NIEHS Spotlight Science Notebook

February 2012

Weis addresses industrial hygiene group on mineral fibersNIEHS Toxicology Liaison Chris Weis, Ph.D., was on the road last month speaking on the link between hazardous mineral fibers and an epidemic of respiratory ailments.

LST fellow makes a move from lab bench to global healthSindura Ganapathi, Ph.D., took an important step in his career when he transitioned from being a trainee to his new role as an associate program officer at the Gates Foundation.

Former staff fellow appointed vice chancellor at ColoradoRobert Boswell, Ph.D., began the new year with yet another addition to his long list of honors and accomplishments since leaving NIEHS in 1986.

Staffers and trainees gain toxicology certificationTwo NIEHS/NTP scientists and two NTP postdoctoral fellows recently took an important step along toxicology’s professional track with DABT certification.

Minisymposium brings epigenetic experts to NIEHSThe daylong minisymposium Jan. 10 at NIEHS showcased scientific presentations by many leaders in the field of epigenetics, chromatin biology, development, and disease.

BPA researchers meet for updates and assessmentNIEHS grantees and government scientists gathered Jan. 17-19 at NIEHS to update their research efforts on bisphenol A in ARRA-funded research projects.

Women’s health takes the spotlightNIEHS welcomed fellow scientists, practitioners, and leaders in women’s health to a consortium for the singular purpose of highlighting women’s reproductive health.

NIH turns 125As NIEHS looks forward to its 50th anniversary, NIH geared up for a celebration of 125 years of turning discovery into health.

Study estimates millions have autoantibodies that target their own tissuesThe first nationally representative sample looked at the prevalence of the most common type of autoantibody known as antinuclear antibodies.

Fry maps arsenic levels across NCGrantee Rebecca Fry, Ph.D., and her colleagues found elevated levels of arsenic over a period of 11 years in a number of counties that border the Carolina slate belt.

Video

Video

Video

NIEHS Spotlight Science Notebook

Public health officials work to keep research first during a tough economyAssociation of Schools of Public Health official Mike Stephens addressed the growing national deficit, specifically its impact on federal funding of public health research.

Prins honored by University of Illinois at ChicagoNIEHS grantee Gail Prins, Ph.D., is one of three researchers who are winners of 2011 Researcher of the Year awards at the University of Illinois at Chicago.

Transcription of membrane-associated DNA highlights Lieb’s encoreUniversity of North Carolina at Chapel Hill professor Jason Lieb, Ph.D., spoke Jan. 20 at NIEHS about how the organization of DNA in the genome affects gene expression.

Armstrong discusses endocrine disruption of synaptic plasticityNIEHS senior investigator David Armstrong, Ph.D., reported on new findings about the regulation of synaptic plasticity by endocrine modulators found in the environment.

This month in EHPIn its feature story of the month, Environmental Health Perspectives examines the impact of environmental exposures on America’s growing obesity epidemic.

Upcoming Falk lecturer Danny ReinbergThe epigenetic biochemist will provide insights into epigenetics research with his talk on “Molecular Mechanisms of Epigenetic Inheritance.”

NIEHS Public Interest Partner honoredMary Lamielle, executive director of the National Center for Environmental Health Strategies, received the 2012 Camden County (N.J.) Freedom Medal.

Superfund promotes safe drinking water at Agua Fria FestivalResearchers and Community Engagement Core leaders were on hand to share health and exposure information on arsenic and lead to the thousands of people at the two-day event.

Kumar explores regulation of male germline stem cell nicheRajendra Kumar, Ph.D., presented new findings that offer insights into the mechanisms responsible for infertility and insufficient production of the male sex hormone.

Registration is underway for NIEHS and HHS national research conferenceOrganizers of the South Atlantic National Research Conference are accepting registrations for a forum March 21-22 at the Raleigh (N.C.) Convention Center.

Audio

Inside the Institute

NIH celebrates King legacy with dance, music, and personal historyThe program featured a talk by toxicologist Lemuel Russell, Ph.D., and three inspirational performances by students from the Duke Ellington School of the Arts.

Long recognized for CFC leadershipOne factor in CFC’s success this year, several observers agree, was the leadership provided by NIEHS Deputy Associate Director for Management Chris Long.

Extramural Research

Extramural papers of the month• New way to remove heavy metals from water

• Perfluorinated compounds and immune response in children

• Menthol lessens irritation from cigarette smoke

• Measuring cockroach allergen in the air

Intramural Research

Intramural papers of the month• Catching DNA polymerase beta in the act of

mutagenic bypass of 8-oxoG

• In utero tobacco smoke exposure associated with illnesses in adult women

• Crystal structure of a kinase advances research for rational drug design

• Phosphorylation status links cellular stress and GR transcriptional response

NIEHS Spotlight

NTP toxicologist Kamal Abdo rememberedNIEHS/NTP colleagues were saddened by the death of Kamal Abdo, Ph.D., Dec. 22, 2011, in Bahama, N.C. at age 73.

Video

Calendar of Upcoming Events

• Feb. 3, in Rodbell A, 11:00 a.m.-12:00 p.m. — Laboratory of Reproductive and Developmental Toxicology Seminar Series, featuring Michael Waterman, Ph.D., speaking on “Structure/Function of CYPs 21A2 and 17A1 in Biosynthesis of Steroid Hormones”

• Feb. 6-7 (offsite event), at the U.S. Environmental Protection Agency, Research Triangle Park, N.C., 8:00 a.m.-5:00 p.m. — NIEHS Data Sharing Workshop

• Feb. 7, in Rodbell Auditorium, 11:00 a.m.-12:00 p.m. — Seminar featuring Ann Reed, M.D., “A Phenotypic Conundrum: My Experience Studying Inflammatory Myositis”

• Feb. 8-9, in Rodbell Auditorium, 8:00 a.m.-5:00 p.m. — NTP Technical Reports Peer Review

• Feb. 10, in Rodbell Auditorium, 11:00 a.m.-12:00 p.m. — Seminar featuring Elise Kohn, M.D., topic TBA

• Feb. 14, in Rodbell Auditorium, 10:00 a.m.-11:00 p.m. — Falk Lecture with Danny Reinberg, Ph.D., speaking on “Molecular Mechanisms of Epigenetic Inheritance.”

• Feb. 15-16, in Rodbell Auditorium, 8:00 a.m.-5:00 p.m. — National Advisory Environmental Health Sciences Council meeting

• Feb. 16, in Keystone 1003, 2:00-3:00 p.m. — Keystone Lecture Seminar Series, featuring Marie-Francoise Chesselet, M.D., Ph.D., exploring “Gene and environment risk factors for Parkinson’s disease: from man to mice and back”

• Feb. 29 (offsite event), at the National Evolutionary Synthesis Center, 2024 W. Main Street, Ste. A200, Durham, N.C., 12:00 p.m. — Postdoc Professional Development Workshop, “Scientific Publishing From the Inside Out,” by Science Magazine Associate Editor Sacha Vignieri, Ph.D.

• March 1, in Keystone 1003, 10:00-11:00 a.m. — Keystone Lecture Seminar Series, with John Rawls, Ph.D., addressing “Host-microbe symbiosis in the zebrafish intestine”

• View More Events: NIEHS Public Calendar

1

NIEHS SpotlightWeis addresses industrial hygiene group on mineral fibers By Eddy Ball

NIEHSToxicologyLiaisonChrisWeis,Ph.D.,wasontheroadlastmonthspeakingonthelinkbetweenhazardousmineralfibersandanepidemicofrespiratoryailments,includingmesothelioma,lungcancer,asbestosis,andnon-malignantpleuraldisease.

Weisaddressedanaudienceofprofessionalsconcernedaboutworkplacesafetyandpublichealthonthefinaldayofthe37thannualmeetingoftheYumaPacificSouthwestsectionoftheAmericanIndustrialHygieneAssociation(AIHA)Jan.18-20attheCrownePlazainIrvine,Calif.Weiswasapresenterduringaspecialsessiontitled“FourthWave:AmbientExposurestoAsbestosandElongatedMineralParticles.”

Weisisamongagrowingnumberoftoxicologists,biomedicalresearchers,andregulatorsstrivingtoraiseawarenessoftheongoinghazardsassociatedwithoccupationalandenvironmentalexposuretoasbestosandasbestos-likefibersfoundinnaturaldeposits,andinengineerednanomaterials(ENMs),whichareusedinagrowingnumberofconsumerandmedicalproducts.

“Overthepasttwodecades,between100,000and200,000deathshavebeenattributedtofiberinhalation,”Weistoldtheaudience.“Betweenthe1960sand1990s,asbestosmortalityincreasednearly20foldandratesofmesotheliomacontinuetorise.”

Opening the asbestos boxWeisemphasizedthatresearchers,industrialhygienists,andoccupationmedicinespecialistsneedtolookbeyondthenarrowlyemployeddefinitionofasbestos,tobetterunderstandthepotentialhealthconsequencesofinhalationofmicro-andnano-sizedfibers.Whilethereisgeneralawarenessofthehazardsofasbestosexposure,hesaid,thereismuchlessawarenessofpotentialhealtheffectsfromexposuretoothernaturallyoccurringminerals,suchaserionite(seestory)andsomeENMs,whichbehaveinwayssimilartoasbestosand,likeerionite,couldturnouttobeevenmoredangerous.

Movingbeyondthewell-knownlinkbetweenasbestosandcancer,Weissummarizedongoingresearchintothemolecularbasisofinflammationandautoimmunitytriggeredbymineralfiberexposure.HealsodescribedNIEHSeffortswithpartnersingovernment,nonprofits,andprivateenterprisetofindbetterwaystodefinethemechanismsoffiberbioactivity,persistence,anddistributioninmammalianmodels.

“Wedon’thavedefinitiveanswersyet,”Weisconcluded,“butwehavereasonstokeeplookingatthesefibers.”Hepointedtothelikelihoodofadditionaldiscoveriesofdepositsoferioniteandotherzeoliteminerals,aswellasthemanyunansweredquestionsaboutthepotentialeffectsofthephysical,chemical,andelectricalcharacteristicsofENMsandothernano-sizedfibersthatarecapableofcrossingprotectivebarriersinthehumanbody.

Return to Table of Contents

Weis joined a lineup of consultants and representatives of government agencies speaking as part of the special session. (Photo courtesy of Steve McCaw)

2

LST fellow makes a move from lab bench to global health By Sonika Patial

IntramuralResearchandTrainingAwardFellowSinduraGanapathi,Ph.D.,tookanimportantstepinhiscareerinJanuary,whenhetransitionedfrombeingatraineeintheLaboratoryofSignalTransduction(LST)tohisnewroleasanassociateprogramofficerintheBillandMelindaGatesFoundationGlobalHealthProgram.

AtNIEHS,GanapathiworkedintheLSTInositolSignalingGroup,headedbyStephenShears,Ph.D.,exploringtheregulationofcellmigrationbyClC-3chloridechannelsandthedevelopmentofinositolphosphatesastherapeuticcandidatestargetingClC-3indiseasescausedbyabnormalcellmigration,suchasatherosclerosisandcancer.

Inkeepingwithitsslogan,“Allliveshaveequalvalue,”theBillandMelindaGatesFoundation,oneoftheworld’slargestnon-profitorganizations,strivestohelpallpeopleleadhealthyandproductivelives.Ganapathiwillbeinvolvedinfundingresearchanddevelopmentofnewinitiativesinsuchareasasvaccines,drugs,anddiagnostics,withthegoalofreducingmaternalandneonatalmortalityandimprovinghealth.Hisrolewillalsoinvolvecoordinatinggrantreviewsandexploringnewinitiativestoimprovematernalandneonatalhealthindevelopingcountries.

Ganapathiacknowledgesthathisdiversebackground,adegreeinveterinarymedicine,researchexperiencefromhisPh.D.studiesandpostdoctoralfellowship,andexperiencegrowingupinadevelopingcountrymadehimaverygoodfitforthejob.HewasalsoabletohighlightthepredoctoralAmericanHeartAssociationgrantawardthathereceivedasevidenceofexperienceingrantwriting,whichwasanimportantpartofthejobdescription.

Starting the hunt early is the key“Keepinganeyeonavailableopportunitiesandstartingthehuntearlywasthekeytomysuccess,”saidGanapathi,whostartedlookingforjobsjustsixmonthsafterjoiningNIEHS.Networking,talkingtopeople,attendingjobandcareerfairs,andkeepingabreastofthejobmarkethelpedhimtargetthekindofjobsthatinterestedhim.“Findingtherightopportunitycanbecomplicated,tosaytheleast,”heexplained.

InadditiontoworkingintheShearsgroup,GanapathiservedasamemberoftheNIEHSTraineesAssembly(NTA)steeringcommittee,aswellastheplanningcommitteefortheBiomedicalCareerFairin2011.“Theseactivitiesnotonlyhelpedbroadenmynetwork,butalsokeptmeupdatedonwhatwashappeningaroundme.Iwasabletogainexperienceinleadershipandteamworkskillsthatareanessentialpartofnearlyeveryjobdescription.”

Ganapathi found his job the old-fashioned way — by answering an advertisement. However, he credits networking with honing his interviewing skills, helping him maintain self-confidence, and creating a compelling CV and cover letter. (Photo courtesy of Sindura Ganapathi)

Linked video:

Learn about some of the innovative ideas in global health the Gates Foundation is supporting (04:12)

(Launches in new window)

Download Media Player: Flash

3

AccordingtoGanapathi,servingastheNTAsteeringcommitteeliaisontotheNIEHSEnvironmentalFactornewsletterandcontributingstorieswerealsousefulintheinterviewprocess.Hewasabletoprovidebothscientificandnon-scientificwritingsampleswhenrequestedduringthesecondroundoftelephoneinterviews,whichcertainlymadehimastrongercandidate.“Ithelpedmeprocessmyapplicationandinterviewmuchfaster,asIhadwell-editedwritingsamplesreadytobesent,”hesaid.

Quality mentoring played a roleSpeakingofhisexperiencewithmentoringatNIEHS,Ganapathisaidhewasgratefulforguidancefromhisgroupleader.“Stevewasverysupportiveandflexibleinthelabandalsoservedasareferenceforthejobapplication,”Ganapathisaid.

Inaddition,hefeltthatPatriciaPhelps,Ph.D.,deputydirectoroftheGraduatePartnershipsProgramintheNIHOfficeofIntramuralTrainingandEducation(OITE)andtheInstitute’sinterimfellowscareerdevelopmentspecialist,wasextremelyhelpfulinpreparinghiscurriculumvitae(CV)andcoverletter.Hehadseveralone-on-onecareerconsultationswithherandthoughtherpresentationson“JobsintheIndustry”gavehimgreaterinsightintoopportunitiesawayfromthebench.Ganapathisaidhehadthreeinterviews,includingoneforhisnewjob,andallofthemweretheresultofadvertisementsontheOITEwebsite.

(SonikaPatial,D.V.M.,Ph.D.isavisitingfellowintheNIEHSLaboratoryofSignalTransductionPolypeptideHormoneActionGroup.)

Return to Table of Contents

Former staff fellow appointed vice chancellor at Colorado By Eddy Ball

FormerstafffellowRobertBoswell,Ph.D.,beganthenewyearwithyetanotheradditiontohislonglistofhonorsandaccomplishmentssinceleavingNIEHSin1986.BeforemovingtotheUniversityofColoradoatBoulder(CU-Boulder),Boswellcompletedafour-yeartrainingexperienceatthebench,nurturinghiscareer-longinterestinthemolecularanddevelopmentalgeneticsofDrosophila.

CU-Boulder,whereBoswellearnedhisPh.D.in1981andwherehereturnedasanassistantprofessorin1986,announcedhisappointmenttothepostofvicechancellorfordiversity,equity,andcommunityengagement,effectiveJan.1.Aprofessorofmolecular,cellular,anddevelopmentalbiologywithalonganddistinguishedcareeratCU-Boulder,BoswellhadheldthepositiononaninterimbasissinceJuly2010.InDecember2011,asearchcommitteenamedhimthesoleinternalfinalistforthepost.

Diversity as a core value at CU-Boulder “Asvicechancellorfordiversity,equity,andcommunityengagement,BobBoswellwillcontinuethevitalworkofestablishingdiversityasacorevalueforCU-Boulder,”ProvostRussellMoore,Ph.D.,

Newly appointed vice chancellor Robert Boswell (Photo courtesy of Regents of the University of Colorado)

4

wasquotedassayingintheuniversity’spressrelease.“Iamcharginghimwithbuildingonhispreviouswork,andthatoftheOfficeofDiversity,EquityandCommunityEngagement[ODECE],toengageourfaculty,staffandstudentsintheseessentialaspectsofouruniversityenvironment.”

“IamhonoredbythisappointmentandameagertocontinueODECE’simportantmissionofmakingdiversityacentralpartofallwedoatCU-Boulder,”saidBoswell.

Teaching, research, and service BoswellwasateachingandgraduateresearchassistantwhilecompletinghisdoctorateatCU-Boulderfrom1975to1981,beforemovingontoaDamonRunyon-WalterWinchellPostdoctoralFellowshipatIndianaUniversityfrom1981to1982,andastafffellowshipatNIEHSfrom1982to1986.HewasamemberofwhatwasthentheEukaryoticGeneStructureSectionoftheLaboratoryofGenetics,workingonprojectsthatincludedalong-termstudyofmutation,“AnalysisofDrosophilaGermCellDetermination.”

AfterreturningtoCU-Boulderin1986,Boswellrosequicklyintheranksofacademiaandwaspromotedtofullprofessorin1991.WhileretaininghisCU-Boulderfacultyappointment,healsoservedasaHowardHughesMedicalInstituteinvestigatorfrom1994to1998.

BoswellbecametheprincipalinvestigatoroftheNIHInitiativeforMaximizingStudentDevelopment,orIMSD,in2003.TheIMSDprogramencourageseducationalinstitutionswithfullydevelopedresearchprogramstoinitiateorexpandinnovativeprogramstoimprovetheacademicandresearchcapabilitiesofunderrepresentedstudents.Boswellwasalsoco-directoroftheColoradoDiversityInitiative,whichseekstoincreasethediversityofstudentsworkinginlabs.

Return to Table of Contents

Staffers and trainees gain toxicology certification By Eddy Ball

TwoNIEHS/NTPscientistsandtwoNTPpostdoctoralfellowsrecentlytookanimportantstepalongtoxicology’sprofessionaltrack,bysatisfyingrequirementsforDiplomateoftheAmericanBoardofToxicology(DABT)certification.DABTcertificationoftenoffersanadvantageinthejobmarketandcareeradvancement,andhasbeenassociatedwithhigherlevelsofcompensation.

TheAmericanBoardofToxicologywasestablishedin1979toadvancestandardsinthefieldoftoxicologyandconferrecognitionuponthosemembersoftheprofessionwho,measuredagainstsuchstandards,demonstratecompetence.Certificationrequirementsincludeacombinationofeducationandexperienceandathree-partexamination.

SeveraltoxicologistsatNIEHS/NTPhavequalifiedforthecovetedDABT,amongthemNIEHS/NTPDirectorLindaBirnbaum,Ph.D.,whoisthefirsttoxicologisttoheadtheInstitute.Birnbaumofferedthenewdiplomateshersincerecongratulations.“Welcometotheclub!”shewrote.“Thismarksaveryimportantmilestoneinyourcareers.”

Carlin, above, and Rider co-chaired a September 2011 workshop in Chapel Hill, N.C., on “Advancing Research on Mixtures.” (Photo courtesy of Steve McCaw)

5

New holders of the DABT are:• DanielleCarlin,Ph.D.,ahealthscientistadministratorwiththeNIEHSSuperfundResearchProgram,whojoinedtheNIEHSDivisionofExtramuralResearchandTrainingin2010,aftercompletingapostdoctoralfellowshipattheU.S.EnvironmentalProtectionAgency

• XiaoqingChang,Ph.D.,avisitingfellowintheNTPBiomolecularScreeningBranchheadedbyRaymondTice,Ph.D.,mentoredbyMichaelDeVito,Ph.D.,leaderoftheExperimentalToxicologyGroupintheNTPToxicologyBranch

• MinervaMercado-Feliciano,Ph.D.,anIntramuralResearchTrainingAwardfellowintheNTPToxicologyBranchheadedbyPaulFoster,Ph.D.

• CynthiaRider,Ph.D.,atoxicologistintheNTPGeneralToxicologyGroupwhojoinedNIEHS/NTPin2010,aftercompletingpostdoctoralworkatDukeUniversityandtheU.S.EnvironmentalProtectionAgency

DiplomatesholdinitialDABTcertificationfor5yearsandmustdemonstratethattheyactivelypracticetoxicology,engageincontinuingeducation,andmaintainexpertknowledgeintheirfieldpriortoreceivingrecertification.

Return to Table of Contents

Rider currently serves as secretary and treasurer of the Mixtures Specialty Section of the Society of Toxicology. (Photo courtesy of Steve McCaw)

Mercado-Feliciano has designed and monitored several toxicology studies on the herbal supplement black cohosh, or Actaea racemosa, and is actively presenting study results at scientific meetings and preparing them for publication in peer-reviewed journals. (Photo courtesy of Minerva Mercado-Feliciano)

In 2011, Chang earned a Society of Toxicology Nanotoxicology Specialty Section Outstanding Postdoc Award and an NIEHS Fellows Award for Research Excellence for her work with micro- and nano-sized fluorescent polystyrene spheres. (Photo courtesy of Steve McCaw)

6

NIH turns 125 By Eddy Ball

AsNIEHSlooksforwardtoits50thanniversary,NIHgearedupforacelebrationof125yearsofturningdiscoveryintohealth.TheNIHStaffTraininginExtramuralProgramskickedofftheNIHquasquicentennialcelebrationwithaspecialeventJan.12titled“NIH:LookingBackandMovingForward,”featuringpresentationsbyNIHscientistsDavidCantor,Ph.D.,oftheOfficeofNIHHistory;DavidM.Morens,M.D.,oftheNationalInstituteofAllergyandInfectiousDiseases;andAlanSchechter,M.D.,oftheNationalInstituteofDiabetesandDigestiveandKidneyDiseases.

NIHtracesitsrootstoAugust1887,whenaone-roomlaboratorywascreatedwithintheMarineHospitalService(MHS),whichlaterbecametheU.S.PublicHealthService(PHS),parentagencyofNIH.

TheMHShadbeenestablishedin1798toprovideforthemedicalcareofmerchantseamen.Inthe1880s,CongresschargedtheMHSwithexaminingpassengersonarrivingshipsforclinicalsignsofinfectiousdiseases,especiallythedreadeddiseasescholeraandyellowfever,inordertopreventepidemics.

The Hygienic Laboratory is bornIn1887,MHSauthorizedJosephKinyoun,M.D.,ayoungMHSphysiciantrainedinnewbacteriologicalmethods,tosetupaone-roomlaboratoryintheMarineHospitalatStapleton,StatenIsland,NewYork.Kinyouncalledthisfacilityalaboratoryofhygiene,inimitationoftheleading-edgeGermanfacilitiesofthetime,andtoindicatethatthelaboratory’spurposewastoservethepublic’shealth.

Withinafewmonths,KinyounhadidentifiedthecholerabacillusandusedhisZeissmicroscopetodemonstrateittohiscolleaguesasconfirmationoftheirclinicaldiagnoses.Threeyearslater,Kinyoun’sHygienicLaboratorymovedtoWashington,D.C.,whereKinyounstartedatrainingprograminbacteriologyforMHSofficers,andconductednumeroustestsofwaterpurityandairpollutionfortheDistrictofColumbiaandCongress.

In1901,Congressappropriated$35,000foranewbuildingtohousethelaboratoryanditsexpandedprograms.In1902,MHSwasreorganizedasPHS,andKenyoun’slabtransitionedintotheDivisionofPathologyandBacteriologywiththreenewcomponentsthatrepresentedthemostfruitfulareasforresearchatthattime—theDivisionsofChemistry,Pharmacology,andZoology.

Scientists worked at the bench of the Hygienic Laboratory at its first facility in Washington, D.C., circa 1899. (Photo courtesy of NIH)

In 1916, four years before the 19th Amendment gave women the right to vote, bacteriologist Ida Bengtson, Ph.D., who was a major figure in typhus research, became the first woman on the professional staff at the PHS Hygienic Laboratory. (Photo courtesy of NIH)

7

TheimportanceofthesenewprogramswasunderscoredbytheprovisionthatthePHScouldhirescientistresearcherswithPh.D.degreestoheadthem.Upuntilthistime,theprofessionalstaffhadbeenlimitedtophysicians.

Withitsrootsestablishedandthelandscapeofmedicineandpublichealthchangingdramaticallyduringthefirstdecadesofthe20thcentury,in1930CongresschangedthenameoftheHygienicLaboratorytotheNationalInstituteofHealth.TheestablishmentoftheNationalCancerInstitutein1937;areorganizationin1948thatmodifiedthenameofNIHtoreflectadditionalinstitutes;andanexpansionofthenumberofnewinstitutesandcenters,includingNIEHSin1966,totheircurrentnumberof27,allhelpedmakeNIHwhatitistoday.

(ThisstorywasadaptedfromnarrativeontheNIHHistorywebsite.)

Return to Table of Contents

Public health officials work to keep research first during a tough economy By Ian Thomas

DuringaJan.11talkatNIEHS,MikeStephensspokeonthegrowingnationaldeficit,specificallyitsimpactonfederalfundingofpublichealthresearch.Currently,theseniordirectorofpolicywiththeAssociationofSchoolsofPublicHealth(ASPH),Stephensmadeitclearthatscientistsandadministratorsalikemustbewillingtorethinktheirwayofdoingbusiness,ifthefieldhopestomaintainitspresentlevelofcommitmenttoresearch.

“VirtuallyeverypolicydebateinWashingtonrightnowissomehowconnectedtothedeficit,”saidStephens,whonotedNIEHS’statusamongNIHinstitutesandcentersasthesecondlargestfunderofASPH-affiliatedresearch.

A half century of growthEstablishedin1953withroughlyadozenschools,ASPHnowshowcasesanimpressiverosterof49educationalinstitutions,includingpublichealthschoolsinMexico,Canada,andFrance.Withanannualenrollmentofnearly26,000students,ASPHmemberschoolsawardabout9,000degreesperyearinvariouscareerpathsinpublicandglobalhealth.

By the 1970s, NIH labs began to look more like their modern counterparts, with computers to aid in the collection, analysis, and display of data from laboratory instruments, such as this mass spectrometer. (Photo courtesy of NIH)

Stephens noted that the average cost of an extramural grant has grown over the years from roughly $250,000 to a hefty $433,000. (Photo courtesy of Michael Stephens)

8

“AlotofpeopletendtothinkofASPHassimplybeingacollectionofsocialworkschoolswithahealthemphasis,andtheydon’ttakeintoaccountthestrengthofthebasicscienceweconduct,”Stephenssaid,whilehighlightingseveralofASPHmemberschools’contributionstothepublichealthfield,suchasdiscoveryofthefirstinfluenzavaccinein1944,theoriginalSalkvaccinein1955,andcontributionstoworkerhealthandsafetystandards.“Ifyoulookbackattheportfolioofourachievementsinthelast50years,thestrengthoftheworkweproduceisplainlyevident.”

Inadditiontodegreeprograms,ASPHmemberschoolsarealsoheavilyinvolvedincontinuingeducationintheworkforce,offeringsome200,000trainingsessionsperyearthroughitsPublicHealthTrainingCenters.

Building a new modelOperatingonanannualbudgetofapproximately$3billion,ASPH’s49schoolsdrawathirdoftheirfundingfromgovernmentsources.However,inatimewhenmostfederalbudgetsareeitherfrozenorshrinking,Stephenswasadamantthatpublichealthofficialsmustbereadytomakesometoughdecisionsinthedaysahead.

“Foryears,we’vegottenaccustomedtotheideaofexpandingbudgetsandgrowingresources,buttherealityisthatitjustisn’tthatwayanymore,”saidStephens,whoaddedthatapplicationsforNIHgrantshitanall-timehighin2011.“Wehavesomereallypromisingscienceonthehorizonfromsomeoutstandingyoungscientists,andit’simperativetothefutureofthefieldthatwecontinuetosupportthoseendeavors.”

AccordingtoStephens,optionsforloweringNIHgrantcostsforfundingnewinvestigatorsarelikelytoincludereductionsofoverallsalariesthatarerecoverablefromagrant,thefundingofalargerquantityoflessexpensivegrants,cappingtheamountornumberofgrantsgiventoasingleinvestigator,andshorteningthelifespanofagrantfromitscurrent4.3-yearaverage.

“ThepartnershipbetweentheschoolsofpublichealthandNIHisanextremelynaturalone,notonlyfromabusinessstandpoint,butalsoaphilosophicalone,becauseofourmutualcommitmenttotheoverallpublichealth,”saidStephens.“Still,mostpeopleinmycommunityagreethatthesupportforbiomedicalresearchhasneverbeenundergreaterstressthanitisnowandit’lltakeallofusworkingtogethertomaintainthelevelofexcellencewe’vecometoexpectofthatcommitment.”

(IanThomasisapublicaffairsspecialistwiththeNIEHSOfficeofCommunicationsandPublicLiaison,andaregularcontributortotheEnvironmentalFactor.)

Return to Table of Contents

NIEHS Legislative Liaison Mary Gant, a veteran on the Washington scene, hosted Stephen’s visit and talk. (Photo courtesy of Jennifer Weinberg)

9

Prins honored by University of Illinois at Chicago By Eddy Ball

NIEHSgranteeGailPrins,Ph.D.,isoneofthreeresearcherswhoarewinnersof2011ResearcheroftheYearawardsattheUniversityofIllinoisatChicago(UIC).Theseawardsrecognizetheeffortsandcommitmentofresearcherswhohavedemonstratedoutstandingresearchachievementstoadvancetheknowledgeintheirfieldofexpertise.

TheUICOfficeoftheViceChancellorforResearchhonoredPrinsforherinternationallyrecognizedleadershipinprostatecancerresearch,particularlyherresearchontheeffectsofearlyexposuretobisphenolA(BPA)onprostatedevelopmentandriskofprostatecancer,whichhasadvancedthefieldanddirectlyinfluencedpublicpolicy.Prinsandherco-winnerswilleachreceiveaone-time$5,000prizeandacommemorativeawardataceremonyFeb.8inChicago.

Prinsisaprofessorofurologyandphysiology,aswellasdirectoroftheAndrologyLaboratoryatUIC.HerlabisaccreditedundertheClinicalLaboratoryImprovementAmendmentsandCAP/COLAcertified.PrinsisareproductivebiologistandalongtimeNIEHSgrantee.ShecurrentlyhasfundingfromthreeNIEHSgrantstoexamineprostatecarcinogenesistriggeredbyearlyandchronicexposurestoestrogensandendocrinedisruptingchemicals.

PrinsispartoftheNIEHSBPAconsortiumledbyJerryHeindel,Ph.D.,aprogramadministratorintheextramuraldivisionatNIEHS.“Gailrichlydeservesthisrecognition,”Heindelsaidoftheaward.“Herresearchisuncoveringmechanismsresponsibleforprostatecancerthatarerootedinexposuretoendocrinedisruptingcompoundswithincriticalwindowsofsusceptibilityduringdevelopment,whichwillhelpinformstrategiesforprimaryandsecondaryprevention.”

Accordingtoitsawardwebsite,UICisoneofonly108CarnegieclassifiedresearchuniversitieswithveryhighresearchactivityintheU.S.,andoneofbutfourIllinoisuniversitiestobehonoredwiththisdistinction.AlongwithPrins,UIChonoredphysicistCeciliaGerber,Ph.D.,forherleadingroleinthediscoveryofthesingletopquarkproductionbyaninternationalcollaborationatFermilab,andgerontologistSusanHughes,Ph.D.,forscholarshipthathassignificantlycontributedtounderstandingtheroleofexerciseinthelivesofolderadults.

Return to Table of Contents

NIEHS Public Interest Partner honoredMaryLamielle,executivedirectoroftheNationalCenterforEnvironmentalHealthStrategies,isoneof14CamdenCounty,N.J.,residentschosentoreceivethe2012CamdenCountyFreedomMedal,honoringthelegacyofMartinLutherKingJr.,fortheirunselfishcontributionstoimprovingtheircommunity.

LamielleisamemberoftheNIEHSPublicInterestPartners,whosemembershiprepresentsdiversegroups,includingdisease,disability,andenvironmentaleducationandadvocacyorganizations.ThePartnersmeet

Prins is shown during a 2010 presentation at NIEHS. She also presented at the BPA grantee meeting in January. (Photo courtesy of Steve McCaw)

10

periodicallywiththeNIEHS/NTPdirectorandstafftoprovideinputandimprovecommunicationwithcommunitiesandorganizationsdirectlyaffectedbytheInstitute’smissionandresearch.

Forthreedecades,Lamiellehasdedicatedherselftopromotingthepublichealthandimprovingthelivesofpeoplesickordisabledbyenvironmentalexposures.Shehasservedondozensoffederalandstateadvisorycommittees,includingtherecentlyconcludedCentersforDiseaseControlandPreventionNationalConversationonPublicHealthandChemicalExposures,andtheU.S.DepartmentofHousingandUrbanDevelopment’sConsortiumofCitizenswithDisabilitiesHousingTaskForce.

ShewasnominatedfortheFreedomMedalbyDianeReibel,Ph.D.,researchassociateatThomasJeffersonUniversityJeffersonMedicalCollegeinPhiladelphia.Inhernomination,Reibelwrote,“ImetMarytwenty-fiveyearsagowhenIbecameillfromchemicalsinmyresearchlaboratory.Mary’sknowledge,support,andadvocacywerealifesaverforme.WhatMarydidforme,shehasdoneforthousandsofpeopleacrossNewJerseyandtensofthousandsnationwide.”

Lamiellewasrecentlyhonoredwiththe2011NewJerseyStateGovernor’sJeffersonAwardsforEnvironmentalStewardshipanda2010U.S.EnvironmentalProtectionAgencyRegion2EnvironmentalQualityAward,thehighestcivilianawardgivenbytheEPA.

TheCamdenCountyFreedomMedalwascreatedin2001tohonortheidealsindicativeoftheslaincivilrightsleader.AccordingtoCamdenCountyFreeholderDirectorLouisCappelliJr.,“ThisisCamdenCounty’swayofhonoringDr.King.”

MedalswerepresentedduringaneveningceremonyJan.20attheCamdenCountyBoathouseatCooperRiver.

Return to Table of Contents

Superfund promotes safe drinking water at Agua Fria Festival By Rebecca Wilson

TheNIEHS-fundedUniversityofArizonaSuperfundResearchProgram(UASRP)madeitsthirdappearanceattheAguaFriaFestivallastfallinDewey-Humboldt,Ariz.ResearchersandCommunityEngagementCoreleaderswereonhandtosharehealthandexposureinformationonarsenicandleadwiththethousandsofpeoplewhoturnedoutforthetwo-dayevent.

Dewey-Humboldtisasmallfarmingcommunitylocatedapproximately80milesnorthofPhoenix,Ariz.It’ssurroundedbyitsminingheritage,withtheabandonedIronKingMineandHumboldtSmeltersituatedontheoppositeedgesoftown.Thefacilities,inoperationfromtheearly1900’suntilthelate1960’s,werecombinedintoasingleSuperfundsitein2008.AccordingtotheU.S.EnvironmentalProtectionAgencySuperfundreport,arsenic,lead,andsulfatearetheprimarycontaminants,whichpermeategroundandsurfacewater,soil,andtheair.

Camden County Freedom Medal winner Mary Lamielle (Photo courtesy of Mary Lamielle)

11

Public health outreachTheUASRPhadseveraldocumentsavailableinbothEnglishandSpanishtosharewithvisitors,includinginformationaboutarsenicandlead,miningresidueortailings,andhowriskassessmentsareconducted.“Eventslikethisaregreatforreachingouttothepublic,”saidSarahWilkinson,Ph.D.,researchtranslationcoordinatorfortheUASRP.“Wearestartingtohaveinformationaleventsinthearea,butatthisfestivalweareabletoreachthepeoplewhodon’tattendthose.”

WilkinsonsaidthatthemostpopulardocumentstheUASRPdistributedwerebookletsinformingreadersaboutwaterqualityinArizonaandadvisingthemonwaterqualitytestingforhouseholdwells.Manyarearesidentsrelyonprivatewellsfortheirwaterand,Wilkinsonsaid,“SomemaynotevenrealizethattheyhaveaSuperfundsiteintheirtown.”

SRP projects in the areaTheUASRPiscurrentlyconductingthreestudiesinthearea,withafourthscheduledtobeginthisyear.ThefirstisledbyRainaMaier,Ph.D.Sheisconductingaphytostabilizationtrialtoassesswhetheraplantcapcanstabilizemetalcontaminantsinminetailings.EricBetterton,Ph.D.,isconductingthesecondproject,usingairsamplerstodeterminewhetherwind-blowndustfromminetailingsitesinthetowncontainmetals.

GraduatestudentMonicaRamirez-Andreottaisleadingthethirdstudy,conductingagreenhousetrialandworkingwithlocalresidentstodeterminethemetalcontentofhomegrownvegetables.Ramirez-Andreottawasthisyear’swinneroftheSRPKarenWetterhahnMemorialAward,andherresearchproject,“Gardenroots,”wasfeaturedintheDecemberissueoftheEnvironmentalFactor(seestory).

Thisyearmarkedthe107thyearthefestivalhasbeenheld,makingitoneoftheoldestinArizona.ParticipantstravelledfromacrossthestateandfromnorthernMexicotoattendtheevent,whichfeaturedparades,musicalacts,races,skillandcraftdemonstrations,andseveralhundredexhibitors.

(RebeccaWilsonisanenvironmentalhealthinformationspecialistwithMDB,Inc.,acontractorfortheNIEHSDivisionofExtramuralResearchandTrainingSRP.)

Return to Table of Contents

SRP researchers Raina Maier, Ph.D., far left, and Todd Camenisch, Ph.D., right, discuss water quality issues with a resident of Dewey-Humboldt, Ariz. (Photo courtesy of UA SRP)

12

Registration is underway for NIEHS and HHS national research conference By Eddy Ball

OrganizersoftheSouthAtlanticNationalResearchConference(SANRC)arecurrentlyacceptingregistrationsforatwo-dayforumMarch21-22attheRaleigh(N.C.)ConventionCenter.Theevent,titled“EngagingtheCommunityforResearchSuccess:WhatScientistsandIRBs[InstitutionalReviewBoards]NeedtoKnow,”isjointlysponsoredbytheNIEHSOfficeofHumanResearchComplianceandtheU.S.DepartmentofHealthandHumanServices(HHS)OfficeforHumanResearchProtections(OHRP).

RegistrationfeesreceivedbyFeb.1are$150.Afterthedeadline,theregistrationfeeis$200.

Theagendacoversarangeoftopicsrelatedtocommunity-engagedresearch,includingstakeholdersandtheirroles,ethicalchallenges,socialandlegalconsiderations,andeffectivecommunication.Theprogramfeaturesplenarysessions,luncheontalks,and14breakoutsessions.Continuingeducationunitswillbeoffered.

Speakersincludemedical,legal,andpublichealthexpertsfromthegovernment,non-profit,andprivatesectors.SeveralNIEHSscientistsandgrantees,includingNIEHS/NTPDirectorLindaBirnbaum,Ph.D.,arescheduledtospeakorleadbreakoutsessions.

SANRCco-sponsorsincludeDukeUniversitySchoolofMedicine,EastCarolinaUniversity,EmoryUniversity,FHI360,HowardUniversity,MedicalUniversityofSouthCarolina,NorthCarolinaCentralUniversity,RTIInternational,UniversityofNorthCarolinaatChapelHill,UniversityofVirginia,U.S.EnvironmentalProtectionAgency,WakeForestUniversitySchoolofMedicine,andAppliedHumanResearchProtections,Inc.

Scholarshipsareavailableforstudentsandpostdocs.

Foradditionalinformationabouttheconferenceandscholarships,contact:JoanPackenham,Ph.D.Director,NIEHSOfficeofHumanResearchCompliancePhone:919-541-9844Email:2012sancconference@mail.nih.gov

Return to Table of Contents

NTP toxicologist Kamal Abdo remembered By Eddy Ball

NIEHS/NTPcolleaguesweresaddenedbythedeathofKamalAbdo,Ph.D.,Dec.22,2011inBahama,N.C.atage73.AbdoissurvivedbyhiswidowJeanette,threesons,threedaughters,ninegrandchildren,andmanyniecesandnephews.

Writingofhislongtimefriendandcolleague,NIEHStoxicologistJamesHuff,Ph.D.,toldJeanetteAbdo,“Theworld,science,andpublichealthandhumanitarianism,especially,havelostagreatman.”AnotherofAbdo’sassociates,retiredNTPtoxicologistRonMelnick,Ph.D.,said,“KamalwasaverydearfriendandIwillalwaysthinkofhimasacheerfulindividualwhocaredaboutpeopleandworkedtopromoteahealthyenvironmentforeveryone.”

13

“Kamal’sdeathisalosstothetoxicologycommunity,”saidNIEHS/NTPDirectorLindaBirnbaum,Ph.D.“Hecombinedhisgenuineconcernaboutpeopleandtheirpublichealthwithscientificrigortohelpmakearealdifferenceinthequalityoftheirlives.”

Testing environmental chemicals for carcinogenicityOneofthefirstNIEHSscientiststojoinNTP,Abdowasa25-yearveteranoftheInstitutewhoretiredinMarch2005afteracareeroverseeingcontractstudiesonthetoxicityandcarcinogenicityofhigh-profilechemicalsandcompounds,suchashexavalentchromium,rotenone,andnaphthalene.ThroughhisworkatNIEHS/NTP,AbdowasoneofseveralresearcherswhosescientificrigorandintegrityhelpedtheNTPtwo-yearrodentstudyemergeasthegoldstandardoftoxicologytestingandcontributetoreducingcancerrisksfromenvironmentalexposures.

AbdowastheNIEHSoriginatorlong-termdirectoroftheProjectontheSafeandEffectiveUseofPesticidesthatwasrequestedbytheU.S.StateDepartmenttocoordinateaMiddleEastregionalprogramtoreduceexposurestopesticidesbyfarmers,farmfamilies,andotheragriculturalworkersinEgypt,Jordan,Israel,andthePalestineTerritoriesaspartoftheMultilateralMiddleEastPeaceProcess.ThisprojectinvolvedthejointeffortofscientistsinMiddleEastnationsworkingtogethertoaddresstheirregionalagricultural,health,andenvironmentalproblems.

MemorialsAdevoutMuslimbornAug.28,1938inShuwaikah,Palestine,AbdowasmemorializedwithaserviceatJamaatIbadAr-Rahman,aSunniMosqueinDurham,N.C.,beforehewaslaidtorestatUnionGroveUnitedMethodistChurchinBahama.Abdo’sfamilyrequestedthatinlieuofflowers,contributionsbemadeinhishonortoJamaatIbadAr-Rahman,3034FayettevilleSt.,Durham,N.C.27707orUnionGroveUnitedMethodistChurch,8009BunnyRoad,Rougemont,N.C.27572.

FriendsandcolleaguesfromNIEHS/NTPgatheredforasecondmemorialJan.14atUnionGroveUnitedMethodistChurchincelebrationofAbdo’slife.

Return to Table of Contents

Shown at an NTP Board of Scientific Counselors meeting circa 2000, Abdo was known for his sense of humor and endearing smile. (Photo courtesy of Steve McCaw)

14

Science NotebookMinisymposium brings epigenetic experts to NIEHS By Ashley Godfrey

SponsoredbytheDivisionofExtramuralResearchandTraining(DERT),aminisymposiumJan.10atNIEHSshowcasedscientificpresentationsbymanyleadersinthefieldofepigenetics,chromatinbiology,development,anddisease.SpeakersfromtheNIEHSintramuralandextramuralcommunitieswereonhandtodiscussfindingsfromtheirlatestresearch(seetextbox).

ThedaylongsymposiumwaspartoftheDERTKeystoneScienceLectureSeminarSeries.DERTscientistsAstridHaugen,LisaChadwick,Ph.D.,andFrederickTyson,Ph.D.,hostedtheevent’s10scientificpresentations.

“NIEHShasmadeacommitmenttotranslatingbasicfundamentalresearchandreallyputtingittoworkforthebenefitofpublichealthanddiseaseprevention,”saidDeputyDirectorRickWoychik,Ph.D.,inhiswelcomingremarks.

WoychikexplainedthesignificanceofepigeneticresearchinrelationtotheInstitute’smission.Environmentalexposureisincreasinglylinkedtochangesinepigeneticprofilesandsubsequentlywithdisease.“Oneareaweareveryinterestedinisbetterunderstandingwhyitisthat,whenyoutaketwodifferentindividualsandyouexposethemtoexactlythesameenvironment,therearedifferentphenotypicoutcomesorhealthoutcomes,”Woychiktoldthenear-capacityaudience.

Epigenetics an emerging frontier in scienceEpigeneticsreferstoheritablechangesintheregulationofgeneactivityandexpressionthatareindependentofanychangeinthegenesequenceitself.Epigeneticmechanisms,suchasDNAmethylationandhistonetailmodifications,canserveastheinterfacebetweenthegenomeandtheenvironment.Whileepigeneticsreferstothestudyofsinglegenesorsetsofgenes,epigenomicsreferstoamoreglobalanalysisofepigeneticchangesacrosstheentiregenome.

Woychik gave the welcome remarks and introduction for the symposium. He ended by emphasizing, “The epigenome serves as an interface between the genome and the environment in complex human disease.” (Photo courtesy of Steve McCaw)

Jack Taylor, M.D., Ph.D., head of the NIEHS Molecular and Genetic Epidemiology Group diligently takes notes during the first session. Taylor said he was interested in the data Stamatoyannopoulos presented, showing that most of the common disease associated variants in the human gene sequence are concentrated in DNA regulatory regions. (Photo courtesy of Steve McCaw)

Linked video:

Watch as Woychik describes the NIEHS commitment to epigenetics research (10:29)

(Launches in new window)

Download Media Player: Quicktime

15

Thedaybeforethesymposium,severalofthespeakersparticipatedinasteeringcommitteeadvisorymeetingfortheNIHRoadmapEpigenomicsMappingConsortium.NIEHSandtheNationalInstituteonDrugAbuseareadministrativeleadsfortheNIHCommonFundeffort.Thegoaloftheconsortiumistoproduceapublicresourceofhumanepigenomicdatatohelpjumpstartbasicbiologyanddisease-orientedresearch.Theconsortiumplanstocontinuetobuildapublicallyaccessiblecollectionofreferenceepigenomes,fromawiderangeofspeciesandhumantissuetypes,whichwillprovidetheframeworkforabroadarrayoffuturestudies.

“Thesteeringcommitteeactuallymetyesterdayandtheyreportedthattherearenow39differentreferencegenomesthatarecompleted,”reportedWoychik,referringtodatanowpostedonline.

Bringing together diverse epigenetic research interestsThesymposiumwasdividedintothreesessions,eachwithadifferentfocusonepigeneticresearch.Thefirstfocusedonepigenomicsanddisease.Thethreespeakersdemonstratedhowepigenomicscanbeusedtounderstandtheepigeneticmechanismsthatcontributetocelltypespecificityandalsotohumandisease.

Inthesecondsession,theemphasiswasonchromatinandtranscription.Thefourspeakerssoughttoanswerthequestionofhowepigeneticmodificationsworkincombination,bothwitheachotherandwithtranscriptionfactorsandotherproteinstodirectgeneexpression.

Finally,thethirdsessionexploredtheroleofepigeneticmechanismsindevelopmentanddisease.Thethreespeakersshowcasedexamplesofthecriticalroleepigeneticsplaysinnormalmammaliandevelopmentthroughdifferentprocesses,includingmaintainingstemcellpluripotency,genomicimprinting,andBcellactivationanddifferentiation.

Translating research into treatment and preventionInherclosingcomments,GwenCollman,Ph.D.,DERTdirector,focusedontheenormousopportunityepigeneticsresearchoffersasaprotectiveandpreventivestrategy.Collmanemphasizedthatthisresearchcouldbeusednotonlytounderstandthecausesofhumandisease,butalsotocreatestrategiesandinterventionsthatwillhelpkeeppopulationsandindividualshealthyandstrong.

“Thereisalottodointhisfieldofepigenetics,andweareonlyatthebeginning,”concludedCollman.“Ihopethetake-homemessageistostaythecourseandhelpususethetoolsandtechnologyandknowledgewehavenow,tobeabletoprotectourhealthinthefuture.”

Ren and his group used genome-wide mapping of parent of origin specific DNA methylation in mouse strains to discover 24 novel methylated regions, with 9 of those outside of any previously known imprinted regions in the genome. (Photo courtesy of Steve McCaw)

Adelman, right, waited for her chance to describe her group’s research on paused polymerase and chromatin architecture. (Photo courtesy of Steve McCaw)

16

Members of the Wade lab were on hand, as many of the leaders in the field of epigenetics, including their own group leader, presented their work. Shown, left to right, are Hrisavgi Kondilis-Mangum, Ph.D., and Lai. (Photo courtesy of Steve McCaw)

Shown, right to left, Tyson joined Kellis and Bartolomei in the audience. Kellis presented his group’s work on the interpretation of the genomics and epigenomics of human disease variants during the morning session, while Bartolomei presented her group’s work on the epigenetic regulation of genomic imprinting during the last session in the afternoon. (Photo courtesy of Steve McCaw)

Wade rounded out the minisymposium with the last presentation of the day. Research from his group has shown that two different types of B cells, naive and memory, have closely related gene expression profiles, but have distinct DNA methylation signatures. (Photo courtesy of Steve McCaw)

Biostatistician Raja Jothi, Ph.D., head of the NIEHS Systems Biology Group, was on hand for the symposia. Jothi’s group is also interested in understanding how transcription regulators and epigenetic modifications control gene expression programs during cellular development and differentiation. (Photo courtesy of Steve McCaw)

Archer presented data from his lab on the molecular mechanisms of hormone-mediated chromatin remodeling. He explained that most of this work was done by Kevin Trotter, a biologist in his group. (Photo courtesy of Steve McCaw)

Bartolomei began her presentation by saying how much she enjoyed being part of the NIH Roadmap Epigenomics Mapping Consortium External Scientific Panel. (Photo courtesy of Steve McCaw)

17

Epigenetics research highlighted by the keystone minisymposium

Session I — Epigenomics and Disease• “Epigenomiccontributionstocellidentityinthehumanbreast,”byMartinHirst,Ph.D.,oftheUniversityofBritishColumbia.WorkingcloselywithcollaboratorswithintheNIHRoadmapEpigenomicsproject,HirstandhisteamhaveundertakenacomprehensivestudyofsequencingbasedmethodologiesforDNAmethylationprofilingofnormalhumanmammaryepithelialcells.

• “WidespreadvariationinregulatoryDNAassociatedwithcommonhumandisease,”byJohnStamatoyannopoulos,M.D.,oftheUniversityofWashington.Stamatoyannopoulosandhisresearchteamhaveusedtheapplicationofnovelmolecularandcomputationaltechnologiestoreadeukaryoticregulatorygenomesandepigenomes,withthegoalofpredictingthefunctionalconsequencesofnon-codinghumangeneticvariation,especiallyinrelationtocommonhumandisease.

• “Comparativeandepigenomicsignaturesforinterpretingdiseasevariants,”byManolisKellis,Ph.D.,oftheMassachusettsInstituteofTechnology.Kellisandhisgrouphavedevelopednewalgorithmsandmachinelearningtechniquesthatcanhelpresearcherswiththeinterpretationofthegenomicsandepigenomicsofhumandiseasevariants.

Session II — Chromatin and Transcription• “Decodingthegenome’ssecondcode,”byBingRen,Ph.D.,oftheUniversityofCalifornia,SanDiego.Renandhislabhavedevelopedahighthroughputmethodforgenome-widemappingofparentoforiginspecificDNAmethylation,andhavealsousedthismethodtocharacterizetheepigenomiclandscapeofhumanembryonicstemcelldifferentiation.

• “Potentiatingsignal-responsivetranscription:adynamicdancebetweenpausedpolymeraseandchromatin,”byKarenAdelman,Ph.D.,headoftheNIEHSTranscriptionalResponsestotheEnvironmentGroup.Adelmanandherresearchgrouphaveusedcutting-edgegenomictechniquestodeterminetheglobaldistributionofpromoter-proximallypausedpolymeraseandhavefoundthatPolIIpausingplaysacriticalroleinestablishinganaccessiblechromatinarchitecturearoundgenepromotersthatfacilitatesfurtherorfuturegeneactivation.

• “Nuclearreceptorsmodulatechromatintoregulatetranscription,”byTrevorArcher,Ph.D.,chiefoftheNIEHSLaboratoryofMolecularCarcinogenesis.Archerandhisgroupareusingcancercellculturemodelsandbiochemicalassaystounderstandthemolecularmechanismsofhormone-mediatedchromatinremodelingtoallowgenetranscription.

• “Chromatinandtranscriptionfactordynamicsindevelopmentanddisease,”byJasonLieb,Ph.D.,oftheUniversityofNorthCarolinaatChapelHill.Liebandapostdoctoralstudent,DanMcKay,Ph.D.,areusingthemodelorganismDrosophilaandatechniquedevelopedinhislabtomapwheretranscriptionregulatoryelementsareinthegenomeduringearlydevelopmentandalsoduringtheformationofdifferentbodystructures.

(continued on next page)

18

(AshleyGodfrey,Ph.D.,isapostdoctoralfellowintheMolecularandGeneticEpidemiologyGroupintheNIEHSLaboratoryofMolecularCarcinogenesis.)

Return to Table of Contents

BPA researchers meet for updates and assessment By Thaddeus Schug

NIEHSgranteesandgovernmentscientistsgatheredJan.17-19atNIEHStoupdatetheirresearcheffortsonbisphenolA(BPA).ThepurposeofthemeetingwastohighlightnewfindingsfromtheresearchprojectsfundedbytheAmericanRecoveryandReinvestmentAct(ARRA)andfortheBPAconsortiumtodevelopacomprehensivedisease-specificassessmentofpossiblehumanhealtheffectsduetoBPAexposure.

NIEHS/NTPDirectorLindaBirnbaum,Ph.D.,welcomedmorethan60attendeestothemeetinganddescribedtheInstitute’sextensivesupportforBPAresearch.

Epigenetics research highlighted by the keystone minisymposium (cont’d)

Session III — Epigenetics and Development• “DNAmethylationdynamicsindevelopment,”byAlexMeissner,Ph.D.,ofHarvardUniversityandtheBroadInstitute.Meissnerandhisresearchgrouphavedevelopedahigh-throughputbisulfitesequencingtechnologyforDNAmethylationanalysisandhaveusedthistoaddressquestionsaboutthetransmissionofepigeneticmarksandalsotoidentifyepigeneticchangesinvolvedinreprogrammingandmaintainingcellularstates.

• “Epigeneticregulationofgenomicimprinting,”byMarisaS.Bartolomei,Ph.D.,oftheUniversityofPennsylvania.Bartolomeiandherlabareusingamousemodelsystemtounderstandthebiologybehindtheepigeneticregulationofgenomicimprintingandhavefurthertranslatedthosefindingstoahumandiseasemodelpossiblyregulatedbysimilarepigeneticmechanisms.

• “EpigeneticreprogrammingduringBlymphocyteactivationanddifferentiation,”byPaulWade,Ph.D.,headoftheNIEHSEukaryoticTranscriptionalRegulationGroup.Wadeandapostdoctoralfellowinhislab,AnneLai,Ph.D.,havebeenusingsurgicallyremovedtonsilcellstostudyDNAmethylationinfourdifferentpopulationsofBcellsandareusingthismodeltostudythepathwayofactivationandultimatedifferentiationofthesecells.

Birnbaum, like Heindel and others at the meeting, has ridden the growing wave of BPA research since the Chapel Hill meeting in 2006 and the consensus statement published the following year. (Photo courtesy of Steve McCaw)

19

“NIEHShasinvestedheavilyinresearchrelatedtoBPAandotherendocrinedisruptingchemicals,”Birnbaumsaid.“Recently,NIEHSawardedtenBPAGrandOpportunityandthreeChallengegrants,andaltogetherwefunded39projectsstudyingthehealtheffectsandrisksassociatedwithBPAexposure.”

Theconsortium,asitnowexists,hasmobilizedthethreeresearchdivisionsatNIEHS/NTP,engagedtheinteragencypredictivetoxicologypartnershipTox21,andiscurrentlysupportingadvancedanimalandhumanclinicalresearch.

Taking aim at endocrine disruptionBPAisachemicalusedtoproducepolycarbonateplasticsandepoxyresins.Polycarbonateplasticshavemanyapplications,includinguseinsomefoodanddrinkpackaging,waterandbabybottles,andotherproducts.Epoxyresinsareusedtocoatmetalproductssuchasfoodcans,bottletops,andwatersupplypipes.BPAcanalsobefoundincertainthermalpaperproducts,includingsomecashregisterandATMreceipts.

HumansareexposedtoBPAwhenthechemicalleachesfromtheseproducts.SomeanimalstudieshaveshownalinkbetweenBPAexposureandavarietyofphysiologicalproblems,suchasinfertility,weightgain,behavioralchanges,earlyonsetpuberty,prostateandmammaryglandcancer,anddiabetes.

An integrated research initiativeAlongwithupdatesonBPAbiomonitoringstudiesandthenewNIEHS/NTP/U.S.FoodandDrugAdministrationconsortium,themeetingwasorganizedintoresearchgroups,withpresentationsandreviewupdatesfromtheirrespectiveareas,aspartofthecoordinatedefforttoadvanceBPAresearch.

• PharmacokineticsGroupResearchUpdate,byWadeWelshons,Ph.D.,andFrederickvomSaal,Ph.D.,oftheUniversityofMissouri

• ImmunityGroupResearchUpdate,byPaigeLawrence,Ph.D.,oftheUniversityofRochester,andRobinWhyatt,Dr.P.H.,ofColumbiaUniversity

Heindel pondered the update on pharmacokinetics. Seated behind him, right, is his colleague Newbold, a fellow veteran specialist in endocrine disruption research at NIEHS. (Photo courtesy of Steve McCaw)

Two of the major players in the consortium were on hand for the discussion — Gwen Collman, Ph.D., left, director of the NIEHS Division of Extramural Research and Training, and John Bucher, Ph.D., associate director of NTP and director of the NIEHS Division of the National Toxicology Program.. (Photo courtesy of Steve McCaw)

Linked video:

Watch a video of Birnbaum’s opening remarks at the BPA minisymposium, which concluding the meeting (09:43)

(Launches in new window)

Download Media Player: Quicktime

20

• CancerGroupResearchUpdate,byRuthKeri,Ph.D.,ofCaseWesternReserveUniversity

• ReproductionGroupReviewUpdate,byShellyEhrlich,M.D.,ofHarvardUniversity;JodiFlaws,Ph.D.,oftheUniversityofIllinois;WilliamRicke,Ph.D.,oftheUniversityofWisconsin;andRethaNewboldofNIEHS

• NeurobehaviorGroupReviewUpdate,byJosephBraun,Ph.D.,ofHarvardUniversity,andHeatherPatisaul,Ph.D.,ofNorthCarolinaStateUniversity

• LowDoseGroupResearchUpdate,byLauraVandenberg,Ph.D.,ofTuftsUniversity

• Metabolism,DiabetesandObesityGroupUpdate,byKimHarley,Ph.D.,oftheUniversityofCalifornia,Berkeley;andRichardStahlhut,M.D.,andBernardWeiss,Ph.D.,oftheUniversityofRochester

Looking aheadJerryHeindel,Ph.D.,themeetingorganizerandhealthscientistadministratorwhooverseesmanyoftheNIEHSBPAgrantssaid,“ThismeetingshowcasedsomeoftheoutstandingscientificprogresswehavemadeinBPAresearch,duetothecollaborativeeffortsoftheARRAgranteesandotherBPAresearchers.”Inadditiontopresentationsduringthe21/2daygranteeportionofthemeeting,therewasapublicminisymposiumheldontheafternoonofthefinalday(seetextbox).

ThemeetingmarkedtheendofARRAsupportforBPAresearch,butworkremainsformembersoftheconsortium.“EventhoughtheofficialARRAfundingperiodhasended,thereisagreatdealofdataforthcoming,andthisconsortiumofscientistsplanstoorganizethefindingsinaseriesofcomprehensivereviewslaterthisyear,”Heindelobserved.“WehopethatthisorganizedeffortwillhelpsolvesomeoftheissuesregardingthehealthandsafetyimplicationsofBPAexposure.”

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

Grantee Gail Prins, Ph.D., right, joined in the discussion of biomonitoring studies. Prins, who studies BPA’s effects on prostate cancer, was honored for her NIEHS-funded work by the University of Illinois at Chicago, where she teaches and conducts research. (Photo courtesy of Steve McCaw)

Rissman pointed to data from her studies projected on the screen behind her. (Photo courtesy of Steve McCaw)

NIEHS lead researcher Ken Korach, Ph.D., standing, was one of several representatives at the meeting from the Institute’s Division of Intramural Research. Korach is chief of the Laboratory of Reproductive and Developmental Toxicology. (Photo courtesy of Steve McCaw)

21

Return to Table of Contents

Women’s health takes the spotlight By Melissa Kerr

NIEHSwelcomedleadingscientiststoameetingJan.20tolaythefoundationforaconsortiumfocusedonadvancingresearchinwomen’sreproductivehealth.Theall-dayeventwasco-hostedbyJerryHeindel,Ph.D.,aprogramadministratorintheDivisionofExtramuralResearchandTraining(DERT)andKarinRuss,nationalcoordinatorofTheCollaborativeonHealthandtheEnvironment(CHE)450-memberFertilityandReproductiveHealthworkinggroupandthemeeting’sfacilitator.

DERTDirectorGwenCollman,Ph.D.,welcomedtheattendeesandopenedthemeetingwithapushforscientiststocontinuethinkingofthewomenforwhomtheresearchcouldprovideanswers.“Women’s

BPA minisymposiumWiththeirplanningandconsensus-buildingbehindthem,attendeesjoinedothersfromNIEHSandNTPJan.19foranafternoonofsciencetalks.

• Introduction and Overview,byBirnbaum,whosurveyedthesubstantialinvestmentbyNIEHS/NTPinunderstandinghowBPAandendocrinedisruptionimpacthumanhealth.Birnbaum,alongwithHeindelandseveralothersatthemeeting,waspartofthehistoricstateofthesciencemeetingheldinChapelHill,N.C.,Nov.28-30,2006(seestory)thatsparkedavirtualexplosionofresearchandpublichealthdiscourseonBPA.

• Developmental Exposure to BPA Affects Multiple Organ Systems,byCatherineVandeVoort,Ph.D.,oftheUniversityofCalifornia,Davis.VandeVoortreportedonfindingsofsignificantchangesinreproductivetract,mammarygland,lung,heart,nervoussystem,andbrainwithBPAexposures.Hergroup’sresearchissheddinglightontheissueofcross-speciesextrapolationintermsofsimilarityandspecies-specificoutcomes.

• BPA and Children’s Growth and Neurodevelopment: Results from the CHAMACOS Cohort Study,byHarley,whoreportedonhergroup’sfindingsinthelongitudinalbirthcohortstudyofchildrenof601pregnantwomenintheSalinasValley,Calif.area.HergroupislookingforassociationsbetweenBPAandabroadrangeofdata,includingquestionnaireresponses,physicalexams,biologicalsamples,teacherreports,andintelligencetestresults.

• Developmental Exposure to BPA, Social Behavior and Gene Expression Across Generations,byEmilieRissman,Ph.D.,oftheUniversityofVirginia.FundedbyAutismSpeaks,RissmanisusingamousemodeltostudythetransgenerationaleffectsofBPAonepigeneticchangesthatshapebehavior.RissmanistestingarangeofbehaviorsandlookingateffectsonbrainmorphologyandbiomarkersassociatedwithpatternsofBPAexposureandnurturing.

• InVivo and inVitro Cardiovascular Effects of BPA,byHong-ShengWang,Ph.D.,oftheUniversityofCincinnati.Wang,whobeganbyremindinghisaudiencethattheleadingcauseofdeathinwomeniscardiovasculardisease,reportedresultsofhisstudiesinaratmodel,wherehefoundassociationsbetweenBPAexposureandfactorsthattriggerorintensifycardiaceventsinwomen,suchasarrhythmogenicspontaneousexcitationandcalciumcyclingabnormalities.

22

reproductivehealthisahugeareacoveringmanydiseasesanddysfunctionsoverthelifetime,andwehavealotofworktodo,”shesaid.“Ibelievethatwhatyouhavestartedhereisanimportantstepintherightdirection.”

Heindelopenedthedaybychallengingattendeestoanswerthequestion,“How[canwe]improveourinteractionsandtheimpactonthefield,andgetthedataouttheretomakeadifference?”Answersrangedfromsuggestionsaboutsharingsamplesandtechnologytoraisingpublicawarenessandeducatinglegislators.

Science on the runAlongwithtwokeynotescientificsessions,theagendaincludedatightscheduleofresearchsummariesfrom15speakers,alleagertodiscusstheirresearchinasmuchdetailaspossiblewithinthetenminutesallottedandconnectwithothers(seetextbox).Withspeakerslimitedtothreeslides,Russcomparedtheformattospeeddating,intendedtointroduceresearchersandpiquethescientists’interestinformingpartnerships.

Themorning’skeynotespeaker,veterangranteeCherylWalker,Ph.D.,ofTexasA&MUniversity,describedherteam’sworkontheinteractionofenvironmentalestrogenexposurewiththeepigenome.“Weareinterestedinhowenvironmentalcompoundsareregulatingthereaders,thewriters,andtheerasersoftheepigeneticprogram,”sheexplained.Herteamisusinganewlydevelopedmicroarraytestingprotocoltoisolatekeyhistonemethylmarksthatmaybecausinganelevatedriskofdiseaselaterinlife.

Theafternoon’skeynotesessionfeaturedJohnMcLachlan,Ph.D.,whoservedasNIEHSscientificdirectorpriortomovingtoTulaneUniversityin1995.McLachlandiscussedtheconceptofdevelopmentalestrogenizationsyndromeandaskedtheaudiencetoquestionhowthestudyofthissyndromeshouldproceed.Despiteextensiveresearchonthetopic,hesaid,“therearehugegapsinmechanisticdatainhumans.”

Outcomes of the dayHeindeljoinedMcLachlaninananimateddiscussionofhowthegroupcouldengagethegeneralpublicandpolicy-makers,aswellasthebroaderscientificcommunity.Women’sreproductivehealthneedssomethingtomakeitresonate,suggestedMcLachlan,thewayBhopalandtheAIDSepidemicmovedpeopletogetinvolvedandtakeaction.

Collman opened the meeting with a personal story about why research in women’s reproductive health is important. (Photo courtesy of Steve McCaw)

Russ passed out index cards and asked attendees to articulate their goals for the day and for the consortium in the long term. She was a gracious, but strict, facilitator who kept speakers to their allotted ten minutes. (Photo courtesy of Steve McCaw)

23

RussconcludedthemeetingbydescribingthewayCHEcouldhelpbringtogetherscientiststoshareresearchonvariousenvironmentalfactorsthatcancontributetodisease.Shespokeabouttheimportanceofreachingouttoprofessionalorganizationsandadvocacygroupsbymakingsciencerelevant.“Beingaformerhealthcareprovider,Iamveryinterestedintranslationtoclinicalpractice,”sheexplained.

Reflectingontheday’spresentationsanddiscussions,Russalsosharedsomeoftheencouragingoutcomesofthemeeting.Shenotedthatonescientistaskedforhelpinanalyzingtissueanddata,anotherofferedtosharebiorepositorysamples,andyetanotherofferedtoshareanewarraytestingtechnology.

ThesewerejustafewexamplesthatRusscameacross,butsheseemeddelightedaboutthefuturecontributionsthegroupwillmakeinwomen’sreproductivehealth.“Theseconcreteoutcomesarevery,veryexciting,”shesaid.SheencouragedtheconsortiumtotakeadvantageofCHEresources,tospreadtheirmessageatpublictalksandatmeetingsofclinicalanddiseasesocieties,andtobuildontherelationshipstheyformedatthemeeting.

Holland came to offer the consortium the use of her laboratory’s extensive biorepository, as well as to speak about her work on how exposure to pollutants, including pesticides, may result in epigenetic effects. (Photo courtesy of Steve McCaw)

The presenters• KevinOsteen,Ph.D.,andKaylonBruner-Tran,Ph.D.,ofVanderbiltUniversity

• DavidCrews,Ph.D.,oftheUniversityofTexasatAustin

• AndreaGore,Ph.D.,oftheUniversityofTexasatAustin

• DavidWaxman,Ph.D.,AlexanderSuvorov,Ph.D.,andNicholasLodatoofBostonUniversity

• NinaHolland,Ph.D.,oftheUniversityofCalifornia,Berkeley

• LouisGuilletteJr.,Ph.D.,andSatomiKohno,Ph.D.,oftheMedicalUniversityofSouthCarolina

• AnaSoto,M.D.,ofTuftsUniversity• RitaLoch-CarusoPh.D.,oftheUniversityofMichigan

• ShannaSwan,Ph.D.,oftheMountSinaiSchoolofMedicine

• MichaelBloom,Ph.D.,UniversityatAlbany• VasanthaPadmanabhan,Ph.D.,UniversityofMichigan

• HughTaylor,M.D.,ofYaleUniversity• CarmenWilliams,M.D.,Ph.D.,oftheNIEHSReproductiveMedicineGroup

Walker described her group’s protein domain microarray strategy for identifying modular signaling units as candidates for empirical verification to determine whether phosphorylation makes a difference in estrogen binding. (Photo courtesy of Steve McCaw)

24

(MelissaKerrstudieschemistryatNorthCarolinaCentralUniversity.SheiscurrentlyaninternintheNIEHSOfficeofCommunicationsandPublicLiaison.)

Return to Table of Contents

McLachlan asked the attendees several questions on how to categorize chemicals with estrogenic properties and the potential effects on a woman’s reproductive system, as well as how to raise visibility of environmental estrogens by capitalizing on concerns about obesity. (Photo courtesy of Steve McCaw)

Williams was one of several NIEHS Division of Intramural Research scientists participating in the meeting. She presented recent findings on infertility and altered gene expression following neonatal exposure to DES and genistein in a mouse model. (Photo courtesy of Steve McCaw)

Best known for his Heinz Award-winning work with alligators, Guillette recently moved from the University of Florida to the Medical University of South Carolina, where he will have the opportunity to translate his wildlife work to clinical research with human subjects. (Photo courtesy of Steve McCaw)

The consortium gathered on the lakeside patio at NIEHS. (Photo courtesy of Steve McCaw)

25

Study estimates millions have autoantibodies that target their own tissues By Robin Mackar

AccordingtoanewNIEHS-fundedstudy,morethan32millionpeopleintheU.S.haveautoantibodies—proteinsmadebytheimmunesystemthattargetthebody’stissuesanddefineaconditionknownasautoimmunity.ThefindingsappearonlineintheJan.11issueofthejournalArthritisandRheumatism.

Thefirstnationallyrepresentativesamplelookingattheprevalenceofthemostcommontypeofautoantibody,knownasantinuclearantibodies(ANA),foundthatthefrequencyofANAishighestamongwomen,olderindividuals,andAfrican-Americans.ThestudywasconductedbyNIEHS/NTPscientists,incollaborationwithresearchersattheUniversityofFlorida.

EarlierstudieshaveshownthatANAcanactuallydevelopmanyyearsbeforetheclinicalappearanceofautoimmunediseases,suchastype1diabetes,lupus,andrheumatoidarthritis.ANAarefrequentlymeasuredbiomarkersfordetectingautoimmunediseases,butthepresenceofautoantibodiesdoesnotnecessarilymeanapersonwillgetanautoimmunedisease.Otherfactors,includingdrugs,cancer,andinfections,arealsoknowntocauseautoantibodiesinsomepeople.

New estimate based on large data set“PreviousestimatesofANAprevalencehavevariedwidelyandwereconductedinsmallstudiesnotrepresentativeofthegeneralpopulation,”saidFrederickMiller,M.D.,Ph.D.,anauthorofthestudyandactingclinicaldirectoratNIEHS.“HavingthislargedatasetthatisrepresentativeofthegeneralU.S.populationandincludesnearly5,000individualsprovidesuswithanaccurateestimateofANAandmayallownewinsightsintotheetiologyofautoimmunediseases.”

Miller,whostudiesthecausesofautoimmunediseases,explainsthatthebody’simmunesystemmakeslargenumbersofproteinscalledantibodiestohelpthebodyfightoffinfections.Insomecases,however,antibodiesareproducedthataredirectedagainstone’sowntissues.Thesearereferredtoasautoantibodies.

Amulti-disciplinaryteamofresearchersevaluatedbloodserumsamplesusingatechniquecalledimmunofluorescencetodetectANAin4,754individualsfromthe1994-2004NationalHealthandNutritionExaminationSurvey(NHANES).TheoverallprevalenceofANAinthepopulationwas13.8percent,andwasfoundtobemodestlyhigherinAfrican-Americanscomparedtowhites.ANAgenerallyincreasedwithageandwerehigherinwomenthaninmen,withthefemaletomaleratiopeakingat40-49yearsofageandthendeclininginolderagegroups.

Along with his duties as acting head of clinical research at NIEHS, Miller also leads the NIEHS Environmental Autoimmunity Group based in Bethesda, Md. (Photo courtesy of Steve McCaw)

NIEHS/NTP Director Birnbaum (Photo courtesy of Steve McCaw)

26

“Thepeakofautoimmunityinfemalescomparedtomalesduringthe40-49agebracketissuggestiveoftheeffectsthatthehormonesestrogenandprogesteronemightbeplayingontheimmunesystem,”saidLindaBirnbaum,Ph.D.,directorofNIEHS/NTPandanauthoronthepaper.

ThepaperalsofoundthattheprevalenceofANAwaslowerinoverweightandobeseindividualsthanpersonsofnormalweight.“Thisfindingisinterestingandsomewhatunexpected,”saidEdwardChan,Ph.D.,anauthoronthestudyandprofessorintheDepartmentofOralBiologyattheUniversityofFlorida.

“Itraisesthelikelihoodthatfattissuescansecreteproteinsthatinhibitpartsoftheimmunesystemandpreventthedevelopmentofautoantibodies,butwewillneedtodomoreresearchtounderstandtherolethatobesitymightplayinthedevelopmentofautoimmunediseases,”saidMinoruSatoh,M.D.,Ph.D.,anotherauthoronthestudyandassociateprofessorofrheumatologyandclinicalimmunologyattheUniversityofFlorida.

TheresearcherssaythepapershouldserveasausefulbaselineforfuturestudieslookingatchangesinANAprevalenceovertimeandthefactorsassociatedwithANAdevelopment.ThepaperisthefirstinaseriesanalyzingthesedatafromtheNHANESdataset,andexploringpossibleenvironmentalassociationswithANA.

Citation:SatohM,ChanEKL,HoLA,RoseKM,ParksCG,CohnRD,JuskoTA,WalkerNJ,GermolecDR,WhittIZ,CrockettPW,PauleyBA,ChanJYF,RossSJ,BirnbaumLS,ZeldinDC,MillerFW.2012.PrevalenceandsociodemographiccorrelatesofantinuclearantibodiesintheUnitedStates.ArthritisandRheumatism;doi:10.1002/art.34380[online2012January11].

(RobinMackaristhenewsdirectorintheNIEHSOfficeofCommunicationsandPublicLiaisonandaregularcontributortotheEnvironmentalFactor.)

Return to Table of Contents

Fry maps arsenic levels across NC By Brant Hamel

WithmorethantwomillionpeopleinNorthCarolinaobtainingtheirdrinkingwaterfromprivatewells,itiscriticalforpublichealthtomonitorthequalityofthegroundwatertheyconsume.AteamofresearchersledbyNIEHSgranteeRebeccaFry,Ph.D.,publishedastudyintheJanuaryissueofthejournalEnvironmentInternationalanalyzinglevelsofarsenic,aknowncarcinogen,inprivatewellwatersystemsacrossthestate.

Co-first author Chan (Photo courtesy of Edward Chan)

Co-first author Satoh (Photo courtesy of Minoru Sato)

27

Fryandhercolleaguesfoundconsistentlyelevatedlevelsofarsenicoveraperiodof11yearsinanumberofcountiesthatbordertheCarolinaslatebelt,includingStanlyandUnioncounties.“OurresultsindicatealargenumberofcontaminatedwellsinNorthCarolinaandsuggestthatongoingmonitoringofwellwatercontaminantsisprudent,”theyconcluded.“Moreover,thesedataprovidenewinformationofspecificareasinNorthCarolinawheretargetedwellmonitoringprogramscanbeusedinacost-effectivemanner.”

A2010OutstandingNewEnvironmentalScientist(ONES)awardee,FryearnedherPh.D.inbiologyatTulaneUniversityandcompletedherpostdoctoralworkattheMassachusettsInstituteofTechnologywithNIEHSgranteeLeonaSamson,Ph.D.,studyingtheeffectsofarsenicinThailandandidentifyingnovelbiomarkersofprenatalarsenicexposure(seestory).AsanassistantprofessorattheUNCGillingsSchoolofGlobalPublicHealth,FryhasexpandedherworktoexaminehowarseniccontaminationinMexicoresultedinalteredepigeneticchanges(DNAmethylation)affectingknowntumorsuppressors(seestory).Forherlateststudy,FrystayedclosetohomeusingnovelGeographicInformationSystemmappingtechniquesandaBayesianstatisticalmodeltoanalyzedatapointsofarseniclevelsdeterminedfromN.C.wellwatersamples.

A significant public health concernArsenicinwaterhasbeenlinkedtocancer,heartdisease,andneurologicaldisorders.Consequently,theEPAregulatesitsleveltoamaximumof10microgramsperliterinpublicdrinkingwater,buttherearenocorrespondingstandardsforprivatewellwater.Fry’steamexaminedmorethan63,000wellmeasurementstakenoveran11-yearperiodbytheN.C.DepartmentofHealthandHumanServices.

Theresearchersusedanovelgeocodingalgorithmtogreatlyincreasethenumberofdatapointsthatcouldbespatiallylocated,givinghermapalevelofdetailthathasnotpreviouslybeenachieved.TheythenappliedaBayesianMaximumEntropyframeworktopredictarseniclevelsinareaswheredatapointshadnotbeencollected.Frynotedthatthemethodologiesdevelopedforthisstudyaregeneralinnatureandcouldbeappliedtoexamineothercontaminantsinfuturestudies.

Onaverage,onlyabouttwopercentofthesampleswereabovetheU.S.EnvironmentalProtectionAgency(EPA)standard,butcertainareashadmoreseverecontamination.Almost20percentofthewellsinStanlyandUnioncountieswereabovetheEPAstandardandonesamplereachedanarseniclevelof806microgramsperliter,or80timesthemaximumlevelsetbytheEPA.

Fry has explored arsenic exposure and its effects among people in Thailand and Mexico. In her most recent study, she and her team took an epidemiological approach to an analysis of the potential public health implications of arsenic in water from private wells in N.C. (Photo courtesy of Rebecca Frye)

County averages are displayed in grayscale, and the number of arsenic analyses in 2009 appears within each county. (Graphic courtesy of Rebecca Fry and Environment International)

28

Accordingtotheresearchers,itisthoughtthatmuchofthearseniccontaminationfoundinthestudyisnaturallyoccurring,duetotheunderlyinggeologyoftheCarolinaslatebeltandknownarsenicdeposits.However,therewerealsoanumberofcountieswithelevatedarseniclevelsthatdonotbordertheCarolinaslatebelt,andadditionalstudieswillbeneededtodeterminethesourceofthecontamination.

Arseniccontaminationisdifficulttomitigate,astherearefewsimpleandcost-effectivetechnologiestodealwiththecontamination.Modificationofwelldepthmaydecreasecontaminationor,iffeasible,householdscanuseanalternativewatersourcetolimitexposure.

Becauseanestimated75,000people,mostwithnoaccesstopublicwatersystems,usewellwaterinthetwocountieswiththehighestlevelsofarseniccontamination,theteamconcluded,increasingwell-monitoringprograms,expandingcommunityeducation,andbiomonitoringofat-riskpopulations,suchaspregnantwomen,shouldbefuturestepsintheseareas.

Citation:SandersAP,MessierKP,SheheeM,RudoK,SerreML,FryRC.2012.ArsenicinNorthCarolina:publichealthimplications.EnvironInt38(1):10-16.

(BrantHamel,Ph.D.,isapostdoctoralfellowintheNIEHSMolecularEndocrinologyGroup.)

Return to Table of Contents

Kumar explores regulation of male germline stem cell niche By Raluca Dumitru

InatalkJan.6atNIEHS,RajendraKumar,Ph.D.,presentednewfindingsonthefundamentalrolethatgonadotropinhormonesplayinmalereproductivehealth,offeringinsightsintothemechanismsresponsibleforinfertilityandhypogonadism,orinsufficientproductionofthemalesexhormone.Withratesofinfertilityontherise,Kumar’sresearchclearlyaddressesasignificantpublichealthconcern.

HostedbyNIEHSleadresearcherHumphreyYao,Ph.D.,Kumar’stalkwaspartoftheLaboratoryofReproductiveandDevelopmentalToxicology(LRDT)SeminarSeries.“Dr.Kumar’sresearchidentifiesnewmolecularmechanismsunderlyingmalegermlinedifferentiation,”Yaosaid.“Componentsofthesemechanismscouldbesusceptibletogeneticmutationsandenvironmentalinsults,whichcouldbethecausesofidiopathicinfertilityinhumans.”

KumarisanassociateprofessorintheDepartmentofMolecularandIntegrativePhysiologyattheUniversityofKansasMedicalCenter.Hisresearchisfocusedtowardsunderstandingthecomplexregulationofthehypothalamus-pituitary-gonadal(HPG)axisbyusinguniquemousemodelsthatreproducehumanreproductivediseases.Hisworkisclinicallyrelevantandwillenhanceunderstandingofthebasicbiologyofthenicheenvironment.Longterm,Kumar’sresearchmaypavethewayforoptimizingconditionsforgermcelltransplantationstudies.

Kumar captivated the audience by showing the role of the microenvironment in setting the stage for proper gametogenesis. (Photo courtesy of Steve McCaw)

29

AsKumarexplained,themalegermlinestemcellnicheiscontrolledbyextrinsic,intrinsic,andepigeneticfactors.Keyeventsinvolvedinfertility,suchasthedevelopmentandproductionofthemaleandfemalegermcellsrequiredtoformanewindividual,orgametogenesis;thesynthesisofsteroidhormones,orsteroidogenesis;andtestisdevelopment,arecarefullyregulatedbytheHPGaxis.Alterationsinthisnetworkcanleadtoabnormalitiesofreproductivetractdevelopmentandmayresultinidiopathicinfertility,aswellastheoccurrenceofgonadotropin-dependenttesticularcancers.

Homing in on follicle stimulating hormone Haploidgametesarisefromatightlycontrolleddifferentiationprocessthatbeginswithprecursorcells,whichundergomultipleroundsofdifferentiationandmaturation.“Themostimportantfactorforapropergametogenesisisthemicroenvironmentorthenichethatisessentialformaintainingspermatogoniaself-renewalcapacityandsubsequentdifferentiation,”Kumartoldtheaudience.“Surprisingly,littleisknownaboutnicheregulationorhowthenicheregulatesthestemcells.”

Inhistalk,Kumarshowedthatfolliclestimulatinghormone(FSH),ahormoneproducedbythepituitarygland,regulatestheproliferationanddifferentiationofSertolicells,amajorcomponentofthegermlinestemcellniche.“Bycontrollingthesomaticcellsindirectly,”Kumarsaid,“gonadotropinhormonessuchasFSHmaintainthemicroenvironmentwithinthereproductivesystem.”IntheabsenceofFSHfromthetestis,themicedisplayedhypogonadism,butwerestillfertile.SothenextquestionwaswhythelossofFSHcausessuchamildphenotype.

Cyclin D2 is important for the maintenance of the germline stem cell niche integritySertolicellproliferationisregulatedbythecyclinDkinasesand,intriguingly,thelossofcyclinD2inamousemodelcreatesaphenotypesimilartotheoneresultingfromthelossofFSH.ToinvestigatewhetherthereareinteractionsbetweentheFSHandcyclinDsignalingpathways,Kumar’steamperformedgenearraysfollowedbycomputationalnetworkanalysis.Theresultsshowedaminimaloverlapbetweenthesetwopathways.Usingknock-outandknock-inmousemodels,KumardemonstratednextthatremovingcyclinD2intheFSHknock-outbackgroundexacerbatesthephenotypeandthemicedisplayedhypogonadism,aswellasinfertility.

Underscoring the importance of research on germline stem cell research, Yao said that impairment of fetal organ development has profound consequences on adult health. (Photo courtesy of Steve McCaw)

Kumar’s talk drew several scientists from the LRDT, including biologist Gina Goulding, center, a member of the NIEHS Gamete Biology Group headed by Mitch Eddy, Ph.D. (Photo courtesy of Steve McCaw)

30

Proper gametogenesis depends on an intact germline stem cell niche Neartheendofhistalk,Kumardescribedthemechanismunderlyingsuchaseverephenotype.Heshowedthattheintegrityofthemembraneofthenicheiscompromisedinthedoublemutant,withthelossofFSHandcyclinD2.Subsequently,thislossofmembraneintegritycausesafailureofthegermcellstoadheretoSertolicells,leadingtospermultrastructureabnormalitiesandinfertility.

Thesepromisingresultsraisenewquestions,suchasunderstandingwhatupstreamfactorregulatescyclinD2.

(RalucaDumitru,M.D.,Ph.D.,isanIntramuralResearchTrainingAward(IRTA)fellowintheNIEHSLaboratoryofMolecularCarcinogenesisStemCellBiologyGroup.)

Return to Table of Contents

Transcription of membrane-associated DNA highlights Lieb’s encore By Jeffrey Stumpf

ShortlyafterhisparticipationatanNIEHSminisymposiumearlierintheweek,UniversityofNorthCarolinaatChapelHill(UNC-CH)professorJasonLieb,Ph.D.,spokeJan.20atNIEHSabouthowtheorganizationofDNAinthegenomeaffectsgeneexpression.AspartoftheLaboratoryofMolecularCarcinogenesis(LMC)SeminarSeries,hostedbystaffscientistHarrietKinyamu,Ph.D.,Liebdemonstratedthattheinteractionsbetweenchromosomesandthenuclearenvelopearelikelyimportantinorchestratingtranscriptionalprograms.

Transcriptionalprocessesdeterminetheextenttowhichgenesareexpressed.Theinitiationofgeneexpressionisinfluencedbypromoters,whichcontainDNAsequencesthatrecruitthebindingoftranscriptionfactors.UnderstandinghowtranscriptionfactorsbindtotheproperDNAsequencesisfundamentaltofuturedevelopmentofcancertherapies,Liebexplained.

“Ourstudiesofgeneregulationwillleadtobetterpredictionsofwhathappenswhentranscriptionalprogramsgohaywireincancer,”Liebsaid,pointingtoBurkitt’slymphomaasanexampleofwhatgoeswrongwhentranscriptionfactorsbindtoinappropriatetargets.“Thesestudiesmayleadtonewtherapies,basedonmaintainingproperchromosomeorganizationandinhibitingtranscriptionfactorbindingtoinappropriatetargets.”

Small DNA loops accommodate high levels of transcriptionUNC-CHpostdoctoralfellowKohtaIkegami,Ph.D.,carriedoutalloftheexperimentsLiebdiscussed,usingthesimple959-celledroundwormCaenorhabditis elegans.Hisworkdeterminedthatbothendsoftheautosomalchromosomesareplasteredtothenuclearmembrane,whilethecentersloopedaway.The1000kilobasemembrane-boundplasteredendscontainedsubdomainsofapproximately60kilobasesthatweredefinedbysmallerchromatinloopsemanatingfromthemembrane.Interestingly,transcriptionoftheloopregionincreasedasthesizeoftheloopdecreased.

Lieb is also the director of the Carolina Center for Genome Sciences. Several days prior to his LMC seminar, Lieb spoke at NIEHS about DNA elements that regulate transcription during fruit fly development, as part of a minisymposium on epigenetics, chromatin biology, development, and disease. (Photo courtesy of Steve McCaw)

31

LiebaskediftheDNAsequencedeterminestheassociationwiththemembrane.ResultsfromanelegantchromosomefusionmutantsuggestedthattheformerlyendDNAregioninthefusedchromosomewasstillmembrane-bounddespitebeinginthemiddleofthechromosome,andthatDNAorchromatincompositiondeterminedbindingtothenuclearenvelope.

Theincreaseintranscriptionatsmallloops,Liebhypothesizes,mayoccurforconvenientuseofcellularresources.“Smallloopsmayconcentratetranscriptionalfactors,allowingincreasedresidencytimesandcomponentrecycling,”Liebremarked.

Nuclear pore proteins interact with the transcription machineryInsearchofotherrelationshipsbetweentranscriptionandthenuclearmembrane,Liebturnedhisattentiontothenuclearpores,channelsthathosttheactivetransportofthousandsofmolecularinteractionspersecond.OnehypothesisisthattranscriptionofhighlyactivegenescouldoccurnearnuclearporestofacilitatethetransportofRNAstotheribosomes.

Liebidentified223locationswherenuclearporeproteinsboundtoDNA.ThesesitescorrespondedtobindingsiteswhereRNApolymeraseIII(polIII)initiatestranscriptionoftRNAsandothersmallRNAsimportantfornormalcellgrowth.

Howimportantisnuclearporelocationtotranscription?Reducingthelevelsofanuclearporeproteinpreventednuclearporeassembly,changinghowthechromosomesinteractwiththenuclearmembrane.Also,lossofnuclearporescausedthemistargetingofthealternativeRNApolymerasepolIItopolIII-specificgenes.“Toourknowledge,thisisthefirstdemonstrationofmodifyingpolymerasespecificityofapromoterwithoutchangingtheDNAsequenceofthepromoter,”Liebconcluded.

Liebwantstoknowwhichoftheseprocessesiscallingtheshots.DoesthePolIItranscriptionmachinerypeelthechromosomeawayfromthenuclearmembrane,ordoesthemembraneactivelypreventPolIIfrombindingtogenes?DoesthePolIIImachinerybringthechromosometothenuclearpore,ordoesthenuclearporefunctionintheinitiationoftranscription?Lieb’sresearchwillbethefoundationforuncoveringwhetherchromosomeassociationwiththenuclearenvelopeisusedasaprimarymechanismtoregulateandcoordinatetranscriptionthroughoutthegenome.

(JeffreyStumpf,Ph.D.,isapostdoctoralfellowintheNIEHSLaboratoryofMolecularGeneticsMitochondrialDNAReplicationGroup.)

Return to Table of Contents

Kinyamu performs research in the LMC Chromatin and Gene Expression Group. (Photo courtesy of Steve McCaw)

Ikegami performed the research that was the basis of Lieb’s seminar. Lieb described the senior postdoctoral fellow as a “fastidious scientist that you should hire.” (Photo courtesy of Kohta Ikegami)

32

Armstrong discusses endocrine disruption of synaptic plasticity By Negin Martin

TheIntegratedToxicologyandEnvironmentalHealthProgram(ITEHP)atDukeUniversityhostedaJan.13presentationbyNIEHSseniorinvestigatorDavidArmstrong,Ph.D.,reportingonnewfindingsabouttheregulationofsynapticplasticitybyendocrinemodulators.Synapticplasticityistheabilitytochangethestrengthofneuronalconnectionsinbraintofacilitatelearningandmemoryformation.

Thepresentation,hostedbyneurotoxicologistEdwardLevin,Ph.D.,waspartoftheITEHPweeklyseminarseries,supportedinpartbytheNIEHSSuperfundResearchProgram.

Armstrong’spresentationfocusedonendocrinedisruptionofoxytocinandthyroidhormonesignalingpathways.Disruptionofthyroidhormonesignalingbyenvironmentaltoxicantsthatresemblethyroidhormoneinstructure,suchasPCBs,flameretardants,anddioxin,couldinterferewithproperdevelopmentofneuronalmaturationandcauselearningdisorders.Oxytocinisknownasasocialneuropeptide,becauseblockingitssecretionormutationsinitsreceptorareassociatedwithsocialdisorders,suchasautism,depression,andimpairedsocialbonding.

Regulation of ion channelsArmstrong,chiefoftheLaboratoryofNeurobiologyandtheheadoftheMembraneSignalingGroupatNIEHS,isanexpertelectrophysiologistwhostudiestheregulationofionchannelsbyendocrinesignaling.Ionchannelsregulatemembranepotentialthatcontrolsneuronalsignalingandsecretionofhormones.Bymonitoringtheeffectsofchemicalsonchannelactivityandsynapticfunctioninculturedcellsandmousebrainslices,Armstrongandhiscolleagueshavediscoveredmolecularmechanismsthatgovernneuronalsignalinganddesignedahighthroughputassaytoscreenforendocrinedisruption.

AcapacityaudienceofyoungtoxicologistsintrainingatDukeattendedthelecturetogaininsightintohowtoexploitdetailedknowledgeofmolecularpathwaysinthedesignofeffectivetoxicologicalscreens.

Armstrong tailored his talk to the toxicological perspectives of his audience, as he described public health concern about exposure to endocrine-disrupting compounds in the environment and the need for faster, more cost-effective screening of chemicals. (Photo courtesy of Steve McCaw)

After his presentation, Armstrong talked with Stapleton, right, about the next steps in advancing their collaborative research. (Photo courtesy of Steve McCaw)

33

Disruption of oxytocin signaling by flame retardant TDCPPAlthoughfluorescentindicatorsofintracellularcalciumhavebeenavailablefordecades,onlyrecentlyhavescientistsatHowardHughesMedicalInstitute’sJaneliaFarmResearchCampusdevelopedanindicator,GCAMP3,thatcanbestablyexpressedinneuronsandreliablyreportindividualcalciumtransientswithoutkillingthecells.Armstrong’slabusedGCAMP3tocreateastablehumancelllinethatcanbeusedtomeasureoxytocinsignaling.OxytocinregulatesneuronalfunctionthroughacalciumsignalingcascadethatisinitiatedbyaGprotein-coupledreceptor.

TheGCAMP3celllinehasbeenusedtodevelopahighthroughputassayonafluorescentplatereaderforidentifyingenvironmentaltoxicantsthatdisruptoxytocinsignaling.TheinitialchemicalsusedtodisruptoxytocinsignalingandtotestthesystemwereflameretardantsprovidedbyenvironmentalchemistHeatherStapleton,Ph.D.,acollaboratoratDukeandtherecipientofanOutstandingNewEnvironmentalScientistawardfromNIEHS.“Toourgreatsurprise,”saidArmstrong,“twooutofthefirsteightcompoundsthatwetesteddisruptedoxytocinsignaling.”

Intheprocessofconfirmingthisresultonsinglecellsusingconfocalmicroscopy,theydiscoveredthattheflameretardantsblockcalciumentryafterstoredepletion.Oxytocin’spotentiationofneuronalsynapsesdependsoncalciumentry,andiscompletelyblockedby50micrometersofTri(2,3-dichloropropyl)phosphate(TDCPP).“Fortunately,nooneisexposedtosuchhighlevelsofTDCPP,”Armstrongnoted,“butwehaveonlytestedeightchemicalssofar.”

Currently,thepredictivetoxicologyconsortiumTox21isusingthenewcelllinetoscreenover1,500chemicalsfortheireffectsonoxytocinsignaling.

(NeginMartin,Ph.D.,isabiologistintheNIEHSLaboratoryofNeurobiologyViralVectorCoreFacility.)

Return to Table of Contents

Mutant thyroid receptor blocks potentiation of

excitatory response in neuronsInaseparateprojectinArmstrong’slab,researchershavediscoveredacytoplasmicsignalingpathwayinvolvingphosphatidyl¬inositol3-kinase(PI3K)thatisactivatedbyTR-beta,anuclearreceptorforthyroidhormone.Thyroidhormonealsopotentiatessynapticresponsesinthehippocampus,butthroughacalciumindependentmechanism.

TheArmstronglaboratoryhascreatedastrainofmicewithmutatedthyroidhormonereceptorthatcannotstimulatePI3K,butstillregulatestranscription.ElectrophysiologicalstudiesperformedonmousehippocampalbrainslicesbyFengxiaMizuno,Ph.D.,aresearchfellowinArmstrong’sgroup,haverevealedthatblockingthyroidhormone-dependentstimulationofPI3Kbymutatingthereceptorpreventspotentiationofexcitatoryresponseinhippocampalneurons.

“NowthatwehaveshownthatsomeoftheeffectsofthyroidhormoneonbraindevelopmentaremediatedbysignalingthroughPI3K,”Armstrongconcluded,“wewouldliketodevelopasimilarcelllineforhighthroughputscreeningofendocrinedisruptorsofthyroidhormonesignalingthroughPI3K.”

34

This month in EHP By Ian Thomas

Initsfeaturestoryofthemonth,theFebruaryissueofEnvironmentalHealthPerspectives(EHP)examinestheimpactofenvironmentalexposuresonAmerica’sgrowingobesityepidemic.Whilemanyscientistsandphysicianshavehistoricallyattributedmuchofthisproblemtopoordietaryhabitsandalackofexercise,agrowingbodyofevidencesuggeststhatenvironmentalexposurestocertainchemicals,knownasobesogens,maybeastrongcontributor.

Inasecondstory,titled”DecodingNeurodevelopment:FindingsonEnvironmentalExposuresandSynapticPlasticity,”EHPexploresthelatestfindingsabouthowenvironmentalfactorsmayaffectsynapticplasticityintheC2portionofthehippocampus,theregionofthebraintaskedwithmemoryandlearningdevelopment.

Inthismonth’sResearcher’sPerspectivepodcast,hostAshleyAhearnsitsdownwithRobertB.Jackson,Ph.D.,todiscusstheimpactofhydraulicfracturingusedinnaturalgasdrillingoncommunityhealth,specificallythemillionsofgallonsofcontaminatedwaterthatitproduces.

Featuredcommentaries,reviews,andresearchthismonthinclude:

• EnvironmentalLeadLevelsAfterHurricaneKatrina

• HealthRisksofLimited-ContactWaterRecreation

• AirPollution,Temperature,andBloodPressureinPeopleWithType2Diabetes

• HealthImpactsoftheBuiltEnvironment

• MaterialCadmiumExposureandBirthSize

(IanThomasisapublicaffairsspecialistwiththeNIEHSOfficeofCommunicationsandPublicLiaison,andaregularcontributortotheEnvironmentalFactor.)

Return to Table of Contents

http://twitter.com/ehponline

35

Upcoming Falk lecturer Danny Reinberg By Angelika Zaremba

EpigeneticbiochemistDannyReinberg,Ph.D.,willpresentthisyear’sannualHansFalkLectureFeb.14.HostedbyNIEHSDeputyDirectorRickWoychik,Ph.D.,Reinbergwillprovideinsightsintoepigeneticsresearchwithhistalkon“MolecularMechanismsofEpigeneticInheritance.”

ReinbergisaprofessorintheDepartmentofBiochemistryattheNewYorkUniversity(NYU)SchoolofMedicine.AftercompletinghisB.S.inChile,hecompletedadoctorateinmolecularbiologyattheAlbertEinsteinCollegeofMedicineinNewYork.In1986,hebecameanindependentinvestigatorattheUniversityofMedicineandDentistryofNewJersey.In2006,ReinbergreceivedanappointmentasaHowardHughesMedicalInstituteinvestigator.Thatsameyear,hemovedtoNYUtocontinuepursuinghispassionforexploringthebiochemistryofgeneexpression.

Reinberg’steamisfocusingonthemolecularmechanismsofepigenetics.Thisfieldofscienceisdefinedasthestudyoftheextra-geneticinformationthatgivesrisetodifferentpatternsofgeneexpressionthatdistinguishdifferentcellsandinfluencephenotype.Theresearchteamisusingmiceandantsasmodelsystemstostudyepigeneticmodifications.Reinberghypothesizesthat,likeothermulticellularorganisms,similarmechanismsareatworkattheorganismlevelinantstoestablishandmaintainanindividualidentityfortheirrespectiverolesinthecolonyandgiverisetodistinctcellidentities.

Geneexpressionpatternregulationisalsoanimportantfactorindifferentdiseases,suchascancer,thatmaybecaused,atleastinpart,byenvironmentalfactors.Woychiksaidofhisguest,“Dr.Reinberghasbeenaleaderinthefieldofstudyingthebiochemistryassociatedwithchangesinchromatinstructurethatdriveepigeneticregulationofthegenome.Withtheincreasinginterestinunderstandingtheinfluenceoftheenvironmentonepigeneticregulationofgeneexpression,hisresearchishighlyrelevanttotheworkatNIEHS.”

HansFalk,Ph.D.,joinedNIEHSin1967andmadeimportantcontributionstotheemergingfieldofenvironmentalhealthscienceduringhiscareerastheInstitute’sfirstscientificdirector.InitiatedbyscientistsandfriendsofFalk,theannualmemoriallectureseriesfeaturesnotedguestspeakerswhohavemadesignificantcontributionstoenvironmentalhealthscienceresearch,amongthemseveralNobelPrizewinners.

(AngelikaZaremba,Ph.D.,isavisitingpostdoctoralfellowintheNIEHSLaboratoryofSignalTransductionInositolSignalingGroup.)

Return to Table of Contents

Reinberg, one of the leading scientists in the field of epigenetics, received the Faculty Research Award from the American Cancer Society. He holds a sculpture of an ant, an unusual, but informative, model for studying modifications in gene expression. (Photo courtesy of NYU)

36

Extramural papers of the month By Nancy Lamontagne

• New way to remove heavy metals from water

• Perfluorinated compounds and immune response in children

• Menthol lessens irritation from cigarette smoke

• Measuring cockroach allergen in the air

New way to remove heavy metals from waterAsystemdevelopedbyNIEHS-supportedengineerscancleanlyandefficientlyremovetraceheavymetalsfromwater.Thelowconcentrationsofthesemetalsmakethemdifficulttoextract.

Theengineerscreatedacyclicelectrowinning/precipitation(CEP)systemthatincreasestheconcentrationoftheheavymetalssothatelectrowinningcanbeused.Electrowinningemploysanelectricalcurrenttotransformpositivelychargedmetalionsintoastablesolidstatethatcanbeeasilyseparatedfromthewaterandremoved.

Intests,theCEPsystemloweredlevelsofcadmium,copper,andnickel—bothindividuallyandasamixture—tonearorbelowmaximumcontaminantlevelsestablishedbytheU.S.EnvironmentalProtectionAgency.Thesystemproducedaverylargereductioninthevolumeoftheheavymetalcontaminants,turningthemintoasolidmetaldepositedonparticlesthatcanbesafelydiscardedorfurtherprocessedtorecoverparticularmetals.

Thetechniqueisscalableandtheresearcherssayitcanbeusedtoremoveotherheavymetals,suchaslead,mercury,andtin.

Citation:GrimshawP,CaloJM,HradilG.2011.Cyclicelectrowinning/precipitation(CEP)systemfortheremovalofheavymetalmixturesfromaqueoussolutions.ChemEngJ175:103-109.

Return to Table of Contents

Perfluorinated compounds and immune response in childrenResearchfundedbyNIEHShasshownthatelevatedexposuretoperfluorinatedcompoundswasassociatedwithreducedimmuneresponsesinchildren.Perfluorinatedcompoundsarewidelyfoundinfoodpackagingandtextiles,buttheirimpactonhumanhealthisnotfullyunderstood.

TheprospectivestudyfollowedchildrenintheFaroeIslands,whicharelocatedintheNorthAtlanticabouthalfwaybetweenScotlandandIceland.Theinvestigatorsassessedprenatalexposurebymeasuringperfluorinatedcompoundsinthemother’sserumduringpregnancy,andlatercheckedforthecompoundsinsamplesfromthechildrenatagefive.Theyfoundthatchildrenwithelevatedexposuretoperfluorinatedcompoundshadlowerantibodyresponsestochildhoodimmunizations.Theantibodyresponsetochildhoodimmunizationreflectshowwelltheimmunesystemisfunctioning.

ReadthecurrentSuperfundResearchProgramResearchBrief.NewissuesarepublishedonthefirstWednesdayofeachmonth.

37

Theresearchersreportthatthisstudyisoneofthefirsttolinkchildhoodexposuretoperfluorinatedcompoundswithimmunesystemdeficiency.Theresultspointtotheimportanceofassessingtheimmunotoxicpotentialofthesecompounds,whicharehighlypersistentandcancontaminatedrinkingwater,aswellasfood.

Citation:GrandjeanP,AndersonEW,Budtz-JorgensenE,NielsenF,MolbakK,WeiheP,HeilmannC.2012.Serumvaccineantibodyconcentrationsinchildrenexposedtoperfluorinatedcompounds.JAMA307(4):391-397.

Return to Table of Contents

Menthol lessens irritation from cigarette smokeAnNIEHS-supportedstudyhasshownthatmenthol,thecoolingagentinpeppermint,counteractstheirritatingeffectsofcigarettesmokeconstituents.Mentholisaddedtomostcommerciallysoldcigarettes.

Theresearchersstudiedacrolein,aceticacid,andcyclohexanone,whichareirritatingcomponentsofcigarettesmokethatvarywidelyintheirchemicalstructureandbiologicalproperties.Usingamousemodelofhumansensoryirritantsensitivity,theinvestigatorsfoundthatthesensationofirritationwassuppressedimmediatelyinmicethatinhaledtheirritantsandmentholataconcentrationlessthanwouldbepresentinsmokefrommentholcigarettes.Whenmentholwasabsent,themicehadmoredifficultyinhalingtheirritantsandexhibitedmorelungirritation.Theexperimentsdemonstratedthatmenthol’scounterirritanteffectsresultedfromactivationofthechemicalreceptorTRPM8.

Bysuppressingreactionssuchascoughing,mentholcouldincreasetheamountofsmokeinhaledandthuspromoteaddictiontonicotine.The2009FamilySmokingPreventionandTobaccoControlActbannedflavoredtobaccoadditivesbutexemptedmentholwhiletheU.S.FoodandDrugAdministrationevaluatedscientificdata.

Citation:WillisDN,LiuB,HaMA,JordtSE,MorrisJB.2011.Mentholattenuatesrespiratoryirritationresponsestomultiplecigarettesmokeirritants.FASEBJ25(12):4434-4444.Story

Return to Table of Contents

Measuring cockroach allergen in the airNIEHSgranteeshavedevelopedanewsamplingandanalysissystemformeasuringexposuretoindoorcockroachallergens.Indoorallergensareonefactorthatcanincreaseriskforasthmadevelopmentorexacerbation.

Cockroachallergenexposureisusuallyassessedbycollectingandanalyzingsettleddust,butthismethodmightnotprovideaccuratemeasurementsofinhaledallergens.Tomeasureairbornecockroachallergen,theresearchersdevelopedatechniquethatinvolvescollectingaseven-dayintegratedtotalsuspendedparticulatesampleatapproximately10to15litersperminute.Theyusedthetechniquetocollectairborneparticlesamplesin19NewYorkCityapartmentsthatwerehometoanasthmaticchildwhowasallergictocockroachallergen.Thenewmethoddetectedallergenin87and93percentofairsamplesinthebedroomandkitchen,respectively,wherecockroachallergenwaspresentinsettleddust.

Sensitiveandquantitativemeasurementsofairbornecockroachallergencouldrevealmoreaboutallergenaerodynamicsinthehomesofchildrenwithasthma.

38

Citation:EspositoWA,ChewGL,CorreaJC,ChillrudSN,MillerRL,KinneyPL.2011.QuantitativemeasurementofairbornecockroachallergeninNewYorkCityapartments.IndoorAir21(6):512-520.

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

Return to Table of Contents

Intramural papers of the month By Brant Hamel, Anshul Pandya, Jeffrey Stumpf, and Emily Zhou

• Catching DNA polymerase beta in the act of mutagenic bypass of 8-oxoG

• In utero tobacco smoke exposure associated with illnesses in adult women

• Crystal structure of a kinase advances research for rational drug design

• Phosphorylation status links cellular stress and GR transcriptional response

Catching DNA polymerase beta in the act of mutagenic bypass of 8-oxoGNIEHSresearcherscontinueaseriesofreportsthatcapturethree-dimensionalstructuresofhumanDNApolymerasebeta(polbeta)performingapotentiallymutagenicevent.Thestructures,publishedintheProceedingsoftheNationalAcademyofSciences,revealhowpolbetabindstoanoxidizedguaninebase,8-oxoG,inthetemplateDNAandinsertstheincorrectdATPnucleotide.

8-oxoGisacommonbasedamageresultingfromoxidativestresscausedbyendogenoussourcesandenvironmentalagents.Organismsthatcannotremove8-oxoGdevelopmutationsthatcanultimatelycausetumorformation.ThemutationsarisefrommutagenicdATPincorporationopposite8-oxoGinsteadofthecorrectdCTPincorporation.Ofthe15humanDNApolymerases,polbetaisrelativelyproficientatmutagenicbypassof8-oxoG,makingitidealforstructuralstudies.

MutagenicbypassrequiresanunconventionalHoogsteenbasepairbetweenthesyn-conformationof8-oxoGanddATP.Polbetastabilizesthesyn-conformationwithhydrogenbondingbetweentheO8oxygenfromthebaseandthesidechainfromarginine-283fromtheenzyme.ThestructuresalsorevealthatthebasepairrequiresadramaticbendoftheDNAbackbone.Theflexibilityofpolbetaallowsmutagenicbypassofoxidizedbases,whichisnecessaryfortoleranceofpotentiallytoxicbasedamage.

Citation:BatraVK,ShockDD,BeardWA,McKennaCE,WilsonSH.2012.BinarycomplexcrystalstructureofDNApolymerasebetarevealsmultipleconformationsofthetemplating8-oxoguaninelesion.ProcNatlAcadSciUSA109(1):113-118.

Return to Table of Contents

39

In utero tobacco smoke exposure associated with illnesses in adult womenArecentepidemiologicalstudyconductedbyNIEHSscientistsfoundanassociationbetweentheexposuretotobaccosmokein uterowithobesity,hypertension,andgestationaldiabetesmellitusinadultwomen.Thisstudyisthefirsttoexaminetherelationshipofgestationaldiabetesmellitustoin uteroexposuretotobaccosmoke.

CarriedoutincollaborationwithscientistsfromtheUniversityofBergeninNorway,UniversityofNorthCarolinaatChapelHill,andtheNorwegianInstituteofPublicHealth,thisresearchincluded74,023womenvolunteersaged14to47.TheanalysiswasbasedontheNorwegianMotherandChildCohortStudy(MoBa)conductedbytheNorwegianInstituteofPublicHealth.MoBaisacohortbasedon108,000pregnanciesfrom90,700womenenrolledfrom1999to2008.

Theresultssuggestedthatwomenexposedtotobaccosmokein uterohavehigheroddsofdevelopingobesity,hypertension,andgestationaldiabetesmellituscomparedwithunexposedwomen.Theprobabilityofdevelopingtype2diabetesmellituswasalsoobservedtoincreaseslightly,butthisincreasewasnotstatisticallysignificant.Thisworkisinagreementwithpreviousstudies,whichhaveestablishedthatprenatalexposuretotobaccosmokeisdetrimentaltothedevelopmentalprocessofthefetus.Thisexposurecanhavealastingimpactonthehealthoftheindividual,evenduringadultlife.

Citation:Cupul-UicabLA,SkjaervenR,HaugK,MelveKK,EngelSM,LongneckerMP.2011.In uteroexposuretomaternaltobaccosmokeandsubsequentobesity,hypertension,andgestationaldiabetesamongwomenintheMoBacohort.EnvironHealthPerspect;doi:10.1289/ehp.1103789[Online29November2011].

Return to Table of Contents

Crystal structure of a kinase advances research for rational drug designInarecentpublicationinNatureChemicalBiology,NIEHSresearchersdescribe,forthefirsttime,thecrystalstructureforakeyinositolpyrophosphatekinase,PPIP5K2.Precursorsandproductsofthiskinaseregulatethebody’smetabolicbalance,whichisunderfrequentenvironmentalinsult.Breakdownofmetaboliccontrolprocessesisevidentindiabetes,cancer,andaging.Therationaldesignofdrugstoimprovehumanhealthisfacilitatedbythemoleculartemplatethatisprovidedbythisatomicleveldescriptionofthestructureandreactionmechanismofthisenzymethatsynthesizesinositolpyrophosphates.

HumanPPIP5K2phosphorylatesIP7toformIP8.Thissynthesisreactionrequirestheformationofhigh-energyphosphoanhydridebonds,inaclassofmoleculesthathavethehighestdegreeofphosphatecongestioninnature.Therefore,thefocusfortheauthorswastodeterminehowtheactivesiteofPPIP5K2accommodatesthephosphates’stericbulkandintenseelectronegativity,andyetretainsselectivesubstratespecificity.TheexactstructureofIP8alsoemergedfromthiswork.

Thisstructuralinformationwillalsobeusefulfordevelopingsmall-moleculeinhibitorsofthekinaseforpossibletherapeuticbenefit.KnowledgeofthestructureofIP8willnowpermititschemicalsynthesis,thedecipheringofitsmolecularinteractionswithreceptors,andthedesignofIP8antagonists.

40

Citation:WangH,FalckJR,HallTM,ShearsSB.2011.Structuralbasisforaninositolpyrophosphatekinasesurmountingphosphatecrowding.NatChemBiol8(1):111-116.Story

Return to Table of Contents

Phosphorylation status links cellular stress and GR transcriptional responseNIEHSresearchershavediscoveredanewpathwaythatlinksenvironmentally-inducedcellularstresstothetranscriptionalresponsemediatedbytheglucocorticoidreceptor(GR).TheGRisanuclearreceptorthatbindstostresshormonestoactivateorrepressthousandsofgenesthatcontrolpathwaysrangingfrommetabolismtotheimmuneresponse.Glucocorticoidsaresomeofthemostwidelyproscribeddrugsintheworldandthisworksuggeststhattheresponseofpatientstothesedrugsmaybealteredbyexternalfactorssuchasinflammationandstress.

AlthoughGRwasknowntobephosphorylatedinresponsetohormonebinding,theauthorsdiscoveredanovelhormone-independentsiteatSer134.Thisaminoacidisphosphorylatedbyp38MAPKinresponsetoavarietyofextracellularstress-inducingpathways,includingglucosestarvation,oxidativestress,andUVirradiation.Significantly,theauthorsfoundthatSer134phosphorylationallowedGRtobind14-3-3zetaproteinsandalteredthesuiteofgenesexpressedbyGR.Ser134phosphorylationisnecessaryfortheinductionofmanygenesinvolvedinmetabolicandendocrinedisorders,aswellastheinflammatoryresponse.

ThisparticularGRpathwaymayalsoexplainpreviousobservationsthatlinkingchronicglucocorticoidexposuretoinsulinresistanceasSer134mayactasametabolicsensorwithincellstodirectthetranscriptionaloutputoftheglucocorticoidreceptor.

Citation:Galliher-BeckleyAJ,WilliamsJG,CidlowskiJA.2011.Ligand-independentphosphorylationoftheglucocorticoidreceptorintegratescellularstresspathwayswithnuclearreceptorsignaling.MolCellBiol31(23):4663-4675.

(BrantHamelPh.D.,isanIntramuralResearchTrainingAward(IRTA)fellowintheNIEHSLaboratoryofSignalTransductionMolecularEndocrinologyGroup.AnshulPandya,Ph.D.,isanIRTAfellowintheNIEHSLaboratoryofNeurobiologyIonChannelPhysiologyGroup.JeffreyStumpf,Ph.D.,isanIRTAFellowintheNIEHSLaboratoryofMolecularGeneticsMitochondrialDNAReplicationGroup.EmilyZhou,Ph.D.,isaresearchfellowintheNIEHSLaboratoryofSignalTransductionInositolSignalingGroup.)

Return to Table of Contents

41

Inside the InstituteNIH celebrates King legacy with dance, music, and personal history By Eddy Ball

NIHofferedattendeessomethingalittledifferentthisyearatitsannualDr.MartinLutherKingJr.ObservanceProgramJan.12inBethesda,Md.AlthoughtheprogramfeaturedanengagingtalkbyAfrican-AmericantoxicologistLemuelRussell,Ph.D.,theeventalsoshowcasedthreeinspirationaldanceandmusicalperformancesbystudentsfromtheDukeEllingtonSchooloftheArtsinWashington,D.C.

ThethemefortheanniversaryofKing’sbirthdayin2012was“Remember,celebrate,act—Adayon,notadayoff,”andtheeventwaswebcasttoNIHfacilitiesinBethesdaandotherlocations,includingNIEHS.

Enlivened by a dreamFollowingawelcomebyAssistantDirectoroftheNIHOfficeofIntramuralResearchRolandOwens,Ph.D.,NIHDirectorFrancisCollins,M.D.,Ph.D.,presentedopeningremarks.CollinsencouragedemployeestovolunteerduringtheJan.16holiday,ashesetthetoneforthespeakersandperformerswhofollowedhim.

“NIH’sannualobservancegivesthechancehere,thismorning,toraiseourawarenessofthechangesthathavebeenmadeasaconsequenceofDr.King’sleadership,”Collinssaid,“recognizing,however,thatwehavenotreachedthatPromisedLand.WestillhavemanythingsthatneedattentionbeforewearetrulytobeabletosaythatourcountryisaplacewherejusticeandfairnessareequallyavailableineverywaythatDr.Kingdreamedof.”

NIH program leaders joined the guest speaker before their talks. Shown, left to right, are Owens, Collins, Stokes, and Russell. (Photo courtesy of NIH and Ernie Branson)

As a child in segregated postwar America, Russell could mark the milestones in his own life in sync with those of the Civil Rights Movement itself. (Photo courtesy of NIH and Ernie Branson)

Linked video:

Watch a Duke Ellington School of the Arts Piano Concert Preview. (00:53)

(Launches in new window)

Download Media Player: Flash

42

Dance, music, and oral history BeforeRussellcametothepodiumforhiskeynotepresentation,“Toxicology,ScientificDevelopment,andCivilRights,”theaudienceexperiencedthefirstofthreeperformancesbyyoungartists.Movingtoatenor’srenditionofthe23rdPsalm,accompaniedbyharpandstrings,ayoungwomanpresentedamoderndanceexpressionoftriumphoveradversitythroughunwaveringfaithinahigherpower.

Russellbeganhistalkabout“WhatIdoandhowIgothere”withasortofprimerontoxicologythatmergedatseveralpointswithkeyeventsfromthecivilrightsstruggleandwhatKing’slifehasmeanttohimasascientistandacitizen.Russellbeganhispersonalnarrativewitha1968photoofhimself,atage8,withhisbrotherandsisterinCompton,Calif.,justafewdaysbeforeKing’sdeathApr.5,1968.

Withphotosandoralhistory,RusselldescribedthemilestonesleadinguptotheCivilRightsActandtheimportanceofdesegregationinthepost-WorldWarIImilitarytotheAfrican-Americanexperiencesince.HereinforcedthemilitaryconnectionwithaphotoofhimselfinuniformatWalterReedArmyMedicalCenter,whereheconductedscientificresearchduringtheearly1990soncyanideionbinding.“Whatweweretryingtodo,”hesaid,“isdevelopsystemstoidentifycandidateantidotes.”

Withhispresentationcomplete,RussellturnedthepodiumovertoOwens,whowelcomeddancersbacktothestage.ThestudentsperformedtwomorenumbersbasedonAfrican-Americanculturalthemes.

Thefirstwasastirringmoderndancerenditionofthecodedslaveescapesong,“WadeintheWater,”withrhythmandbluesinspiredmusicalaccompaniment,featuringafinaleofballet-influencedmovementbyagroupoffemaledancersdressedinwhite.

Thesecondbroughtamalemoderndanceensembletothestage,asachorusperformedanacappellaversionofthespiritual,“SometimesIFeelLikeaMotherlessChild(ALongWayfromHome).”

Working togetherTheeventconcludedwithremarksbySheilaStokes,actingdirectoroftheNIHOfficeofEqualOpportunityandDiversityManagement,whichsponsoredtheobservance.“ManyofustodaycantalkaboutthelegacyofDr.MartinLutherKingJr.,”Stokestoldtheaudience.“Iamheretodaybecauseofthehardworkthatothersputintoembracinghisvision,embracinghismessage.”

StokesendedtheprogrambyremindingattendeesoftheuniversalityofKing’slegacy.“It’sacombinedandcollectiveeffort.…It’saboutwhatwedoasapeopletogether.”

Return to Table of Contents

Three of the students from the Duke Ellington School danced gracefully to the rhythm of “Wade in the Water.” (Photo courtesy of NIH and Ernie Branson)

Male dancers moved to the haunting lyrics and music of “Sometimes I Feel Like a Motherless Child.” (Photo courtesy of NIH and Ernie Branson)

43

Long recognized for CFC leadership By Eddy Ball

NIEHSandNIHenjoyedabanneryearforpledgestotheCombinedFederalCampaign(CFC).Onefactorinthisyear’ssuccessonthehomefront,severalobserversagree,wastheleadershipprovidedbyNIEHSDeputyAssociateDirectorforManagementChrisLong,whoservedaschairpersonoftheGreaterNorthCarolina(N.C.)CFCLocalFederalCoordinatingCommittee.

InamessagetoNIHCFCchairsJan.6,U.S.NationalLibraryofMedicineAssociateDirectorforAdministrativeManagementandNIH2011CFCchairpersonToddDanielsonpraisedLong’scontributiontothe2011campaign.“I’dberemissifIdidn’ttipmyhattoNIEHSfortheirserviceintheGreaterNorthCarolinaCFC,”Danielsonwrote.“CongratulationstoChrisLongwhodidastellarjobasstatewidechair!”

A Happy New Year, indeedDanielsonwasrighttobefilledwithNewYearcheer,ashereportedontheperformanceofthe27institutesandcenters.NIHexceededits2011goalof$2.4millionby$150,000,raising106percentofitsgoal.WiththeadditionofpledgesmadebetweentheofficialcloseofthecampaignDec.15andthefinalaccountingDec.31,NIEHSraisedatotalof$113,526,animpressive108percentofitsgoalof$105,000.

IntheGreaterN.C.CFCcampaign,onlythemuchlargerworkforcesattheU.S.EnvironmentalProtectionAgencyandU.S.PostalServiceraisedmorethanNIEHSemployees.TheGreaterN.C.AreaCFCnowincludescountiesthatwerepreviouslywithintheboundariesoftheCFCofCentralCarolinas,thePiedmontTriadCFC,theResearchTriangleAreaCFC,and18countiesthatwerenotpreviouslyassociatedwithaCFC,servingmorethan27,000federalemployeesin56NorthCarolinacountiesand7SouthCarolinacounties.

Thisyear,theGreaterN.C.CFCraisedmorethan$1.3million.But,withmanyagencies,particularlythePostalService,facingthespecterofsignificantcuts,reducedhours,anddownsizing,theoverallcampaignfinishedabout15percentbelowlastyear.“Wefeareditwouldbemuchworse,soIamhappywedidthiswell,”saidLong,“NIEHSwasoneofthefewbrightspotsinaverydifficultfundraisingyear.”

Reflectingonthe2011CFC,NIEHS/NTPDirectorLindaBirnbaum,Ph.D.,whosupportedLong’sserviceasstatewidechairandralliedemployeesduringtheCFCcampaignatNIEHS,thankedLongandNIEHSco-chairsCindyInnesandRonCannon,Ph.D.,fortheirhardworkanddedication.“Thesetotalsareespeciallyimpressiveduringatimeofhighunemploymentandhardtimesformanyfamiliesinourcommunities,”shewrote.“Chris,Cindy,Ron,andthemanygenerouspeopleatNIEHSandelsewheremakemeproudtobeafederalemployeeandapartoftheNIEHSandNIHcommunities.”

Long said he feels a commitment to give back to the community (see text box). “My mother was a United Way executive director, so it’s in my blood.” (Photo courtesy of Steve McCaw)

44

Return to Table of Contents

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

The Long tradition of service at home and abroadSincejoiningNIEHSin2007,LonghasprovidedleadershipandsupportforcharitableeffortsbyNIEHSemployees,includingtheannualCFCandFedsFeedFamiliesdrives.Previously,attheU.S.EnvironmentalProtectionAgency,heservedaschairpersonoftheResearchTriangleAreaCFCandservedontheboardofdirectorsoftheU.S.PartnershipforEducationforSustainableDevelopment.

HehasalsoworkedasastaffexecutivefortheBoyScoutsofAmerica,volunteeredmorethantwodecadesasaBigBrother,andhelpedstartacharityservingasmallvillageinNicaragua.