NIEHS Spotlight Science Notebook

January 2012

2011 papers of the yearOf the nearly 3,000 papers published by NIEHS-supported researchers in 2011, 23 publications were chosen as papers of the year.

Distinguished lecturer discusses the mechanism of action of amphetamineNeuroscientist Susan Amara, Ph.D., gave a presentation Dec. 13 focused on the mechanism of action of amphetamine on dopamine and glutamate transporters.

NIEHS selects 2012 ONES awardeesNIEHS has announced funding for seven early stage tenure-track investigators as 2012 Outstanding New Environmental Scientist (ONES) awardees.

Researchers find potential new avenue for cancer therapiesThe research team, comprised of scientists from NIEHS and several other institutions, published its data online in the Dec. 19 issue of The Journal of Clinical Investigation.

Seminar explores the potential of bioinformatics in autism researchPresenters outlined techniques for taking advantage of computational and screening approaches to expand the existing knowledge base surrounding autism.

Tox21 begins screening 10,000 chemicalsIn December, a high-speed robotic screening system, aimed at protecting human health by improving how chemicals are tested in the U.S., began screening compounds.

NIEHS collaborates on autism database federationFunded by NIEHS and four other NIH institutes and centers, the National Database for Autism Research has launched a precedent-setting data-sharing collaboration.

Balbus discusses health adaptation at climate change summitA side event presentation Dec. 8, organized by NIEHS, explored early warning systems and frameworks for vulnerability and adaptation assessments for human health.

Copeland named chief of Laboratory of Molecular GeneticsWilliam Copeland, Ph.D., who leads the Laboratory of Molecular Genetics Mitochondrial DNA Replication Group, had served as acting chief since July 2011.

Grantee honored by association of science teachersNIEHS grantee Kathleen Vandiver, Ph.D., was recognized for her more than 20 years of significant contributions to Massachusetts science education.

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NIEHS Spotlight Science Notebook

Birnbaum and staff hold conversation with NIEHS PartnersFollowing morning presentations, Partners enjoyed a nearly three-hour informal lunchtime conversation with NIEHS/NTP Director Linda Birnbaum, Ph.D.

Nano Grand Opportunities researchers share findingsThis was the final meeting of the consortium, which began in 2009 with 13 two-year grants funded from the American Recovery and Reinvestment Act.

Holian discusses lung inflammation caused by nanoparticlesNIEHS grantee Andrij Holian, Ph.D., presented the latest results from his experiments on the health and safety aspects of engineered nanomaterials Dec. 6 at NIEHS.

Hundreds of rare genetic variants may cause a common autism phenotypeCatalina Betancur, M.D., Ph.D., delivered a presentation Nov. 30 at NIEHS titled “Deconstructing ‘idiopathic’ autism: One behavioral syndrome, hundreds of genes.”

NTP board moves initiatives forwardFaced with a full agenda of reports and concept clearances, the NTP Board of Scientific Counselors (BSC) accomplished quite a bit during its Dec. 15, 2011, session at NIEHS.

NICEATM workshop report on vaccine testing now availableThe NTP-sponsored workshop, which is described in the current issue of Procedia in Vaccinology, was held Sept. 14-16, 2010, at NIH in Bethesda, Md.

mHealth Summit highlights advances in mobile health technologyRepresentatives from NIEHS joined more than 3,500 leaders from around the world to engage in constructive dialogue about leading-edge mobile health technologies.

NIEHS postdocs learn the value of options at NC biotech career dayNIEHS postdocs joined dozens of their colleagues at the N.C. Biotechnology Center Dec. 9 for the third installment of the organization’s Ph.D. career series.

Kleckner offers glimpses inside a living E. coli cellDuring a Nov. 21 seminar at NIEHS, Nancy Kleckner, Ph.D., presented exciting findings from her group’s recent work on the physical biology of chromosomes.

Award-winning summer intern accepted by StanfordNIEHS summer intern Greeshma Somashekar learned in December that one of America’s premiere scientific institutions is now officially on her list of possibilities.

Freedman represents NIEHS/NTP at conference in PeruJonathan Freedman, Ph.D., represented NIEHS/NTP leadership at the II International Congress and IV Peruvian Congress of Toxicology meeting Nov. 21-23 in Lima, Peru.

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Inside the Institute

Institute staff honored at 2011 NIEHS awards and international dayNIEHS welcomed federal staff and contractors to Rodbell Auditorium Dec. 6 for its annual Awards Ceremony and International Day festivities.

CFC enjoys another record yearCombined Federal Campaign Dec. 15, 2011, setting yet another record by raising $110,000 in pledges from more than 200 employees.

NTA celebrates grand opening of resource roomWith a ceremonial coffee hour and open house Nov. 30, the NIEHS Trainees Assembly proudly opened the doors to its new resource room in the F module of Building 101.

NIEHS Spotlight

NTP advisor named as fellow of the Collegium RamazziniNTP Board of Scientific Counselors chair David Eastmond, Ph.D., is among the latest group of fellows selected by the Collegium Ramazzini.

Volunteers translate NIEHS cookstove research in GuatemalaNIEHS/NTP Director Linda Birnbaum, Ph.D., received an unexpected holiday gift Dec. 24, thanking her for NIEHS research on respiratory illness and indoor air pollution.

Science Notebook

Casey presents at international meeting in HungaryAt an expert meeting in Budapest, Nov. 30-Dec. 2, 2011, NICEATM Assistant Director Warren Casey, Ph.D., discussed in vitro methods for identifying endocrine disruptors.

NIEHS to hold minisymposia on epigenetics and BPAAs part of its Keystone Science Lecture Seminar Series, NIEHS will present minisymposia in January, organized by its Division of Extramural Research and Training.

This month in EHPThe journal’s lead story for January examines a new strategy for evaluating the impact of regional and local-level climate changes on public health.

Society for Investigative Dermatology to meet May 9-12 in RaleighA diverse group of some 1,500 M.D. and Ph.D. scientists from around the globe will gather to present and exchange findings on dermatology and skin biology.

Stokes builds international partnerships for advancing alternative testingRear Adm. William Stokes, D.V.M., joined other scientists from around the world at meetings in Japan on promoting and validating alternatives to animal testing.

Extramural Research

Extramural papers of the month• Rice consumption and arsenic exposure in

pregnant women • Consuming canned soup linked to higher

BPA levels

• Dietary compounds could help protect kidney function

• Estrogen lessens effects of obesity and alcohol on breast cancer

Intramural Research

Intramural papers of the month• Caffeine strengthens connections between neurons

in a little-known area of the brain

• Exposures to certain early-life factors may contribute to an early onset of uterine fibroids

• Snail and Slug activate TGF-beta in breast cancer

• Pregnane X receptor regulates liver metabolism

Calendar of Upcoming Events

• Jan. 6, in Rodbell A, 11:00 a.m.-12:00 p.m. — Laboratory of Reproductive and Developmental Biology Seminar Series featuring Raj Kumar, Ph.D., speaking on “Regulation of Male Germline Stem Cell Niche by FSH”

• Jan. 10, in Rodbell Auditorium, 8:30 a.m.-5:00 p.m. — Keystone Science Lecture Seminar Series “Minisymposium: Epigenetics, Chromatin Biology, Development, and Disease,” register

• Jan. 13 (offsite event), in the Levine Science Research Center, Room A247, at Duke University in Durham, N.C., 12:00-1:00 p.m. — Integrated Toxicology and Environmental Health Program presentation by David Armstrong, Ph.D., titled “Endocrine disruption of synaptic plasticity in the postnatal mouse hippocampus”

• Jan. 16, in Rodbell Auditorium, 8:00 a.m.-5:00 p.m. — Bisphenol A (BPA) Grantee Meeting

• Jan. 19, in Rodbell Auditorium, 1:00-5:00 p.m. — Keystone Science Lecture Seminar Series symposium on BPA

• Jan. 20, in Rodbell Auditorium, 8:30 a.m.-5:00 p.m. — Women’s Reproductive Environmental Health Consortium Meeting

• Jan. 23-24, in Rodbell Auditorium, 8:30 a.m.-5:00 p.m. — Interagency Breast Cancer and Environmental Research Coordinating Committee Meeting

• Jan. 30, in Rodbell B, 11:00 a.m.-12:00 p.m. — Presentation by Michael Diamond, M.D., topic TBA

• View More Events: NIEHS Public Calendar

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NIEHS SpotlightTox21 begins screening 10,000 chemicals By Robin Mackar

InDecember,ahigh-speedroboticscreeningsystem,aimedatprotectinghumanhealthbyimprovinghowchemicalsaretestedintheU.S.,begantesting10,000compoundsforpotentialtoxicity.Thecompoundscoverawidevarietyofclassifications,andincludeconsumerproducts,foodadditives,chemicalsfoundinindustrialprocesses,andhumanandveterinarydrugs.

Testingthis10,000compoundlibrarybeginsanewphaseofanongoingcollaborationbetweentheNationalInstitutesofHealth,theU.S.EnvironmentalProtectionAgency,andtheU.S.FoodandDrugAdministration,referredtoasTox21.NIHpartnersincludeNIEHS/NTPandtheNIHChemicalGenomicsCenter(NCGC),partoftheNIHCenterforTranslationalTherapeutics(NCTT),housedattheNationalHumanGenomeResearchInstitute(NHGRI).

“Therehasneverbeenacompoundlibrarylikethisbefore,”saidNIEHS/NTPDirectorLindaBirnbaum,Ph.D.

BirnbaumisespeciallyexcitedthatsomeofthecompoundstheNTPhasbroughtforwardfortestingaremixturesofchemicals.“Allofusareexposedtomanydifferentchemicalsatthesametime,notjustonechemicalatatime,”shesaid.“Thesenewtechnologiesallowustomorerapidlyadvanceourunderstandingofnotonlyindividualchemicals,butmixturesofchemicalsaswell.”

AsubsetoftheNTPportionofthe10,000compoundlibrarywillfocusonpilottestingseveralformulationsormixturesofcompounds,apriorityareaforNIEHS/NTP.Thelibraryconstituentswereselectedafterathoroughanalysisofexistingscientificstudies,morethan200publicchemicaldatabases,andchemicalnominationsreceivedfrominternalandexternalpartners.Eachtestcompoundwillundergoathoroughchemicalanalysistoverifyitsidentityanddetermineitspurity,concentration,andstability.

Thegoalofthetestingistoprovideresultsthatwillbeusefulforevaluatingwhetherthesechemicalshavethepotentialtodisruptprocessesinthehumanbodytoanextentthatleadstoadversehealtheffects.

ThecompoundswillbetestedintheTox21roboticscreeningsystemattheNCGCinRockville,Md.TheTox21robot,unveiledearlierthisyear,waspurchasedwithfundsprovidedbytheNTPaspartofitscontributiontotheTox21partnership.

At the dedication of the robotic system in March (see story), Birnbaum said, “This robot truly exemplifies a remarkable collaboration effort between four federal organizations that showcases how we can all bring our strengths and resources to the table to build the framework for a new predictive toxicology.” (Photo courtesy of Steve McCaw)

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“Therobothasundergonerigoroustestingsinceitwasinstalledandunveiledearlierthisyear.It’sreadytostarttestingthislargecompoundlibrary,”saidNHGRIDirectorEricGreen,M.D.,Ph.D.“ThisisamilestoneforTox21,becauseitwillallowustotestchemicalsataratepreviouslyimpossibleforanyonetodobyhand.”

Thedevelopmentofmethodsforevaluatingchemicaltoxicityhasthepotentialtorevolutionizetheassessmentofnewenvironmentalchemicalsandthedevelopmentofnewdrugsfortherapeuticuse.

“WearehappytocontributeNCGC’spharmaceuticalcollectionofapproximately3,500compoundsofapprovedandinvestigationaldrugsaspartoftheTox21program,”saidNCTTScientificDirectorChristopherAustin,M.D.“Drugtoxicityisoneoftheprimaryreasonsthatthedevelopmentofnewdrugsfailsandapproveddrugsareremovedfromthemarket,andtheabilitytobetterpredicttoxicitywouldimprovetheefficiencyofdrugdevelopmentenormously.”

AlltestingresultswillbeavailabletothepublicthroughNIHandEPAchemicaltoxicitydatabases.

(RobinMackaristhenewsdirectorintheNIEHSOfficeofCommunicationsandPublicLiaisonandaregularcontributortotheEnvironmentalFactor.)

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NIH partners in Tox21Atrulyhistoriccollaboration,Tox21bringstogethercombinedresourcestohelpfurthertheindividualmissionsofitsmembers.

TheEPAseekstounderstandthemolecularbasisofsuchchemicalstobetterprotecthumanhealthandthatoftheenvironment.

“TheTox21partnershipintegratesrevolutionaryadvancesinmolecularbiology,chemistry,andcomputerscience,toquicklyandcost-effectivelyscreenthethousandsofchemicalsinusetoday,”saidPaulAnastas,Ph.D.,assistantadministratoroftheEPAOfficeofResearchandDevelopment.“TheinnovativeroboticsscreeningtechnologywillgeneratechemicaltoxicitydatathatEPAhasneverhadbefore.”

TheFDA,alsoapartnerinTox21,emphasizesthevalueofthiseffortforthepublic.“TheTox21rapidassessmentofdrugtoxicitycanbecomeapowerfulsafetytoolforprotectingtheAmericanpublic.Italsohasthepotentialtohelpbringinnovativedrugstomarketbyallowingdrugdeveloperstoidentifyunsafecandidatedrugsearly,”saidJanetWoodcock,M.D.,directoroftheFDACenterforDrugEvaluationandResearch.

Development of high-throughput robotic systems is integral to Green’s vision for NHGRI to integrate genomics and medicine. (Photo courtesy of NHGRI)

Like several other stakeholders in Tox21, Austin hopes that robotic screening can shorten the lengthy 10- to 15-year process of drug development. (Photo courtesy of NHGRI)

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NIEHS collaborates on autism database federation By Eddy Ball

FundedbyNIEHSandfourotherNIHinstitutesandcenters(ICs),theNationalDatabaseforAutismResearch(NDAR)haslaunchedaprecedentsettingdata-sharingcollaboration.

NDAR,whichisledbytheNationalInstituteofMentalHealth(NIMH),representsafederationofdatawiththeAutismGeneticResourceExchange(AGRE),anAutismSpeaksprogram.NDARmaybethelargestrepositorytodateofgenetic,phenotypic,clinical,andmedicalimagingdatarelatedtoresearchonautismspectrumdisorders(ASD),includingaportfolioofgrantssupportedbyNIEHSforresearchonenvironmentalfactorsinvolvedinASD(seestory).

“AccesstothisexpandedrepositoryofdatawillbeextremelyimportantforNIEHS-fundedresearch,”saidCindyLawler,Ph.D.,theNIEHShealthscienceadministratorwhooverseestheInstitute’sautismportfolio.“Theabilitytoaskquestionsabouthowgeneticandenvironmentalfactorsactjointlytoaffectautismriskwillbeenhancedgreatly,asmorestudiescapturedataonenvironmentalexposuresandsharethosedatathroughNDAR,wheretheycanbeintegratedwithmanyotherrichdatasetsthatwillresidethere.”(Seerelatedstory).

Maximizing resourcesInapressreleaseDec.12,NIMHDirectorThomasInsel,M.D.,wasquotedassaying,“ThecollaborationbetweenAGREandNDARexemplifiestheeffortsofgovernmentandstakeholderstoworktogetherforacommoncause.NDARcontinuestobealeaderintheefforttostandardizeandshareASDdatawiththeresearchcommunity,andservesasamodeltoallresearchcommunities.”

InthequesttounderstandASDanddeveloppreventiveandinterventionalstrategiesforthedisorders,thenewfederationenablesinvestigatorstoaccessdata,tools,andcomputationaltechniquesinNDARandothermajorpublicandprivateautismdatabasessimultaneously.Byintegratingresultsfrommultiplesources,NDARprovidesarichdatasetformultipleuses,suchasdatamining,aggregation,andviewsintothedatasupportingresearchpublications.

DatabasespreviouslyfederatedwithNDARincludeAutismSpeaks’AutismTissueProgram,theKennedyKriegerInstitute’sInteractiveAutismNetwork(IAN),andtheNIHPediatricMRIDataRepository.AGREcurrentlyhousesaclinicaldatasetwithdetailedmedical,developmental,morphological,demographic,andbehavioralinformationfrompeoplewithASDandtheirfamilies.

Lawler oversees some $7 million of NIEHS funding each year for autism research. (Photo courtesy of Steve McCaw)

In a talk at NIEHS earlier this year (see story), Insel said he welcomed collaborations with environmental health scientists in the search for what factors contribute to ASD. (Photo courtesy of NIMH)

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WiththeexpansionoftheNDARfederationtoincludeAGRE,approvedNDARuserswillhaveaccesstodatafromthe25,000researchparticipantsrepresentedinNDAR,aswellas2,500AGREfamiliesandmorethan7,500participantswhoreportedtheirowninformationtoIAN.

A trans-NIH effort AlongwithNIEHSandNIMH,NIHICssupportingNDARaretheEuniceKennedyShriverNationalInstituteofChildHealthandHumanDevelopment,theNationalInstituteofNeurologicalDisordersandStroke,andtheNIHCenterforInformationTechnology.

(ThisstorywasadaptedfromanNIMHpressreleasewrittenbyKarinLee.Forfurtherinformation,contactLeeattheNIMHPressOfficebyphoneat301-443-4526orbyemailatNIMHpress@mail.nih.gov.)

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Balbus discusses health adaptation at climate change summit By Eddy Ball

PoliticianswillnodoubtcontinuetodebateinthemonthsaheadabouttheaccomplishmentsofthelatestU.N.ClimateChangeConferenceheldinDurban,SouthAfricalastmonth(seetextbox).

Butasdelegatesstruggledwithhowtostemclimatechangeontheinternationalagreementlevel,asideeventpresentationDec.8on“SavingLives—AdvancesinHealthAdaptationforClimateChange,”organizedbyNIEHSSeniorAdvisorforPublicHealthJohnBalbus,M.D.,exploredearlywarningsystemsandframeworksforvulnerabilityandadaptationassessmentsforhumanhealth.BalbusgavetheopeningtalkdescribingU.S.effortstohelppeopleandcommunitiesbecomemoreresilienttothehealtheffectsofclimatechangeintheirdailylives.

JoiningBalbus,whorepresentstheU.S.DepartmentofHealthandHumanServices(HHS)ontheU.S.GlobalChangeResearchProgram,asspeakersattheeventwereDiarmidCampbell-Lendrum,D.Phil.,andBillBreed.Campbell-Lendrum,aseniorscientistinthedepartmentofPublicHealthandEnvironmentattheWorldHealthOrganization(WHO),spokeonearlywarningsystemsforvector-bornediseasesinAfrica,andBreed,thedirectoroftheGlobalClimateChangeTeamattheU.S.AgencyforInternationalDevelopment(USAID),describedhisagency’sactivitiesdealingwithfamine,drought,andotherhealthissuesinAfrica.

A year with dramatic evidence of climate changeBalbusopenedhisguardedlyupbeattalkwithareviewoftheimpactofclimatechangeonthepeopleintheU.S.during2011.Hepointedtotherecord12billion-dollardisasterscausedbyhurricanes,heatwaves,drought,wildfire,andfloodslastyear,withnear-recordlevelsofsummerdrynessandrainfall.Equally

Balbus outlined efforts to provide information to the public health community. He said people in every sector need to evaluate the positive and negative effects of adaptation efforts. (Photo courtesy of Steve McCaw)

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disturbing,headded,wasawaveofnewrecordsforsummernighttimeminimumtemperatures,interferingwiththecircadianrhythmthathelpspeoplecopephysiologicallyandpsychologicallywiththestressofhighdaytimetemperatures.

Therecordlevelofweatherstressin2011,Balbussaid,hashelpedreinforcethemessagethatclimatechangehasseriousimplicationsforhumanhealth,withsome1,000deathsdirectlyattributedtoeventsassociatedwithclimatechange.Acrosssectors,publichealthprofessionalsarebecomingincreasinglyinterestedinpreparingfortheeffectsofclimatedisruption.

Integrating research on the health effects of climate change“Thepublichealthcommunityhasreallyemerged,”Balbussaid.“It’sbecomingcleartomoreandmorepeoplethatmanyofthemeasuresweneedtoundertakeactuallyimprovehealthwitheconomicbenefitsthatcanoffsetthecostofclimatechangemitigation.”Theresulthasbeenasignificantexpansionofeffortstobetteranticipateweatherevents,identifysusceptiblepopulationsasfardownastotheneighborhoodandblocklevel,andintegrateawarenessofclimatechangeacrossgovernmentalandprofessionalsectors.

BalbuspointedtosupportbytheCentersforDiseaseControlandPreventiontostateandlocalpublichealthdepartments,forneedsassessmentandmappingstudieswithGISsoftwareandalgorithmstodevelopeffectiveadaptationprogramsforearlywarningandforhelpingpeoplecopewithclimateevents.Hedescribedtheupsurgeininteragencyefforts,suchastheinteragencycrosscuttingClimateChangeandHumanHealthGroupco-chairedbyNIEHS,andinitiativestobringclimatechangeunderstandingtobearontheactivitiesofothergovernmentagenciestohelpshapetheirongoingactivities.

“Wehaveanuphillbattle,”Balbusconceded,butincreasedawarenessishelpingpeoplelearntoasktherightquestionsaboutthepositiveandnegativeeffectsoftheirplansandactivities.AnewNationalClimateAssessment,nowunderwayanddueforcompletionin2013,willimproveunderstandingofclimatechangeimpactsacrosstheUnitedStates,headded.

NinenewNIHgrantsadministeredbyNIEHSaresupportingresearchonvulnerabilitytohealtheffectsofclimatechange,theeffectivenessofinterventions,andthepossiblenegativeeffectsofsomeadaptations(seestory).

“Climate change will generally challenge health systems across the world,” Campbell-Lendrum explained, pointing to the need for what he described as preventive public health plus. His presentation examined parallels between what is being done about adaptation and early warning in the U.S. with what is happening in Africa. (Photo courtesy of WHO)

“We’re looking at health in the context of a changing environment,” Breed said. Like his colleagues, he emphasized that climate change research can impact aspects of life in ways that may not be intuitive, such as in agriculture, urban planning, and architecture. (Photo courtesy of the U.S. State Department)

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In addition to his Dec. 8 presentation, Balbus was also a part of a side event Dec. 7, “U.S. Federal Actions for a Climate Resilient Nation,” which highlighted Executive Branch and private sector actions on climate change. (Photo courtesy of John Balbus)

U.N. Climate Change Conference 2011The17thConferenceoftheParties(COP17)totheUnitedNationsFrameworkConventiononClimateChange(UNFCCC)and7thSessionoftheConferenceofthePartiesservingastheMeetingoftheParties(CMP7)totheKyotoProtocolgatheredscienceandpolicyexpertsfromaroundtheworldNov28-Dec.9fortwoweeksofdiscussionsandnegotiations.

In1992,RiodeJaneirohostedthehistoricEarthSummit,aU.N.eventunprecedentedbothforitssizeandthescopeofitsconcerns.The172statesrepresentedthere—108byheadsofstateorgovernment—adoptedtheUNFCCC,whichconstitutesthepoliticalframeworktoimplementandupdateaninternationalglobalclimatechangestrategy.Theconventionallowscountriestocreateinstrumentstosupportthemitigationandadaptationeffortsofdevelopingcountries.

Undertheconvention,governmentsgatherandshareinformationongreenhousegasemissions,nationalpolicies,andbestpracticeswiththegoaloflaunchingnationalstrategiesforaddressinggreenhousegasemissionsandadaptingtoexpectedimpacts,includingtheprovisionoffinancialandtechnologicalsupporttodevelopingcountries.

In1997,thepartiesadoptedanaddendumtotheconvention,knownastheKyotoProtocol,whichimplementstheobligationscontainedintheconventionunderthecommonbutdifferentiatedresponsibilityprinciple,byestablishingspecificemissiontargetsfordevelopedcountries.Likewise,theprotocolestablishesthemarketmechanismsthatpromoteprivatesectorinvolvementintheglobalemissionreductioneffort.

In2011,forthethirdconsecutiveyear,theU.S.StateDepartmentoperatedaU.S.CenteratthemeetingtoshowcaseU.S.climateactionsandfosterdiscussiononkeyissues.TheU.S.CenterhostedsideeventsatCOP17/CMP7sponsoredbyU.S.governmentagencies,suchasHHS,andotherorganizationswithinterestsrelatedtoclimatechange.

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Copeland named chief of Laboratory of Molecular Genetics By Eddy Ball

NIEHSScientificDirectorDarrylZeldin,M.D.,announcedDec.1theselectionofleadresearcherWilliamCopeland,Ph.D.,aschiefoftheInstitute’sLaboratoryofMolecularGenetics(LMG).Copeland,wholeadstheLMG’sMitochondrialDNAReplicationGroup,hadservedasactingchiefsinceJuly,whenhesucceededlongtimeLMGChiefJanDrake,Ph.D.

CongratulatingCopelandonhisappointment,ZeldinexpressedhisconfidenceinCopeland’sleadershipandhispursuitofscientificexcellence.“IhavenodoubtDr.CopelandwillcontinuetoleadtheLaboratoryofMolecularGeneticsinanoutstandingmanner,whileengagingincutting-edgeresearch,”Zeldinwrote.“Dr.Copeland’sresearchhascontributedsignificantlytotheunderstandingofmitochondrialrelateddiseases,mitochondrialDNAmutagenesis,andthemechanismoftoxicityofnucleosidereversetranscriptaseinhibitors.”

Mutagenesis centralConsideredtobeoneofthepremiercentersforthestudyofenvironmentallylinkedgeneticmutation,theLMGiscomposedofninegroups,withsome70scientistsinvestigatingthefundamentalmechanismsofgeneticstabilityandinstability.Theirresearchintotheinterplayofenvironmentandmutationhasmadeimportantcontributionstotheunderstandingofarangeofhumandiseases,includingcancer,neurologicaldisease,anddiseasesrelatedtoaging.

Copeland,whojoinedNIEHSin1993,hasdevotedhisscientificcareertothestudyofwhatheconsidersoneoftheleastunderstoodandmostintractabletotreatmentofallhumandiseases,authoringorco-authoringmorethan96peer-reviewedpublicationsinthefield.Amonghislab’smanybreakthroughsintheunderstandingofmitochondrialdisease,thegroup’sstudiesonchangesofmitochondrialDNAreplicationandstabilitycausedbydisease-associatedmutationsinthesolemitochondrialpolymerasehavecharacterizedmutationsthatcausedisease,andalsodescribednovelmethodsthatallowfurthercharacterizationofdiseasemutationsandenvironmentalhealtheffects.

“Inheritedmitochondrialdiseaseshaveamortalityrateroughlythatofcancer,withveryhighratesofprematuredeath,”Copelandexplains.Heisamongleadingexpertswhomaintainthatinheritedandinducedmitochondrialdefectsandtheireffectsonenergyproductionalsocontributetothecommondiseasesofaging,suchastype2diabetes,Parkinson’sdisease,stroke,andAlzheimer’sdisease.

AsheadofLMG,Copelandplanstoleadbyexampleintheadvancementofmoleculargeneticsresearch.Heisalsocommittedtosupportingthelab’sstrongmentoringprogram.HisoutstandingcontributionstotrainingandcareerdevelopmentwererecognizedbyNIEHStraineeswithhisselectionasMentoroftheYearin2005,andbyNIHwiththe2006Director’sMentoringAward.

InadditiontohisresearchatNIEHS,Copelandtranslateshisresearchthroughservicetoeducationandadvocacygroups.Heisaspokespersonformitochondrialdiseaseresearchtoresearchers,clinicians,andpatientsthroughhiscontributionstotheMitochondriaResearchSocietyaspresidentfrom2005to2007andtheUnitedMitochondrialDiseaseFoundation(UMDF)inseveralleadershiproles(seetextbox).

Copeland chaired the 2011 UMDF symposium in July (see story), which featured presentations by several NIEHS intramural researchers and grantees. (Photo courtesy of Steve McCaw)

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Grantee honored by association of science teachersNIEHSgranteeKathleenVandiver,Ph.D.,becameamemberoftheMassachusettsHallofFameforScienceEducatorsduringtheannualconferenceoftheMassachusettsAssociationofScienceTeachersinNovember2011.TheawardhonorsVandiver’smorethan20yearsofsignificantcontributionstoMassachusettsscienceeducation.

Vandiverisco-directorofcommunityoutreachandeducationcorefortheNIEHS-fundedMassachusettsInstituteofTechnology(MIT)MassachusettsCenterforEnvironmentalHealthSciences(CEHS).Vandiver’sprogramshelptocreateengagingwaystoteachabstractscientificconcepts,suchasmoleculargenetics,withmodelsmadefromLEGObricks.

“KathyhasdoneanexcellentjobofusingtheLEGOkittohelpstudentsandteachersunderstandthelinksbetweenenvironmentalexposuresandhumanhealth,”saidNIEHSProgramAnalystLiamO’Fallon.“ItisatrulyengagingapproachthatmakesCEHSeducationandoutreachmoreeffective.”

Appreciation for service to the United Mitochondrial Disease FoundationByUMDFCEOandExecutiveDirectorCharlesMohan

Dr.CopelandbringsfreshinsightandenergytotheUMDFasheembracesanytaskwerequestofhim.AlongwithhispastserviceastheUMDFGrantReviewCommitteeco-chairmanandchairmanfrom2004to2008,hecontinuestoreviewUMDFgrantapplications.AschairoftheUMDFResearchPolicyReviewCommittee,Dr.CopelandleadsthereviewofUMDF-fundedgrantprojectreportsandmakesrecommendationsregardingnewprecedent-settinggrantpolicies.HeisontheUMDFAsktheMitoDocteam,answeringbasicresearchandgeneticsquestionsforourpatientsandfamilymembers.Dr.CopelandservesontheScientificandMedicalAdvisoryBoardandthe2012symposiumplanningcommittee.Hewaschairofthe2011symposiumplanningcommitteeandservedonthecommitteeforfouryearspriortothat,aswell.

Dr.Copelandisarealteacher,andislookeduptoasaleaderinthemitochondrialcommunity,bothlayandprofessional.Moldingthemindsoffuturegenerationsofresearchers,heencourageshisentirelabstafftoattendoursymposium,givesleading-edgesymposiumlectures,andparticipatesininformalconversationswithlayandscientificattendees.

TosaythatweattheUMDFappreciateandenjoyDr.Copelandisanunderstatement.Havinghimonourteamhasdirectlyenhancedourmissiontopromoteresearchandeducationforthediagnosis,treatment,andcureofmitochondrialdisorders,andtoprovidesupporttoaffectedindividualsandfamilies.

Shown, left to right, Thomas Vaughn, head and chair of Massachusetts Hall of Fame for Science Educators, joined Vandiver and Richardson at the presentation. (Photo courtesy of Kim Vandiver)

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Appealing to the senses to communicate abstract concepts“Itisn’tjustthatImakemodels,”saidVandiver,whotaughtsixth-gradescienceinLexington,Mass.,from1990to2005.“What’sdifferentisIdesigntheprojectssothatthemodelsandlessonsintrinsicallyemphasizethekeyconceptsinsteadofallthedetails.Andit’shelpfulforstudentstoengagewiththepointofthelessoninatactile,memorableway.”

Vandivercontinuestoexplorehowtomakeabstractconceptscleartostudents.ArecentexhibitintheMITMuseum,LearningLab:TheCell,usedLEGObricksputtogetherbytheparticipantstoemphasizetheconnectionbetweenDNAandhealth.

InanMITEdgertonCenterproject,fundedinpartbytheNationalAeronauticsandSpaceAdministration(NASA)andsupportedbyCEHS,VandiveriscurrentlycollaboratingwiththeBostonpublicschoolssystem’ssciencedepartmenttopilotthehands-onLEGODNAcurriculuminbiologyclasses,andtoprovideteacherprofessionaldevelopmentsessionsandclassroomsupport.Theproject,whichbeganinMay2010,wasimplementedlastspringandcontinuesthisyear.Thematerialsareverypopularwithteachersandstudents,especiallyEnglishasaSecondLanguagestudents.

MarilynRichardson,ateacherwhonominatedVandiver,firstmetheratanMITCEHSteachersummerworkshopin2007.Richardsonsaid,“Ihadn’ttaughtlifescienceinmanyyears,andworkingwiththeLEGOkitshelpedmerefocusonbiologicalissuesandhelpedmedoabetterjobofteaching.”Sixth-gradersandAPbiologystudentsalikearepickinguptheconcepts,aswellasadultlearnerssuchasnursesandengineers,corroboratingthatthemodelsembodyuniversaldesignprinciples.DifferentLEGOsetshavebeencreatedtoaddressthefundamentalsinDNA,proteins,proteinsynthesis,celldivisionandchromosomes,andchemicalreactionssuchasphotosynthesis.

Vandiversaidshewaspleasedtoberecognizedforcreatingtoolsforhands-onlearning,andnotedtherearemanyworthyanddeservingteachersinMassachusetts,whoseworkCEHSappreciatesandwishestohonor.

(ThisstorywasadaptedfromaDec.8MITnewsreleasebyDebbieLevey,aneditorattheMITDepartmentofCivilandEnvironmentalEngineering.)

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Birnbaum and staff hold conversation with NIEHS Partners By Eddy Ball

TheNIEHSPublicInterestPartnersjoinedinaconversationwithNIEHS/NTPDirectorLindaBirnbaum,Ph.D.,andstaffDec.1inFriendshipHeights,Md.WhilethemeetingfeaturedengagingpresentationsonnanomaterialsresearchbykeyNIEHS/NTPscientists,thegatheringalsoofferedPartnersanopportunitytoshapetheafternoonagendaduringanalmostthree-hourinformallunchtimeconversationonavarietyoftopics.

TheNIEHSdirectorandstaffmeetperiodicallywiththePublicInterestPartnerstoseekinputandimprovecommunicationwithcommunitiesandorganizationsdirectlyaffectedbythemissionandresearchofNIEHS.Themembershiprepresentsdiversegroupsincludingdisease,disability,andenvironmentaleducationandadvocacyorganizations.ThegrouplendsgrassrootsperspectivestotheresearchagendaofNIEHS,andservesasakeycontributortothetranslationofresearchfindingsforthepublic,policymakers,andprivatefoundations.

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Duringherintroductorycomments,Partnersco-chairKarenMiller,whoispresidentoftheHuntingtonBreastCancerActionCoalition,describedtheproductivelong-termrelationshipbetweenNIEHSandthePublicInterestPartners.“OvertheyearsthePartnershavehadmanyopportunitiestocontributeandparticipate,”shesaid.ThesupportprovidedbyNIEHStoshareinformationamongNGOs[non-governmentalorganizations]isinvaluable.”

A primer on nanomaterialsTherapidlygrowingnumberofproductsthatcontainnanomaterialsenteringthemarketeachyearposesaconcernforenvironmentalhealthscientistsbecausesolittleisknownaboutthepossibleharmfulhealtheffectsofexposure.

Althoughthenanomaterialsaremanufacturedfromwell-studiedelements,suchascarbon,nickel,andgold,manipulationofsize,shape,andotherphysicalandelectricalpropertiescanmakethembehavemuchdifferentlythantheirparentelements.Atthenanolevel,materialscanalsobecomemorebioactivebecausetheycanpassthroughmembranebarriersinthebodymoreeasilythanmicro-scaleorlargerparticles.Understandingnanomaterialsismadeevenmorechallengingbecausedifferentmanufacturingprocessescanmeanthesameproduct,suchasasingle-wallcarbonnanotube,maybehavedifferentlydependingonwhereitwasproduced.

Tooffertheirinsightonnanomaterialsandnanotechnology,scientistsrepresentingthethreedivisionsatNIEHSpresentedreportsontheirresearchagendas:

• DivisionoftheNTPDeputyDirectorforScienceNigelWalker,Ph.D.,spokeonhazardassessment

• DivisionofExtramuralResearchandTrainingScientistHealthAdministratorSriNadadur,Ph.D.,describedtheNIEHSnanomaterialsgrantportfolio

• DivisionofIntramuralResearchrespiratorybiologyleadresearcherandClinicalResearchUnitMedicalDirectorStavrosGarantziotis,M.D.,discussedbasicresearchatNIEHS

During lunch and into the mid-afternoon, Birnbaum, center, let the Partners direct the conversation. (Photo courtesy of John Schelp)

Leyla McCurdy, senior director at the National Environmental Education Foundation, expressed her appreciation for the Partners meetings. “NIEHS has contributed tremendously to the scientific knowledge on environmental health and has made it easily accessible to us, empowering us to educate our constituents.” (Photo courtesy of John Schelp)

Garantziotis, above, and his fellow scientists spoke from their seats, reinforcing the conversational informality of the gathering. (Photo courtesy of John Schelp)

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“ThepresentersatthePartnersmeetingtookthemysteryoutofnanotechnology,”BettyMekdeci,executivedirectorofBirthDefectResearchforChildrenandPartnersco-chair,saidafterwards.“Wewereintroducedtothesubjectthoughafascinatingshowandtellpresentationfollowedbythebasicscienceandpossibleadverseeffectsofnanotechnology.”

Mekdeciandcolleaguesalsoappreciatedtheopen-endedlunchtimediscussion.“TheafternoonwasalivelyandenergeticQandA[questionandanswer]exchangebetweenDr.BirnbaumandallthePartners,”shesaid.

The seating arrangement helped NIEHS representatives interact with individual Partners. Shown, left to right, NIEHS Toxicology Liaison Chris Weis, Ph.D., joined Partners members Kari Christianson, program director with DES Action USA, and Virginia Ladd, president and executive director of the American Autoimmune Related Diseases Association. (Photo courtesy of John Schelp)

Walker left behind the staples of scientific lectures, the podium and PowerPoint slides, but he brought along familiar items to demonstrate the different sizes and shapes of nanomaterials. (Photo courtesy of John Schelp)

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Nano Grand Opportunities researchers share findings By Thaddeus Schug

MembersoftheNIEHSnanotechnologyGrandOpportunities(NanoGO)grantprogramgatheredDec.8-9,2011,inResearchTrianglePark,N.C.,toupdatetheirresearcheffortsonengineerednanomaterials(ENMs).Thiswasthefinalmeetingoftheconsortium,whichbeganin2009with13two-yeargrantsfundedfromtheAmericanRecoveryandReinvestmentAct.Theprimarygoalsofthisprogramweretodevelopreliableandreproduciblemethodsandmodelstoassessexposure,exposuremetrics,andbiologicalresponsetonanomaterials.

The13granteeswerebroughttogetherintoaconsortiumtofacilitateinterdisciplinarycommunication,developresearchsynergies,andconductcollaborativeresearch

Nadadur, right, chatted with NIEHS Deputy Director Rick Woychik, Ph.D., during the meeting. Woychik has taken special interest in the nanotechnology programs at NIEHS. (Photo courtesy of Steve McCaw)

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projects.SeveralotherNIEHS-fundedresearchers,withinterestsinnanotechnology,alsojoinedtheconsortiumandprovidedvaluableexperimentalinput.TheNanoGOconsortiumfunctionsasaframeworkforgranteestoworktogethertowardthecommongoalofdevelopingmethodstoachievegreaterharmonizationofresearchresultsforhazardassessmentofENMs.

SriNadadur,Ph.D.,themeetingorganizerandahealthscientistadministratoratNIEHSwhooverseesmuchoftheInstitute’sportfolioonnanomaterialsinhealthandsafety,explained,“Wehaveseenagreatdealofprogressinmeetingtheoverallgoalsoftheconsortium.Thisgroupofscientistsworkedthroughmanychallengingtechnicalissuesthatareuniquetonanomaterials,todevelopprotocolsandachievereliableandreproducibleexperimentalresults.”

Consortium activitiesTheNanoGOconsortiumwasanactivehubofcommunicationamonggranteesforthedurationofthetwo-yearfundingperiodbetween2009and2011.Theconsortiumprovidedfrequentopportunitiesforresearcherstointeract,astheyworkedcloselytogethertoplan,implement,andtroubleshootbothindividualandcollaborativeresearchprojects.

Akickoffmeetingin2009introducedresearcherstothediverseskillsandareasofexpertiserepresentedbytheconsortiummembers,andallowedthemtobeginplanningcollaborativeprojects.Progressmeetingsin2010and2011enabledparticipantstoassesspreliminaryresults,andrefinetheirmethodstoaddresschallengesandinconsistencies.

Duringthismeeting,consortiummemberssharedfinalresultsandsummarizedlessonslearned.Inbetweenthesefourin-personmeetings,consortiummemberscommunicatedthroughfrequentconferencecalls,toshareexperiencesandresults,identifyproblems,andrefinemethodsandprotocols.

Round-robin test resultsInadditiontoindividualprojects,consortiumresearchersconductedseveralcollaborativeresearchprojects.Thesewerestructuredasaseriesofround-robintests,inwhichsimilaroridenticalmethodswereusedtoperforminvitroandinvivotestsconcurrentlyatthirteendifferentlaboratoriesaroundthecountry.Researchersworkedtogethertodesigntheoverallstructureofthetests,identifytargetENMs,determineappropriateassays,selectcellandanimalmodels,andrefineresearchmethodsandprotocolsasthetestsproceeded(seetextbox).

Theresearchersplantopublishtheresultsfromthesestudiesintwoseparatepapers,laterthisyear,intheNIEHSpublicationEnvironmentalHealthPerspectives.

James Bonner, Ph.D., an associate professor in the Department of Environmental and Molecular Toxicology at North Carolina State University, was a leader in developing protocols for the in vivo testing experiments. (Photo courtesy of Steve McCaw)

Andre Nel, M.D., Ph.D., a professor and division chief of NanoMedicine at the University of California, Los Angeles, and his lab contributed to both the in vitro and in vivo round-robin experiments. (Photo courtesy of Steve McCaw)

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(ThaddeusSchug,Ph.D.,isahealthscientistadministratorintheNIEHSDivisionofExtramuralResearchandTraining(DERT)andaregularcontributortotheEnvironmentalFactor.PriortojoiningDERTin2011,hewasapostdoctoralresearchfellowintheNIEHSLaboratoryofSignalTransduction.)

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Kent Pinkerton, Ph.D., left, led a group of researchers studying the pulmonary effects of ENMs in rats. Nigel Walker, Ph.D., right, is the NTP lead on the nanotechnology safety program. (Photo courtesy of Steve McCaw)

Shown, left to right, consortium members Frank Witzmann, Ph.D., Edward Crandall, M.D., Ph.D., and Galya Orr, Ph.D., participated in meeting discussions. (Photo courtesy of Steve McCaw)

Round-robin testing of ENMsTheconsortiumchoseseveralwell-studiedandcommerciallyabundantnanomaterialsthatalsopossessedawiderangeofphysicalandchemicalproperties,includingzincoxide(ZnO);threeformsoftitaniumdioxide(TiO2P25sphere,anatase,orangular,sphere,andanatasenanobelt);andthreemulti-walledcarbonnanotubes.TheselectedENMswerecharacterizedcentrally,toensureconsistencyoftestmaterialsacrossalllaboratoriesandprovideasharedsourceofdetailed,accurateinformationaboutthematerials.

In vitrostudieswereperformedateightlaboratories.Twocellviabilityassays(MTSandLDH)andapro-inflammationcytokineassay(IL-1b)wereusedtoassesstheeffectsof24-hourexposuretoZnO,TiO2,andcarbonnanotubesonthreecelllines.

In vivostudieswereperformedatsevenlaboratories,withfourusingmiceandthreeusingrats.MicewereexposedtoTiO2nanomaterialsandcarbonnanotubesthroughoropharyngeal,ormid-throat,aspiration.RatswereexposedtoTiO2nanomaterialsthroughintratrachealinstillation,administeringtheENMinvehicledirectlytothelungandbypassingthenasalcavity.

Effectsweremeasuredatvarioustimepointsusingtotalcellnumbers,differentialcellcountingtoshoweffectsonneutrophilia,imagingofENMsinbronchoalveolarlavagecells,histopathologyimages,totalproteinlevels,andlevelsoflactatedehydrogenase(LDH),amarkerforacuteorchronictissuedamage.

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mHealth Summit highlights advances in mobile health technology By Ryan Campbell

RepresentativesfromNIEHSandtheNationalClearinghouseforWorkerSafetyandHealthTrainingjoinedmorethan3,500leadersfromtechnology,business,research,andpolicycommunitiesaroundtheworldtoengageinconstructivedialogueabouttheroleofmobilehealthtechnologiesinthe21stCentury,atthe2011mHealthSummitDec.5-7,2011,inWashington,D.C.

RepresentingNIEHSatthemeetingwerestafffromtheWorkerEducationandTrainingProgram(WETP)andtheDivisionofExtramuralResearchandTraining.

Smartphoneswithinternetcapabilitieshavechangedthewayinwhichpeoplemanagetheirhealth.mHealthdeliverson-the-gohealthinformationtosmartphonesviaapplicationsandInternet-basedWebpages.mHealthcanteachsomeonehowtoeatahealthydiet,managediabetes,chooseadoctor,orquitsmoking.In2011,smartphonesaccountedformorethanhalfofcellphonesales,sothepossibilityofdisseminatinghealthinformationandmanaginganindividual’shealthhaslimitlesspotential.

Thisyear’ssummitfeaturedkeynotespeakersKathleenSebelius,secretaryoftheU.S.DepartmentofHealthandHumanServices,andReginaBenjamin,M.D.,theU.S.surgeongeneral.“Whenwetalkaboutmobilehealth,wearetalkingabouttakingthebiggesttechnologybreakthroughofourtimeandusingittotakeononeofthegreatestnationalchallengesofourtime,”Sebeliussaidinherkeynoteaddress.Thethree-dayeventincludedfourteenconcurrentthemedtracksessionscoveringawiderangeofmobilehealthtopicsrelatedtobusiness,policy,research,andtechnology.

The NIEHS presence at mHealthDavidBalshaw,Ph.D.,NIEHSprogramadministratorfortheNIHGenes,Environment,andHealthInitiativeExposureBiologyProgram(EBP),ledasessionandpresentedresearchaboutrecenttechnologicaladvancementsrelatedtomonitoringenvironmentalexposuresthatinteractwithageneticvariationtoresultinhumandisease.Thepresentationincludeddemonstrationsofmonitoringdevicestoaidinminimizinghumanexposuretohealth-impairingpollutants.

Hughes, left, and Bandera talked in front of the WETP poster about Cell Podium’s services for just-in-time training for emergency incidents. Information messages and videos can be broadcast to individuals who need information, just at the time they need it, to respond to an emergency or learn about their health. (Photo courtesy of Chip Hughes)

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“ThetermmHealthmaybevaguebutthereisnorefutingthetremendousprogressbeingmadealongtechnologicalfronts,”explainedCesarBandera,Ph.D.,aWETPgranteeanddeveloperoftheCellPodiummobilemultimediamessagingservice,whopresentedaposterinconjunctionwiththeNationalLibraryofMedicineandNIEHS.“TheSummitalsoconveyedanincreasedfocusonsystemintegration,suchthatmobiledevicesoperatewithinaprocessinvolvingthepatient,careprovider,andpayer.”Banderapresentedhisresearch,illustratingthefunctionsandutilizationofmobiletechnology,duringthepostersessionatthesummit.

TheNationalClearinghouseforWorkerSafetyandHealthTraininghadanopportunitytonetworkandprovideinformationandoutreachattheNIEHSinformationboothinthemHealthexhibitor’shall.ClearinghousestaffalsoansweredsummitattendeequestionsaboutNIEHS,itsprograms,anditsdevelopmentofmobilehealthtechnologies.

(RyanCampbellisonthestaffofMDB,acontractorfortheWETPandNIEHSSuperfundResearchProgram.)

Balshaw oversees EBP grants that, among other things, are dramatically improving the quality and reducing the size of personal monitoring devices that can warn of exposures to hazardous agents and communicate real-time information about exposure to researchers. (Photo courtesy of Steve McCaw)

MDB employees Ryan Campbell, left, and Dusty Russell, worked the NIEHS display in the NIH Pavilion at the mHealth Summit. (Photo courtesy of Chip Hughes)

Funding opportunityArecentFundingOpportunityAnnouncement(FOA)issuedDec.5,2011,solicitsSmallBusinessInnovationResearch(SBIR)fornoveltechnologiesthatarefield-deployableandlab-based,highlightingtheNIEHScommitmenttomHealth.

“Thereisanurgentneedformobiletechnologydevelopment,toidentifyexposureswithincommunitiesandtorelayhealthandsafetyinformationinatimelymanner,”saidChipHughes,directoroftheNIEHSWorkerEducationandTrainingProgram.

Grantees,suchasBandera,havedemonstratedthepotentialofmultimediamessaginginpatienteducation.ThroughagrantfromNIEHS,andinconjunctionwiththeNIEHSCenterforEnvironmentalExposuresandDiseaseattheUniversityofMedicineandDentistryofNewJersey,CellPodiumbroadcastsvideosonbreastcancerandtheenvironment,onaweeklybasistocellphoneuserswhosignupforasubscriptionviaemailatbreastcancer@cellpodium.com.

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NIEHS postdocs learn the value of options at NC biotech career day By Ian Thomas

NIEHSpostdocsjoineddozensoftheircolleaguesattheNorthCarolinaBiotechnologyCenter(NCBC)Dec.9forthethirdinstallmentoftheorganization’scareerseries,titled“ScienceIndustryCareers:DiscoverytoProductDevelopment.”HeldatNCBC’smainfacilityinResearchTrianglePark,theeventexposedattendeestoarangeofindustrycareerpaths,availabletoscientistswhoholdaPh.D.

“Scienceandpharmacologyarenodifferentthananyotherfieldwhenitcomestothejobmarket,”saidDrewApplefield,Ph.D.,abusinessandtechnologydevelopmentassociatewithNCBCandtheevent’smoderator.“Withthatinmind,wewantedtogivenewscientistsenteringthesefieldsachancetoexploretheiroptions,bothinandoutofresearch,aswellasachancetonetworkwithactualmembersoftheindustry.”

Spanningthemajorityoftheday,theeventconsistedofthreeprimarysegments.Thefirstfeaturedadiscussionofthedrugdevelopmentprocess,whilethesecondaddressedtheroleofregulatoryaffairs.Finally,thedayconcludedwithapaneldiscussionandaresumereviewsession.

Accordingtoseveralattendees,theworkshopaddedtotheirunderstandingofcareeroptions.“Ilearnedalottoday,particularlywithregardtothedrugdevelopmentprocessandtheregulationsthatdealwithit,”saidNIEHStraineeEmilyZhou,Ph.D.

A complex processLedoffbyJonathanStocker,theassociatedirectorofclinicaldevelopmentforClinPharmConsulting,themorningbeganwithastep-bystep-breakdownoftheNewDrugApplication(NDA)developmentprocess.Stockerdiscussedthepre-clinical,ordiscoverystage,theclinicalstage,featuringthethreephasesofclinicaltrials,theFDAevaluationstage,andfinallythepost-approval,orcommercializationstage.

“MovinganNDAfromthebenchtop,throughleadoptimizationintotheclinicalstagealoneisalongandcomplicatedprocessthattakesmanyyears,”saidStocker,whofocusedmuchofhispresentationonthepre-clinicalandclinicalstages.“Makingthisprocesshappenrequiresawiderangeofpeoplefromboththeacademicandentrepreneurialarenas.Soitreallybehoovesnewscientiststobecomefamiliarwithboth.”

Stocker said of the long and expensive process of drug development, “It’s hard, but very exciting.” (Photo courtesy of Steve McCaw)

NIEHS postdoctoral fellow Emily Zhou, Ph.D., took advantage of the morning break to network with Schuller and learn more about careers in regulatory affairs. (Photo courtesy of Steve McCaw)

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Regulating an industryInthesecondsession,attendeeswereversedintheworldofpharmaceuticalregulatoryaffairs.AsdescribedbyCharity-AnneSchuller,Ph.D.,associatedirectorofregulatoryaffairsforPPDInc.,thisfieldinvolvesreading,understanding,andinterpretingoflawssurroundingdrugdevelopment,soastoinsurepropercomplianceonthepartofmanufacturers.

“Ultimately,theroleoftheFDAistoprotectthepublichealthbypassinglawsthatassurethesafety,efficacy,andsecurityofthemedicalproductsonthemarket,”saidSchuller,anadjunctprofessorwithCampbellUniversity’sclinicalresearchprogram.“Thatrequiresafluentunderstandingofalotofcomplextopicswhichmeansthatwe,asregulatoryspecialists,canoftentimesfindourselveswearingalotofdifferenthatswithinthecompaniesweworkfor.”

Shifting gearsTheNCBiotechcareerdayconcludedwithapaneloffourmembers,eachofwhombegantheircareersasresearchscientistsbeforeeventuallymovingintoindustry.Throughoutthehour,paneliststookturnsansweringquestionsfromtheaudience,whilesharingtheirrespectiveexperiencesandinsightsaboutthefield.Whiletheirstoriesmayhavediffered,theiradvicetoattendeeswasunanimous.

“Alwaysknowyouroptions,”saidAmberBarnes,Ph.D.,apanelistandseniormedicalwriterwhobeganhercareerasanoncologyresearcher.“Noteveryoneiscutouttospendtheirentirecareerworkingfromthebench,andifyoudecidetoshiftgears,likeIdid,it’suptoyoutoarmyourselfwiththetoolsyou’llneedtomakethattransition.”

ThePh.D.careerworkshopserieswasorganizedbyShobhaParthasarathi,Ph.D.,technologydevelopmentdirectoroftheBCNCBusinessandTechnologyDevelopmentProgramandheadoftheCenter’sIndustrialFellowshipProgram(IFP).Thefirsttwosessionsfocusedon“LifeScienceIndustryCareers:BenchtoBoardroom”and“AgenciesandResearchInstitutes.”

(IanThomasisapublicaffairsspecialistintheNIEHSOfficeofCommunicationsandPublicLiaisonandaregularcontributortotheEnvironmentalFactor.)

Meanwhile, NIEHS postdoc Andy Seipel, Ph.D., used his break to talk with colleagues from other institutions. According to Parthasarathi, the workshop attracted Ph.D.s from as far away as East Carolina University. (Photo courtesy of Steve McCaw)

Career Day Panelists• AmberBarnes,Ph.D.

– SeniorMedicalWriter,Pharmanet/i3

• BobBlack,Ph.D.– VicePresident,ScionNeuroStim

• DominiquePifat,Ph.D.– SeniorConsultant,BiologicsConsultingGroup

• LeoDiNapoli,Ph.D.– AssociateDirectorforRegulatoryAffairs,CatoResearch

The panelists talked about their circuitous career paths and how they’ve become comfortable with change. Shown above are Pifat, right, and DiNapoli. (Photo courtesy of Steve McCaw)

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Award-winning summer intern accepted by Stanford By Ian Thomas

Afterspendingmuchofherfallsemesterapplyingtocolleges,NIEHSsummerinternGreeshmaSomashekarlearnedinDecember2011thatoneofAmerica’spremierescientificinstitutionsisnowofficiallyonherlistofpossibilities.Anaward-winningmemberofthe2011NIHSummerInternshipProgramatNIEHS,SomashekarwasformallyacceptedintoprestigiousStanfordUniversityaspartoftheclassof2015.

“Iwasecstatictogetthenews,”recalledSomashekar,aseniorattheNorthCarolinaSchoolofScienceandMathematics(NCSSM)inDurham,N.C.“Stanfordhasexcellentschoolsinengineeringandthesciences,andtheideaofstudyinginsuchacollaborativelearningenvironment,withthatmanyresources,isreallyremarkabletothinkabout.”

WhileatNIEHS,SomashekarspentthebulkofhertimeintheInstitute’sMatrixBiologyGroup.WorkingunderthewatchfuleyeofStavrosGarantziotis,M.D.,medicaldirectoroftheNIEHSClinicalResearchUnit,shequicklyestablishedherselfasapartofthegroup,researchingproteinsinlungtissue.

“Stanfordhasmadeatremendousselection,”saidGarantziotis.“Greeshmawasanoutstandingstudentinhertimewithus,andboththeuniversityandthescientificcommunity,asawhole,wouldbefortunatetohaveher.”

Barnes, who seems to flourish in the shifting environment of the private sector, told the audience, “Don’t feel that you’re making a decision for the rest of your life.” (Photo courtesy of Steve McCaw)

Black, an engineer who now works in medical device development for a small firm, has also worked in academia and for a large corporation. He described his career as a random walk. (Photo courtesy of Steve McCaw)

During the Summer Internship Program poster session July 28, 2011, Somashekar, right, was on hand at her poster to explain her findings and methodology to fellow interns, postdoctoral fellows, and senior scientists. (Photo courtesy of Steve McCaw)

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Inadditiontocapturingtophighschoolstudenthonorsforherposterpresentationattheconclusionofthesummer,SomashekarwasalsofeaturedinanNIEHSvideochroniclingthestudents’timeintheSummerInternshipProgram.

A journey of great expectationsBeforeherpossiblemovetotheWestCoast,Somashekarhasabusyscheduletocompletein2012atNCSSM.AsoneoffourfinalistsintheNorthCarolinaInternationalScienceChallenge,sheandherpeerswilltraveltoChinainMarchtorepresenttheU.S.attheBeijingYouthScienceCreationCompetition.

“Havingyourresearchrecognizedbyapanelofyourpeersisalwaysagreatfeeling,buthavingtheopportunitytopresentthatworkontheinternationalstageistrulyanincrediblehonor,”shesaid,notingherexcitementaboutgettingtoseetheGreatWallofChina.

A true love of scienceStill,ashappyassheisaboutheraccomplishmentsandthechancetotravelabroad,Somashekaristhefirsttopointoutthatitalwayshasbeen,andwillcontinuetobe,aboutthescience.

“Naturally,I’msuremyresearchinterestswillevolveovertime,butfornowIfindmyselfreallydrawntobiomedicalengineering,”shesaid,addingthatshehopestoearnherundergraduatedegreeineitherbioengineering,biomedicalcomputation,orhumanbiology,beforeeventuallyattendingmedicalschool.“Inmanyways,we’reonlynowscratchingthesurfaceofhowcomputersciencecaninfluencemedicalresearch,andthat’sreallyexcitingstufftome.”

(IanThomasisapublicaffairsspecialistfortheNIEHSOfficeofCommunicationsandPublicLiaisonandaregularcontributortotheEnvironmentalFactor.)

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Freedman represents NIEHS/NTP at conference in Peru By Eddy Ball

Tryasshemay,NIEHS/NTPDirectorLindaBirnbaum,Ph.D.,can’tattendeverymajormeetingthatNIEHSco-sponsors.Foronesuchmeeting,theIIInternationalCongressandIVPeruvianCongressofToxicologyinLima,PeruNov.21-23,2011,BirnbaumtappedNIEHS/NTPleadresearcherJonathanFreedman,Ph.D.,toattendinherplace.

Garantziotis also serves as the principal investigator for the NIEHS Laboratory of Respiratory Biology. (Photo courtesy of Steve McCaw)

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FreedmanisheadoftheNTPBiomolecularScreeningBranchWormToxGroup,whichusesmedium-throughputscreeningtostudyresponsetotransitionmetalsinanematode,orroundworm,model.“LindafeltthecontentofthemeetingwouldbeinterestingtotheNIEHScommunity,”Freedmansaidafterwards.“Also,shelikestheideaofInstitutescientistsgoingtolessfrequentedlocationstopromotetheNIEHSmissionandenvironmentalhealthingeneral.”

Advancing global environmental health“NIEHScancontributealottoemergingcross-disciplinarytoxicologyprogramsworldwide,”Birnbaumexplained.“Notsurprisingly,toxicologistsindevelopingcountrieslooktoNIEHS/NTPasamodelforwhatgoodprogramsshouldbedoing.”

ThecongresswasorganizedbytheAcademic/ProfessionalSchoolofToxicologyoftheNationalUniversityofSanMarcosinLima,theoldestuniversityinSouthAmericaandwidelyconsideredtheleadinguniversityinPeru.Likemanydevelopingcountries,especiallyoneswithawealthofmineralresources,Peruisfacedwithdevelopingthescientificinfrastructuretodealwiththreatstoitspopulation’senvironmentalhealth.

Thegoalsofthecongressweretopromoteamultidisciplinaryapproachtogeneralandenvironmentaltoxicology,disseminateinformationaboutriskstohealthandtheenvironmentfromtoxicants,stimulatescientificinvestigationespeciallyintheareaofmechanismsoftoxicity,andemphasizetheneedtoprevent,detect,andtreatintoxications.Theagendaincludedaseriesofprecongresscourses,roundtables,themedconferences,andplatformsessions.

TheSpanishSocietyofToxicologyco-sponsoredtheevent.SocietyofToxicology(SOT)memberparticipationinthecongressandotherscientificactivitiesinPeruwasfundedbytheSOTEducationCommitteethroughtheGlobalToxicologyScholarProgram.

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NTP advisor named as fellow of the Collegium Ramazzini By Eddy Ball

NTPBoardofScientificCounselorschairDavidEastmond,Ph.D.,isamongthelatestgroupoffellowsselectedbytheCollegiumRamazzini,anorganizationofinternationalscholarswhoworktowardssolutionsofoccupationalandenvironmentalhealthproblemsaroundtheworld.

EastmondisaprofessorofcellbiologyattheUniversityofCalifornia,Riverside(UCR)andchairoftheuniversity’sDepartmentofCellBiologyandNeuroscience.Heisactivelyinvolvedinresearchandteachingintheareasoftoxicologyandriskassessment.AlongwithhisserviceontheNTPBoardofScientificCounselors,EastmondhascontributedtoanumberofU.S.andinternationalpanelsongenotoxicityandcarcinogens.

NIEHS/NTP representative Jonathan Freedman (Photo courtesy of Steve McCaw)

Crest of the National University of San Marcos

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InaUCRpressreleaseissuedNov.28,2011,Eastmondwasquotedassaying,“IamverypleasedandhonoredtobeselectedasafellowoftheCollegiumRamazzini,andlookforwardtoworkingwiththisesteemedgroup.”

Recognition for international distinction in environmental healthWith190fellowsfromcountriesaroundtheworld,theCollegiumRamazziniisaninternationalscientificsocietythatexaminescriticalissuesinoccupationalandenvironmentalhealth,withaviewtowardsactiontopreventdiseaseandpromotehealth.Thefellowsareprofessionalsofclearpersonaldistinctionandintegrity,distinguishedbytheircontributionstooccupationalandenvironmentalhealth.

EastmondjoinstheselectgroupofCollegiumRamazzinifellows,whichincludesseveralcurrentandformerNIEHSscientists,advisors,andgrantees.NIEHS/NTPDirectorLindaBirnbaum,Ph.D.,formerNIEHSDirectorKennethOlden,Ph.D.,NTPAssociateDirectorJohnBucher,Ph.D.,andSuperfundResearchProgramDirectorWilliamSuk,Ph.D.,arefellows,alongwithotheroutstandingpastandpresentNIEHSscientists,includingCarlBarrett,Ph.D.,DavidHoel,Ph.D.,JamesHuff,Ph.D.,GeorgeLucier,Ph.D.,RonaldMelnick,Ph.D.,andWalterRogan,M.D.

FormerNIEHSDirectorDavidRall,M.D.,Ph.D.,wastherecipientoftheannualRamazziniAwardin1989.OneofEastmond’scolleaguesontheNTPBoardofScientificCounselors,MelissaMcDiarmid,M.D.,oftheUniversityofMaryland,isalsoaCollegiumRamazzinifellow.

The Collegium Ramazzini carries on the legacy of the father of occupational medicineFoundedin1982,theCollegiumderivesitsnamefromItalianphysicianandUniversityofModenaProfessorBernardinoRamazzini(1633–1714),whoauthoredoneofthefoundingandseminalworksofoccupationalmedicineandplayedasubstantialroleinitsdevelopment.Hisbook,DeMorbisArtificumDiatriba(DiseasesofWorkers),outlinedthehealthhazardsofchemicals,dust,metals,repetitiveorviolentmotions,oddpostures,andotherdisease-causativeagentsencounteredbyworkersin52occupations.

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Collegium Ramazzini fellow David Eastmond (Photo courtesy of UCR)

The collegium’s logo features an 18th century drawing of the group’s namesake, Bernardino Ramazzini. (Photo courtesy of the Collegium Ramazzini)

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Volunteers translate NIEHS cookstove research in Guatemala By Eddy Ball

NIEHS/NTPDirectorLindaBirnbaum,Ph.D.,receivedanunexpectedholidaygiftDec.24,thankingherforNIEHSresearchonrespiratoryillnessandindoorairpollution.

Thenote,frombiochemistJohnPaulsrud,Ph.D.,amemberoftheZionsville[Ind.]UnitedMethodistChurchandaretiredresearchstaffmemberatIndianaUniversitySchoolofMedicine,pointedtoarecentreportaboutresearchledbyNIEHSgranteeKirkSmith,Ph.D.Smithestimatesthatindoorairpollutionfromcookingoveropenfireskillsalmost1.6millionchildrenworldwideeachyear(seestory).

TheUnitedPressInternationalonlinereport,Paulsrudsaid,helpedraisehiscongregation’sawarenessofthepotentialpreventivehealthimpactofefficientwood-burningcookstovesforpeopleindevelopingcountries,inspiringonemembertodonatefundstopurchase100Guatemalan-producedstovesforindigenousMayans.

“Todate,”Paulsrudwrote,“70familieshavereceivedstoves.”InstallingthestovesispartofamissionaryprograminGuatemalafocusedonhealthcare,literacy,sanitation,andconstructionimprovementstostrengthencommunityinfrastructure.Thefull-timemissionstaffincludesaGuatemalandentist,physician,andsocialworker.

Paulsrud,hiswife,andothermembersoftheZionsvillecongregationarepartofaneffortbytheUnitedMethodistChurch’sMissionGuatemalaandothernon-governmentalorganizations.ThegroupdocumentedtheirpublichealthpreventioneffortswithphotosbyPaulsrudthattellthestoryofhowNIEHSresearchcanleadtomeaningfulchangeonthefrontlinesofglobalpublichealth.

Like millions of households worldwide, before receiving their new cookstove, this family prepared meals over a poorly vented open fire. NIEHS research has linked air pollution from open fires, such as this one, to an increase in respiratory and other preventable disease. (Photo courtesy of John Paulsrud)

The children of this indigenous Mayan family spent much of their time with their mother as she cooked, which meant they, too, were exposed to potentially harmful levels of particulate matter from incomplete combustion. (Photo courtesy of John Paulsrud)

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The final steps of the process involve venting the smoke to the outside and sealing gaps between parts of the new stove. (Photo courtesy of John Paulsrud)

Mission Guatemala volunteers assemble the stove by lifting precast concrete pieces into place. (Photo courtesy of John Paulsrud)

The extended family can now look forward to cleaner air and cleaner walls in their Guatemalan home. The new stove is also more efficient, which can translate into less time and effort spent gathering fuel. (Photo courtesy of John Paulsrud)

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Science Notebook2011 papers of the year By Ian Thomas

Ofthenearly3,000paperspublishedbyNIEHS-supportedresearchersin2011,23publicationswerechosenaspapersoftheyear.

Extramural papers of the year• Amyloid-binding compound extends lifespan in C. elegans

• Mitochondrial, but not nuclear, Ligase3 is required for cellular viability

• Rapid evolution in Hudson River tomcod

• Sperm may be harmed by BPA exposure

• Less toxic and more effective carbon nanotubes for drug delivery

• DNA damage mapped out

• Autism and prenatal vitamins

• Mitochondrial dysfunction in children with autism

Intramural papers of the year• Mutations resulting from subtle chemical “trickery”

• Innate immunity linked to DNA damage response

• NIEHS study investigates the impact of poised RNA polymerase II on neuronal gene transcription

• A novel mechanism that may underlie learning and memory

• Two point mutations may influence the efficacy of breast cancer treatment

• Aprataxin structure links DNA repair mechanism to neurodegenerative disease

• IL-35 production by regulatory T cells reverses allergic asthma

• Overcoming phosphate congestion in high energy signaling molecules

NTP papers of the year• Global gene profiling in mice: similarities in the molecular landscape with human liver cancer

• Chemical genomics profiling of environmental chemical modulation of human nuclear receptors

• Gene expression alterations in immune system pathways in the thymus after exposure to immunosuppressive chemicals

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• Genomic biomarkers of phthalate-induced male reproductive developmental toxicity: A targeted rtPCR array approach for defining relative potency

• Aloe vera non-decolorized whole leaf extract-induced tumors in rats share similar molecular pathways with human sporadic colorectal tumors

• Voluntary exercise protects hippocampal neurons from trimethyltin injury

• Prenatal perfluorooctanoic acid exposure in CD-1 mice: low-dose developmental effects and internal dosimetry

Extramural papers of the year

Amyloid-binding compound extends lifespan in C. elegansNIEHS-supportedresearchersattheBuckInstituteforResearchonAgingreportthatachemicaldyethatlightsupamyloidproteinclumpscharacteristicofAlzheimer’sdiseasealsoslowsaginginthenematode,C. elegans.Thelifespan-boostingeffectsofthedye,calledThioflavinT(ThT)orBasicYellow1,supporttheideathatthebuildupofmisshapenproteinsisoneofthefundamentaleventsintheagingprocess.Usingroundworms,researchersfoundthatoptimumdosesofThTreversedtheeffectsofmutationsthatcausemuscleproteinstomisfoldandbecomeparalyzedataparticulartemperature.TheteamalsofoundthatwormsthatlackgenesimportanttodealingwithmisshapenproteinsdonotlivelongerwhenfedThT.

Citation:AlavezS,VantipalliMC,ZuckerDJ,KlangIM,LithgowGJ.2011.Amyloid-bindingcompoundsmaintainproteinhomeostasisduringageingandextendlifespan.Nature472(7342):226-229.

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Mitochondrial, but not nuclear, Ligase3 is required for cellular viabilityAmulti-institutionalteamofscientistshasdeterminedthatmitochondrialDNAligaseIII(Lig3),anenzymeinvolvedinvariousDNArepairpathways,isnecessaryforcellulargrowthandviability,ascomparedtothenuclearversionoftheenzyme.ThesefindingsweremadethroughaseriesofexperimentsthatincorporatedvariousformsofthegenecodingforLig3inmouseembryonicstemcells.ThisapproachenabledthemtodeterminethatmitochondrialLig3,butnotnuclearLig3,isnecessaryforcellviability.TheyalsofoundthatsubstitutionofLig1forLig3inthemitochondriamaintainscellularviability.

Citation:SimsekD,FurdaA,GaoY,ArtusJ,BrunetE,HadjantonakisAK,VanHoutenB,ShumanS,McKinnonPJ,JasinM.2011.CrucialroleforDNAligaseIIIinmitochondriabutnotinXrcc1-dependentrepair.Nature471(7337):245-248.

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Rapid evolution in Hudson River tomcodNewresearchfindingsbyNIEHSgranteessuggestthatHudsonRivertomcodhaveundergonerapidevolution,inresponsetoindustrialcontaminationoftheriverwithpolychlorinatedbiphenylsoverthelast50years.Investigatorsfoundchangesinthegenethatcodesforthearylhydrocarbonreceptor2(AHR2),whichmediatestoxicityinearlylifestages.BecausetheHudsonRiverfishisresistanttothetoxiceffectsofPCBs,theyareabletoaccumulatemoreofthechemical,whichisthentransferredfurtherupthefoodchainthroughthelargerfishthatconsumethem.

Citation:WirginI,RoyNK,LoftusM,ChambersRC,FranksDG,HahnME.2011.MechanisticbasisofresistancetoPCBsinAtlantictomcodfromtheHudsonRiver.Science331(6022):1322-1325.

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Sperm may be harmed by BPA exposureResearchershavefoundthaturinaryconcentrationsofbisphenolA(BPA)mayberelatedtodecreasedspermqualityandconcentration.Thestudyincluded190menandmeasuredspermconcentration,motility,shape,andDNAdamageinsemensamplesfromtheparticipants.BPAwasdetectedin89percentofthemen’surinesamples.Spermconcentrationwasabout23percentlowerinmeninthetopquartileofexposure,ascomparedwiththelowestquartile.Thehighestexposedmenalsohadabout10percentmoredamagedspermthanthelowestexposedgroup.

Thesefindingsareconsistentwithpreviousresearch,thoughinvestigatorsarecontinuingthisstudywithalargercohorttoconfirmtheirfindings.

Citation:MeekerJD,EhrlichS,TothTL,WrightDL,CalafatAM,TrisiniAT,YeX,HauserR.2010.SemenqualityandspermDNAdamageinrelationtourinarybisphenolAamongmenfromaninfertilityclinic.ReprodToxicol30(4):532-539.

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Less toxic and more effective carbon nanotubes for drug deliveryInvestigatorshavefoundthatsingle-walledcarbonnanotubestreatedwithpolyethyleneglycol(PEG)makemoreeffectiveandlesstoxicdrugdeliveryvehiclesthanuntreatednanotubes.TheresearcherslayeredcarbonnanotubeswithPEG,whichhasbeenshowntoimprovetheirdispersioninaqueoussolutions.BothPEG-treatedanduntreatednanotubeswerethenincubatedwiththechemotherapeuticdrugcisplatinandinjectedintolaboratorymice.Untreatednanotubeswerefoundtoclumptogetherinlungtissue,whilePEG-treatednanotubesshowedlittleornoaccumulation.

Theseresultsgivefurthercredencetotheuseofdrugdeliverysystemsutilizingsingle-walledcarbonnanotubes.

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Citation:BhirdeAA,PatelS,SousaAA,PatelV,MolinoloAA,JiY,LeapmanRD,GutkindJS,RuslingJF.2010.DistributionandclearanceofPEG-single-walledcarbonnanotubecancerdrugdeliveryvehiclesinmice.Nanomedicine(Lond)5(10):1535-1546.

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DNA damage mapped outUsingdifferentialepistasismaps,researchershavedocumentedhowacellulargeneticnetworkiscompletelyreorganizedinresponsetoDNAdamagingagents.Toachievethis,scientistsfocusedon400genesthatgovernsignaltransductionpathwaysinyeast.ThemapwascreatedbyidentifyinggeneinteractionsbeforeandafterexposuretoaDNA-damagingagent,similartocompoundsusedinchemotherapy.Surprisingly,theyfoundthatmostoftheinteractionsidentifiedafterdrugexposurewerenotpresentwithouttheexposure,leadingthemtobelievethatthegeneticnetworkwascompletelyreprogrammedbyDNAdamage.

Thisdiscoveryrepresentsanewfrontierinprobingdynamicinteractionsthatenablecellstosurviveandthriveinvaryingenvironmentalandgeneticcontexts.

Citation:BandyopadhyayS,MehtaM,KuoD,SungMK,ChuangR,JaehnigEJ,BodenmillerB,LiconK,CopelandW,ShalesM,FiedlerD,DutkowskiJ,GuenoleA,vanAttikumH,ShokatKM,KolodnerRD,HuhWK,AebersoldR,KeoghMC,KroganNJ,IdekerT.2010.RewiringofgeneticnetworksinresponsetoDNAdamage.Science330(6009):1385-1389.

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Autism and prenatal vitaminsInastudyof566subjects,comparingagroupofautisticchildrentoacontrolgroupofnormallydevelopedchildren,researchersfoundthatmotherswhodidn’ttakeprenatalvitaminswereatgreaterriskofhavinganautisticchild.

Researchersexaminedmaternalintakeofprenatalvitaminsinthethreemonthsbeforeconceptionandthefirstmonthofpregnancy,andtheylookedforgenotypesassociatedwithautism.Inadditiontofindingadistinctdose/responserelationship,scientistsfoundthattheoddsratioforautismriskinmotherswhotookprenatalvitaminswas1.8,whereasmotherswhodidn’ttakevitaminsfacedanoticeablyhigherriskat7.2.Thissuggeststhatthematernal-fetalenvironmentcanmagnifytheeffectsofasusceptibilitygene.

Citation:Citation:SchmidtRJ,HansenRL,HartialaJ,AllayeeH,SchmidtLC,TancrediDJ,TassoneF,Hertz-PicciottoI.2011.Prenatalvitamins,one-carbonmetabolismgenevariants,andriskforautism.Epidemiology22(4):476-485.

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Mitochondrial dysfunction in children with autismInthisstudy,theinvestigatorsproposethatmitochondrialdeficienciesinbraincellsmightleadtosomeofthecognitiveimpairmentsassociatedwithautism.Whilethestudydoesnotidentifyanactualcauseofautism,itdoessuggestthatcumulativedamageandoxidativestressinmitochondriacouldinfluenceboththeonsetandseverityofthedisorder.Althoughthestudyincludedonly10autisticchildrenand10age-matchedcontrols,itsfindingsmayeventuallyleadtonewinsightsonearlydiagnosis,treatment,andpreventionefforts,thoughlargerstudiesarenecessarymovingforward.

Citation:GiuliviC,ZhangYF,Omanska-KlusekA,Ross-IntaC,WongS,Hertz-PicciottoI,TassoneF,PessahIN.2010.Mitochondrialdysfunctioninautism.JAMA304(21):2389-2396.

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Intramural papers of the year

Mutations resulting from subtle chemical “trickery”WhenWatsonandCrickfirstdescribedthestructureoftheDNAhelixin1953,theyproposedthatmutationsmightresultfrommismatcheswhosegeometrymimicsthatofcorrectbasepairs.Thispaperprovidesthefirstdirectstructuralevidenceforthisidea,andrevealshowthechemicalcomplexityofgeneticinformationcansometimestrickevenanormal,healthycellintomakingamistake,forgood,enablingevolution,orbad,resultingindisease.ItisanexampleofenvironmentalhealthscienceresearchthatfitsbeautifullyintoPillar1,fundamentalresearch,intheemergingNIEHSstrategicplan.Weneedtounderstandhowthingsworkundernormalcircumstancesifweeverhopetoreallyunderstandtheconsequencesofenvironmentstress.

Citation:BebenekK,PedersenLC,KunkelTA.2011.ReplicationinfidelityviaamismatchwithWatson-Crickgeometry.ProcNatlAcadSciUSA108(5):1862-1867.

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Innate immunity linked to DNA damage response Thisstudy,thefirsttocomeoutofthenewNIEHSClinicalResearchUnit,revealsastronglink,inhumansubjects,betweenchromosomelesionsthatcanbeinducedbyenvironmentalagents,theimmune-inducedinflammatoryresponse,andindividualsusceptibility.TheinvestigatorsdemonstratedthatmostoftheToll-likereceptor(TLR)familyofinnateimmunegenes,whichdealwithinfectiousagentsinresponsivetoDNAdamage,aredirectlyregulatedbythetumorsuppressorp53,andtheyidentifiedthefirstfunctionalconsequencesofaSNPintheTLR8promoter.ThesefindingsonindividualdifferencesinTLRinductionbyp53activationandDNAdamageshouldproveusefulinthedevelopmentofTLR-targetedvaccinesandTLR-basedcancertreatments.

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Citation:MenendezD*,ShatzM*,AzzamK,GarantziotisS,FesslerMB,ResnickMA.2011.TheToll-likereceptorgenefamilyisintegratedintohumanDNAdamageandp53networks.PLoSGenet7(3):e1001360.(*co-firstauthors).

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NIEHS study investigates the impact of poised RNA polymerase II on neuronal gene transcription Activity-dependentplasticityofsynapsesisanimportantprocessinthedevelopmentofbraincircuitry,atimewhenthebrainissusceptibletoenvironmentalinsults.Rapidactivity-dependentinductionofgenesplaysacriticalroleinconsolidatingsynapticchanges,soanunderstandingofhowthisoccurscouldprovideimportantcluesintotargetsofenvironmentaltoxicants.

Citation:SahaRN,WissinkEM,BaileyER,ZhaoM,FargoDC,HwangJY,DaigleKR,FennJD,AdelmanK,DudekSM..2011.Rapidactivity-inducedtranscriptionofArcandotherIEGsreliesonpoisedRNApolymeraseII.NatNeurosci14(7):848-856.

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A novel mechanism that may underlie learning and memorySincesmokingissuspectedtobeprotectiveinAlzheimer’sdiseasethroughactiononnicotinicacetylcholinereceptors(nAChRs),anddrugsactingonthesereceptorsimprovecognitivefunction,thescientistsinvestigatedhowendogenousacetylcholineactingthroughnAChRsaffectedcellularmodelsoflearningandmemory.Thelong-termaimofthisworkistounderstandthebraincircuitsinvolvedinenvironmentaldiseaseandaidinthedevelopmentoftherapeuticstotreatthesediseases.

Citation:GuZ,YakelJL.2011.Timing-dependentseptalcholinergicinductionofdynamichippocampalsynapticplasticity.Neuron71(1):155-165.

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Two point mutations may influence the efficacy of breast cancer treatment Thispaperdescribestheinitialdevelopmentandcharacterizationofamutantestrogenreceptoralphamousemodelthatsegregatesthetissueandphysiologicalfunctionalityofthetwotranscriptionactivationfunctions

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tocertaintissues.Endocrinedisruptingchemicals(EDCs)activatethismutantthroughtheAF-1similartoTamoxifenandwillallowassessmentoftheEDCtissueselectivemechanismofaction.

Citation:AraoY,HamiltonKJ,RayMK,ScottG,MishinaY,KorachKS.2011.EstrogenreceptoralphaAF-2mutationresultsinantagonistreversalandrevealstissueselectivefunctionofestrogenreceptormodulators.ProcNatlAcadSciUSA108(36):14986-14991.

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Aprataxin structure links DNA repair mechanism to neurodegenerative disease Exposuretoenvironmentaltoxicantsandstressors,chronicinflammation,andcellularrespirationallcontributetoproductionofoxidativeDNAdamage,includingDNAstrandbreaksandDNAbasedamage,thatwhenmetabolized,cangiverisetocytotoxic5’-adenylationDNAlesions.ThisstudyprovideskeyinsightsintothechemistryandbiologyofDNA-5’-adenylationgenomerepairbyaprataxin,andexplainshowmutationsinthehumanaprataxingeneresultinsmall,butdevastatingchangestotheaprataxinproteinshapethatunderliethecripplingheritableneurodegenerationdiseaseataxiawithoculomotorapraxia1(AOA1).

Citation:TumbaleP,AppelCD,KraehenbuehlR,RobertsonPD,WilliamsJS,KrahnJ,AhelI,WilliamsRS.2011.Structureofanaprataxin-DNAcomplexwithinsightsintoAOA1neurodegenerativedisease.NatStructMolBiol18(11):1189-1195.

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IL-35 production by regulatory T cells reverses allergic asthmaSomepreviousstudieshaveshownthattheprevalenceofallergicasthmaisassociatedwithexposuretoenvironmentalendotoxin,whereasotherstudieshaveshownthatendotoxincanprotectagainstthedevelopmentofasthma.Thebasisforthisapparentparadoxhasbeenunclear.ThispapershowsthatalthoughendotoxincanprimeThelper2(Th2)andTh17responsestoinhaledallergens,italsoinducesTregulatory(Treg)cellproliferation.ThepaperfurtheridentifiedaspecifictypeofTregcellthatsuppressesallergicresponsesbyproducingtherecentlyidentifiedcytokine,IL-35.

Citation:WhiteheadGS,WilsonRH,NakanoK,BurchLH,NakanoH,CookDN.2012.IL-35productionbyinduciblecostimulator(ICOS)-positiveregulatoryTcellsreversesestablishedIL-17-dependentallergicairwaysdisease.JAllergyClinImmunol129(1):207-215.

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Overcoming phosphate congestion in high energy signaling moleculesInositolpyrophosphatesregulatethebody’smetabolicbalance,alife-sustainingprocessthatisunderconstantenvironmentalpressure.Breakdownofmetaboliccontrolprocessesisevidentinillnessessuchasdiabetes,cancerandaging.Therationaldesignofdrugstoimprovehumanhealthisfacilitatedbythemoleculartemplatethatisprovidedbyouratomicleveldescriptionofthestructureandreactionmechanismofanenzymethatsynthesizesinositolpyrophosphates.

Citation:WangH,FalckJR,HallTM,Shears,SB.2011.Structuralbasisforaninositolpyrophosphatekinasesurmountingphosphatecrowding.NatChemBiol8(1):111-6.

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NTP papers of the year

Global gene profiling in mice: similarities in the molecular landscape with human liver cancerHepatocellularcarcinoma(HCC)isanimportantcauseofmorbidityandmortalityworldwide.AlthoughtheriskfactorsofhumanHCCarewellknown,themolecularpathogenesisofthisdiseaseiscomplexand,ingeneral,treatmentoptionsremainpoor.

UsingglobalgeneexpressionprofilingintheB6C3F1rodentmodel,researchersidentifiedthedysregulationofseveralmediatorssimilarlyalteredinhumanHCC,includingre-expressionoffetaloncogenes,upregulationofprotooncogenes,downregulationoftumorsuppressorgenes,andabnormalexpressionofcellcyclemediators,growthfactors,apoptosisregulators,andangiogenesisandextracellularmatrixremodelingfactors.Thesedataprovidefurthersupportfortheuseofthismodelinhazardidentificationofcompoundswithpotentialhumancarcinogenicityrisk,andmayhelpinbetterunderstandingthemechanismsoftumorigenesisresultingfromchemicalexposureintheNTPtwo-yearcarcinogenicitybioassay.

Citation:HoenerhoffMJ,PandiriAR,LahousseSA,HongHH,TonTV,MasindeT,AuerbachSS,GerrishK,BushelPR,ShockleyKR,PeddadaSD,SillsRC.2011.GlobalgeneprofilingofspontaneoushepatocellularcarcinomainB6C3F1mice:similaritiesinthemolecularlandscapewithhumanlivercancer.ToxicolPathol39(4):678-699.

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Chemical genomics profiling of environmental chemical modulation of human nuclear receptorsInresponsetothegrowingdemandformoreefficientandcost-effectivemeansofassessingenvironmentalchemicaltoxicity,theU.S.Tox21programhasproposedanumberofalternativestrategiesfortoxicitytestinganddatascreening.Thegoalofthisstudywastodevelopmethodstoevaluatethedatageneratedfromtheseassays,toguidefutureassayselectionandprioritization.

Byexaminingroughly3,000environmentalchemicalsagainstapanelof10humannuclearreceptorsforreproducibility,scientistsdeterminedtheassaystobeappropriateintermsofbiologicalrelevance.Theywerealsoabletoformulatedata-drivenstrategiesfordiscriminatingtruesignalsfromartifactsandtoprioritizeassaysbasedondataquality.

Citation:HuangR,XiaM,ChoMH,SakamuruS,ShinnP,HouckKA,DixDJ,JudsonRS,WittKL,KavlockRJ,TiceRR,AustinCP.2011.Chemicalgenomicsprofilingofenvironmentalchemicalmodulationofhumannuclearreceptors.EnvironHealthPerspect119(8):1142-1148.

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Gene expression alterations in immune system pathways in the thymus after exposure to immunosuppressive chemicalsDysregulationofpositiveandnegativeselection,antigenpresentation,orapoptosisinthethymuscanleadtoimmunosuppressionorautoimmunity.Thisstudyhypothesizedthatgenomicanalysisofthymusafterchemical-inducedatrophywouldyieldtranscriptionalprofilesthatsuggestpathwaysoftoxicityassociatedwithreducedfunction.

Byexposingrodentstofourimmunosuppressiveagentsandevaluatingchangesingeneexpression,investigatorsfoundthatallfourchemicalsinducedthymicatrophyandchangesinboththerelativeproportionandabsolutenumberofCD3(+),CD4(+)/CD8(-),CD4(-)/CD8(+),andCD4(+)/CD8(+)thymocytes.

Genomicanalysisrevealedgeneexpressionchangesinseveralpathwaysthatarecommonlyassociatedwithxenobiotic-inducedimmunesystemperturbations,particularlythosethatcontributetothedevelopmentandmaturationofthymicTcells.

Citation:FrawleyR,WhiteKJr,BrownR,MusgroveD,WalkerN,GermolecD.2011.Geneexpressionalterationsinimmunesystempathwaysinthethymusafterexposuretoimmunosuppressivechemicals.EnvironHealthPerspect119(3):371-376.

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Genomic biomarkers of phthalate-induced male reproductive developmental toxicity: A targeted rtPCR array approach for defining relative potencyMaleratfetusesexposedtocertainphthalateesters(PEs)duringsexualdifferentiationdisplayreproductivetractmalformationsduetoreductionsintestosterone(T)productionandtheexpressionofsteroidogenesis-andINSL3-relatedgenes.Inthecurrentstudy,researchersexaminedkeytargetgenesrepresentingsexualdeterminationanddifferentiation,steroidogenesis,gubernaculumdevelopment,andandrogensignalingpathwaystoranktherelativepotencyofseveralPEs.

DespitespeculationofPPARinvolvementintheeffectsofPEsonthefetaltestis,noPPAR-relatedgeneswereaffectedinthefetaltestesbyexposuretoanyofthetestedPEs.Furthermore,thepotentPPARalphaagonist,WY-14643,didnotreducefetaltesticularTproductionfollowingGD14-18exposure,suggestingthattheanti-androgenicactivityofPEsisnotPPARalpha-mediated.

Citation:HannasBR,LambrightCS,FurrJ,EvansN,FosterPM,GrayLE,WilsonVS.2011.Genomicbiomarkersofphthalate-inducedmalereproductivedevelopmentaltoxicity:AtargetedrtPCRarrayapproachfordefiningrelativepotency.ToxicolSci;doi10.1093/toxsci/kfr315[Online22November2011].

[abstract]

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Aloe vera non-decolorized whole leaf extract-induced tumors in rats share similar molecular pathways with human sporadic colorectal tumorsResearchbyNTPandtheNationalCenterforToxicologicalResearchhasdemonstratedadose-dependentincreaseinlargeintestinaltumorsinF344ratschronicallyexposedtoAloebarbadensisMiller(Aloe vera)non-decolorizedwholeleafextract(AVNWLE)indrinkingwater.

Themorphologicalandmolecularpathwaysofthesetumorswerethencomparedtohumancolorectalcancer(hCRC)literature.Histologicalevaluationofthelargeintestinaltumorsindicatedeightoftwelveadenomas(Ads)andfouroftwelvecarcinomas(Cas).MutationanalysisofeightAdsandfourCasidentifiedpointmutationsinexons1and2oftheKrasgene(twoofeightAds,twooffourCas),andinexon2oftheCtnnb1gene(threeofeightAds,oneoffourCas).Inconclusion,theAVNWLE-inducedlargeintestinaltumorsinF344ratsshareseveralsimilaritieswithhCRCatthemorphologicalandmolecularlevels.

Citation:PandiriAR,SillsRC,HoenerhoffMJ,PeddadaSD,TonTV,HongHH,FlakeGP,MalarkeyDE,OlsonGR,PogribnyIP,WalkerNJ,BoudreauMD.2011.Aloeveranon-decolorizedwholeleafextract-inducedlargeintestinaltumorsinF344ratssharesimilarmolecularpathwayswithhumansporadiccolorectaltumors.ToxicolPathol39(7):1065-1074.

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Voluntary exercise protects hippocampal neurons from trimethyltin injuryIntheperiphery,exerciseinducesinterleukin(IL)-6todownregulatetumornecrosisfactor(TNF),elevateinterleukin-1receptorantagonist(IL-1RA),decreasinginflammation.IL-6productioninthehippocampusfollowingexercisesuggeststhepotentialofasimilarprotectiveroleasintheperipherytodown-regulateTNFalphaandinflammation.

Usingachemical-inducedmodelofhippocampaldentategranulecelldeathdependentuponTNFreceptorsignaling,researchersdemonstratedneuroprotectioninmicewithtwoweeksaccesstorunningwheel.InIL-6deficientmice,exercisedidnotattenuatetrimethyltin-inducedtremorandadiminishedlevelofneuroprotectionwasobserved.ThesedatasuggestacontributoryroleforIL-6inducedbyexerciseforneuroprotectionintheCNSsimilartothatseenintheperiphery.

Citation:FunkJA,GohlkeJ,KraftAD,McPhersonCA,CollinsJB,JeanHarryG.2011.Voluntaryexerciseprotectshippocampalneuronsfromtrimethyltininjury:possibleroleofinterleukin-6tomodulatetumornecrosisfactorreceptor-mediatedneurotoxicity.BrainBehavImmun1063-1077.

[abstract][story]

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Prenatal perfluorooctanoic acid exposure in CD-1 mice: low-dose developmental effects and internal dosimetryToinvestigatethelow-doseeffectsofperfluorooctanoicacid(PFOA)onoffspring,timed-pregnantCD-1miceweregavagedosedwithPFOAforallorhalfofgestation.Inbothstudies,theoffspringofallPFOA-treateddamsexhibitedsignificantlystuntedmammaryepithelialgrowthasassessedbydevelopmentalscoring.

EvaluationofinternaldosimetryinoffspringrevealedthatPFOAconcentrationsremainedelevatedinliverandserumforuptosixweeksandthatbrainconcentrationswerelowandundetectableafterfourweeks.Also,PFOA-inducedeffectsonmammarytissueoccurredatlowerdosesthaneffectsonliverweightinCD-1miceandpersisteduntil12weeksofagefollowingfull-gestationalexposure.

Citation:MaconMB,VillanuevaLR,Tatum-GibbsK,ZehrRD,StrynarMJ,StankoJP,WhiteSS,HelfantL,FentonSE.2011.PrenatalperfluorooctanoicacidexposureinCD-1mice:low-dosedevelopmentaleffectsandinternaldosimetry.ToxicolSci122(1):134-145.

[abstract]

(IanThomasisapublicaffairsspecialistwiththeNIEHSOfficeofCommunicationsandPublicLiaison,andaregularcontributortotheEnvironmentalFactor.)

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Distinguished lecturer discusses the mechanism of action of amphetamine By Anshul Pandya

NeuroscientistSusanAmara,Ph.D.,deliveredthelatesttalkintheNIEHSDistinguishedLectureSeriesDec.13,2011,withapresentationfocusedonthemechanismofactionofamphetamineonthedopamineandglutamatetransporters.Thesetransportersareresponsiblefortheclearanceoftheneurotransmittersdopamineandglutamatefollowingtheirreleaseatsitesofneuronalcommunicationinthenervoussystemknownassynapses.

AmaraspecializesinthestructureandfunctionofbrainneurotransmittertransporterproteinsandistheThomasDetreprofessorandchairofneurobiologyattheUniversityofPittsburgh.SheisalsothemostrecentpastpresidentoftheSocietyforNeuroscience,thelargestorganizationofneuroscientistsintheworld.NIEHSleadresearcherJerrelYakel,Ph.D.,hostedthetalk.

Hercurrentresearchisfocusedonelucidatingthebiochemicalpathwaysthatmediatedopaminetransporterinternalizationbyamphetamine.Understandingthismechanismisimportantbecausethedopaminetransporterservesasatargetforavarietyofclinicallyusedmedicationsandrecreationallyabuseddrugs.

The actions of amphetamine “Whilereuptakeinhibitorsofserotonin,norepinephrine,anddopaminearewidelyusedclinicallytotreatdepression,”Amarasaid,“weknowmuchlessaboutthemechanismofactionofamphetamines,whichalsotargetthethreebiogenicaminetransportsystems.”Inhertalk,Amarastressedthatcocaineandamphetamines,bothcommonlyabusedpsychostimulants,havedifferentactionsonthedopaminetransporter.

Cocaineinhibitsthedopaminetransporteratthecellsurface,whereasamphetamine,inadditiontobeinganinhibitorofthedopaminetransporter,enterstheneurons.Amara’sresearchhasfoundthatonceitentersneuronalcytoplasm,amphetamineactivatesintracellularsignalingpathwaysandcausestheinternalizationofthedopaminetransporter.

“The key is to understand the functioning of the transporters of neurotransmitters in the brain, so that they can be targeted by new drugs to treat psychiatric disorders,” Amara said. (Photo courtesy of Steve McCaw)

Amara engaged the audience with intriguing information about the action of amphetamine on a cellular level and the pathways involved. (Photo courtesy of Steve McCaw)

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Neartheendofhertalk,Amaradescribedtheactionofamphetamineonaneuronalglutamatetransporter.Similartoitseffectonthedopaminetransporter,amphetaminealsocausestheinternalizationoftheglutamatetransporter.Shewentontoshowexperimentaldatasuggestingthatinorderforamphetaminetomediatetheinternalizationoftheglutamatetransporter,thetransporterrequiresaparticularstretchoffiveaminoacidsthatarelocatedintheC-terminusorneartheendofitsproteinstructure.Removingtheseaminoacidsblocksglutamatetransporterinternalizationbyamphetamine.

Interaction with NIEHS postdocs Afterherlecture,AmarajoinedNIEHSpostdoctoralfellowsforabrownbaglunch.ItwasanopportunityfortheseyoungscientiststotellAmaraabouttheirownresearchinterestsandseekheradviceregardingtheircareers.Amarabrieflyspokeaboutherresearchandcareerprogression,andabouttheprospectsofresearchfundingforbiomedicalscienceinthecurrentbudgetaryenvironment.ShealsomentionedherlobbyingeffortwithCongressduringhertenureasthepresidentoftheSocietyforNeuroscience,infavorofkeepingresearchfundingatcurrentlevels.

(AnshulPandya,Ph.D.,isanIntramuralResearchTrainingAward(IRTA)fellowintheNIEHSLaboratoryofNeurobiologyIonChannelPhysiologyGroup.)

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NIEHS selects 2012 ONES awardees By Eddy Ball

NIEHShasannouncedfundingforsevenearlystagetenure-trackinvestigatorsas2012OutstandingNewEnvironmentalScientist(ONES)awardees.Thehighlycompetitive,five-yearONESgrantswilltotalapproximately$4millionforthefirstyear,andtheawardees,liketheirpredecessorsinthefive-year-oldprogram,willvisitNIEHStopresenttalksabouttheirresearchprojects.

ThenewawardeesreflectthebroadrangeofNIEHSresearchinterests.

• LaurenAleksunes,Pharm.D.,Ph.D.,anassistantprofessorintheErnestMarioSchoolofPharmacyDepartmentofPharmacologyandToxicologyatRutgers,TheStateUniversityofNewJersey

Amara and Yakel listened to questions raised by audience members after the talk. (Photo courtesy of Steve McCaw)

Audience members listened to the Amara talk with keen interest. From right to left, Thomas McCormack, Ph.D., Christian Erxleben, Ph.D., Ezequiel Marron, Ph.D., Bernd Gloss, Ph.D., Erica Scappini and Fengxia Mizuno, Ph.D. (Photo courtesy of Steve McCaw)

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• UlrikeDydak,Ph.D.,anassistantprofessorofhealthsciencesinthePurdueUniversitySchoolofHealthSciences,withanadjunctappointmentattheIndianaInstituteforBiomedicalImagingSciencesatIndianaUniversitySchoolofMedicine

• StaceyHarper,Ph.D.,anassistantprofessorofChemicalEngineeringintheOregonStateUniversitySchoolofChemical,Biological,andEnvironmentalEngineering

• JoelMeyer,Ph.D.,anassistantprofessorofenvironmentaltoxicologyintheDukeUniversityNicholasSchooloftheEnvironment

• BrandonPierce,Ph.D.,anassistantprofessorofepidemiologyinTheUniversityofChicagoDepartmentofHealthStudies

• ChristyPorucznik,Ph.D.,anassistantprofessorintheUniversityofUtahSchoolofMedicinePublicHealthProgram

• VishalVaidya,Ph.D.,anassistantprofessorofmedicineandenvironmentalhealthatHarvardMedicalSchoolandtheHarvardSchoolofPublicHealth

“Thisgrantisdesignedtoserveasthefoundationofasuccessfulresearchcareer,”saidNIEHSTrainingandCareerProgramsHealthScientistAdministratorCarolShreffler,Ph.D.“Theprogramstrivestobuildalong-termrelationshipbetweentheawardeesandNIEHS.”

“We,indeed,havemadethisaverycompetitiveprocess,”Shrefflernoted,“andwelookforwardtohavingtheseawardeesmakesomeveryseminalcontributionsinthefieldofenvironmentalhealthsciences.”

A former NIEHS-supported postdoc at The University of Kansas Medical Center in the lab of Curtis Klaassen, Ph.D., Aleksunes will pursue her studies on the disposition of environmental chemicals during pregnancy. (Photo courtesy of Rutgers University)

A physicist who focuses on the investigation of human in vivo metabolism, Dydak will utilize neuroimaging for early diagnosis of manganese toxicity in humans and rodents, expanding on preliminary research funded through an NIEHS exploratory grant. (Photo courtesy of Purdue University)

A former postdoc in the NIEHS-funded Environmental Health Sciences Center at Oregon State University, Harper plans to conduct integrative studies to define drivers of nanomaterial toxicity. (Photo courtesy of Stacey Harper)

A former postdoc in the NIEHS Laboratory of Molecular Genetics, Meyer will expand his investigation of the role of mitochondrial DNA damage in neurodegeneration. (Photo courtesy of Duke University)

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Researchers find potential new avenue for cancer therapies By Robin Arnette

Recentfindingsinmicesuggestthatblockingtheproductionofsmallmoleculesproducedinthebody,knownasepoxyeicosatrienoicacids(EETs),mayofferanovelstrategyfortreatingcancerbyeliminatingthebloodvesselsthatfeedtumors.ThisresearchisthefirsttoshowthatEETsworkinconcertwithvascularendothelialgrowthfactor(VEGF),aproteinknowntoinducebloodvesselgrowth.Together,EETsandVEGFpromotemetastasis,orthespreadofcancer,byencouragingthegrowthofbloodvesselsthatsupplynutrientstocancercells.

Theresearchteam,comprisedofscientistsfromNIEHSandseveralotherinstitutions,publisheditsdataonlineintheDec.19issueofTheJournalofClinicalInvestigation.

EETs, a double-edged sword in health and diseasePreclinicalresearchsuggeststhatpatientswithavarietyofvascularconditions,suchasdiabetes,hypertension,inflammation,stroke,andheartattack,maybenefitbyincreasingtheirEETlevels,becausethecompoundscausebloodvesselstodilate,andreducetissueinflammationandcelldeath.However,previousworkhasalsodemonstratedthatEETsmaketumorcellsgrowfaster,andcausethemtomigrateandbecomemetastatic.DarrylZeldin,M.D.,NIEHSscientificdirectorandauthoronthepaper,saidhebelievedthathumanmetabolismhastoachieveacertainharmonyinregardtoEETs.

Partially supported by an NIEHS Superfund Research Program grant during his postdoc, Pierce will continue research with a Bangladesh cohort, studying the effects of arsenic exposure on telomeres. (Photo courtesy of Brandon Pierce)

A former lieutenant commander in the United States Public Health Service, who was supported by an NIEHS training grant during graduate school, Porucznik will investigate peri-conceptional biomonitoring as part of her interests in preventive medicine. (Photo courtesy of Christy Porucznik)

A recipient of an NIEHS Pathway to Independence Award in 2007, and former summer intern at NIEHS during graduate school, Vaidya will study fibrinogen signaling in kidney tissue repair. (Photo courtesy of Vishal Vaidya)

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“ThebodyhastoproduceenoughEETstomaintainahealthycardiovascularsystemwithoutpromotingcancer.Ithastobalancethedouble-edgedswordjustright,”Zeldinsaid.

TofindouthowEETsencouragethedevelopmentofcancer,theteamcreatedtwomicestrains,onewithhighlevelsofEETsandonewithlowlevelsofEETs.

“ThemicewithhigherEETsdevelopedmoremetastatictumorscomparedtothemicewithlowerEETs,”Zeldinsaid.“Often,thetumoritselfwillproducemoreEETs,whichcanspeeduptumorgrowthanditssubsequentspread,butouranalysisdemonstratedthattheEETsproducedbythesurroundingtissuesencouragedtumorgrowthandmigration.”

MatthewEdin,Ph.D.,aresearchfellowinZeldin’sgroup,isoneoftheauthorsonthepaperandhelpeddevelopthemicestrains.HesaidEETsdirectlyleadtothecreationofnewbloodvessels,alsoknownasangiogenesis,whichthecancercellsneedinordertoreceiveoxygenandnutrientstogrow.Heequatedtheprocesstowhathappenswhenabuilderbeginsconstructinganewhousingdevelopment.

“Oneofthefirstthingsconstructioncrewshavetodoisbuildtheroads,sothatmaterialsandworkerscanbetransportedtothesite,”Edinsaid.“Incancer,EETsacceleratetheroadbuilding,allowingthehousingdevelopmenttoexpandquickly.”

Maintaining balance with an experimental antagonistAccordingtoDipakPanigrahy,M.D.,anauthoronthepaperandaresearchassociateattheDana-Farber/Children’sHospitalCancerCenter,Boston,EETshaveapotentstimulatoryeffect,promotingcancergrowthandmetastasis,aprocessthatcouldbeeffectivelyinhibitedusingnovelantagonists,suchasEEZE,whicharecompoundsthatinterferewiththispathwayinmice.EEZEhasnotbeenapprovedforhumanuse,andisonlyusedforresearch.

“EEZEisstructurallysimilartoEETs,butitblockstheeffectofEETsanddramaticallyslowstumorigenesis,”Panigrahyexplained.

MarkKieran,M.D.,Ph.D.,anotherauthorofthiscollaborativestudyandalsofromDana-Farber,commentedontheimportanceoftheresearch.

“Theidentificationofanoldpathwaystudiedformanyyearsincardiovasculardiseasehasfoundanewroleinregulatingcancergrowthandmetastasis,theprimarycausesofcancerrelateddeaths,”hesaid.“Withthesefindings,opportunitiestobetterunderstandtheunderlyingmechanismsthatdrivecancer,andthusthedevelopmentofeffectivetherapiesfortheirtreatment,movesonestepclosertoareality.”

In addition to his role as scientific director, Zeldin heads the Molecular and Cellular Biology Group and Environmental Cardiopulmonary Disease Group in the NIEHS Laboratory of Respiratory Biology. (Photo courtesy of Steve McCaw)

Edin was second author on the 31-member team of researchers. (Photo courtesy of Steve McCaw)

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Citation: PanigrahyD,EdinML,LeeCR,HuangS,BielenbergDR,ButterfieldCE,BarnesCM,MammotoA,MammotoT,LuriaA,BennyO,ChaponisDM,DudleyAC,GreeneER,VergilioJA,PietramaggioriG,Scherer-PietramaggioriSS,ShortSM,SethM,LihFB,TomerKB,YangJ,SchwendenerRA,HammockBD,FalckJR,ManthatiVL,IngberDE,KaipainenA,D’AmorePA,KieranMW,ZeldinDC.2011.Epoxyeicosanoidsstimulatemultiorganmetastasisandtumordormancyescapeinmice.JClinInvest;doi:10.1172/JCI58128[Online19December2011].

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Seminar explores the potential of bioinformatics in autism research By Ian Thomas

AutismexpertsfromaroundthecountrygatheredNov.29-30attheMarriottinResearchTrianglePark,N.C.,foratwo-daydiscussionsponsoredbyNIEHSonbioinformaticsanditsroleinautismresearch.Focusingonthegeneticandenvironmentalcauses,thegroupoutlinedanumberofcutting-edgetechniquesfortakingadvantageofleading-edgecomputationalandscreeningapproachestoshareinformation,generatenewhypotheses,andexpandtheexistingknowledgebasesurroundingautismspectrumdisorders(ASD).

“Atpresent,NIEHScommitsroughly$7millionayeartoautismresearchand,whilewe’vemadesomegreatprogressinrecentyears,weneedtodomore,”saidNIEHS/NTPDirectorLindaBirnbaum,Ph.D.,amemberoftheU.S.DepartmentofHealthandHumanServices’InteragencyAutismCoordinatingCommittee.“AccordingtothelatestfiguresfromtheCDC[CentersforDiseaseControlandPrevention],nearly1in100kidsareaffectedbyautism.Meetingslikethishelpusworktowardthegoalofmoreeffectivetreatmentandprevention.”

When genes and the environment collideAmajorthemethroughouttheeventwasthat,whilegeneticandenvironmentalfactorsmustalwaysbestudiedindividually,itisthecombinedinfluenceofboththatcouldprovevitaltodiscoveringnewmethodsoftreatmentandprevention.

“Alltooofteninautismresearch,thegeneticviewpointisseenasacompetitortotheenvironmentalviewpointwhenitcomestocausation,”saidCindyLawler,Ph.D.,ascientificprogramadministratorfortheNIEHSCentersforChildren’sEnvironmentalHealthandDiseasePreventionResearch.“Ourgoalforthismeetingwastobringmembersofbothsidestogetherinthehopesoffosteringagreaterunderstanding,sothatonecanactuallyinformtheother,ratherthaneclipseit.”

Furthercomplicatingthematteristhemisperceptionthatautismisasingulardisease,Lawleradded.

“It’skeytorememberthatautismisactuallyagroupofneurodevelopmentaldisorders,”saidAutismSpeaks’ChiefScienceOfficerGeraldineDawson,Ph.D.“Eventhougheachdisordercontainsthesamethreecoresymptoms—socialimpairment,communicationimpairment,andrestrictedrangeofactivities—it’simportant

Birnbaum noted that autism cases among boys outnumber those of girls, 4 to 1. (Photo courtesy of Steve McCaw)

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torecognizethatthisconditioninvolvesmultipleinfluencesandetiologies,withenvironmentalfactorsbeingonepieceofthiscomplexpuzzle.”

The technological edgeBioinformaticsistheapplicationofcomputerandinformationtechnologytoanalyze,dissect,andcatalogbiologicaldataforthepurposesofformulatingandtestingnewscientifichypotheses.Thisinvolvestheuseofnumerousinformaticsresources,suchasdatabases,modelingandimagingprograms,anddataminingsoftware,amongothers.

“Alloftheinformationcontainedinourdatabasecomesdirectlyfromthescientificliteratureitself,”saidAllanPeterDavis,Ph.D.,projectmanagerfortheComparativeToxicogenomicsDatabase,whichisfundedinpartbyNIEHS.“So,forinstance,ifascientisthasaquestionaboutaparticulargene-diseaserelationship,heorshecansimplytrackthatpieceofdatabacktotheoriginalsourcematerial.”

Still,Davisandothersagreethatautomatedstatisticscanonlygosofar.

“WehireprofessionalPh.D.curatorswhodonothingbutreadthesepapersandlookspecificallyforchemical-gene-diseaseinteractions,whicharethenformattedandcatalogedintothedatabase.Thishumanelementiscrucialbecauseithelpstoeliminatealotofthefactualambiguitiesthatbasictextminingtendstocreate,”hesaid.

A complex approach for a complex problem“OurnumberonefocusatNIEHShasalwaysbeenonprevention,”saidBirnbaum.“Asweallknow,autismisacomplexgroupofdisorders,whichwillrequirecomplexapproachesinordertobetterunderstand.Bioinformaticsisonesuchtoolthatallowsustodothat.”

(IanThomasisapublicaffairsspecialistintheNIEHSOfficeofCommunicationsandPublicLiaisonandaregularcontributortotheEnvironmentalFactor.)

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Dawson outlined Autism Speaks’ ongoing commitment to genetic and environmental health research. (Photo courtesy of Steve McCaw)

Leading minds from the genetic, environmental, and technological fields listened as speakers discuss the collective impact of all three on public health, including Autism Speaks’ Dusan Bosnjakovic, center, and NIEHS grantee Heather Volk, Ph.D., right. (Photo courtesy of Steve McCaw)

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Kleckner offers glimpses inside a living E. coli cell By Jeffrey Stumpf

DuringaNov.21seminaratNIEHS,molecularbiologistNancyKleckner,Ph.D.,bypasseddecadesofherowngroundbreakingresearchinthebiologyofprokaryotictransposonsandmeiosis,tofocusonrecentexcitingworkinthephysicalbiologyofchromosomes.HostedbyNIEHSpostdoctoralfellowRichardGradman,Ph.D.,KlecknerspokeaspartoftheLaboratoryofMolecularGenetics(LMG)FellowsInvitedLectureseries.

Kleckner,theHerchelSmithProfessorofMolecularBiologyatHarvardUniversity,entertainedtheNIEHSaudiencewithstunningimagesofdynamicallychangingchromosomesincellsofthemodelbacteriaE. coli.WhileDNAresearchmostlyfocusesonmoleculesthataffectbasicprocessesinmaintenance,replication,andrepair,Klecknerprovidedadifferentanglewithresearchdescribinghowphysicalandmechanicalforcesmightunderliechromosomebehaviorandfunction.

Stress and stress relief could explain the even spacing of meiotic crossoversCorrectlyassuminganaudienceofphysicsnovices,Klecknerprovidedthefollowingexample.Pullingonarubberbandwillcauseittocomeundertensiontoproducewhatiscalledtensilestress.Cuttingtherubberbandwillalleviatethatstressnotonlyatthepointofthecut,butalsoalongthelengthoftherubberband,aphenomenontermedredistributionofstress.Thesameprinciplewillapplyanalogouslytoimpositionandreliefofpushingorcompressionstress.Thisprinciple,Klecknerargues,couldunderlietheevendistributionofcrossovereventsthatoccurduringmeiosis.

“Allmechanicalsystemsincludesuchredistributionofstress,whichineffectprovidesamethodofcommunication,”Klecknerremarked.“Evenspacingofthecrossovereventsrequirescommunicationalongthechromosome,becausethepositionsoftheseeventsarenotgeneticallyspecified.Instead,occurrenceofaneventatonepositionintrinsicallydisfavorstheoccurrenceofanothereventnearby.”

Ifthesiteofacrossoverisdeterminedbyastress-promotedprocess,theresultwillbereductionofstresslocally,resultinginreducedprobabilityofanothernearbycrossover.

Crossovereventsduringmeiosisarerequiredforsegregationofmeioticchromosomes.Defectsincrossingover,ortheirdistributionalongchromosomes,canleadtonondisjunction,theimproperseparationofchromosomestogametes.Thus,considerationsofhowcrossovereventsarelocatedmaybeimportantinstudyingnondisjunctioninhumans.Klecknermentionedthatthenondisjunctionrateinhumancellscanbeupto10percent,butadmitsthatstudyingthemanycausesfornondisjunctionrepresentswhatshedescribedasawholeotherlineofwork.

LMG fellows invited guest lecturer Nancy Kleckner (Photo courtesy of Nancy Kleckner)

Gradman is a member of the LMG Sontaneous Mutation and DNA Repair Group. (Photo courtesy of Steve McCaw)

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The tangled web that cells weaveQuestioningthepossibilityofanorganizedshapeoftheDNAofbacterialchromosomes,callednucleoids,Klecknershowedimagesofnucleoidscapturedbyepifluoresencemicroscopy.TimelapsedimagesdemonstratedthatDNAinE. colimaintainsadynamicshapedescribedasahelicalellipsoid,whichcanbeeitherleft-handedorright-handed.Klecknershowedvideosthatshowcasedhowthenucleoids,whichhaveasubstructurecomprisedofdynamiclongitudinalbundles,moveelegantlyasdefinableobjects.“TheDNAhasashape,”shejoked.“It’snotjustabagofspaghetti.”

SowhatdeterminesthenucleoidshapeinE. coli?Klecknerexplainedpartoftheanswerbymeansofaconceptcalledradialconfinement.Herobservationssuggestthatbacterialcellsuseshapetoseparatetheirchromosomes,asaprimordialprecursortothemorecomplicatedfilamentousnetworkofthemitoticspindlefoundineukaryoticcells.

“Thenucleoidisanellipsoidthatislongitudinallyverystiffor,intechnicalterms,thepersistencelengthoftheellipsoidisgreaterthantheradiusofthecellcylinder,”Klecknerobserved.“DuringDNAreplication,thisellipsoidevolvesintoahelicoidalshape,becauseitisforcedaroundthecellperipheryandheldinplacebyfriction,likearubberrodtrappedinacylinder.Asthetwosisternucleoidsemergeduringreplication,thestressresultingfromthisconfinementincreasesuntil,finally,thetwoentitiesforcetheirwayintoanend-to-endrelationship.”

(JeffreyStumpf,Ph.D.,isapostdoctoralfellowintheNIEHSLaboratoryofMolecularGeneticsMitochondrialDNAReplicationGroup.)

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Holian discusses lung inflammation caused by nanoparticles By Jeffrey Stumpf

Engineerednanomaterials(ENMs)maybesmall,buttheiruniquepropertiesmakethemusefulformanycommercialandmedicalapplications.However,thesamepropertiesthatmakeENMssousefulinthemarketplace,alsomaketheirinteractionswithbiologicalsystemsdifficulttoanticipateandcriticallyimportanttoexplore.

NIEHSgranteeAndrijHolian,Ph.D.,atoxicologistanddirectoroftheCenterforEnvironmentalHealthSciencesatTheUniversityofMontana,presentedthelatestresultsfromhisexperimentsonthehealthandsafetyaspectsofENMsDec.6,aspartoftheInstitute’sKeystoneseminarseries.

ENMsaregenerallydefinedasparticleslessthan100nanometersinsize,withmanydifferentshapesandsurfaceproperties.Theycanbemadefromnumerousmaterials,includingcarbon,titaniumdioxide,gold,silver,andselenium,andtheyareusedinthemanufactureofarapidlygrowingrangeofproducts.Becauseoftheirsizeandcomposition,nanoparticlesmayenterthecellandbeunabletobedegradedeffectively.

The host of Holian’s talk was NIEHS Health Scientist Administrator Sri Nadadur, Ph.D., who oversees a portfolio of nanomaterials Grand Opportunities grants. (Photo courtesy of Steve McCaw)

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WhileENMs,suchascrystallinesilicahavebeenlinkedtosuchdiseasesaslungfibrosis,othersarenotactiveinthecell.“Therealchallengeistounderstandwhatdefinesaharmfulandbenignnanomaterial,”explainedHolian.“Itisnotobviousfromthemakeupofthematerialwhatdefinesabioactivematerial.”

Toaddressthepotentialdangerofnanoparticlestohumanhealth,Holianexposedlungepithelialcellsandmacrophagestoarangeofnanomaterials.Hisseriesofexperimentswerepartofanefforttodeterminepropertiesofnanoparticlesthatcauseharm,toidentifymechanismsthatcausebioactivity,andtodiscoverwaystomodifynanoparticlesthatcouldimprovetheirsafety,whilemaintainingasmuchoftheirutilityaspossible.

In nanoparticle toxicology, size mattersHolianexplainedthatpredictingthepotentialpathologyoftheseparticlesischallenging,becauseofthepreponderanceofpropertiesthatmaypossiblyperturbthecell.Besidesthesize,shape,andmakeupofthematerial,nanoparticlesdifferinsurfacechemistry,charge,andhydrophobicity.

“Thechangesinthedistributiononcethismaterialhasbeeninhaled,whereitgoesinthelung,andhowrapidlyitdisappearsisanotherwholedimensionthatislayeredontopofthisfield,”remarkedHolian.

OneexperimentHoliandescribedwasacomparisonofimmuneresponsesofmacrophagesafterfourhoursofexposuretotitaniumdioxideparticlesofdifferentshapes,includingnanospheres,shortnanobelts,andlongnanobelts.Unlikethesmallerandmoresphericalcounterparts,thelongnanobeltscausedthegreatestinflammatoryresponseandpersistedinthelungsforweeks.ForHolian,theimportanceofnanoparticleshapeledtocomparisontoanotherwell-knownenvironmentalhazard.

“Clearly,itwasthelengthofnanobeltsthatwasanimportantdeterminantofbiologicaloutcome,”explainedHolian,“similartolongasbestosfibers,whicharealsothemostbioactive.”

Besidessizeandshape,Holianalsostudiedthebiotoxicityofmultiwalledcarbonnanotubeswithdifferentmetalcontentsandsurfacemodifications.Heconcludedthatnickelcontentincreasedinflammatoryresponseandcytotoxicity,whileaddingsurfacecarboxylgroupsreducedbioactivity.

Holian explained that the persistence of ENMs in the body makes them a concern for toxicologists. (Photo courtesy of Steve McCaw)

Holian’s talk drew scientists from across the Institute. Shown above is NIEHS Health Scientist Administrator Danielle Carlin, Ph.D., who was one of several attendees from the Institute’s Division of Extramural Research and Training. (Photo courtesy of Steve McCaw)

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The next stepAddressingthesocialandeconomicramificationsoffutureregulationsofnanoparticles,HolianadvocatedacautiousapproachinmakingconclusionsaboutthesafetyofENMs.“Wedon’treallyunderstandallofthescienceourselves[yet]andthelastthingwewantisapreemptivestrikethatmaynotbeaccurate,”Holiansuggested.“Butwearepreemptivelytryingtostudythis[issueofsafety].Weneedtodothisworkandsharethisinformationwiththepublic.”

Aboveall,Holiancautioned,“Wedon’tneedanotherasbestosepidemic.”

Additionally,HolianarguedthatthefutureofregulatingnanoparticlesisanissueweighingthevalueofENMsagainsttheirrisktohumanhealth.“Thesenanobeltshavetremendousvalueinelectronicindustriesandfiltration.Ifwelookatlongsilverandgoldnanowires,Isuspectthattheyallwillbebioactive,”Holianpostulated.“Thegoalmaybetoreducehumanexposure,notnecessarilytoeliminatenanoparticleproduction.”

(JeffreyStumpf,Ph.D.,isapostdoctoralfellowintheNIEHSLaboratoryofMolecularGeneticsMitochondrialDNAReplicationGroup.)

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NTP board moves initiatives forward By Ernie Hood

TheNTPBoardofScientificCounselors(BSC)accomplishedquiteabitinitsDec.15,2011,sessionatNIEHS.HighlightsofthemeetingincludedupdatesbytheNTPdirectorandassociatedirector,threechemicalnominations,ahairdyeworkshopproposal,areportontheNTPdiabetesandobesityworkshop,andpresentationofaproposedreviewprocessfortheReportonCarcinogens(seetextbox).

Beforemovingintoitspackedagendaofreportsandproposals,theBSCheardfromNIEHS/NTPDirectorLindaBirnbaum,Ph.D.,whothankedthreedepartingmembersfortheircontributions.BirnbaumpresentedcertificatesandlettersofappreciationtoMitziNagarkatti,Ph.D.,RuthannRudel,andGinaSolomon,M.D.,whosetermsexpiredDec.27,2011.

Chemical nominations evaluatedTheBSCapprovedNTPresearchandtestingconceptsforthreechemicals,movingeachofthemtothenextstepintheprocessofbeingdevelopedintoanNTPresearchprogram.Twoarehighproductionvolume(HPV)compounds,whilethethirdisusedmainlyinlaboratorysettingsandhasbeenimplicatedinthedeathsoftwoworkers.

Sulfolaneisasolventusedmainlyinnaturalgasandpetroleumrefining,withU.S.productionin2006estimatedat10-50millionpounds.NominatedtotheNTPbyseveralagenciesandofficialsfromthestateofAlaskaandtheAgencyforToxicSubstancesandDiseaseRegistry,sulfolanehasbeendetectedinnearly300drinking

As she does at each BSC meeting, Birnbaum opened the meeting by updating BSC members on activities at NIEHS since their last gathering. (Photos courtesy of Steve McCaw)

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waterwellswithinthetownofNorthPole,Alaska,possiblyasaresultofactivitiesatanearbypetroleumrefinery.ItisalsopresentatothersiteswithinCanada.Sulfolanehasnotbeentestedforchronictoxicityorcarcinogenicactivity,andBSCmemberElaineFaustman,Ph.D.,fromtheUniversityofWashington,expressedahighlevelofsupportforgoingforwardwithfurtherevaluationbyNTP.FellowconceptreviewerMelissaMcDiarmid,M.D.,oftheUniversityofMarylandSchoolofMedicine,agreed,noting,“ThisispreciselythesituationthattheNTPissupposedtoserve.”

TheHPVclassofchemicalscalledphenolicbenzotriazoles(PBZTs)wasnominatedtotheNTPbyNIEHS.UsedasUVstabilizerswithinproductstoincreasestabilitytolight,thereare10HPVPBZTsamongthe29compoundsintheclass,someofwhichareusedinfoodcontactpolymersandadhesives,cosmetics,sunscreens,andfragrances.Withhighproductionandhighpotentialforhumanexposure,thechallengewillbetoprioritizewhichofthechemicalstoevaluateforpotentialhealthhazards,andwhichtestswilleventuallyyieldaclassevaluation.BSCconceptreviewersrecommendedthattheNTPstartitsprogramonPBZTswithADME(absorption,distribution,metabolism,excretion)andtoxicokineticsteststodeterminewhethertheactiveagentisaparentcompoundorametabolite,andthenmoveonwithatestingfunnelstrategysimilartothatusedinthepharmaceuticalindustryfordrugdiscovery.

Thethirdproposedcompound,trimethylsilyldiazomethane(TMSD),wasnominatedbytheOccupationalSafetyandHealthAdministration(OSHA),duelargelytotherecentdeathsoftwochemistsexposedtotheagentinthelaboratoryworkplace.TMSDisasyntheticmethylatingreagentusedfororganicsynthesisandinanalyticalmethods,suchasgaschromatography.Originallydevelopedasalesstoxicandmorestablesubstituteforthehighlyexplosivecompounddiazomethane,thereiscurrentlyverylittletoxicitydataonTMSD,butdermalandinhalationexposuresarelikelyinoccupationalsettings.TheBSCrecommendedmovingforwardwiththeproposedNTPtestingprogram,buturgedthatextremecautionbeexercised,includingtheuseofappropriatepersonalprotectiveequipmentbytestingpersonnel,duetothepresumedacutetoxicityofthecompound.

Hair dye workshop supportedTheBSCfavoredaproposedworkshoponpermanenthairdyes.AccordingtoNTPpresenterRuthLunn,Dr.P.H.,theconferencewouldadvancethestateofthesciencerelatedtopotentialhumanhealthhazardsassociatedwiththewidelyusedproducts,byfocusingdiscussionsondatagaps,researchstrategies,andtestingmethods.Potentialcarcinogenicityisamajorconcern,butstudiestodatehavebeenunclear.Becausetherearesomanydifferentchemicalsinvolved,andthedyesareallmixtures,determiningsafetyoftheproductspresentsquiteachallenge.SeveralBSCmembersnotedthattherearemanyscientificquestionstobeaddressed,andtheneededstudieswillbecomplex.Despitethat

Bucher presented his report about program events, highlights, and developments, and later returned to the podium to outline the Report on Carcinogens new review process. (Photos courtesy of Steve McCaw)

Nagarkatti gave a report on the NTP technical reports peer review. (Photo courtesy of Steve McCaw)

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cautionarynote,theBSCsupportedmovingforwardwithorganizingtheworkshop.ArepresentativefromthePersonalCareProductsCouncil,inattendance,commendedtheNTPfortacklingthisissue,andsaidtheindustrylooksforwardtoworkingwithNTPtoaddressthisimportantsubject.

ThenextBSCmeetingisscheduledforJune21-22.

(ErnieHoodisacontractwriterfortheNIEHSOfficeofCommunicationsandPublicLiaison.)

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NIEHS/NTP toxicologist Chad Blystone, Ph.D., presented the research and testing concepts on sulfolane and PBZTs considered by the BSC. (Photo courtesy of Steve McCaw)

Kristina Thayer, Ph.D., director of the NTP Office of Health Assessment and Translation, briefed the BSC on the NTP Workshop on the Role of Environmental Chemicals in the Development of Diabetes and Obesity, held Jan. 11-13, 2011 in Raleigh, N.C. (Photo courtesy of Steve McCaw)

Eastmond kept the proceedings moving briskly, during the committee’s daylong session. (Photo courtesy of Steve McCaw)

Proposed RoC review processTheBSCalsospenttimelisteningtocommentsfromthepublicandreceivinganupdatefromtheNTPonproposedchangesonhowthecongressionallymandatedReportonCarcinogens(RoC)wouldbedeveloped.

TheproposedchangestotheRoCareintendedtoincreasethetransparencyandopennessofhowtheNTPreviewssubstances.Numerousopportunitiesforpublicinputarebuiltintotheprocess.

NTPAssociateDirectorJohnBucher,Ph.D.,walkedtheBSCthroughanumberofchangesthattheNTPhasmadesincetheoriginalproposedreviewprocesswasreleasedforpubliccommentOct.31,2011.Sincethen,theNTPhasheldapubliclisteningsession,whichbrought19speakers,andapubliccommentperiod,allowingtheNTPanopportunitytorevisetheprocesstoaccommodatesomeoftheissuesraisedbythepublic.

Ashethankedeveryoneforinput,Buchersaidallinputhasbeenconsideredandsomerevisionshavebeenmade.Bucherillustratedchangestotheprocess,whichiscomprisedoffourparts:nominationandselectionofcandidatesubstances;scientificevaluationofcandidatesubstances;publicreleaseofthedraftRoCmonographandpeerreview;andHHSapprovalandreleaseofthelatesteditionoftheRoC.

BSCchairDavidEastmond,Ph.D.,fromtheUniversityofCalifornia,Riverside,toldtheNTP,“TheBSCsupportswhatyouaretryingtodo,andsupportsyougoingforward.”

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Hundreds of rare genetic variants may cause a common autism phenotype By Brant Hamel

CatalinaBetancur,M.D.,Ph.D.,visitedNIEHSNov.30asapartoftheKeystoneScienceLectureSeminarSeries.Shedeliveredapresentationtitled“Deconstructing‘idiopathic’autism:Onebehavioralsyndrome,hundredsofgenes,”whichillustratedhowraredefectsinmanydifferentgenescouldgiverisetoacommonphenotypediagnosedasautism.ThepresentationwashostedbyCindyLawler,Ph.D.,ascientificprogramadministratorintheDivisionofExtramuralResearchandTrainingatNIEHS.

BetancurisaninvestigatorforINSERM(theFrenchNationalInstituteofHealthandMedicalResearch)attheUniversitéPierreetMarieCurieinParis.Herresearchfocusesonunderstandingthegeneticunderpinningsofautismwithafocusontheheterogeneousmutationsthatgiverisetocommonbehavioralsymptoms,possiblythroughgene-geneandgene-environmentinteractions.

Autism is not a single disorderBetancurexplainedthatautismspectrumdisorderisnotasingledisorder,butratherisasetofbehavioralmanifestationsthatmayarisefromanyoneofhundredsofindividualgeneticdefects.Althoughautisticpatientshavecommonbehavioralsymptoms,suchasdecreasedsocialinteraction,theetiologyofthediseasemaybevastlydifferentbetweenpatients.Inthemajorityofthecases,thecauseofautismisnotknown.Betancurhasbeenabletopinpointtheraregeneticmutationsthathavegivenrisetoabout20percentofautisticcasesandmakesapersuasiveargumentthat,withmorescreeningandenhancedtechnologies,manymorecasesofidiopathicautism,orautismofunknowncause,wouldlikelybediagnosedasresultingfromdiverseandraregeneticdefects.

Betancurexplainedthatautismismuchlikeintellectualdisabilityandepilepsy,whichalsoresultfromaplethoraofindependentgeneticmutations,yetproduceacommonphenotype.Interestingly,manyofthegenesknowntobeinvolvedinautismarealsolinkedtootherdisorders,suchasintellectualdisability,epilepsy,andschizophrenia.Betancursaidthatoutof91X-linkedgenesassociatedwithintellectualdisability,45ofthemalsowerelinkedtoautism.Itisnotyetclearwhyinsomecasesthesamemutationmayresultinintellectualdisabilityandinothersautism,butitmaydependonothergenetic,environmental,orchancefactors.

Searching for rare variants to understand etiology of autismBetancurdescribedherworkwiththeParisAutismResearchInternationalSibpairStudy,whichlookedat677familieswithautismspectrumdisorderfromFranceandSweden.Withmetabolicscreeningandasearchformicrodeletionsandmicroduplications,herteamwasabletodeterminegeneticcausesfor20percentofcasesthathadnopreviousmoleculardiagnosis.Mostofthecauseswereextremelyraregeneticdefectsthatwouldnotbecommonlyscreenedfor.

Betancur explained to audience members that hundreds of rare genetic defects can give rise to the common behavioral phenotype known as autism. She was one of several experts who participated in a two-day NIEHS-sponsored symposium on “Bioinformatics and Computational Approaches to Integrate Genes and Environment in Autism Research.” (Photo courtesy of Steve McCaw)

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AsBetancurobserved,oneofthedifficultiesinshowingthatageneticdefectisinvolvedinautismarisesfromtheconceptsofvariableexpressivityandincompletepenetrance.Asanexampleofincompletepenetrance,BetancurpointedtocasesofautismcausedbyDiGeorgesyndrome,adeletionofaportionofchromosome22inheritedfromparentswhodonothaveanysignsofautism.Inothercasesvariableexpressivityoccurswherethesamegeneticdefectgivesrisetodifferentbehavioraleffects,asinthecaseofafamilywithmutationsinneuroligin4.Onebrotherwiththemutationhadaseverecaseofautism,whiletheotherbrotherwiththeidenticalmutationhadamildercaseofAsperger’ssyndrome.

Betancurconcludedthatmoresystematicmolecularscreeningisnecessarytodiagnosethemanyraregeneticdefectsthatcontributetothecommonbehavioralmanifestationknownasautism.Shearguedthataparadigmshiftwasnecessary,sothatphysiciansandresearcherswouldstopthinkingaboutautismasasinglediseasewithacommoncauseorsetofcommoncauses,butratherasaheterogeneousmixofmanyraredefectswithvariableclinicaloutcomes.

(BrantHamel,Ph.D.,isapostdoctoralfellowintheNIEHSMolecularEndocrinologyGroup.)

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Lecture host Lawler oversees the NIEHS portfolio of grants funding research into the environmental causes of autism. (Photo courtesy of Steve McCaw)

New genes involved in autismBetancur’sworkhasledtothediscoveryofnewgenesandsignalingpathwaysinvolvedinsomecasesofautism.Mutationsinbothneurexins,whichresideonpresynapticneurons,andneuroligins,whichresideonpostsynapticneuronsandinteractwithneurexins,arelinkedtoautism.

BetancurandhercolleagueshavebeenabletoshowthattheintracellularproteinSHANK3,downstreamofthissignalingpathway,isalsoinvolvedintheetiologyofautism.SHANK3defectswerefoundinthreeindependentfamiliesincludinga22q13deletioninonefamily,alsoknownasPhelan-McDermidsyndrome;aframeshiftmutationinanother;and,interestingly,athirdfamilywherethesonhadaduplicationofSHANK3resultinginAsperger’s,whilethedaughterhadadeletionofSHANK3resultinginautism.

BetancurestimatedthatSHANK3mightbeinvolvedinabout0.5percentofglobalautismcases.Shesaidthatalthoughthatsoundslikeasmallnumber,itwouldactuallymakeitoneofthemostcommoncausesofautismthatcanbetracedtoaspecificgeneticmutation.

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NICEATM workshop report on vaccine testing now available By Debbie McCarley and Cathy Sprankle

AworkshoporganizedlastyearbytheNTPInteragencyCenterfortheEvaluationofAlternativeToxicologicalMethods(NICEATM)andtheInteragencyCoordinatingCommitteeontheValidationofAlternativeMethods(ICCVAM)isthesubjectofthecurrentissueofthejournalProcediainVaccinology.

TheInternationalWorkshoponAlternativeMethodstoReduce,Refine,andReplacetheUseofAnimalsinVaccinePotencyandSafetyTesting:StateoftheScienceandFutureDirectionswasconvenedtoreviewthestateofthescienceofavailablealternativemethodsforhumanandveterinaryvaccinepotencyandsafetytesting.Workshopparticipantsalsoidentifiedspecificactivitiesthatwillbeneededtoadvancetestmethodswiththepotentialtoreduce,refineandreplaceanimaluseforvaccinetesting.

Identifying high priority vaccines for alternative testingTheworkshopdescribedinthecurrentProcediainVaccinologywasheldSept.14-16,2010,atNIHinBethesda,Md.Nearly200scientistsfrom13countriesattendedtheworkshop.Over30invitedparticipantsincludedscientistsfromU.S.governmentresearchandregulatoryagenciesaswellasrepresentativesfromthegovernmentsofJapan,Canada,theUnitedKingdom,theNetherlands,andtheEuropeanUnion.Nationalandmultinationalcorporationsandresearchinstitutionswerealsorepresented.Theworkshopreportiscomprisedof27manuscriptsandsummarizestheplenarysessionspeakerpresentationsaswellastheconclusionsandrecommendationsdevelopedbytheworkshopparticipants.

“Oneofthekeyaccomplishmentsofthisworkshopwastheidentificationofthehighestpriorityvaccinesforfuturereduction,refinement,andreplacementefforts,”notedRearAdm.WilliamStokes,D.V.M.,directorofNICEATM.“Targetingspecificvaccineswillhelpfocusresearchandvalidationeffortsthatcanhavearealimpactonanimaluseandanimalwelfare.”Headdedthatrabiesvaccineswereidentifiedasoneofthehighpriorityvaccines.Reduction,refinement,andreplacementofanimaluseforrabiesvaccinepotencytestingwasthesubjectofarecentworkshopinOctoberorganizedbyNICEATMandICCVAM.

As acting chair of ICCVAM, Jodie Kulpa-Eddy, D.V.M., of the U.S. Department of Agriculture, welcomed participants to the workshop. (Photo courtesy of William Stokes)

In her keynote speech, Rear Adm. Anne Schuchat, M.D., director of the National Center for Immunization and Respiratory Diseases within the CDC, underscored the important role of safe and effective vaccinations in promoting public health. (Photo courtesy of William Stokes)

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Recommending alternative methodsVaccinesimproveanimalandhumanhealthbypreventinginfectiousdiseasesinpeopleandanimals.Asaresultofwidespreadhumanvaccination,smallpoxhasbeengloballyeradicated,andmanyotherdiseasessuchaspolio,measles,andrubellanowoccuronlyrarelyinNorthAmerica.Veterinaryvaccinespreventawiderangeofdiseasesinmanyanimalpopulations,andcontributetohumanhealthbycontrollingdiseasessuchasrabiesthatcanbetransmittedfromanimalstohumans.However,testingnecessarytoensurevaccineeffectivenessandsafetycaninvolvelargenumbersofanimals,andresultinsignificantanimalpainanddistress.NICEATMandICCVAM,whosemissionistopromotealternativemethodsthatcanreduce,refine(enhanceanimalwell-being,orlessenoravoidpainanddistress),andreplaceanimaluseintesting,identifiedalternativetestmethodsforvaccinepotencyandsafetytestingasoneitshighestprioritiesinafive-yearplanissuedin2008.

Inadditiontoprioritizingspecificvaccinesforfutureefforts,recommendationsmadebytheparticipantsoftheSeptember2010workshopincluded:

• Specificnon-animalantigenquantificationapproachesthathavesuccessfullyreplacedanimalsforpotencytestingforsomevaccinesshouldbeexpandedforusewithothervaccinesthroughidentification,purification,andcharacterizationofvaccineprotectiveantigens.

• Proceduresshouldbeimplementedtoreduceboththenumbersofanimalsusedandthepainanddistressexperiencedbyanimalswhileandwhereanimaltestingisstillneeded.

• Effortsshouldbemadetofacilitateinternationalharmonizationandcooperation,aswellasclosercollaborationbetweenhumanandveterinaryvaccineresearchers,asthiswillallowfasterprogresstowardsreduction,refinement,andreplacementofanimaluse.

TheworkshopwasorganizedbyNICEATMandICCVAMinpartnershipwiththeEuropeanCentrefortheValidationofAlternativeMethods,theJapaneseCenterfortheValidationofAlternativeMethods,andHealthCanada.Theworkshopwasco-sponsoredbytheSocietyofToxicology.

(DebbieMcCarleyisthespecialassistanttoRearAdm.WilliamStokes,D.V.M.,directorofNICEATM.CathySprankleisacommunicationsspecialistwithILS,Inc.,supportcontractorforNICEATM.)

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Workshop organizersNICEATMandtheICCVAMBiologicsWorkingGroup(BWG)wereprimarilyresponsiblefororganizingtheworkshop.TheBWGisco-chairedbyJodieKulpa-Eddy,D.V.M.,oftheU.S.DepartmentofAgriculture(USDA),andRichardMcFarland,M.D.,Ph.D.,oftheCenterforBiologicsEvaluationandResearchattheU.S.FoodandDrugAdministration(FDA).Kulpa-EddyisalsocurrentlychairofICCVAM.InadditiontoFDAandUSDA,theBWGincludesscientistsfromtheCentersforDiseaseControlandPrevention(CDC),U.S.DepartmentofDefense,U.S.DepartmentoftheInterior,NIEHS,andtheNationalInstituteofAllergyandInfectiousDiseases.StokesandWarrenCasey,Ph.D.,deputydirectorofNICEATM,aretheNIEHSrepresentativesontheBWG.

Materialsfromtheworkshop,includingtheagenda,presentationsfromtheworkshop,andabstractsofposterspresentedattheworkshoppostersession,areavailableontheNICEATM-ICCVAMwebsite.

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Stokes builds international partnerships for advancing alternative testing By Debbie McCarley and Cathy Sprankle

RearAdm.WilliamStokes,D.V.M.,directoroftheNTPInteragencyCenterfortheEvaluationofAlternativeToxicologicalMethods(NICEATM),representedNIEHSandNICEATMatinternationalscientificmeetingsinNovember.StokesjoinedotherscientistsfromaroundtheworldatmeetingsoftheJapaneseSocietyforAlternativestoAnimalExperiments(JSAAE)andtheadvisorycounciloftheJapaneseCenterfortheValidationofAlternativeMethods(JaCVAM).Thesemeetingswerepartofacontinuingefforttobuildglobalpartnershipstoadvancealternativestoanimaltesting.

Atthe24thannualmeetingoftheJSAAENov.10–11inSendai,Japan,StokesprovidedanupdateonrecentprogressandfutureplannedactivitiesofNICEATMandtheInteragencyCoordinatingCommitteeontheValidationofAlternativeMethods(ICCVAM),whichNICEATMadministers.Stokes’presentationsummarizedNICEATMandICCVAMcontributionstowardsreducing,refining(enhancinganimalwelfareandeliminatingordecreasingpainanddistress),andreplacinganimaluseforsafetytesting.ThepresentationalsonotedU.S.interagencyeffortstoacceleratedevelopmentanduseofmoreefficientsafetytestingapproacheswiththepotentialtobetterprotecthumanhealth.

WhileattheJSAAEconference,Stokesattendedamanagementteammeetingforanongoingstudytoevaluateatestmethodthatuseshumancellstoidentifysubstanceswiththepotentialtocauseallergiccontactdermatitis.Stokesandothermeetingattendeesreceivedanupdateandprovidedfeedbackoncurrentprogress.Resultsofthestudycouldsupporttheuseofthismethodtoreduceorreplaceanimaluse.“Participationinvalidationstudiestoevaluatenewtestmethodsisanimportantaspectofourinternationalinteractions,”Stokescommented.“Collaborationintheearlierstagesoftestmethoddevelopmentgreatlyincreasesthechancesthatwe’lllateragreeonrecommendationsontheappropriateusesofanewtestmethod.”

Stokes joined participants at the Japanese advisory council meeting. Shown above, left to right, are Mike Inskip, senior biologist, Environmental Health, Science, and Research Bureau, Health Canada; Akiyoshi Nishikawa, M.D., Ph.D., director of Biological Safety Research Center, National Institute of Health Sciences, Japan; Stokes; Soon Young Han, Ph.D., director general of Toxicological Evaluation and Research Department, National Institute of Food and Drug Safety Evaluation, Korea; Yasuo Ohno, Ph.D., director general, National Institute of Health Sciences, Japan; Joachim Kreysa, head In Vitro Methods Unit, Joint Research Centre, Institute for Health and Consumer Protection, Italy; Kojima; Takuya Ikeda, Charles River Laboratories, Japan; and Tsutomu Kurosawa, Osaka University, Japan. (Photo courtesy of William Stokes)

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A cornerstone of NICEATM’s international interactionsStokesalsoprovidedJSAAEattendeeswithanoverviewoftheInternationalCooperationonAlternativeTestMethods(ICATM).ICATMisaninternationalpartnershipamongnationalvalidationorganizationsthatpromotetheadvancementofrefinement,reduction,andreplacementalternativesforanimaltesting.TheEuropeanUnion,U.S.,Japan,Canada,andSouthKoreaarecurrentlymembersofthecooperationagreement.TheICATMpartnerscooperateandcollaborateontestmethodvalidationstudies,peerreviewofnewtestmethods,anddevelopmentofharmonizedrecommendationsforhownewtestmethodscanbeused.

ICATMcoordinationmeetingstakeplaceseveraltimesayearandprovideanopportunityforthefiveICATMorganizationstodiscussactivitiesinthethreemajorareasofcooperation.ThemeetingsareplannedtocoincidewithmeetingsoftheSocietyofToxicologyandothergatheringsofmutualinteresttotheparticipantorganizations.“TheseregularinteractionsallowtheICATMpartnerstodevelopgoodcommunicationsandworkingrelationships,whichsupportourcollaborationsontestmethoddevelopment,”notedStokes.

Stokes participates in Japanese advisory council meetingAnotherimportantinteractionactivityfortheICATMpartnersisliaisonmembershipononeanother’sadvisorycommittees.FollowingtheICATMmeeting,StokesattendedameetingoftheadvisorycouncilofJaCVAM,NICEATM’scounterpartorganizationinJapan.ThemeetingtookplaceattheJapaneseMinistryofHealth,Labour,andWelfareinTokyo.TheJaCVAMadvisorycouncilservesasimilarroleastheScientificAdvisoryCommitteeonAlternativeToxicologicalMethods(SACATM).JaCVAMDirectorHajimeKojima,Ph.D.,attendedtheSACATMmeetinginJune.

WhileattendingtheJaCVAMadvisorycouncilmeeting,StokespresentedanupdateofNICEATM-ICCVAMandICATMactivitiesandanoverviewofU.S.initiativestoreduce,refine,andreplaceanimaluseintesting,includingoutcomesoftherecentNICEATM-ICCVAMworkshoponalternativemethodsforrabiesvaccinetesting.

(DebbieMcCarleyisthespecialassistanttoRearAdm.WilliamStokes,D.V.M.,directorofNICEATM.CathySprankleisacommunicationsspecialistwithILS,Inc.,supportcontractorforNICEATM.)

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Casey presents at international meeting in Hungary By Debbie McCarley and Cathy Sprankle

WarrenCasey,Ph.D.,deputydirectoroftheNationalToxicologyProgram(NTP)InteragencyCenterfortheEvaluationofAlternativeToxicologicalMethods(NICEATM),participatedinanexpertmeetinginBudapest,Hungary,Nov.30-Dec.2,2011.Caseydiscussedin vitromethodsforidentifyingendocrinedisruptors(EDs),substancesthatmightinterferewithnormalhormonefunction.

CaseypresentedupdatesonNICEATM–ICCVAMED-relatedactivitiesattheNinthMeetingoftheValidationManagementGroupforNon-AnimalTesting,sponsoredbytheOrganisationforEconomicCo-operationandDevelopment(OECD).

Casey’spresentationsfocusedprimarilyonanin vitromethodproposedforidentifyingEDsthatinterferewithnormalestrogenfunction.Thismethod,theBG1Lucestrogenreceptor(ER)transcriptionalactivation(TA)testmethod,alsoknownastheLUMI-CELL®ERassay,useshumanovariancancercellstoidentifysubstancesthatmightactasERagonistsorantagonists,tostimulateorinhibitestrogenicactivity.

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NICEATM-sponsored validationNICEATMsponsoredaninternationalvalidationstudyoftheBG1LucERTAtestmethodin2010,andconvenedaninternationalindependentscientificpeerreviewpaneltoevaluatethestudyresultsearlierthisyear.ThepeerreviewwassponsoredbytheInteragencyCoordinatingCommitteeontheValidationofAlternativeMethods(ICCVAM),aninteragencycommitteeoftheU.S.governmentadministeredbyNICEATM.

ICCVAMfinaltestmethodrecommendationsareprovidedintheICCVAMTestMethodEvaluationReport:TheLUMI-CELL®ER(BG1LucERTA)TestMethod:AnInVitroAssayforIdentifyingHumanEstrogenReceptorAgonistandAntagonistActivityofChemicals.TheserecommendationsarethebasisforadrafttestguidelinecurrentlybeingconsideredforadoptionbytheOECDTestGuidelinesProgramme.Ifadoptednextyear,theBG1LucERTAtestmethodcouldthenbeusedinternationallyasascreeningtesttoidentifysubstanceswithERagonistandantagonistactivity.

TheNICEATM–ICCVAMevaluationoftheBG1LucERTAtestmethodalsosupportedthedevelopmentofaperformance-basedtestguidelinebeingconsideredbyOECD.Performance-basedtestguidelinesprovidestandardsbywhichtestmethodsthatassessasimilarbiologicalendpointcanbeevaluated.

NICEATMandICCVAMhaveacommitmenttobuildingglobalpartnershipstoadvancealternativestoanimaltesting.ParticipationineventssuchastherecentOECDmeetingisanimportantpartofdevelopingthosepartnerships.

Casey, left, received his NIH Merit Award from NIEHS/NTP Director Linda Birnbaum, Ph.D. (Photo courtesy of Steve McCaw)

Casey recognized for work on endocrine disruptorsAttheNIEHSAwardsCeremonyDec.6,Caseyreceiveda2011NationalInstitutesofHealth(NIH)MeritAward(seerelatedstory).Theawardwasinrecognitionofhisexcellentperformanceinleadingtheinternationalvalidationandinteragencyevaluationofnewtestingmethodstosupportthefederalgovernment’sendocrinedisruptorchemicalscreeningprogram.

CaseyjoinedNIEHSinFebruary2010,afteranumberofyearsatGlaxoSmithKlineanditspredecessorcompanies,wherehewasaseniorscientistindiscoveryandinvestigativetoxicology.Heistheauthororco-authorof28publicationsinpeer-reviewedjournalsandholdsthreepatents.

CaseyreceivedhisundergraduatedegreeinbiochemistryandhisPh.D.inmicrobiologyfromNorthCarolinaStateUniversity(NCSU).CaseyalsoservesasanadjunctassociateprofessorintheNCSUDepartmentofMicrobiologyandisaDiplomateoftheAmericanBoardofToxicology.

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Concerns about endocrine disruptorsEDscaninterferewiththenormalfunctionofhormonesintheendocrinesystem.Studiesindicatingthatanimalpopulationsexposedtohighlevelsofthesesubstanceshaveanincreasedincidenceofreproductiveanddevelopmentalabnormalitieshaveraisedconcernsaboutthepotentialhumanhealtheffectsofthesesubstances.Whiletheimpactofendocrinedisruptorsonhumanhealthremainspoorlydefined,thesegrowingconcernshavedriveninternationalinterestintheavailabilityofmethodsthatcanprovideaccurateandtimelyidentificationofpotentialendocrinedisruptors.

TheNICEATM-sponsoredvalidationstudyoftheBG1LucERTAtestmethodincludedparticipatinglaboratoriesfromtheU.S.,Europe,andJapan.DatafromthisstudywerereviewedataMarch2011independentpeerreviewpanelmeetingsponsoredbyICCVAM.ThepeerreviewpanelagreedwithdraftICCVAMrecommendationsthattheBG1LucERTAtestmethodwasappropriateforuseasascreeningtesttoidentifysubstanceswithERagonistandantagonistactivity.

FinalICCVAMrecommendationswillbetransmittedtofederalagenciessoon.ThedrafttestguidelinecurrentlyunderconsiderationbyOECDreflectstheICCVAMrecommendations.

MoreinformationabouttheNICEATM-sponsoredvalidationstudyandtheICCVAMevaluationoftheBG1LucERTAtestmethodisavailableontheNICEATM–ICCVAMwebsite.

(DebbieMcCarleyisthespecialassistanttoRearAdm.WilliamStokes,D.V.M.,directorofNICEATM.CathySprankleisacommunicationsspecialistwithILS,Inc.,supportcontractorforNICEATM.)

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This month in EHP By Ian Thomas

Initsfirstleadstoryof2012,theJanuaryissueofEnvironmentalHealthPerspectives(EHP)examinesanewstrategyforevaluatingtheimpactofregionalandlocal-levelclimatechangesonpublichealth.Downscalingclimatemodelsoffersaclearerpictureofhowlocalclimatemaybeaffectedinthefuture,byincorporatingspecificgeographicdetailsintoageneralcirculationmodel.

Inasecondnewsstory,titled“TrendingNow:UsingSocialMediatoPredictandTrackDiseaseOutbreaks,”EHPexploreshowpublichealthresearchersarenowusingrapidinformation-exchangeplatforms,suchascellphones,socialmedia,andotherweb-enabledapplications,topredictandtrackoutbreaksofinfectiousdiseases.

Thismonth’sResearcher’sPerspectivePodcastfeaturesadiscussionwithNIEHSgranteeRobertWright,M.D.,coauthorofastudyontheneurodevelopmentaleffectsofmanganeseandleadco-exposureappearinginthisissue.

http://twitter.com/ehponline

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Otherresearchthismonthincludes:

• PersistentOrganicPollutantsandCarotidAtherosclerosis

• CommunityAsbestosExposureinMinneapolis,Minnesota,fromLibbyVermiculite

• Co-benefitsfromReducedCarTravel

(IanThomasisapublicaffairsspecialistwiththeNIEHSOfficeofCommunicationsandPublicLiaison,andaregularcontributortotheEnvironmentalFactor.)

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NIEHS to hold minisymposia on epigenetics and BPA By Eddy Ball

AspartofitsKeystoneScienceLectureSeminarSeries,NIEHSwillpresenttwominisymposiainJanuary,organizedbytheNIEHSDivisionofExtramuralResearchandTraining(DERT).

Thefirst,exploringEpigenetics,ChromatinBiology,Development,andDisease,willbeheldJan.10from8:00a.m.to5:00p.m.inRodbellAuditorium.

Theeventwillfeaturetalksbytenscientists,includingresearchersfromtheNIEHSintramuralprogram,grantees,andotherspecialistsinthefieldofepigenetics.TheprogramwillbemoderatedbyDERTscientistsLisaChadwick,Ph.D.,AstridHaugen,andFredTyson,Ph.D.Atentativeagendaandlistofspeakersispostedonline.

Registrationisfreeandopentothepublic.

ThesecondwillfeaturefourNIEHS-granteesdiscussingtheirlatestfindingsaboutbisphenolA(BPA)exposureandhealth.HostedbyNIEHSHealthScientistAdministratorJerryHeindel,Ph.D.,thetalkswilltakeplaceJan.19from1:00p.m.to5:00p.m.inRodbellAuditorium.Atentativeagendaandlistofspeakersispostedonline.

Noregistrationisrequiredforthisevent.

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Society for Investigative Dermatology to meet May 9-12 in Raleigh By Eddy Ball

TheSocietyforInvestigativeDermatology(SID)willholditsannualmeetingattheRaleigh(N.C.)ConventionCenterMay9-12,assemblingadiversegroupofsome1,500M.D.andPh.D.scientistsfromaroundtheglobetopresentandexchangefindingsondermatologyandskinbiology.

Themeetingisalsoapartofthesociety’scelebrationofits75thanniversaryasaprofessionalorganization,foundedin1937toadvanceandpromotethe

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sciencesrelevanttoskinhealthanddiseasethrougheducation,advocacy,andscholarlyexchangeofscientificinformation.InadditiontoitsprofessionaldevelopmentmeetingsandannualretreatsfordermatologyresidentsandPh.D.students,SIDpublishestheJournalofInvestigativeDermatology.

Meeting detailsSIDoffersdiscountedearlyregistrationsthroughMarch16.Thegroupwillacceptabstractsubmissionsandapplicationsforneeds-basedKligmanTravelFellowshipAwardsbyresidents,trainees,students,orjuniorfacultythroughJan.12.

Themeetingwillfeaturefivenamedandfourstate-of-the-artplenarylecturesontopicsrangingfromstemcellregulationandgenomictrackingofmicrobialpathogenstonextgensequencingandimmunesystemregulation,alongwithafullscheduleofconcurrentminisymposia.

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Extramural papers of the month By Nancy Lamontagne

• Rice consumption and arsenic exposure in pregnant women

• Consuming canned soup linked to higher BPA levels

• Dietary compounds could help protect kidney function

• Estrogen lessens effects of obesity and alcohol on breast cancer

Rice consumption and arsenic exposure in pregnant women NIEHSgranteesreportthaturinaryarsenicconcentrationswerehigherforpregnantwomenwhohadrecentlyconsumedricethanforthosewhohadnot.Thefindingshighlighttheneedtomonitorarseniclevelsinfood.

Theresearcherstestedforarsenicintheurineof229pregnantwomeninNewHampshire,73ofwhomreportedeatingriceduringthetwodaysbeforeurinecollection.Thearsenicconcentrationofthetapwaterinthewomen’shomeswasalsotestedtoidentifyanyexposurefromdrinkingwater.Thewomenwhoreportedeatingriceduringthetwodayspriortourinecollectionhadamediantotalurinaryarsenicconcentrationof5.27microgramsperliter,whichwassignificantlydifferentfromthe3.38microgramsperlitermedianconcentrationforthosewhodidnotconsumerice.

Theresearchersnotetheneedformoreresearchtodetermineanyhealthimpactsofthissourceofexposure.Anyidentifiedhealthriskswillalsoneedtobeweighedagainstthenutritionalbenefitsofeatingrice.

Citation:Gilbert-DiamondD,CottinghamKL,GruberJF,PunshonT,SayarathV,GandolfiAJ,BakerER,JacksonBP,FoltCL,KaragasMR.2011.RiceconsumptioncontributestoarsenicexposureinUSwomen.ProcNatlAcadSciUSA108(51):20656-20660.

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ReadthecurrentSuperfundResearchProgramResearchBrief.NewissuesarepublishedonthefirstWednesdayofeachmonth.

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Consuming canned soup linked to higher BPA levelsResearchersfundedbyNIEHSfoundthatagroupofvolunteerswhoconsumedaservingofcannedsoupeverydayforfivedayshadmorethana1,000percentincreaseinurinarybisphenolA(BPA)concentrationsthanwhenthesameindividualsconsumedfreshsoupdailyforfivedays.TheendocrinedisruptorBPAisusedintheliningofmetalfoodandbeveragecansandhasbeenshowntohaveadversehealtheffects.

Theresearchersrecruited75volunteersandaskedagroupofthemtoconsumea12-ounceservingofvegetariancannedsoupeachdayforfivedays,whiletherestconsumed12ouncesofvegetarianfreshsoup,preparedwithoutcannedingredients,dailyforfivedays.Afteratwo-daybreak,thegroupsreversedtheirassignments.

TheresearchersdetectedBPAin77percentoftheurinesamplestakenafterfreshsoupconsumptionandinallofthesamplesaftercannedsoupconsumption.Eatingaservingofcannedsoupdailywasassociatedwitha1,221percentincreaseinBPAconcentrationcomparedtolevelsinurinecollectedafterconsumptionoffreshsoup.EventhoughtheelevationinurinaryBPAconcentrationsmightbetemporary,theresearcherscommentthattheirfindingscouldbeimportant,especiallyasmoreandimprovedalternativestoepoxyliningsaredeveloped.

Citation:CarwileJL,YeX,ZhouX,CalafatAM,MichelsKB.2011.CannedsoupconsumptionandurinarybisphenolA:arandomizedcrossovertrial.JAMA306(20):2218-2220.

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Dietary compounds could help protect kidney functionNIEHS-fundedresearchershaveshownthatcompoundsfoundinvegetablesandcinnamonhelpedreducekidneydamage,andpreservekidneyfunctioninamicemodelofdiabetes.Medicinesusedtoprotectkidneyfunctioninpeoplewithdiabetesoftencausetoxicity,sobettertherapiesareneeded.

Theresearchersexperimentedwithsulforaphane,whichisfoundinvegetablessuchasbroccoliandcauliflower,aswellascinnamicaldehyde,aflavorcomponentofcinnamon.ThesecompoundsactivateatranscriptionfactorcalledNFE-2-relatedfactor2(Nrf2),whichregulatesexpressionofvariousgenestoneutralizefreeradicalsandacceleratetoxinremoval.

TheyinduceddiabetesinNrf2deficient(-/-)mice,aswellasthosethatexpressedNrf2(+/+),andthenadministeredsulforaphaneorcinnamicaldehydetwoweekslater.InthemiceexpressingNrf2,bothcompoundsimprovedkidneyperformance,minimizedkidneydamage,andsignificantlylesseneddiabetes-associatedsymptoms,suchashighbloodsugar,excessivethirst,andweightloss.SinceonlythemiceexpressingNrf2showedbeneficialeffects,theseresultsindicatethatthecompoundsactivatetheNrf2pathway.

TheresearchersconcludethatthestudylaysthefoundationforclinicalevaluationandfuturedevelopmentofnewNrf2activatorsthatcouldpreventtheonsetandprogressionofkidneyproblemsthatareassociatedwithdiabetes.

Citation:ZhengH,WhitmanSA,WuW,WondrakGT,WongPK,FangD,ZhangDD.2011.TherapeuticpotentialofNrf2activatorsinstreptozotocin-induceddiabeticnephropathy.Diabetes60(11):3055-3066.

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Estrogen lessens effects of obesity and alcohol on breast cancerObesityandalcoholconsumptionincreaseriskfordevelopingbreastcancerandfattyliver,aconditionwherefataccumulatesinlivercells.AstudyperformedbyNIEHSgranteeshasshownthatestrogencanprotectagainsttheseadversehealtheffects.

Theresearchersusedfemalemicethatmimicpostmenopausetostudytheeffectofalcoholconsumption,obesity,andestrogensupplementationonbreastcancer.Overweightandobesemiceconsumedeitherwateroralcohol,wereimplantedwithplaceboorestrogenpellets,andtheninjectedwithMet-1breastcancercells.Themicethatconsumedalcoholweremoreinsulinsensitiveanddevelopedlargertumorsthanthosethatconsumedwater,andtheobesemicedevelopedtumorsthatwereslightlylargerthanthoseintheoverweightmice.However,allthemicereceivingestrogenexperiencedlossofbodyfat,increasedinsulinsensitivity,suppressedtumorgrowth,reducedgrowthfactors,andlessenedretentionoffatinthelivercells.

Citation:HongJ,HolcombVB,KushiroK,NúñezNP.2011.Estrogeninhibitstheeffectsofobesityandalcoholonmammarytumorsandfattyliver.IntJOncol39(6):1443-1453.

(NancyD.LamontagneisasciencewriterwithMDB,Inc.,acontractorfortheNIEHSDivisionofExtramuralResearchandTraining,SuperfundResearchProgram,andWorkerEducationandTrainingProgram.)

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Intramural papers of the month By Raluca Dumitru, Anshul Pandya, and Sonika Patial

• Caffeine strengthens connections between neurons in a little-known area of the brain

• Exposures to certain early-life factors may contribute to an early onset of uterine fibroids

• Snail and Slug activate TGF-beta in breast cancer

• Pregnane X receptor regulates liver metabolism

Caffeine strengthens connections between neurons in a little-known area of the brainArecentstudypublishedbyNIEHSscientistssuggestshowandwherecaffeinemightactinthebraintoincreasecognitivefunction.Previousresearchshowsthatcaffeineactsbyblockingtheinhibitoryeffectsofadenosineoncyclicadenosinemonophosphate(AMP)productioninthebrain.Thisstudyrepresentsthefirstdemonstrationoflong-lastingsynapticplasticityinducedbyinvivoexposuretocaffeine,asreportedinthejournalNatureNeuroscience.

Asawidelyconsumedstimulant,caffeine’seffectsonsynaptictransmissionintheCA2areaofthehippocampus,whereadenosineA1receptorsarehighlyenriched,werenotknown.Ratsweredividedintothreegroupsandgivendosesequivalenttotwolargecupsofcoffee,ahighlycaffeinatedenergydrink,oradosethatexceededmostpeople’sdailyconsumption.AlldosesofcaffeinestrengthenedtheconnectionsbetweenneuronsofCA2,butnotinotherareasofthehippocampus,abrainstructureimportantforlearningandmemory.

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Theseresultsprovideapleasinglysimpleexplanationforthecommondailyhumanexperience.Adenosinelevelsincreaseinthebrainduringtheday,inhibitingtheproductionofcyclicAMP.Althoughtheseeffectsrecoverduringsleep,caffeineacceleratesrecoverybyblockinganyresidualadenosineactionandstrengthenstheactivityofCA2synapsesofthehippocampus.ThisdiscoveryalsoraisesexcitingnewquestionsabouttheroleofCA2neuronsinbrainfunction.

Citation:SimonsSB,CaruanaDA,ZhaoM,DudekSM.2011.Caffeine-inducedsynapticpotentiationinhippocampalCA2neurons.NatNeurosci;doi:10.1038/nn.2962[Online20November2011].

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Exposures to certain early-life factors may contribute to an early onset of uterine fibroidsResearchersinvolvedintheNIEHSSisterStudyfoundassociationsbetweenexposuretoseveralearly-lifefactorsandthedevelopmentofearly-onsetuterinefibroidsinblackwomen.Thesefindings,whichreplicatemanyoftheteam’spreviouslypublishedassociationsamongwhitewomen,addsupporttosomehypothesesregardingtheetiologyoffibroidsinwomen.

Uterinefibroidsarehighlyprevalentbenigntumors,withanestimatedclinicalprevalenceashighas50percentforblackwomencomparedto25percentforwhitewomen.Blacksnotonlyhaveanincreasedriskofdevelopingfibroids,butalsosuffermoreseveresymptomsthanwhites.

Thescientistsexaminedearly-lifeexposuretoseveralfactorsinblackwomenaged35-59yearsofageenrolledintheSisterStudycohort.Theresearchersfoundanelevatedriskofearly-onsetuterinefibroidsinassociationwithin uterodiethylstilbestrol(DES)exposure,in uteroexposuretomaternaldiabetesormaternalhypertensivedisorder,havingbeenbornpreterm,havingamonozygotictwin,beingthefirstbornchildofateenagemother,andconsumptionofsoyformula.

Althoughtheassociationswithmultiplebirthandmaternalhypertensivedisorderwerenotseenforwhitewomen,thegeneralconsistencyofearly-lifefindingsforblacksandwhitessupportsapossibleroleofearly-lifefactorsinfibroiddevelopment.

Citation:D’AloisioAA,BairdDD,DeRooLA,SandlerDP.2011.Early-lifeexposuresandearlyonsetuterineleiomyomatainblackwomenintheSisterStudy.EnvironHealthPerspect;doi:10.1289/ehp.1103620[Online2November2011].

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Snail and Slug activate TGF-beta in breast cancerForthefirsttime,scientistsatNIEHSandSRAInternational,Inc.havedeterminedthetranscriptionalconsequencesofexogenousexpressionofSnailandSluginbreastcancer.SnailandSlugaretranscriptionalrepressorsthathavebeenproposedtomediateepithelialtomesenchymaltransition,whichhasbeenimplicatedintumormetastasis.

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ResearchersfollowedSnailandSlugexpressionbyperformingmicroarrayanalysisinaMCF-7breastcancercelllinethatdidnotexpressdetectablelevelsofSnailandSlug.Adenovirus-infectedcellsservedasthecontrol.MicroarrayanalysisshowedthatgenesinvolvedintheTGF-betasignalingpathwaywereupregulated,whilegenesresponsibleforadifferentiatedmorphologyweredownregulatedfollowingSnailorSlugexpression.Importantly,theoverexpressionofSnailandSlugchangedthetranscriptionalsignaturefromluminaltoamorebasalbreastcancerthatiscommonlyassociatedwithhighlyinvasivecancers.

ThisstudysuggeststhatthecellmigrationinducedbySnailorSlugexpressioncouldbeblockedbytheadditionofTGF-betainhibitors,asinhibitionofTGF-betadidnotappeartoaffectthegenerepressioninducedbySnail.However,theabilityofcellstomigratewasaffected.Therefore,thesequentialtreatmentswithestrogenicagoniststhatcontroltumorgrowthandTGF-betainhibitorstopreventcellmigrationmayhavetherapeuticbenefits.

Citation:DhasarathyA,PhadkeD,MavD,ShahRR,WadePA.2011.ThetranscriptionfactorsSnailandSlugactivatethetransforminggrowthfactor-betasignalingpathwayinbreastcancer.PLoSOne6(10):e26514.

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Pregnane X receptor regulates liver metabolismNIEHSresearchershaveuncoveredthemechanismfortherepressionoftheestrogensulfotransferase(SULT1E1)genebyrifampicin(RIF),anantibacterialandantifungalagent.ThisworkmakestheSULT1E1genethefirstgenethatisrepressedbypregnaneXreceptor(PXR)tobeunderstoodatthechromatinstructurelevel.ThesefindingshaveimportantpublichealthimplicationsastheysuggestthatPXRandconstitutiveactive/androstanereceptor(CAR)maycooperateinregulatinghepaticlevelsofactiveestrogens,therebyaffectingthephysiologyandpathophysiologyofhumanliver.

ThesamegroupofNIEHSscientistspreviouslypublishedastudydemonstratingthattheactivationoftheSULT1E1genebyxenobioticsismediatedbyCAR,andthatPXRactivationbyRIFrepressedtheSULT1E1geneinhumanprimaryhepatocytesandhepatocellularcarcinomacells.Thecurrentstudybuildsupontheearlierstudy.

Usingchromatinimmunoprecipitationandchromatinconformationcaptureassays,theresearchteamidentifiedthehepatocytenuclearfactor4alpha(HNF4alpha)asthetargetofPXRtorepresstheSULT1E1geneinhumanprimaryhepatocytesandhepatocellularcarcinomacells.Indoingso,theseinvestigatorshavedeterminedhowPXRcross-talkswithHNF4alpha,disruptinganactivechromatinstructureandrepressingthetranscriptionofSULT1E1gene.ThisPXRandCARcooperationinregulatingestrogenlevelsinthehumanlivermayaffectthephysiologyoftheliver.

Citation:KodamaS,HosseinpourF,GoldsteinJA,NegishiM.2011.LigandedpregnaneXreceptorrepressesthehumansulfotransferaseSULT1E1promoterthroughdisruptingitschromatinstructure.NucleicAcidsRes39(19):8392-8403.

(RalucaDumitru,M.D.,Ph.D.,isanIntramuralResearchTrainingAward(IRTA)fellowintheNIEHSLaboratoryofMolecularCarcinogenesisStemCellBiologyGroup.AnshulPandya,Ph.D.,isanIRTAfellowintheLaboratoryofNeurobiologyIonChannelPhysiologyGroup.SonikaPatial,D.V.M.,Ph.D.,isavisitingfellowintheLaboratoryofSignalTransductionPolypeptideHormoneActionGroup.)

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Inside the InstituteInstitute staff honored at 2011 NIEHS awards and international day By Ian Thomas

NIEHSwelcomedfederalstaffandcontractorstoRodbellAuditoriumDec.6foritsannualNIEHSAwardsCeremonyandInternationalDayfestivities.Asoneofthebiggesteventsoftheyear,the2011ceremonyrecognizedindividualsandgroupsforoutstandingaccomplishments,whilealsohonoringNIEHS’richculturaldiversitywiththeannualInternationalDaycelebrationafterwards.

“Thisceremonyspotlightsthehardworkanddedicationofsomanyworthypeople,andit’salwayssuchapleasuretobeapartofit,”saidNigelWalker,Ph.D.,NTPdeputydirectorforscienceandtheevent’smasterofceremonies.

Merits of the highest honorAmongthemostdistinguishedofawardspresentedattheceremonywerethe25NIHMeritAwards,honorsgivenonbehalfoftheNIEHSdirectorinrecognitionofoutstandingcontributionstowardleadership,scientificresearch,andscientificandadministrativemanagement.

“WinningaMeritAwardisatestamenttothededicationandinnovationofeveryoneinvolvedwithNIEHS’ethicsprogram,”saidDavidResnik,J.D.,Ph.D.,abioethicistwho,alongwithhisteamfromtheNIEHSEthicsOffice,garneredacompliancescoreof100percentforitsethicsandresearchconducttrainingprograms.“Butbeyondthat,italsosignifiesthisInstitute’scommitmenttomaintainingstrongethicalstandards,andI’mexceptionallyproudtobepartofit.”

OtherawardspresentedweretheNIEHSUnsungHeroAwards,recognizingemployeeswhomakevaluablecontributionsthathaveahugeimpactontheprogramsoftheInstitute,andtheNIEHSPeerAwards,honorsnominatedbycolleaguesthathonoremployeeswhohaveconsistentlyprovidedextraordinaryassistancetotheirfellowworkers.

“Ireallycan’ttellyouwhatawonderfulhonoritistowinthisaward,”saidAmyJohnson,anUnsungHeroAwardwinnerandamemberofNIEHSsince1978.“Scientistsareanincrediblebreedofpeople,andIfeelsoveryfortunatetohaveworkedalongsidesomeofthebestduringmytimehere.”

TheceremonyalsorecognizedwinnersoftheGreenChampionsAwards,FellowsAwardsforResearchExcellence(FARE),andNIHDirector’sAwards,allpresentedearlierintheyear.

Walker was an engaging host who moved the ceremony along with his good-natured anecdotes about colleagues, including Birnbaum, that kept the audience laughing and attentive. (Photo courtesy of Steve McCaw)

Although Walker commanded the podium during most of the ceremony, Birnbaum had the last word, as she thanked all of the employees at NIEHS for their contributions to the Institute’s mission. (Photo courtesy of Steve McCaw)

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Proud reflectionNIEHShadnoshortageofachievementin2011.BeittheInstitute’sfield-leadingworkwiththeGuLFSTUDY,ahealthstudyofoilspillcleanupworkers,oritshighlypublicizedreleaseofthe12thReportonCarcinogens,theInstituteanditspersonnelcontinuetoraisethebarastheymoveforwardinto2012andbeyond.

“OursincerestcongratulationsgoouttoeveryonehereatNIEHS,foraphenomenaljobin2011,”saidNIEHS/NTPDirectorLindaBirnbaum,Ph.D.“Regardlessofwhetheryouwonanawardtoday,youalldeserveone,whichiswhyIconsideritsuchanhonortobeyourdirector.”

Thereisacompletelistavailableofall2011Merit,UnsungHero,Peer,SpecialAppreciation,andHonorableMentionawardees.

A collage of cultureFollowingtheawardsceremony,attendeeswereinvitedtothecafeteriaforanafternoonoffood,music,andeducationaldisplays,complimentsofthe2011InternationalDay.Highlightedbyitselaboratemenu,featuringanarrayofIndian,LatinAmerican,Asian-Pacific,andNativeAmericandishesamongothers,thecelebrationtreatedvisitorstoamulticulturalspectrumofentertainment,includingafashionshowofinternationalholidayattire,traditionalChristmastreedecorating,andNativeAmericanstorytelling.

“InternationalDayisonedayoftheyearwhenwerecognizealloftheculturesthatarerepresentedacrossNIEHS,”saidBradCollins,achemistandprogramofficerwithNTPwhochairstheNIEHSDiversityCouncil.“Peoplecomefromallovertheworldtoworkhere.Becauseofthat,Instituteemployeescanexperienceafantasticvarietyofdifferentculturesand,moretimesthannot,theyneedonlylooktothenextlaborcubicaltodoit.”

Leading off the ceremony was the presentation of the first of two Unsung Hero Awards to NTP Technical Writer/Editor Charles Alden, Ph.D., for maintaining the high standards expected of the NTP Technical Report Series. (Photo courtesy of Steve McCaw)

The ceremony concluded with the recognition of recipients of earlier awards, such as trainees who were FARE winners. (Photo courtesy of Steve McCaw)

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(IanThomasisapublicaffairsspecialistwiththeNIEHSOfficeofCommunicationsandPublicLiaison,andaregularcontributortotheEnvironmentalFactor.)

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International Day is always a memorable time for the children of NIEHS employees. They can come with their parents or participate as a part of the First Environments Daycare program located on the adjacent EPA campus. (Photo courtesy of Steve McCaw)

The band Saludos Compay played a range of Latin music for listening and dancing. (Photo courtesy of Steve McCaw)

The food was tasty, plentiful, and varied. Shown above, left to right, postdoctoral fellows Raj Gosavi, Ph.D., and Sindura Ganapathi, Ph.D., prepared for a hearty afternoon snack. (Photo courtesy of Steve McCaw)

In a joyous burst of enthusiasm, Dona McNeill, left, joined Bono Sen, Ph.D., dressed in traditional Indian attire, in a spontaneous dance. (Photo courtesy of Steve McCaw)

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CFC enjoys another record year By Eddy Ball

NIEHSwrapped-upitsannualevent-packedCombinedFederalCampaign(CFC)Dec.15,2011,settingyetanotherrecordbyraising$110,000inpledgesfrommorethan200employees.The2011campaignsurpasseditsowngoalof$105,000andlastyear’srecordof$107,000.

Inanannouncementtoemployees,NIEHS/NTPDirectorLindaBirnbaum,Ph.D.,offeredthosewhomadetherecordpossiblehersincerethanks.“Iamsoproudofyouforhelpingnotonlyourcommunity,butalsothoseinneed,”shesaid.“Yourvoluntarygivingissomuchappreciatedintimeswhenoureconomyissuffering.”

BirnbaumalsorecognizedtheexceptionalperformanceofCFCco-chairsRonCannonandCindyInnes,aswellasdivisionchairsandco-chairs.Truetohermessagethroughoutthecampaign,Birnbaum,whosupportedtheeffortwithfrequentemailstoemployees,hadafinalwordforNIEHSemployees.

“Iwouldliketoremindyou,asthe2011NIEHSCFCcampaignactivitiesarewindingdown,thatlastminutevoluntarydonationcanstillbeaccepted,”shesaid.

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Division chairs and co-chairsExtramural Research and Training ElizabethRuben(Chair)DanielleCarlinBarbGittleman

Intramural ResearchBobPetrovich(Chair)DavidArmstrongTerryBlankenship-ParisShannonDuncanGinaGouldingGezellJonesPatJohnson

NTPRachelFrawley(KeystoneChair)EliNeyDeniseLaskoVeronicaRobinsonCynthiaRiderDianeSpencerPatStocktonSheilaWithers

Office of DirectorDebbieWales(Chair)JudyHanson

Office of Human ResourcesFranCowens

Office of ManagementDonaMcNeill(Chair)PatBarbourLindiaEngramJennEvansJimMcDonoughDudleyRinerTamekaThomas

Office of Research FacilitiesPaulPoliachik

CFC co-chair Cindy Innes (Photo courtesy of Steve McCaw)

CFC co-chair Ron Cannon (Photo courtesy of Steve McCaw)

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NTA celebrates grand opening of resource room By Ed Kang

WithaceremonialcoffeehourandopenhouseNov.30,theNIEHSTraineesAssembly(NTA)proudlyopenedthedoorstoanewresourceroomthatisspecificallydesignedtoaccommodatetheinterestsoftheInstitute’s220-pluspostdoctoralstudentsandfellows.Thegrandopeningwasreasonforcelebration,astheNTAhaslongwantedaspacethatwouldperformtripledutyasaresourceroom,ameetingspaceforcommitteemeetings,andaprivatelocationforpostdocstorehearseandconductinterviews.

NIEHSresearchfellowshavebigplansforthemodest-sizedroomthatwillsupportthegoalsoftheNTAtoorganizeandpromoteeducationalactivities,includingtrainingcoursesandseminars.“It’sbeenalongtimecoming,”saidformerNTASteeringCommitteeco-chairNishaCavanaugh,Ph.D.,apostdoctoralfellowintheDNARepairandNucleicAcidEnzymologyGroup.“Thiswillbeaconvenientandcentralplaceforsteeringcommitteeandsubcommitteemeetings.”

A central nexus for traineesThissentimentwasechoedbySarahSwerdlow,Ph.D.,apostdoctoraltraineeintheMechanismsofMutationGroup.“Thisisgoingtobeverygoodforus.We’reinlabsspreadoutacrosstheInstitute,sotohaveoneplace,justforus,isgoingtoreallyenhancethepostdocexperience.”

“Wealsohavelotsofstuff,”addedJillHesse,Ph.D.,referringtoyearsofarchivedmeetingnotes,aswellascurrentresources,contacts,andbrochures.Hesse,whoworksintheEnvironmentalStressandCancerGroup,pointedtothebenefitsofhavingacommonplaceforalltheseresources.“Nowpostdocsknowrightwheretogoforalltheirneeds,”shesaid.

Oneexampleoftheresourceroom’sbenefitwasprovidedbytheNTASteeringCommitteeontherecentNIEHSScienceAwardsDayposterjudging.“Itwasreallyimportantforthepostdocstoseethefeedbackprovidedbythejudgingpanel,”Cavanaughcommented.“Theresourceroomprovidedaneasy-to-access,centralrepositoryforthosescoringsheets,soanyone,anytimecouldcomeandreviewtheirfeedback.”

Warm beverages, snacks, and, of course, fellowship mark the opening of the NTA resource room, which is now officially open for business. Shown, left to right, are postdoctoral fellows Tracy Clement, Ph.D., Hesse, Cavanaugh, Tammy Collins, Ph.D., and Ashley Godfrey, Ph.D. (Photo courtesy of Steve McCaw)

Various brochures, training materials, and applications will now have a full-time home. Formerly, these resources were housed in different offices throughout the Institute. Shown, left to right are Clement, Godfrey, and postdoctoral fellow Vijayakanth Pagadala, Ph.D. (Photo courtesy of Steve McCaw)

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ThenewroomalsohelpstofulfillanotherNTAgoalofassistingpostdocsinidentifyingandseekingfutureemploymentopportunitiesinbothtraditionalandnon-traditionalcareerpaths.Hessenotedthattheprivacyofthenewspacewillbeconduciveforpracticingordoingactualinterviews,eitherinpersonorbyphone.“It’snotpracticaltohavethesetypesofconversationsatthebenchorinasharedworkspace.”

Hesseandothersenthusiasticallyadded,“WeloveDr.Miller!”referringtoDavidMiller,Ph.D.,chiefoftheLaboratoryofToxicologyandPharmacologyandformeractingNIEHSscientificdirector.Miller’songoingsupportofthepostdoccommunityandtheeffortsoftheNTAenabledtheuseofthespace,andprovidedthenecessaryfurniture,phones,anddataconnectivity.

TheNTAresourceroomislocatedintheFmoduleofBuilding101inroomF182.

(EdKangisapublicaffairsspecialistintheOfficeofCommunicationsandPublicLiaisonandaregularcontributortotheEnvironmentalFactor.)

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The NTA-hosted coffee hour drew thirsty and curious postdocs to enjoy the new space for the first time. (Photo courtesy of Steve McCaw)

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The e-Factor, which is produced by the Office of Communications and Public Liaison, is the staff newsletter at the National Institute of Environmental Health Sciences. It is published as a communication service to NIEHS employees. We welcome your comments and suggestions. The content is not copyrighted. It can be downloaded and reprinted without permission. If you are an editor who wishes to use our material in your publication, we ask that you send us a copy for our records.• Director of Communications: Christine Bruske• Writer-Editor: Eddy Ball• Science Editor: Robin Arnette