’sprimaryresearchfocusistheapplicationofmassspectrometry‐basedpro‐teomicapproachestotheanalysisandquanti icationofdifferentialproteinexpressionincomplexbiologicalmatricesforthediscoveryofcandidatebiomarkersofdiseaseinfoodanimals.Dr.Boehmer’sresearchsupportseffortsintheOf iceofNewAnimalDrugEvalua‐tion (ONADE) to identifybiomarkers that couldbeused to evaluate theef icacyofnewveterinary drugs, especially drugs intended for use in food animals that have anti‐in lammatory claims. Speci ic studies have involved the identi ication of biomarkers ofcoliformmastitis inbovinemilk,aswellastheevaluationofantimicrobialpeptidespre‐sentinbovinebronchial luidduringpneumonia.Analysesarecurrentlybeingconductedtoevaluatetheresponseofcandidatebiomarkerstodrugadministration,whichcouldfa‐cilitate theuse of biomarkers to assess drug ef icacy, and could lead to the approval ofnewveterinarydrugsforuseinfoodanimals.

JamieBoehmer,Ph.D.

Of iceofResearchDivisionofAnimalResearch


Fellow:ZohraOlumee‐Shabon,Ph.D.

48

Scienti icandProfessionalBackgroundB.S.,M.S.YaleUniversityPh.D.UniversityofOxfordFDAexperience—9yearsResearchInterestsAdenovirusesarecommonDNAvirusesthatcanbeengineeredtocreatenon‐replicatinggenetherapyvectors.Therearecloseto100clinicaltrialsintheUSthatuseadenovirusvectorsforgenedeliveryoranti‐tumortherapy.Administeringthesevectorsthroughthevascularsystemwouldbeanidealrouteinmanysituations,potentiallyallowingadenovi‐rusvectors to targetavarietyof tissuesorwidely‐disseminatedmetastatic tumors.Onesigni icantbarrier is thatadenovirusvectorsarequicklycleared fromthecirculationbymacrophages inthe liver,which limitstheamountofvectorthatcanreachthe intendedtarget.Wehaverecentlyidenti iedthecellularreceptorsandprocessesthatareresponsi‐bleforthisvectorclearance,andfurtherworkiscenteredonhowtodesignvectorsthatevadethesereceptors.Anotherdif icultbarriertogenetherapywithadenovirusvectorsisthebody'sabilitytodetectvirus‐basedvectorsthroughtheinnateimmunesystem,whichcan triggeravarietyofpotentiallydangerous responses.Wearestudyingmacrophages,cytokines, complement and other types ofmediators to learnwhy they have an innateabilitytorecognizeandrespondtoadenovirusvectors.Ourlongtermgoal istodevelopvectorsthataresaferandmoreeffective.

AndrewByrnes,Ph.D.

DivisionofCellularandGeneTherapiesOf iceofCellular,TissueandGeneTherapiesCenterforBiologicsEvaluationandResearch

Fellow:GinaConenello,Ph.D.

49

Scienti icandProfessionalBackgroundB.S.BiologyM.S.BiologyPh.D.ToxicologyAmericanBoardofToxicologyDiplomatFDAexperience—9yearsResearchInterestsMutagenesisandcarcinogenesis,especiallyinearlybiomarkersforcarcinogenexposureusingmutationdetectionandanalysisandgeneexpressionanalysisofmRNAandmi‐croRNA.

TaoChen,Ph.D.,D.A.B.T.

DivisionofGeneticandReproductiveToxicologyNationalCenterforToxicologicalResearch

Jefferson,AR

Fellow:XinrongChen,Ph.D.

50

Scienti icandProfessionalBackgroundB.S.UniversityofCalifornia,DavisM.S.UniversityofCalifornia,DavisPh.D.UniversityofCalifornia,DavisResearchInterestsDr.Chu’sresearchfocusesonanalyticalmethoddevelopmentfordrugresiduesinbiologi‐calmatricesandontheirmetabolismanddispositioninanimals.Hiscurrentresearchef‐fortsareaimedatdevelopinganalyticalmethodologiesforhormonesandfortheirmetab‐olites.ConventionalmethodsofdetermininghormoneresiduestypicallyinvolveaninitialhydrolysisofthephaseIIconjugatesfollowedbyderivatizationanddetectionongaschro‐matography–mass spectrometry. Information concerning the identity of the conjugates(glucuronidesorsulfates),however,islostafterhydrolysis.Forthisreason,Dr.Chuisin‐vestigatingnewapproachesofdetectingandquantifyingtheintactphaseIIconjugatesus‐ingliquidchromatography–tandemmassspectrometry.

Pak‐SinChu,Ph.D.

DivisionofResidueChemistryCenterforVeterinaryMedicine

Fellow:WeiSong,Ph.D.

51

Scienti icandProfessionalBackgroundM.S.MT(ASCP)Ph.D.MT(ASCP)FDAexperience—3yearsResearchInterestsInfectiousdiseases;Microbiology;Immunology;Host‐parasiterelationshipsininfectiousdiseases;virulencemechanismsofmicroorganisms;hostdefensemechanisms;develop‐mentofdiagnostictestsforinfectiousdiseasesofanimals

MaureenDavidson,Ph.D.

Of iceofResearchDivisionofAnimalandFoodMicrobiology


Fellow:MariaCruz‐Fisher,Ph.D.

52

Scienti icandProfessionalBackgroundB.S.CollegeofWilliam&MaryPh.D.UniversityofVirginiaResearchInterestsSince1994,Dr.DurforhasservedwithintheCenterforDevicesandRadiologicalHealth’sOf iceofDeviceEvaluationasScienti icReviewerandIDE/PMATeamLeaderinthePlas‐ticandReconstructiveSurgeryBranch. Inthisroleheperformedandsupervisedthere‐viewofthe irstcellularmedicaldevicestoreceiveFDAapprovalaswellasotherproductscomposedofprotein,polysaccharideandbiomimeticcomponentsthatareusedtotreatadiverse arrayof indications (e.g.,wound repair, surgical adhesionprophylaxis, and cos‐meticcorrectionofsofttissuedefects).

CharlesDurfor,Ph.D.

DivisionofGeneral,RestorativeandNeurologicalDevicesOf iceofDeviceEvaluation


Fellows:AlexanderBailey,Ph.D.andRebeccaRobinson,Ph.D.

53

Scienti icandProfessionalBackgroundB.S.NorthDakotaStateUniversityPh.D.NorthDakotaStateUniversityFDAexperience—9yearsResearchInterestsMy research interests are largelybeen in the ields of bacterial pathogenesis, zoonoses,foodsafety,andmolecularmethodsforpathogencharacterization.Speci icareasofinter‐est includeunderstanding thedistributionofentericpathogens,and theirvirulenceandantimicrobial resistance factors in foodproductionenvironments.Byunderstanding thedistributionmechanismsofpathogens,wemaybeabletodevelopinterventionstoreducethespreadofpathogenicmicroorganismsfromfoodsourcestohumans.Iamalsointerest‐ed in thedevelopmentofmethods tobetterunderstand thecontributionofplasmiden‐coded genes to enhanced bacterial function. Plasmids are capable of horizontal genetransfer,whichcouldfacilitatethespreadofantimicrobialresistanceandincreasedviru‐lenceamongbacterialeadingtomoredif iculttotreatinfections.Thusamorecomprehen‐siveunderstandingofplasmidgeneticsandassociatedphysiologyshouldultimatelyleadtoimprovedpublichealth.

StevenFoley,Ph.D.

DivisionofMicrobiologyNationalCenterforToxicologicalResearch

Jefferson,AR

Fellow:KuppanGokulan,Ph.D.

54

Scienti icandProfessionalBackgroundPh.D.UniversityofTennesseeFDAexperience—8yearsResearchInterestsTheCenterforFunctionalGenomicsuseshigh‐informationcontentgenomicstechnologies(e.g.,expressionmicroarrays,arrayCGH/SNParrays) inthedevelopmentofmechanisticandbiomarkerdatatosupportimprovedsafetyassessments.Whole‐genomecommercialarrays, aswell as in‐house fabricatedcustommicroarrays, showgreatpromise indrug‐safetyevaluation,andFDAisactivelyencouragingthisnewtechnology.Majorefforts in‐clude:(1)discoveryandvalidationofpreclinicalpredictivetoxicologybiomarkers,(2)de‐velopmentandapplicationofnewhigh‐throughput tools, and (3) servingasanFDAre‐source for genomics issues. Of particular interest are (1) the translation of non‐clinicalpredictivebiomarkerstotheclinicand(2)theglobal integrationofgenomic,proteomic,andmetabolomic information for a systems toxicology approach tobiomarkerdevelop‐ment.

JamesFuscoe,Ph.D.

Director,CenterforFunctionalGenomicsDivisionofSystemsToxicology


Fellow:YunGe,Ph.D.

55

Scienti icandProfessionalBackgroundM.S.BrighamYoungUniversityM.P.H.HarvardUniversityM.D.UniversityofUtahDr.P.H.HarvardUniversityFDAexperience—5yearsResearchInterestsDatasystemsforepidemiologicresearchandregulatorypurposestoenhancepublichealthandprotection.

JohnGardner,M.D.,Dr.P.H.

Of iceofInformationManagementOf iceoftheCommissioner

Fellow:XingfangLi,M.D.

56

Scienti icandProfessionalBackgroundFDAexperience—10+yearsResearchInterestsLearn‐Apply’ approach todrugdevelopmentand regulatorydecisionmaking. Quantita‐tiveClinicalPharmacologyorPharmacometrics..Modelingandsimulationofclinicaltrials.Clinicaltrialdesign.DoseoptimizationusingPharmacometrics.Quantifyingthein luenceofpoliciesandregulations

JogaGobburu,Ph.D.

DivisionofPharmacometricsOf iceofClinicalPharmacologyOf iceofTranslationalSciences


Fellow:MichaelBewernitz,Ph.D.

57

Scienti icandProfessionalBackgroundPh.D.KansasUniversityMedicalcenterAcademyifToxicologicalSciencesFellowFDAexperience—23yearsResearchInterestsThepropertiesofnanomaterials‐suchassmallsize,largesurfacearea,andhighreactivity‐thatimparttremendouspotentialfortechnologicaladvancesarealsotheverypropertiesthat may be responsible for adverse clinical effects. There is a paucity of safety infor‐mationandourlabisthereforefocusedonthephysicochemicalcharacterizationofnano‐materials,identifyingmethodstoassesspotentialhazards,understandingadversebiologi‐cal effects, and characterizing absorption and tissue distribution in laboratory animalmodelsandhumans.Thisknowledgebaseiscriticalinordertodevelopamoreconsistentandpredictableregulatorypathwayforaddressing issuesofsafetyandef icacyofnano‐basedmedicalproducts.

PeterGoering,Ph.D.

LaboratoryofToxicologyDivisionofBiology

Of iceofScienceandEngineeringLaboratoriesCenterforDevicesandRadiologicalHealth

Fellow:MarthaBetz,Ph.D.

58

Scienti icandProfessionalBackgroundPh.D.UniversityofCamerino,ItalyPost‐DoctoralFellowship,UniversityofFlorida,Gainesville,FLFDAexperience—1yearResearchInterestsCreutzfeldt‐Jakobdisease (CJD) and its variant (vCJD) are rare, fatal, neurodegenerativedisordersknownastransmissiblespongiformencephalopathies(TSEs),orpriondiseases.ThenatureoftheagentscausingTSEsandtheirmechanismofreplicationarestillcontro‐versialissues.TSEsaretransmissiblebybloodandbloodandtissueproducts,butthereisnoante‐mortemtesttoscreendonors.OurresearchfocusesonTSEagentsinbloodwiththe inalgoalofreducingtransfusiontransmissionrisksandimprovingthesafetyoftheblood supply. Speci ically,we are interested in how infectivity is transmitted and repli‐catesinblood,whatbloodcomponentsharborinfectivity,howtoscreenforinfectedblooddonationsandhowtoremovetheinfectiousagentfromblood.TSEassaysaretechnicallychallenging,andtraditionalapproacheshavefailedsofar.Wearetestingapromisingal‐ternativetechnologycalledproteinmisfoldingcyclicampli ication(PMCA)thatmayhavesuf icientsensitivitytodetectPrPTSE,thesurrogatemarkerforinfectivity,inplasma.Weare alsoproducing largepanels ofmonkeyplasma samples infectedwith vCJD agent asbiological reference standards to validate blood screening tests. Our efforts to removalTSEinfectivityfromblooduseaf inityligandsimmobilizedonbeadsassembledinto ilterdevices. Inallourstudies,weuseexperimentalanimalmodels tomeasure infectivity inblood,includingexaminationofneuropathologicalchangesinbrainsoftheanimalstocon‐irmTSE.

LuisaGregori,Ph.D.

DivisionofEmergingandTransfusionTransmittedDiseasesOf icerofBloodResearchandReview

CenterforBiologicsResearchandEvaluation

Fellow:JulieNemecek,Ph.D.

59

Scienti icandProfessionalBackgroundB.S.OuachitoBaptistUniversityM.S.OklahomaStateUniversityPh.D.MississippiStateUniversityFDAexperience—7yearsResearchInterestsDespiteadvancementofantimicrobialregimensandimprovedpublichealth,Staphylococ‐cusaureus,agram‐positivebacteriumthatresidesontheskinandmucousmembranesofapproximately30%ofhealthyindividualsandashighas90%ofhealthcareworkers,re‐mains an importantbacterialpathogen responsible fornumerousdisease syndromes inhumansandanimalsworldwide.Justasimportantisthecontinualriseinthenumberofmethicillin(oxacillin)‐resistantS.aureus(MRSA)notonlyinisolatesacquiredinhospitals,butalsothoseencounteredinthecommunity.BecauseS.aureusisnotoriousforacquiringmultipleantibioticresistancedeterminants,ithasbecomeincreasinglyimportantthatal‐ternativesotherthanantibiotictherapybedevelopedforthepreventionandtreatmentofdiseasescausedbyS.aureus.Inordertodevelopanalternativeapproaches,webelieveacomprehensiveanalysisofallextracellularproteinsproducedbyanumberofrepresenta‐tive S. aureus strains is required.Our recenteffortshaveutilizedone‐dimensional SDS‐PAGEandnanoliquidchromatographycoupledwithmassspectrometryintandemtogen‐erateacomprehensiveextracellularproteinpro ileforS.aureusUAMS‐1,aclinicalosteo‐myelitisisolates,anditsagrandsarAglobalregulatormutants.Thisapproachhasidenti‐iedseveraldifferenceswithrespecttotheabundanceofcertainproteinswhicharenowunderinvestigationastotheirroleinvirulenceandwhetherornottheseproteinscouldbeusedaspotentialtargetsforthedevelopmentoftherapiesforthetreatmentofdiseasecausedbyS.aureus.

MarkHart,Ph.D.

DivisionofMicrobiologyNationalCenterforToxicologicalResearch

Jefferson,AR

Fellow:HaijingHu,Ph.D.

60

Scienti icandProfessionalBackgroundB.S.CornellUniversityM.S.UniversityofWisconsin‐MadisonPh.D.UniversityofWisconsin‐MadisonFDAexperience—18yearsResearchInterestsEffects of processing on the formation, destruction and detection of natural toxins andchemical contaminants;Effectsofprocessingonbioactive foodcomponents;Developingbest practices for detecting and controlling food allergens and microbial pathogens infoodmanufacturingfacilities.

LaurenJackson,Ph.D.

Of iceofFoodSafetyDivisionofFoodProcessingScienceandTechnology

FoodChemistryandNutritionTeamCenterforFoodSafetyandAppliedNutrition

BedrockPark,IL

Fellow:ElizabethGrasso,Ph.D.

61

Scienti icandProfessionalBackgroundB.S.FoodScienceM.S.FoodSciencePh.D.FoodEngineeringFDAexperience—22yearsResearchInterestsProcessing factors effecting extended shelf life of food,. New preservation technology.Softwarevalidationcriteriaforcomputerizedprocesscontrolsystems.Validatinglow‐acidcannedfoodprocessingsystems.Pasteurizationprocessingforjuiceandtreenuts.Asepti‐callyprocessedfoodscontainingparticulates.

JohnLarkin,Ph.D.

PEB/DFPST/OFSCenterforFoodSafetyandAppliedNutrition

Summit‐Argo,IL

Fellow:HongliuDing,Ph.D.

62

Scienti icandProfessionalBackgroundFDAexperience—10yearsResearchInterestsBloodandcelltherapyproductrecoverytechnologiesandeffectsondonors;invitroas‐saysforassessmentofcellproductcharacterizationandpotency.

EllenLazarus,M.D.

Captain,U.S.PublicHealthServiceDirector,DivisionofHumanTissues

Of iceofCellular,Tissue,andGeneTherapiesCenterforBiologicsResearchandEvaluation

Fellow:Yun‐ShangPiao,Ph.D.

63

Scienti icandProfessionalBackgroundM.D,GeorgetownUniversityFDAexperience—7yearsResearchInterestsScienti icpolicy‐focusedresearchonfoodallergies.Understandinghealthrisksassociatedwithlowlevelfoodallergenexposures.Evaluatingconsumerdatabasestoquantifyaller‐genichazardsfromfood.

IamcurrentlytheprogramleadforCFSAN’sStrategicResearchPlanonfoodallergens.Ialsohaveclinicalresearchaf iliationsatGeorgetownUniversityandhavebenchresearchexperiencewithanimalmodelsofasthma

StefanoLuccioli,M.D.

Of iceofFoodAdditiveSafetyCenterforFoodSafetyandAppliedNutrition

Fellow:ErnestKwegyir‐Afful,Ph.D.

64

Scienti icandProfessionalBackgroundM.D.,Ph.D.JohnsHopkinsUniversityCouncilforExcellenceinGovernmentFellowFDAexperience—11yearsResearchInterestsTheOf iceofDeviceEvaluation,CenterforDevicesandRadiologicalHealth(CDRH)con‐ducts premarket reviewof cutting edge therapeutic anddiagnostic device technologies.ThiscomponentoftheFDAevaluatesthesafetyandeffectivenessofnewmedicaldevicespriortotheirintroductionintothemarketplace.Dr.Lukehasresearchinterestsinclinicalstudy design, clinical endpoints assessment, and scale development (including patient‐reportedoutcomes)forbothef icacyandsafetydeterminationofmedicalproducts.Spe‐ci icattributesofmedicaldevicesandtheirimpactonblindingandvariabilitywhenusedin thehandsofcliniciansand impactonclinical trialvalidityandoutcomearecurrentlybeingassessed.

MarkhamLuke,M.D.,Ph.D.

ClinicalDeputyOf iceDirectorOf iceofDeviceEvaluation


Fellow:MaryamMokhtarzadeh,Ph.D.,andSuzanneSchwartz,Ph.D.

65

Scienti icandProfessionalBackgroundFDAexperience—4yearsResearchInterests1. Useofquantitativeapproachestocharacterizethebene it‐riskofprescriptiondrugsto

patientsreceivingnewprescriptions.2. Todevelopamodelofthepublichealthimplicationsofdifferentpatternsforusingan‐

tihypertensivedrugs.3. Tooptimizetrialdesignforstudyinganti‐hypertensivesinpediatricsusingmodeling

andsimulationtechniques.

RajanikanthMadabushi,Ph.D.

Of iceofClinicalPharmacologyCenterforDrugEvaluationandResearch

Fellow:Tzu‐YunChang‐McDowell,Ph.D.

66

Scienti icandProfessionalBackgroundB.S.UniversityofMarylandFDAexperience—15yearsResearchInterestsAsBranchChiefoftheCardiacElectrophysiologyandMonitoringBranchoftheDivisionofCardiovascularDevices(DCD)intheCenterforDevicesandRadiologicalHealth,Mr.Mallishasprimaryoversightfortheregulatoryreviewscienceevaluationofcardiovascularmed‐icaldevices,includingthosewhichfeaturecombinationsofbiologicsandmedicaldevices.

EliasMallis,B.S.

Chief,CardiacElectrophysiologyandMonitoringDevicesDivisionofCardiovascularDevices

Of iceofDeviceEvaluationCenterforDevicesandRadiologicalHealth

Fellows:AlexanderBailey,Ph.D.

andRebeccaRobinson,Ph.D.

67

Scienti icandProfessionalBackgroundB.S.UniversityofSouthFloridaPh.D.UniversityofSouthFloridaFDAexperience—12yearsResearchInterestsStrategicImprovementinTechnology,MethodologyandCapabilitiesinvolvingRegulatoryBiological/MicrobiologicalMassSpectrometry

WilliamMartin,Ph.D.

Paci icRegionalLaboratorySouthwestOf iceofRegulatoryAffairs

Irvine,CA

Fellow:SarahPierce,Ph.D.

68

Scienti icandProfessionalBackgroundPh.D.ChemistryFDAexperience—4yearsResearchInterestsThedevelopmentofepigenetictherapiesforcancerisoneofthemostactivelyemergingareasinclinicaloncology.Epigeneticprocessessuchaschromatinremodeling,DNAmeth‐ylation, histone acetylation andRNAi‐mediated gene silencingplay a central role in thegenesisofmostcancers.Manycancertherapiestargetingtheseprocessesareunderdevel‐opmenttooptimizethetreatmentoutcomeofbothhematopoieticmalignanciesandsolidtumors.Despitemajoradvances inpre‐clinical indings,themajorityofcancertherapiesfail inclinical trialsduetoseveretoxicityandoff‐targeteffects.Our long‐termgoal is toidentifybiomarkerstomaximizethepredictivevalueofpreclinicaldatasupportingclini‐caltrialsincancerepigenetictherapies.Theacquiredinformationwillaidinmakingmoreinformedreviewdecisionswithrespecttosafety,ef icacyanddosingofthesedrugs.

AkhileshNagaich,Ph.D.

DivisionofTherapeuticProteinsOf iceofBiotechnologyProductsOf iceofPharmaceuticalSciences


Fellow:SudipanKarmakar,Ph.D.

69

Scienti icandProfessionalBackgroundPh.D.GeorgiaInstituteofTechnologyM.S.GeorgiaInstituteofTechnologyB.S.UniversityofMichiganResearchInterestsTheDivisionofSolidandFluidMechanics(DSFM)withintheOf iceofScienceandEngi‐neeringLaboratories(OSEL)havethreemainresearchgroups:solidmechanics, luidme‐chanics,andultrasonics.Withinthesolidmechanicsgroup,ourresearchprojectsarefo‐cusedoninvestigatingtherootcausesoffailureintraditionalandemergingmedicalprod‐uctstohelppreventfuturemajoradverseevents.Currentinterests inthisgroupare(1)Developmentoftestmethodstoevaluatetheeffectofmechanicalloadingonbioabsorba‐blemedicalimplantsand(2)Theeffectsofvertebroplastydevicesonadjacentlevelfrac‐ture inwomen and (3) Investigation of factors resulting inmechanical failure of over‐lappedstentsinswine.

SrinidhiNagaraja,Ph.D.

Of iceofScienceandEngineeringLaboratoriesDivisionofSolidandFluidMechanics


Fellow:ShikhaGupta,Ph.D.

70

Scienti icandProfessionalBackgroundB.A.WesleyanUniversityM.D.YaleUniversitySchoolofMedicineM.Div.YaleDivinitySchoolPh.D.HarvardUniversityFDAexperience—3yearsResearchInterestsMyresearchhasfocusedontwobroadareasofpediatricresearchethics: theethicalas‐pectsofpediatricclinicalinvestigationsinvolvingFDAregulatedproducts,andempiricalinvestigations intodifferent aspects of parent and childdecision‐making concerning re‐searchparticipation.AtFDA,speci icareasofinterestincludeethicalaspectsofdifferenttrialdesigns,thechoiceofcontrolgroups(includingplacebocontrols),theuseofanimalmodels,theassessmentofresearchrisksandthepossibilityofdirectbene it,andethicalaspectsofinternationalpediatricresearch.Myacademicresearchhasfocusedonriskper‐ception,voluntarychoice,andthebalancingofrisksandpotentialbene itsinmakingade‐cision about the design of clinical trials.My academic research has been funded by theGreenwall Foundation, the National Science Foundation, and the National Institutes ofHealth.

Robert“Skip”Nelson,M.D.,Ph.D.

PediatricEthicistOf iceofPediatricTherapeutics


Fellows:JasonGerson,Ph.D.andPatriciaBright,Ph.D.

71

Scienti icandProfessionalBackgroundM.D.Ivano‐FrankivskMedicalUniversityPh.D.KyivNationalMedicalUniversityFDAexperience—18yearsResearchInterestsTheroleofgeneticandepigeneticchangesintheetiologyofcancer.

IgorPogribny,M.D.,Ph.D.

DivisionofBiochemicalToxicologyNationalCenterforToxicologyResearch

Jefferson,AR

Fellow:NatalieSimpson,Ph.D.

72

Scienti icandProfessionalBackgroundM.D.JohnHopkinsUniversityPh.D.JohnHopkinsUniversityResearchInterestsHuman Immunology, ImmuneTolerance,and the ImmunogenicityofBiologicTherapeu‐tics.Mylabsresearchprogramrepresentsaunionofmylong‐standinginterestinimmuneactivationandimmunetolerancewiththeregulatorymissionoftheAgencytounderstandthe immunogenicity of biologic therapeutics and to developmeans of circumventing it,includingtheinductionofimmunetolerance.Ourstudiesencompass3of5researchdisci‐plinesidenti iedbytheAgencyascentrallyimportanttoourregulatorymission;manufac‐turingscience,safety(immunogenicity),andbiologicalcharacterization(cellulartargets).

JackRagheb,M.D.,Ph.D.

LaboratoryofImmunologyDivisionofTherapeuticProteinsOf iceofBiotechnologyProducts


Fellow:KristinaHoward,D.V.M.,Ph.D.

73

Scienti icandProfessionalBackgroundB.S.UniversityofZurich,SwitzerlandPh.D.UniversityofBasel,SwitzerlandFDAexperience—2yearsResearchInterestsLentivirusesarecomplexretrovirusesthatincludehumanimmunode iciencyvirusessuchasHIV‐1.Weareworkingonthedesignofsaferlentiviralvectorsfortransgenedeliveryinvitro, ex vivo and in vivo. A special emphasis is on targetable vectors for cell‐speci ictransductionandonvectorscapableofsite‐speci icintegration.

JakobReiser,Ph.D.

DivisionofCellandGeneTherapiesCenterforBiologicsEvaluationandResearch

Fellow:SeraphinKuate,Ph.D.

74

Scienti icandProfessionalBackgroundB.A.UniversityofRochesterPh.D.UniversityofFloridaResearchInterestsTheCenter forHepatotoxicologyaddressescritical liver‐injury issuesbyapplyinga sys‐tems‐toxicologyapproach.Thegoal is to improve the identi icationofhepatotoxic com‐poundspriortohumanexposureandtoaugmentthedetectionofearlysignsofinjuryinhumansinducedbydrugs,chemicals,anddiseaseprocesses.Biomarkerswillbeidenti iedusingintegratedgenomics,metabolomics,proteomics,andbioinformaticsapproaches.Inorder to ensure that the integrated approach addresses real‐world FDA needs, a broadworkinggroupwasformedconsistingofexpertsinpreclinicalandclinicallivertoxicity.

WilliamSalminen,Ph.D.,D.A.B.T.

DirectoroftheCenterforHepatotoxicityDivisionofSystemsToxicology


Fellow:AkhtarAli,Ph.D.

75

Scienti icandProfessionalBackgroundB.S.VirginiaPolytechnicInstituteandStateUniversityM.S.AmericanUniversityAmericanBoardofToxicologyDiplomatResearchInterestsThe numerous products regulated by theOf ice of Cellular, Tissue, andGeneTherapies(OCTGT)includegenetherapy(exvivotransductionofcellsanddirectinjectionofprod‐uct),tumorvaccines,xenotransplantation,humanstemcells(embryonic,fetal,andadult),varioushumantissuepreparations(fetalandadult),combinationproducts(biologic‐drug,biologic‐device,etc…),andtissueengineeredtissues.Bylaw,eachinvestigationalproductmustbeshowntobeadequatelysafe,usuallyviatheconductofinvitrostudiesand/orinvivostudiesinanimals(termed‘preclinical’),foradministrationintohumanswithtarget‐ed diseases/injuries; however, this pathway for many of these products have few/noprecedentstoguideinthecomprehensiveassessmentofsafety.Ms.Serabianisresponsi‐ble foroverseeing thepreclinical review, regulation, andpolicydevelopment for all celland gene therapyproducts that areunder the regulatorypurviewofOCTGT/CBER. Sheleadsanexpertgroupofscientiststhatareresponsibleforthescienti icreviewofallpre‐clinical studies submitted to OCTGT in support of their safe use in human trials. ThisgroupinteractswithindividualsinCenterforDevicesandRadiologicalHealth(CDRH)inthepreclinicalreviewofcertainproductthatincludetissueengineeredproductsandre‐generative medicine products, and biologic‐device combinations. Areas of interactionswithCDRHhave includedcardiac/vascular,orthopedic,andneurological.She isalso therepresentativeforCBER/FDAintheexpertworkinggroupsfortheInternationalConfer‐enceonHarmonisation(ICH),providingexpertinputonthepreclinical(Safety)guidelinesthatarepublished.ShehasalsoinitiatedaseriesofdiscussionbetweenCBERpharmacol‐ogy/toxicologystaffandmembersoftheBiotechnologyIndustryOrganization(BIO),whoareresponsibleforthepreclinicaltestingofinvestigationalbiologics.Sheactivelypartici‐patesandoverseestheparticipationofreviewersinhergroupsasrepresentativesofOC‐TGTat intracenter, intercenter, interagency,national, and internationalmeetings,work‐shops,andsymposiumsintheareaofcellularandgenetherapy.

MercedesSerabian,M.S.,D.A.B.T.

Chief,Pharmacology/ToxicologyBranchDivisionofClinicalEvaluationandPharmacology/Toxicology

Of iceofCellular,TissueandGeneTherapiesCenterforBiologicsEvaluationResearch

Fellows:AlexanderBailey,Ph.D.

andRebeccaRobinson,Ph.D.

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Scienti icandProfessionalBackgroundM.S.,Ph.D.,EotvosLorandUniversity,Budapest,HungaryUniformedServicesUniversity,Bethesda,MarylandResearchAssistantProfessor,1997‐2004FDAexperience—5yearsResearchInterestsBcellsproduceantibodies thatmarkpathogens forelimination.Bcellactivation iscon‐trolledatmultiplestepsthroughdynamicengagementofanarrayofreceptors,ensuringadequateresponsestoclearpathogensyetavoidingexcessiveorautoimmuneresponses.TherecentdiscoveryofsixFc‐receptorlike(FCRL)proteinswithsignalingpotentialandpreferential B lineage expression has considerably broadened the network of possiblelymphocyte co‐receptors. Importantly, FCRL are implicated in tumor development andautoimmunity.Duetotheirrestrictedexpressiononspeci icsubsetsofBcells,FCRLarealsopotential new tumormarkers and candidate targets of tumor immunotherapy.Ourlaboratoryhasbeen investigating the regulationof FCRLgene expressionand the func‐tionalrolesofFCRLproteins.Onecurrentfocusistoidentifyonco‐virusesandoncogenesthatperturbFCRLgeneexpression.Betterunderstandingofthefunctionsandtranscrip‐tional regulationofFCRLwillhelpde ine the roleofFCRL in tumor formationandpro‐gression. Inaddition,weaim to identifyproteins that interactwithFCRL5eitheras lig‐andsorascellularproteins, inordertoilluminateFCRL5function.BetterunderstandingofthefunctionsandtranscriptionalregulationofFCRLwillhelpde inetheroleofFCRLindiseaseinitiationandprogression.Resultsofthisworkcan:(1)Facilitatereviewofprod‐uctstargetingFCRLandrelatedtargetsonB‐lymphocytes,(2)Provideinsightintomecha‐nismsthatleadtoderegulatedFCRLproteinexpressionindiseasedcells,(3)Elucidatethespeci ic contributionsofviralproteinsandhostoncogenes to cancer, and (4)HelpwithpredictingpotentialadverseeffectsthatmayresultifnormalBcellsareaffectedbythera‐piesthattargetFCRLmolecules.

MateTolnay,Ph.D.

DivisionofMonoclonalAntibodiesOf iceofBiotechnologyProducts


Fellow:BazarragchaaDamdinsuren,Ph.D.

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Scienti icandProfessionalBackgroundB.S.NorthernIllinoisUniversityM.S.LoyolaUniversityofChicagoPh.D.CornellUniversityFDAexperience—18yearsResearchInterestsBehaviorofmicroorganismsinfoodsandfoodprocessingenvironments;mechanismsofcontrol for ensuringmicrobiological safetyof foods;developmentof improvedmethodsforsampling,samplepreparation,detection,andidenti icationofmicroorganismsinfoodsandfoodprocessingenvironments.

MaryLouTortorello,Ph.D.

Of iceofFoodSafetyDivisionofFoodProcessingScienceandTechnology


Fellow:AnnemarieBuchholz,Ph.D.

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Scienti icandProfessionalBackgroundB.S.NorthernIllinoisUniversityM.S.IllinoisInstituteofTechnologyPh.D.UniversityofSouthernCaliforniaFDAexperience—9yearsResearchInterestsProjectscenteringonthedevelopmentofmolecularmethodstodetectpathogensinfoods:

1.Detectionofhighriskpathogens(selectagents)includingBacillusanthracis,YersiniapestisandFrancisellatularensisusingBSL‐3safetyprocedures;

2.DetectionoflowlevelsofE.coliO157:H7internalizedinleafygreensusingqPCR;

3.UseofmagneticbeadtechnologytodetectHepatitisAinfoodmatrices.

DonnaWilliams‐Hill,Ph.D.

Paci icRegionalLaboratorySouthwestOf iceofRegulatoryAffairs

Irvine,CA

Fellow:RosaleeHellberg,Ph.D.

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Scienti icandProfessionalBackgroundFDAexperience—2yearsResearchInterests1.Toimprovetoolstoquantifyandpredictdose‐relatedadverseeventriskinpatientswithimpairedrenalfunction.

2.Todevelopnovelpredictivemodelsofdrugsafetyandef icacyinpatientswithim‐pairedkidneyfunction.

3.Tostreamlineclinicaltrialsindrugdevelopmentfrombetterquanti icationandpredic‐tionofdose‐relatedsafetyandef icacyoutcomesinthechronickidneydiseasepopulation.

NancyXu,M.D.

DivisionofCardiovascularandRenalProductsOf iceofNewDrugsI


Fellow:ZenghuiMi,M.D.,Ph.D.

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Scienti icandProfessionalBackgroundB.S.JarvisChristianCollegePh.D.HowardUniversityFDAexperience—10yearsResearchInterestsMolecularbiomarkerdiscoverandmolecularassaydevelopment.

HaileYancy,Ph.D.

DivisionofAnimalResearchOf iceofResearch


Fellow:MarlaSwain,Ph.D.

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ProgramStaff

Jeffery B. Rexrode II Program Analyst Office of Scientific Professional Development Office of the Chief Scientist Office of the Commissioner

Jill L. Zung Program Analyst Office of Scientific Professional Development Office of the Chief Scientist Office of the Commissioner

fda commissioner's fellowship program class of 2010

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