NIEHS Spotlight Science Notebook

February 2014

NIEHS exposome faculty connects scientists from across the instituteScientists from all corners of the institute meet in January to explore what studying the exposome can mean at NIEHS.

Research supported by NIEHS informs policy and regulatory discussionNIEHS-funded researchers found themselves, this winter, at center stage in the national discussion concerning public health policy and regulatory issues.

International collaboration aims to reduce animal testingThe NTP alternative methods program met with international partners Nov. 26-27 in Italy to reach important agreements for advancing 21st century safety testing.

Harvard SRP collaboration honored for risk communicationThe Kids + Chemical Safety website receives Risk Communication award for providing parents with peer-reviewed information on chemical risks to children.

Using nanomedicine to improve human healthMaterials scientist Joseph DeSimone, Ph.D., explored the use of nanoparticles to design better medicines and vaccines in an NIEHS Distinguished Lecture Jan. 24.

New NTP atlas helps standardize nonneoplastic lesion diagnosesIn January, NTP debuted a new web-based resource that will help pathologists worldwide better diagnose, record, discuss, and discriminate among rodent lesions.

Scientists begin to fill in the gaps in understanding about frackingNew studies by NIEHS-funded researchers are helping raise awareness of the potential environmental public health impact of this unconventional natural gas drilling method.

Community engagement drives new pilot study on fracking and air qualityA team of NIEHS-funded researchers met Jan. 9 with citizens of Carroll County, Ohio, marking one of the first steps in the one-year project.

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Wastewater treatment offers a view into environmental chemicals’ risksArizona State University researchers analyzed biosolids from municipal wastewater treatment plants to identify contaminants of emerging concern.

NTP scientists achieve coveted toxicology certificationThis winter, two NTP contract scientists and two NTP postdoctoral fellows received Diplomate of the American Board of Toxicology certification.

NIEHS Spotlight Science Notebook

Grantees named AAAS fellowsFour NIEHS grantees will be among new fellows honored this year by the American Association for the Advancement of Science at its annual meeting in Chicago.

NIEHS fellow begins career in educational writingIn December, former NIEHS fellow Jacqueline de Marchena Powell, Ph.D., translated her postdoc experience into a career as a science writer.

High-throughput screening examines multiple effects of 1060 compounds on zebrafishLarge systematic in vivo toxicological study finds nearly half the chemicals tested show significant biological responses and detects responses other methods would miss.

Study identifies novel compounds more mutagenic than parent PAHsSRP researchers discover novel nitrated-PAHs that form under normal combustion conditions and have greater mutagenic properties.

Using teeth to uncover developmental susceptibility to chemical mixturesChildren’s baby teeth can reveal prenatal and early childhood exposures to a variety of chemicals — data useful for researching health impacts in later life.

Webinar highlights new insights about childhood leukemiaIn a webcast seminar Jan. 8, two NIEHS-funded scientists from the University of California, Berkeley presented new findings about childhood leukemia.

Postdoc transitions into career in biopharmaceuticalsAfter three years at NIEHS, Jeremy Weaver, Ph.D., found his perfect match with a position as a process development scientist at Grifols Therapeutics Inc.

2014 calendar features artwork by NIEHS postdocThis September, artwork by Sheila Yong, Ph.D, will be on display in offices, labs, and cubicles around the world, as part of Abcam’s new desk calendar.

Biostatistics intern reaches national semifinals for science competitionNIEHS summer intern Mitas Ray was named semifinalist in the Intel Science Talent Search, earning awards for himself and his school, Enloe High School in Raleigh, N.C.

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Talk explores link between endometriosis and the estrogen receptorA meeting of the NIEHS Receptor Mechanisms Discussion Group Jan. 7 featured a seminar by postdoctoral fellow Katherine Burns, Ph.D.

Inside the Institute

NIEHS CFC raises more than $100,000Led by DERT co-chairs, employees respond with enthusiastic support for more than 300 organizations that deliver services to those in need.

NIEHS inaugurates new facilities for fitness, research, and trainingBirnbaum and staff celebrate newly remodeled main building facilities at Jan. 8 open house.

Extramural Research

Extramural papers of the month• Transcription factor influences codon choice and

protein evolution

• Compound from mold linked to symptoms of Parkinson’s disease

• New tool for assessing ovarian cancer

• Partnership identifies chemical-gene-disease interactions for inclusion in database

Intramural Research

Intramural papers of the month• Scientists closer to understanding stem cell self-

renewal and differentiation

• Estrogen receptor alpha involved in DES-induced gene expression in male mice

• Identification of a novel mechanism that suppresses glucocorticoid signaling

• Factors critical during early stages of heart development clarified

This month in EHPThe February issue of Environmental Health Perspectives (EHP) highlights health effects on the Navajo population of earlier uranium mining, and radioactive consequences of fracking.

Myles Brown to give distinguished lectureThe second NIEHS distinguished lecture of 2014 will be presented Feb. 11 by prominent physician scientist Myles Brown, M.D., at 11:00 a.m. in Rodbell Auditorium.

Science Notebook

Calendar of Upcoming Events

• Feb. 5, in Rodbell Auditorium, 8:30 a.m.-5:00 p.m. — Bisphenol A Grantee Meeting

• Feb. 6, in Rodbell Auditorium, 9:00-10:00 a.m. — Keystone Science Lecture Seminar Series with Carl White, Ph.D., addressing “Novel Countermeasures Against Chemically Induced Airways Injury”

• Feb. 7, in Rodbell Auditorium, 11:00 a.m.-noon — African American History Month with Crystal deGregory, Ph.D., speaking on “Herstory: Civil Rights (and Wrongs) at Home and Abroad”

• Feb. 11, in Rodbell Auditorium, 11:00 a.m.-noon — Distinguished Lecture Series presentation on “Genetics and Epigenetics of Hormone Dependence” by Myles Brown, M.D.

• Feb. 12-13, in Rodbell Auditorium; Feb. 12, 8:30 a.m.-5:30 p.m., Feb. 13, 8:30 a.m.-1:00 p.m. — Transgenerational Inheritance in Mammals after Environmental Exposure Grantee Meeting

• Feb. 13, in Rodbell Auditorium, 1:00-2:00 p.m. — Keystone Science Lecture Seminar Series with Andrea Gore, Ph.D., discussing “Environmental Endocrine Disruption of the Brain: Past, Present, and Future”

• Feb. 13 (offsite event), in the Trent Center for Bioethics, Humanities, and History of Medicine, Room 40, Duke University, noon-1;00 p.m. — Richard Kwok, Ph.D., discussing “The Gulf Study: Investigating the Human Health Effects of the BP Deepwater Horizon Oil Spill”

• Feb. 14 (offsite event), in the Levine Science Research Center, Room 247, Duke University, noon-1:00 p.m. — Integrated Toxicology and Environmental Health Program Spring 2014 Seminar Series, featuring Daniel Baden, Ph.D., exploring “From Beach to Bedside: Getting our Feet Wet in Translational Marine Science”

• Feb. 19-20, in Rodbell Auditorium; Feb. 19, 8:30 a.m.-5:30 p.m., Feb. 20, 8:30a.m.-2:00 p.m. — National Advisory Environmental Health Sciences Council

• Feb. 20, in Rodbell Auditorium, 2:00-5:00 p.m. — Launch of NIEHS-WHO Collaborating Center

• View More Events: NIEHS Public Calendar

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NIEHS SpotlightNIEHS exposome faculty connects scientists from across the institute By Kelly Lenox

ScientistsfromacrossNIEHSgatheredJan.10tohelpinauguratetheInstitute’sexposomefaculty.Thiswasthesecondmeetingofthenewlyformedgroup,whichisworkingtodeveloptheconceptandstudyofexposomescienceatNIEHS.

Theexposome,orthemeasureofaperson’slifelongexposurestoagents,bothinternalandexternal,isattractingincreasedattentionfromenvironmentalhealthscientistsworldwide.

CreationoftheexposomefacultysupportsGoal3oftheNIEHS2012-2017StrategicPlan,whichcallsfortransformingexposuresciencebyenablingconsiderationofthetotalityofhumanexposuresandincorporatingexposurescienceintohumanhealthstudies.Prioritiesidentifiedunderthegoalincludedefininganddisseminatingtheconceptoftheexposome,andcreatingthetoolsandtechnologies,aswellasresearchcapacity,neededtocharacterizetheexposome.

Grappling with definitionsDefinitionsoftheexposomehavevariedsinceChristopherWild,Ph.D.,acancerepidemiologist,firstcoinedthewordina2005journalarticle.AccordingtoDavidBalshaw,Ph.D.,actingchiefoftheNIEHSExposure,Response,andTechnologyBranchandExposureBiologyResearchProgramlead,thescientificcommunityislookingtoNIEHSforleadershipasaprimarydeliberativebodyfordefiningtheemergingfieldoftheexposomeandexposomics.

Balshawremindedparticipantsnottooverlooktherationalebehindstudyingtheexposome.Wild’sinitialdefinitionoftheexposomeasthetotalityoflife-courseexposuresfromtheprenatalperiodonwardsisagrandvisionandtechnicallydaunting.

“Definitionscanbedivisive.Theessenceoftheexposomeisthatitwillallowustoidentifytheassociationsbetweenexposureanddiseasewithoutpreformedhypotheses,”saidBalshaw.“Ratherthanaskingwhatistheassociationbetweenparticulatematterexposuresandasthma,wecanaskthebroaderquestionofwhataretheenvironmentalfactorsthatdeterminethisbiologicalendpoint.Thescienceoftheexposomeisinhowyouperformthatanalysis.”

Longnecker offered examples of how current epidemiological studies might differ from exposome studies. “For instance, [one study] used dust samples, but not air samples,” he said. (Photo courtesy Steve McCaw)

Balshaw described the exposome as a means of discovering associations between environmental exposures and a biological point of interest. (Photo courtesy Steve McCaw)

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Obtaining, storing, and processing data gets expensiveMatthewLongnecker,M.D.,Sc.D.,headoftheNIEHSBiomarker-basedEpidemiologyGroup,discussedthreecohortstudiescurrentlyunderway—theSisterStudy,theGuLFSTUDY,andtheNorwegianMotherandChildCohortStudy—anddescribedhowdatarequirementsforexposomestudiesmightdifferfromtheneedsofthestudies.

“Insomecases,thedatasofarrepresentonepointintime.Dataandsamplesizeareoftenlimitedbytheexpenseofcollectingandstoringsamples,aswellasdataprocessing,”hesaid.

Monitoring external and internal exposuresNext,BalshawdescribedactivitiesoftheGene,Environment,andHealthInitiativeExposureBiologyProgram,fundedfrom2007-2011toexplorewhetherexposurecouldbemeasuredinanewmanner.Theprogramfocusedondevelopingtoolsforexposureassessmentinthepersonalenvironment,includingmonitorsforexternalexposure,usingstressmetricsandinformationonabuseofsubstances,andmeasuringbiologicalresponses.

Involving communities in data collectionThethirdspeaker,LiamO’FallonoftheNIEHSPartnershipsforEnvironmentalPublicHealth(PEPH)program,reportedoncommunityengagementactivitiestoexplorehowtheexposomerelatestopublichealthwork.O’Fallonpointedtooneexampleofhowcommunitiescanbeinvolvedincollectingthenecessarilyextensivedata.

“TheEnvironmentalHealthSciencesCoreCenteratEmoryUniversityisworkingwithcommunitypartnerswhounderstandtheutilityoftheexposome,”heexplained.

AspartoftheEnvironmentalHealthChatseries,PEPHrecentlyreleasedapodcastthatexplainstheconceptoftheexposomeandhowitcanhelpcommunityorganizationsaddresstheirenvironmentalhealthconcerns.

Coming soon: workshop and webinarsTheexposomefaculty’srolerangesfromprovidingaforumtodiscussanddefinetheexposomeconcept,tofosteringcollaborationsacrossNIEHSrelatedtotheexposome.Furthermore,planscallforabimonthlywebinarseriestobeginsoon,aswellasaworkshoplaterintheyear.

“Many different organizations have observed that there are multiple exposures they have to deal with, but to them it seems scientists look at one exposure and one health outcome,” said PEPH program lead O’Fallon. “That isn’t reflective of their realities. The exposome is an opportunity to more realistically examine environmental justice and environmental health disparities.” (Photo courtesy Steve McCaw)

Richard Kwok, Ph.D., is the lead associate investigator for the GuLF STUDY, mentioned during Longnecker’s discussion on exposure data. (Photo courtesy Steve McCaw)

Listen as Gary Miller, Ph.D., of Emory University, and others describe how understanding the exposome can help protect people at a societal level (06:43).

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Balshawsummeduptherolebysaying,“TheexposomefacultyisfirstandforemostaforumtotalkaboutwhattheexposomeisandwhatweasanInstituteshouldbedoing.”

Daniel Shaughnessy, Ph.D., is a Health Scientist Administrator for the NIEHS Exposure Biology Research Program. (Photo courtesy Steve McCaw)

The work of David Miller, Ph.D., chief of the Toxicology and Pharmacology Laboratory, includes understanding how blood-brain barrier transport function is altered by environmental stressors and disease. (Photo courtesy Steve McCaw)

Scott Masten, Ph.D., director of the NTP Office of Nominations and Selection, is interested in applying exposome research to the prioritization of substances studied by the NTP. (Photo courtesy Steve McCaw)

Like other scientists in NTP, Darlene Dixon, D.V.M., Ph.D., head of the Molecular Pathogenesis Group, is interested in how exposome science intersects with the studies in her lab. (Photo courtesy Steve McCaw)

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Research supported by NIEHS informs policy and regulatory discussion By Eddy Ball

NIEHS-fundedresearchersfoundthemselves,thiswinter,atcenterstageinthenationaldiscussionconcerningpolicyandregulatoryissuesrelatedtoenvironmentalpublichealth.

InanarticlereleasedDec.24,2013,underscoringthelong-termeffectsofenvironmentalexposureonmajorpublichealthproblems,formerNewJerseyGovernorChristineToddWhitman(1994-2001)pointedtothreelarge-scalestudies,twoofthemledbyNIEHSin-housescientistsandgrantees.Whitman’seditorial,“Assessingthelong-termcostsofignoringtheenvironment,”appearedinNJSpotlight,anonlinenewsservicethatfeaturesinsightsandinformationonissuescriticaltoNewJersey.

ADec.16,2013,NewYorkTimesfeaturestory,“F.D.A.questionssafetyofantibacterialsoaps,”lookedbehindthescenesofthenewU.S.FoodandDrugAdministration(FDA)requirementthatmanufacturersdemonstratethesafetyofantimicrobialsoaps,citingresearchbyscientistssupportedbytheNIEHSSuperfundResearchProgram(SRP).

ThestoryincludedaninterviewwithSRPgranteeRolfHalden,Ph.D.,directoroftheCenterforEnvironmentalSecurityatArizonaStateUniversity.AlongwithSRPgranteesBruceHammock,Ph.D.,andIsaacPessah,Ph.D.,oftheUniversityofCalifornia,Davis,andRobertTukey,Ph.D.,oftheUniversityofCalifornia,SanDiego,HaldenisoneofseveralNIEHS-fundedscientistswhohaveconductedinterdisciplinarystudiesontheextentofenvironmentalpollutionbytheantimicrobialstriclosanandtricloban,andtheirpotentialeffectsonhumanhealth.

Whitman highlights NIEHS researchAsthefirstintheNJSpotlightcollectionofyear-endessaysfromthosewhohavesatintheN.J.governor’schair,Whitman’seditorialfocusedonthelong-termeffectsofrepeatedenvironmentalexposures.

“Recentstudieslinkingvarioushealthandeconomicimpactsofenvironmentalcontaminationshouldcausepolicymakerstoreevaluatetheirprioritieswhenitcomestoenvironmentallegislationandregulation,”Whitmanwrote.“Threekeyareasofresearchinthisareastandout:theconnectionbetweencertainpesticidesandParkinson’s,thecorrelationbetweenelevatedleadingasolinewithcrimerates,andthelinkbetweenairpollutionandautism.”

Twoofthestudiesthatinspiredhercommentary—oneonpesticidesandParkinson’s,theotheronairpollutionandautism—wereledbyNIEHS-fundedresearchers.ThethirdstudyonleadandcrimeratescitedpreviousNIEHS-fundedresearch,andacknowledgedtheeditorialassistanceofformerNIEHSScientificDirectorJohnMcLachlan,Ph.D.,ofTulaneUniversity.

“Inourbenevolentmissiontogrowtheeconomy,weshouldnotbeintoogreatarushtoignoreenvironmentaltestingandresults,”arguedWhitman.“Thepricewepayattheendismuchgreaterthanwecanafford,bothintermsofdollarsandhumanlives.”

Whitman also served as administrator of the U.S. Environmental Protection Agency 2001-2003. Like Halden, she takes into consideration both the human health and financial costs of preventable environmental exposures to harmful chemicals. (Photo courtesy of Christine Whitman)

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Halden applauds FDA decision“It’sabigdealthattheyaretakingthison.Theseantimicrobialshavetakenonalifealloftheirown,”saidHalden,whosestudieshavefoundthattriclosanandtriclocarban[anotherantimicrobial]persistevenafterwastewatertreatment.“Theirusehasreallyproliferated.”

StudiesbyHammockandothershavedemonstratedthattheantimicrobialsinliquidandbarsoapscandisruptdevelopmentinanimals,suggestingsimilareffectsinhumans.AccordingtoFDAscientists,thereisnoevidenceofclearlydemonstratedbenefitstobalanceanypotentialrisksfromexposuretothechemicals.

Theuseofthesesoapshasbecomewidespread,andtheantimicrobialchemicalsfoundinthemarenowalsousedinarangeofconsumerproducts.TheCentersforDiseaseControlandPreventionfoundthechemicalsintheurineofthree-quartersofAmericans.Haldensaidthechemicalsaccumulateinbiotalivinginsurfacewaterandsoil,andhepointedtoonestudythatfoundthechemicalsinthebreastmilkof97percentofthewomentested.

“Thesechemicalsinterferewiththeregulationofthehumanbody,”Haldensaid.“Thefascinatingthingisthatthepublichasnottakennoteofthisissue.”

Citations:CherednichenkoG,ZhangR,BannisterRA,TimofeyevV,LiN,FritschEB,FengW,BarrientosGC,SchebbNH,HammockBD,BeamKG,ChiamvimonvatN,PessahIN.2012.Triclosanimpairsexcitation-contractioncouplingandCa2+dynamicsinstriatedmuscle.ProcNatlAcadSciUSA109(35):14158-14163.

KamelF,GoldmanSM,UmbachDM,ChenH,RichardsonG,BarberMR,MengC,MarrasC,KorellM,KastenM,HoppinJA,ComynsK,ChadeA,BlairA,BhudhikanokGS,WebsterRossG,WilliamLangstonJ,SandlerDP,TannerCM.2013.Dietaryfatintake,pesticideuse,andParkinson’sdisease.ParkinsonismRelatDisord;doi:10.1016/j.parkreldis.2013.09.023[Online1October2013].

MielkeHW,ZahranS.2012.Theurbanriseandfallofairlead(Pb)andthelatentsurgeandretreatofsocietalviolence.EnvironInt43:48-55.

RobertsAL,LyallK,HartJE,LadenF,JustAC,BobbJF,KoenenKC,AscherioA,WeisskopfMG.2013.Perinatalairpollutantexposuresandautismspectrumdisorderinthechildrenofnurses’healthstudyIIparticipants.EnvironHealthPerspect121(8):978-984.

SchebbNH,AhnKC,DongH,GeeSJ,HammockBD.2012.Wholebloodisthesamplematrixofchoiceformonitoringsystemictriclocarbonlevels.Chemosphere87(7):825-827.

VenkatesanAK,PyckeBF,BarberLB,LeeKE,HaldenRU.2012.Occurrenceoftriclosan,triclocarban,anditslesserchlorinatedcongenersinMinnesotafreshwatersedimentscollectednearwastewatertreatmentplants.JHazardMater229-230:29-35.

WaltersE,McClellanK,HaldenRU.2010.Occurrenceandlossoverthreeyearsof72pharmaceuticalsandpersonalcareproductsfrombiosolids-soilmixturesinoutdoormesocosms.WaterRes44(20):6011-6020.

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Halden is a professor of environmental engineering. “Public health engineering saves lives and money,” he said. “More than half of humanity’s health problems are dependent, either directly or indirectly, on environmental factors.” (Photo courtesy of Rolf Halden)

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International collaboration aims to reduce animal testing By Catherine Sprankle

Governmentsaroundtheworldrequirechemicalandchemicalproducttestingtoidentifypotentialhazards,sothatappropriatelabelingforsafehandling,use,anddisposalmaybeapplied.TheU.S.sharesaninterestwithothercountriestodiscovermoreefficienttestingmethodsthatreduceoreliminateanimaluse.

TheInternationalCooperationonAlternativeTestMethods(ICATM),aninternationalpartnershippromotingthereplacement,reduction,andrefinementofalternativesforanimaltesting,metNov.26-27,2013,attheEuropeanCommissionInstituteforHealthandConsumerProtection(IHCP)inIspra,Italy.NTPInteragencyCenterfortheEvaluationofAlternativeToxicologicalMethods(NICEATM)DirectorWarrenCasey,Ph.D.,representedtheInteragencyCoordinatingCommitteeontheValidationofAlternativeMethods(ICCVAM)atthemeeting.NICEATMprovidessupportforICCVAMactivities,andCaseyisanICCVAMcommitteemember.

“Thiswasanextremelyproductivemeeting,”notesCasey.“TheattendeesreachedsomeagreementsthatshouldfacilitateU.S.regulatoryagencies’adoptionofmethodsthathaveundergonepeerreviewoutsidetheUnitedStates,whichwillresultinmoreefficienttestingandlessanimaluse.”

Advancing international adoption of alternative test methodsICATMfacilitatesinternationalcooperationinvalidation,peerreview,anddevelopmentofrecommendationsonuseofnewtestmethods.Caseyandtheotherparticipantsatthemeetingmadesomekeydecisionstosupportthosegoals,includingthefollowingagreements.

• UseoftheEuropeanTSAR(TrackingSystemforAlternativeTestMethodsReview,Validation,andApproval)asthecommontrackingdatabasefornewtestmethodsdevelopedbyICATMpartners.

• Theneedtodefinebestpracticesforvalidationstudyactivities,suchaschemicalselection,thecompositionandroleofstudymanagementteams,andconsiderationofinternationalclassificationsystems.

• Theneedtoestablishandadheretobestpracticesforcompilingdatafromtraditionalanimalstudiesforuseinvalidationofnewmethods,withNICEATMskinsensitizationandendocrinedisruptordatabasestoserveastrialcases.

The ICATM meeting took place at IHCP, which is located near Lake Maggiore in northern Italy. The IHCP hosts the European Union Reference Laboratory for Alternatives to Animal Testing, which represents Europe in ICATM. (Photo courtesy of the Institute for Health and Consumer Protection)

Linked video:Watch a European union video released in January on the science behind development of 21st century safety testing using alternative methods (11:23)

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Inadditiontotheproceduraldiscussions,theNovembermeetingincludedupdatesoncurrenttestmethodevaluationandvalidationactivitiesinEurope,Japan,Korea,andtheU.S.

CaseyprovidedtwoupdatesonU.S.activities.OnefocusedonthereinventionofICCVAM,asoutlinedbyNIEHSandNTPDirectorLindaBirnbaum,Ph.D.(seestory).

TheothersummarizedrecentNICEATMandICCVAMactivities,includingevaluationsofacutetoxicityandeyesafetytests;aworkshopfocusedonreductionandreplacementofanimaluseforLeptospiravaccinetesting;andactivitiessupportingTox21anddevelopmentofhigh-throughputscreeningtests.AttendeesatthemeetingalsohadtheopportunitytotourtheJointResearchCentre’sGoodLaboratoryPracticefacilityusedtoconducthigh-throughputscreeningexperiments.

ICATMcurrentlyincludesmemberorganizationsfromtheEuropeanUnion,U.S.,Japan,Canada,andSouthKorea.ICATMcoordinationmeetingstakeplaceseveraltimesayearandprovideanopportunityforthefivememberorganizationstodiscussactivitiesintheirmajorareasofcooperation.RegularinteractionsallowtheICATMpartnerstodevelopgoodcommunicationsandworkingrelationships,whichsupportcollaborationsontestmethoddevelopment.

(CatherineSprankleisacommunicationsspecialistwithILSInc.,supportcontractorforNICEATM.)

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Harvard SRP collaboration honored for risk communication By Sara Mishamandani

TheKids+ChemicalSafetywebsite,supportedinpartbytheNIEHS-fundedHarvardSuperfundResearchProgram(SRP)ResearchTranslationCore(RTC),receivedthe2013RiskCommunicationAwardJan.15fromtheAllianceforChemicalSafety.Thesiteprovidesup-to-dateinformationonhealthhazardsofchemicalsandthesafeuseofchemicalsaroundchildren.

“WewantedtofindawaytouseexpertiseattheHarvardSRPCenter,relatedtohealtheffectsofmetalsandtheirmixturesinchildren,toinformpublicaudiences,”saidKatherinevonStackelberg,Sc.D.,leadontheHarvardwebsiteeffort.“Wehavebeenpartneringwiththewebsiteforthepastyear,whichwasalreadysetupbyToxicologyExcellenceforRiskAssessment(TERA).Thisstrategiccollaborationallowsustoheardirectlyfromparentsandothersabouttheirconcerns.”TERAisanindependent,non-profitorganizationdedicatedtoscientificcollaborationandbroadcommunicationofriskscienceinsupportofpublichealthprotection.Itreceivesfundingfromavarietyofsources,includingthechemicalindustry,government,andthegeneralpublic.

A researcher operates a staining platform in the high-throughput screening facility at IHCP. Attendees at the ICATM meeting had an opportunity to tour facilities used to conduct high-throughput screening experiments. (Photo courtesy of the Institute for Health and Consumer Protection)

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Chemical hazards and children’s safety ThroughtheAskanExpertfeatureonthesite,individualscansubmitquestionsorconcernsrelatedtochemicalexposuresandchildsafety.Agroupofpeerreviewers—fromtheHarvardSRP(includingvonStackelberg),CincinnatiDrugandPoisonInformationCenter,NSF,andTERA—thenhavetheopportunitytoweighinontheresponse,ensuringpeerreviewofallwebsitecontent.ArticlesavailableonthesiteincludetheAskanExpertresponses,aswellastopicschosenbyreviewers,suchaschemicalsafetyconcernsthatmaybereceivingmediaattention.

“IserveasthepointofcontactforHarvardSRPandsendoutallrequestsforreviewandcommenttootherSRPresearchers,”saidvonStackelberg.“Peoplefromdifferentorganizations,includingHarvardSRP,worktogetherconstructivelytoprovideinformationbasedonthecurrentstateofthescience.”

Encouraging bidirectional communication“Wewereattractedtothispartnershipbecausewewanttoenhanceourbidirectionalengagementwiththegeneralpublic,”saidvonStackelberg.“WedisseminateinformationthroughtheHarvardSRPwebsite,seminars,andsocialmedia,buttheKids+ChemicalSafetysitegivesusanopportunitytohearwhatpeoplewanttoknowaboutchildren’senvironmentalhealthandchemicalsafety.”

TheHarvardRTCisactivelyexploringcross-disciplinarymethodsforresearchsynthesis,gatheringevidencefrommanydifferentsourcestoansweraparticularquestion.TheHarvardCenterforRiskAnalysis,whichhoststheHarvardRTC,heldaworkshopinOctober2013todiscussmethodsforresearchsynthesisandthechallengesofcombiningresearchtopromoteevidence-baseddecision-making.Atthe2013SocietyforRiskAnalysisannualmeeting,vonStackelberggaveapresentationontheresultsofasystematicreviewusinganadverseoutcomepathwayframework,basedontheHarvardresearchsynthesisworkshop.

“TheopportunitytoreviewandcreatecontentfortheKids+ChemicalSafetywebsiteallowsustoputthatideaintopracticebyevaluatingscientificevidenceandincorporatinguncertaintytohelpparentsmaketheirowninformeddecisionsbasedonscientificfindings,”saidvonStackelberg.

(SaraMishamandaniisaresearchandcommunicationspecialistforMDBInc.,acontractorfortheNIEHSSuperfundResearchProgramandDivisionofExtramuralResearchandTraining.)

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Harvard SRP RTC co-leader von Stackelberg is working with TERA and other website supporters to answer difficult questions related to children and chemical safety. (Photo courtesy of Katherine von Stackelberg)

The Kids + Chemical Safety site features a variety of topics from the benefits and risks of flame retardants in homes, to chemical risks in children’s toys, as well as information to help parents better understand science terminology when researching chemical hazards.

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NTP scientists achieve coveted toxicology certification By Eddy Ball

Thiswinter,twoNTPcontractscientistsandtwoNTPpostdoctoralfellowstookanimportantstepalongtoxicology’sprofessionaltrack,bysatisfyingrequirementsforDiplomateoftheAmericanBoardofToxicology(DABT)certification.DABTcertificationoftenoffersanadvantageinthejobmarketandcareeradvancement,andhasbeenassociatedwithhigherlevelsofcompensation.

TheAmericanBoardofToxicologywasestablishedin1979toadvancestandardsinthefieldoftoxicologyandconferrecognitionuponthosemembersoftheprofessionwho,measuredagainstsuchstandards,demonstratecompetence.Certificationrequirementsincludeacombinationofeducationandexperience,aswellasathree-partexamination.

SeveraltoxicologistsatNIEHSandNTPhavequalifiedforthecovetedDABT,amongthemNIEHSandNTPDirectorLindaBirnbaum,Ph.D.,whoisthefirsttoxicologisttoheadtheInstitute.Birnbaumofferedthenewdiplomateshersincerecongratulations.

“Thismarksaveryimportantmilestoneinyourcareers,”Birnbaumsaid.“AchievingtheDABTinvolvesalotofhardworkonyourpart.ItalsoreflectsthequalityofthescienceconductedbyNTPandtheexcellenttrainingyou’vereceivedfromourseniorscientistshere.”

ThenewrecipientsoftheDABTare:

• MamtaBehl,Ph.D. • ArunPandiri,Ph.D.• MichaelBoyle,D.V.M. • SheetalThakur,Ph.D.

Behl is a former NTP fellow and current contract toxicologist in the NTP Systems Toxicology Group, a part of the Toxicology Branch, which oversees rodent studies. (Photo courtesy of Steve McCaw)

An Intramural Research Training Award (IRTA) fellow in the NTP Pathology Group, Boyle is also a Diplomate of the American College of Veterinary Pathologists (DACVP) and a Ph.D. candidate at North Carolina State University. (Photo courtesy of Steve McCaw)

A contract pathologist in the NTP Investigative Pathology Group, Pandiri also holds DACVP certification. (Photo courtesy of Steve McCaw)

Thakur is an IRTA fellow in the NTP Systems Toxicology Group. (Photo courtesy of Steve McCaw)

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DiplomatesholdinitialDABTcertificationfor5years,andmustdemonstratethattheyactivelypracticetoxicology,engageincontinuingeducation,andmaintainexpertknowledgeintheirfieldpriortoreceivingrecertification.

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Grantees named AAAS fellows By Eddy Ball

FourNIEHSgranteeswillbeamongnewfellowshonoredthisyearbytheAmericanAssociationfortheAdvancementofScience(AAAS).Thescientists,whowereelectedasfellowsintheBiologicalSciencesandMedicalSciencessections,willreceiveacertificateandrosetteFeb.14inChicago,duringtheAAASFellowsForum,whichispartoftheassociation’sannualmeeting.

AAASistheworld’slargestgeneralscientificsociety,andpublishesthejournalScience.Foundedin1848,thesocietyincludesmorethan261affiliatedsocietiesandacademiesofscience,servingabout10millionpeople.Anonprofitorganization,thesocietyisopentoall,andfulfillsitsmissionbyadvancingscienceandservingsocietythroughinitiativesinsciencepolicy,internationalprograms,andscienceeducation.

The2013AAASfellowsincludethefollowingdistinguishedscientistswhoenjoysupportbyNIEHS:

• FrankGilliland,M.D.,Ph.D.,isaprofessorofpreventivemedicineanddirectstheDivisionofEnvironmentalHealthwithintheKeckSchoolofMedicineattheUniversityofSouthernCalifornia(USC).HeisthedirectoroftheNIEHS-supportedSouthernCaliforniaEnvironmentalHealthSciencesCenter.

• OliverHankinson,Ph.D.,whoholdsanNIEHSgrantfortraininginmoleculartoxicology,isaprofessorofpathologyandlaboratorymedicineattheUniversityofCalifornia,LosAngeles.In2000,hebecamethefoundingdirectoroftheuniversity’sdoctoralprograminmoleculartoxicology.

• MichaelKastan,M.D.,Ph.D.,isexecutivedirectoroftheDukeCancerInstituteatDukeUniversity.AlongwithgrantsfromtheNationalCancerInstitute,KastanreceivesNIEHSsupportforstudiesofcellularstressresponsesignalingpathways.

• RobMcConnell,M.D.,isaprofessorofpreventivemedicineanddeputydirectoroftheNIEHS/EPA-supportedChildren’sEnvironmentalHealthCenteratUSC.HeistheleadresearcherontwoNIEHSgrants.

Gilliland studies asthma etiology and exacerbation, lung function growth in children, respiratory illness-related school absenteeism, and lung cancer etiology and early detection. (Photo courtesy of Steve McCaw)

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NIEHS fellow begins career in educational writing By Aleksandra Adomas

AftercompletingpostdoctoraltrainingintheNIEHSLaboratoryofNeurobiology,JacquelinedeMarchenaPowell,Ph.D.,beganacareerasamedicalsciencewriterandeditorDecember2013withEducationandTrainingSystemsInternational(ETSI).LocatedinChapelHill,N.C.,ETSIprovidestrainingmaterialsforpharmaceutical,biotech,andmedicaldevicecompanies.Powell’sfirstprojectwastodevelopaneducationalmoduleforsalesrepresentativesandphysiciansondisordersofthereproductivesystem.

Followingin-depthresearchoncareeroptionsinlifesciences,Powellfocusedonwriting.AseriesofinformationalinterviewsreassuredPowellthatawritingjobwouldbeagoodmatchforherpersonality,values,andskills,aswellasapotentialstepping-stonetootherpositions.

Negotiation powerWhenPowellfirstlearnedaboutETSIfromherprofessionalcontacts,shewasnotdiscouragedbythelackofvacancyannouncementsonthecompanywebsiteandsubmittedherresumewithageneralinquiryaboutemploymentopportunities.Thatledtoanonlinewritingtest,thenaninvitationtointerview.

Seekingstrategyadviceandsupport,PowellmetwithDeniseSaunders,Ph.D.,careercounselorwiththeNIHOfficeofIntramuralTrainingandEducation.Powellrecallsitasacrucialmeeting.“IknewImightneedtoacceptapaycutforanentry-levelindustryposition,soImadealistofotherthingsthatwereimportanttome,”shesaid.

Hankinson received the Society of Toxicology’s 2011 Distinguished Toxicology Scholar Award. His research focuses on how environmental pollutants, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin and benzo[a]pyrene, can cause cancer and other diseases. (Photo courtesy of Oliver Hankinson)

Kastan is also a professor in the departments of pharmacology and cancer biology at Duke University, as well as pediatrics. (Photo courtesy of Michael Kastan)

McConnell’s research has demonstrated connections between traffic-related air pollution and such conditions as asthma and autism. (Photo courtesy of Robert McConnell)

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Saundersexplainedthatinthehiringprocess,theonlytimethejobseekerhasleverageisimmediatelyafteranofferisextended.ThisknowledgegavePowellconfidencetoengageinnegotiationsonceshereceivedthejoboffer,andshewasabletosuccessfullynegotiateflexibleworkinghours.

NIEHS community supportPowellexpressedgratitudeforthesupportshereceivedfromtheNIEHScommunityduringherjobsearch.“I’mveryfortunatetohavemetanumberofoutstandingmentors,”sheexplained.Saundersguidedherthroughjoboffernegotiations.TammyCollins,Ph.D.,directoroftheNIEHSOfficeofFellows’CareerDevelopment,offeredPowellassistanceinbrainstormingpotentialcareeroptions.

Huei-ChenLao,abiologistondetailasascienceeducationandoutreachcoordinatorintheNIEHSOfficeofScienceEducationandDiversity,showedPowellthatmarketingskillsarevitalwhenlookingforajob.

EddyBall,Ph.D.,formerEnvironmentalFactor(e-Factor)editor,notonlyhelpedPowellwithgainingwritingexperience,butalsogaveherconstructiveadviceonexpandingherprofessionalnetwork.“Duringtheinterview,Iusedthee-Factorexperiencetohighlightmywritingskillsandinterestinawritingcareer,”Powellsaid.“SummarizingresearchpapersfortheIntramuralPapersoftheMonthsection[ofthenewsletter]washelpfulwhenIwasaskedtodescribemyownresearchinlaylanguage.Italsodemonstratedmyabilitytounderstandcomplexconceptsandtranslatethemforanonscienceaudience,”sheadded.

Finally,PowellgratefullyacknowledgedthesupportshereceivedfromPatriciaJensen,Ph.D.,headoftheNIEHSDevelopmentalNeurobiologyGroup.Duringher31/2yearsofpostdoctoraltraining,PowellworkedwithJensen,studyingasetofneuronsinthemousebrainthatreleasenorepinephrine,animportantneuromodulator.Powellwasinvolvedinthedevelopmentoftwomouselinesthatallowselectivemanipulationofdifferentsubpopulationsofnorepinephrine-releasingneurons.

(AleksandraAdomas,Ph.D,isaformerresearchfellowintheNIEHSLaboratoryofMolecularCarcinogenesis.)

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Postdoc transitions into career in biopharmaceuticals By Sheila Yong

JeremyWeaver,Ph.D.,exploredmanycareeroptionsduringhistimeasapostdoctoralfellowatNIEHS.HefoundhisperfectmatchinapositionasaprocessdevelopmentscientistatGrifolsTherapeuticsInc.,whichhebeganJan.13.

Powell’s advice to other postdoctoral fellows is to start applying for jobs early on in the postdoctoral training, to use LinkedIn to open up contacts and research position titles, and to attend local networking events like the ones organized by the American Medical Writers Association and the North Carolina Regulatory Affairs Forum. (Photo courtesy of Steve McCaw)

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WeaverobtainedhisPh.D.inAnimalSciencefromCornellUniversity,andjoinedtheNIEHSLaboratoryofSignalTransductioninNovember2010.HisresearchintheInositolSignalingGroup,ledbyStephenShears,Ph.D.,focusedonenzymesthatsynthesizeinositolpyrophosphates,andhowthesesmallsignalingmoleculesregulatecellularprocessesinresponsetoenvironmentalinsultsanddiseasedevelopment.

“Iwasinitiallyinterestedincareersinacademicorgovernmentresearch,becauseIenjoybothbenchscienceandtheopportunitytomentoryoungscientists,”Weaversaid.However,uponfurtherresearch,hediscoveredothercareerpossibilitiesinindustrythatalignbetterwithhispersonalvalues,whilestillallowinghimtopursuehispassioninscientificresearchandmentoring.

The right training for the jobWeaver’snewpositionisatechnicallychallengingone.Itinvolvespurifyingcandidateproteindrugsfromvariousexpressionsystemsandbloodplasmatobeusedinclinicaltrials.Forthatreason,hisworkissubjecttostringentexperimentalandqualitycontrol.

AtNIEHS,Weaveracquiredextensiveknowledgeaboutproteinpurificationplatformsandskillsthataretransferrabletohisnewjob.Besideslearningnewskillsinthelab,WeaveralsoreceivedassistancefromthestaffmembersattheNIEHSproteinexpressioncorefacility,whosharedtheirexpertisewithhimandhelpedbroadenhisresearchexperience.

WeaverisalsogratefultoShearsforallowinghimtheflexibilitytopursuehisresearchandcareerinterests.HesaidthatShearstookanactiveinterestinensuringhissuccess,andwasalwaysavailabletoofferadvice.“Stevehadmybestinterestsatheart,andwasactuallytheonewhoencouragedmetoconsidercareersinindustry,”henoted.

ShearsconsidersWeaveravaluablememberofhisteam.“Jeremywasnotonlyfearlessatlearningtechniquesinourgroupthatwerenewtohim,butalsomadesignificantimprovementstothemonseveraloccasions,”hecommented.ShearsisconfidentthatWeaverwillcontinuetoexcelinhisfuturescientificendeavors.

Career development and networkingApartfromhisresearchresponsibilitiesatNIEHS,WeaveralsoinvestedeffortinbuildinghisprofessionalnetworkbyattendingnetworkingeventsintheTrianglearea,includingthoseattheNCBiotechnologyCenterandTriangleBiotechTuesdays.HealsofrequentlyparticipatedineventswithinNIEHS,suchasthebrownbaglunchesandcoffeehourorganizedbytheNIEHSTraineesAssembly.Theseeventsallowedhimtointeractwithprofessionalsandfellowtraineeswithsimilarcareeraspirations.“Ilearnedhowtopresentmyselfandmyresearchtootherscientists,aswellastoreflectonmyownstrengthsandweaknesses,”Weaverexplained.Theseskillshelpedhimtremendouslyduringhisjobinterview.

Weaverfoundhisjobtheold-fashionedway—byansweringanadvertisement.Nevertheless,thecareerdevelopmentopportunitiesatNIEHSgavehimanedgeoverotherapplicants.HecreditedTammyCollins,Ph.D.,directoroftheOfficeofFellows’CareerDevelopment,forreviewinghisresume,aswellasvariouscareer-relatedworkshopsthathelpedpreparehimforthejobmarket.

Weaver hopes to return in April, to host the discussion panel on careers in contract research organizations at the NIEHS Biomedical Career Fair. He looks forward to getting together with his former fellow trainees again and sharing his new work experience. (Photo courtesy of Steve McCaw)

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Inparticular,hecitedthemanagementbootcampandthewritingworkshopbyDukeUniversityProfessorGeorgeGopen,J.D.,Ph.D.,astwoofthehighlights.“Whileattendingtheseeventswasasmalltimeinvestmentonmypart,itcaughttheinterviewers’attention,”hesaid.

AsaprocessdevelopmentscientistatGrifols,Weaverlooksforwardtoparticipatinginthedrugdevelopmentprocess.“GrifolsorganizesPatientDay,anannualeventwhichinvitespatientsusingmedicationsfromthecompanytovisitthesite,”heexplained.“HavingthedrugsIpurifygobeyondclinicaltrialsandhelpimprovepatients’liveswouldbeanabsolutelyrewardingexperience.”

(SheilaYong,Ph.D.,isavisitingfellowintheNIEHSInositolSignalingGroup.)

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2014 calendar features artwork by NIEHS postdoc By Eddy Ball

Thisyear,SeptemberwillbeaspecialmonthforSheilaYong,Ph.D.,avisitingfellowintheNIEHSInositolSignalingGroup.That’swhenherartwork,whichispartofthe2014deskcalendardistributedbythelaboratorysupplycompanyAbcam,willbeondisplayinoffices,labs,andcubiclesaroundtheworld.

Yongwasoneof13scientist-artistswhoseworkwaschosenintheAbcamMollyCalendarArtContestheldlastsummer.ContestantswereinvitedtosubmitoriginalartworkfeaturingAbcam’smascot,Molly.ThecompanydescribesthemascotasamolecularDolly,referringtotheclonedsheepfeaturedonfrontpagesworldwidein1989,whenthefirmwasfoundedinCambridge,U.K.

“Thecontestwaswhimsicalandlotsoffun,”Yongsaid.“Liketheothers,myentry,‘Molly’sLambsFirstDayatSchool,’satisfiedtheonlyspecificrequirement—thattheartworkincludeMolly,withhermolecularspace-filledtorsoandantibodylegs.Therestwascompletelyuptothecontestants.”

ThecalendarshowsMollyinavarietyofsettings,includingworkinginherlab,sittingathomebythefireside,soaringintheair,andrelaxingonMiamiBeach.

WinnersincludedscientistsfromtheU.S.,Canada,U.K.,Spain,andJapan.Theprizesaremodest—a$45cashvoucher,personalizedteeshirt,andexclusiveMollyprintcreatedbythecompany’sMollydesignexpert.But,eachmonth,thewinningartistwillalsobefeaturedwithabiographyontheAbcamcalendarpage,wherethe2014calendarisavailablefreeofcharge.

AccordingtoAbcamrepresentativeFrancescaAxe,thecalendarcanalsoberequestedbyemailatmailrequests@abcam.comwiththesubjectline“calendar–[countryofresidence],”forexample“calendar–US.”

The cover suggests the calendar’s whimsical tone, with Molly frolicking in extracellular space. (Photo courtesy of Abcam)

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Biostatistics intern reaches national semifinals for science competition By Ian Thomas

NIEHSsummerinternMitasRaywasrecognizedinDecember2013asoneof300semifinalistsfortheprestigiousIntelScienceTalentSearch(IntelSTS)competition.AsenioratEnloeHighSchoolinRaleigh,N.C.,Raywasselectedfromapoolof1,794entrants,representing489highschoolsin45statesandtheDistrictofColumbia,aswellassevenoverseasschools.

“Asearlycareermilestonesgo,thiswasahugehonor,”saidRay,whogotthenewsofhisnominationviatextwhileinclass.“IhavetogivealotofthecredittomymentorsatNIEHS.Theywerealwaysthereforguidanceandsupport,but,intheend,theygavemethespaceIneededtoreallyrunwiththisprojectandmakeitmyown.”

Winning the contest was an early holiday present for Yong, who proudly displays her cash voucher, Molly print, and her page from the calendar. “Participating in the contest reminded me of how much I used to enjoy art,” she noted. In addition to her experiments at the bench in signal transduction, she is a veteran contributing writer for the NIEHS Environmental Factor, as well as a translator fluent in Mandarin Chinese. (Photo courtesy of Steve McCaw)

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IntelSTSisamongthenation’smostdistinguishedprecollegesciencecompetitions,boastinganimpressivelistofalumni,manyholdingsomeoftheworld’smostcovetedscientificawards,includingtheNobelPrizeandNationalMedalofScience.

All about the numbersRayspentthemajorityofhissummerworkingintheNIEHSBiostatisticsBranch,taskedwithexploringstatisticalissuesofrelevancetoenvironmentalhealth.There,underthetutelageofKeithShockley,Ph.D.andGraceKissling,Ph.D.,Raydelvedheavilyintotherealmsofcomputerscienceandchemicaltesting,whiledevelopinghisaward-winningresearch.

“Alotoftheprocessesbywhichwetestchemicalstodayareextremelylimited,becauseoftheirhighcostandlowthroughput,”saidRay.“Thegoalofthisprojectwastodesignanewmethodusingcomputerscienceandcell-basedassaysthatwouldallowustotestawiderangeofchemicalsatonceandinafractionofthetime.”

“WorkingwithMitaswasawonderfulexperience,”saidKeithShockley,Ph.D.,oneofRay’smentorsatNIEHS.“He’sareallyenergeticandself-motivatedperson,andifhistimewithusisanyindication,he’sgotabrightfutureaheadofhiminscience.”

Looking forwardInadditiontohissemifinalistnomination,Rayalsoearneda$1,000cashprizeforhiswork—aprizethatIntelSTSmatched,dollarfordollar,andpresentedtoEnloeforitscommitmenttoeducationalexcellenceinscience,math,andengineering.

“IthinkthegreatestthingaboutanhonorlikeIntelSTSisthatitpushesyoutoworkevenharderthanyoualreadydo,”saidRay.“That’sanadmirablethinginanyfield,muchlessonelikecomputerscience,wherethingsarealwayschanging.”

IntelSTSisaprogramoftheSocietyforScienceandthePublic,anonprofitmembershiporganizationdedicatedtopublicengagementinscientificresearchandeducation.

(IanThomasisapublicaffairsspecialistwiththeNIEHSOfficeofCommunicationsandPublicLiaison,andaregularcontributortotheEnvironmentalFactor.)

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Ray hopes to study computer science at the University of California, Berkeley; the Massachusetts Institute of Technology; or Carnegie Mellon University. (Photo courtesy of Steve McCaw)

Ray, left, and Shockley discuss the finer points of Ray’s project. (Photo courtesy of Steve McCaw)

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Science NotebookUsing nanomedicine to improve human health By Robin Arnette

Moore’sLawstatesthatthenumberoftransistorsonacomputerchipwilldoubleapproximatelyeverytwoyears.SinceIntelco-founderGordonMooreofferedthatassessmentin1965,thedevelopmentofsmallerandsmallertransistorshasallowedcomputingpowertodoubleevery18months.Byborrowingthemanufacturingtechniquesofthemicroelectronicsindustry,today’sbiomedicalandchemicalengineersaredesigningbettermedicinesandvaccinesusingnanotechnology.

OneoftheresearchersattheforefrontofnanomedicineisJosephDeSimone,Ph.D.,founderofLiquidiaTechnologies,ananotechnologycompanybasedinResearchTrianglePark(RTP),N.C.Aspartofthe2014NIEHSDistinguishedLectureSeries,DeSimonevisitedtheInstituteJan.24totalkaboutmakingorganicparticlesfortherapeutics.GaryBird,Ph.D.,staffscientistintheNIEHSCalciumRegulationGroup,hostedtheseminar.

Perspective rooted in materials scienceDeSimoneisamaterialsscientistbytrainingandholdsprofessorshipsattheUniversityofNorthCarolinaatChapelHillandNorthCarolinaStateUniversity.Hehasspunoffseveralotherbiotechfirms,butthebasisforallofhisentrepreneurialpursuitsistheworkhisteamperformedinhisuniversitylab.

Atthebeginningofhistalk,heprovidedcontextforhowscientistshaveacceleratedthegrowthofnanotechnology.“Intheearly70s,youcouldonlyfitabout2,300transistorsintothecoupleofsquarecentimetersofacomputerchip,becauseeachtransistorwasalittlebiggerthanaredbloodcell—about10microns,”DeSimonesaid.

Linked video:Watch DeSimone discuss the process of making therapeutic nanoparticles at his 2011 TEDMED talk. (19:44)

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DeSimone is the Chancellor’s Eminent Professor of Chemistry at UNC, William R. Kenan Jr. Distinguished Professor of Chemical Engineering at NCSU, and founder of several local biotech companies. (Photo courtesy of Steve McCaw)

NIEHS and NTP Director Linda Birnbaum, Ph.D., shared DeSimone’s excitement about bringing down the cost of vaccines, during the question-and-answer session. (Photo courtesy of Steve McCaw)

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“Today’schiphasbillionsoftransistorsinthatsamearea,so,biologically,Moore’sLawhasgonefromthesizeofasinglecelltoavirusparticle.”

Using nature as a templateDeSimonesaidthattheinspirationforthesize,shape,chemicalproperties,andmechanicsofhisnanoparticlescomesfromnature.Forinstance,afterstudyinghowahelicoptermapleseedcreatesaerodynamiclift,heshapedonegroupofparticleslikeit.Bymimickingamapleseed’snaturalautorotationwhenfallingthroughair,theseparticlesfloateffortlesslythroughthelung’sairwaywheninhaled,deliveringtheirpharmaceuticalcontent.

Inanotherexample,DeSimoneandhisteamexaminedthephysicalpropertiesofredbloodcells.Heexplainedthatthesecellsaresoftwhenyoung,permittingthemtosqueezethroughextremelysmallsinusoidsinthespleen.Asthesecellsnear120days,theaveragelifeexpectancyofaredbloodcell,theystiffen,becomingunabletotravelthroughthespleen.

“That’showthebodyremovesoldredbloodcells,sousingsomeofcharacteristicsofmechanobiologyallowsustounderstandhowtoevadebiologicalbarriers,”DeSimonesaid.Mechanobiologyisanemergingfieldofscienceattheinterfaceofbiologyandengineering.

PRINTing better medicines and vaccinesAftertheparticledesignphaseisdone,thenextstepistoproducelargequantitiesofparticlesusingatechniqueDeSimone’steamdeveloped.Theprocess,knownasparticlereplicationinnon-wettingtemplates,orPRINT,physicallyetchesaformintosilica,poursliquidfluoropolymersintoit,andzapstheliquidwithlightsothatithardens.

Atthispoint,DeSimonesaiditessentiallylookslikeanicecubetray,butonthenanoscale.Then,techniciansfillthetraywithaliquidformofacancerdrug,antibiotic,orwhatevertherapeuticagenttheywanttostudy.Otherprocessingstepsultimatelyleadtothecreationofparticleshavingtheprecisionanduniformityofmicrocircuits.

“WeconvertedthistoaGMP[goodmanufacturingpractice]-compliantprocess,”DeSimonesaid,referringtothemanufacturingprocessattheLiquidiafacilityhousedinRTP.“Itallowsustodeliveradrugstrategyofchemotherapeutics,vaccines,andimmunostimulatoryapproachesforcancer.”

ThePRINTmethodhasbeensosuccessfulthatLiquidiareceivedthefirsteverequityinvestmentinafor-profitbiotechfirmfromtheBillandMelindaGatesFoundation.WhenDeSimoneandBillGatesmet31/2yearsago,bothmencameawayfromthemeetingbelievingtheycouldusethistechnologytodrivedownthecostofvaccinesandimproveglobalaccess.

NIEHS Scientific Director Darryl Zeldin, M.D., a lung disease specialist, was especially interested in DeSimone’s inhalation data. (Photo courtesy of Steve McCaw)

Bird said DeSimone’s research has had an enormous impact on bridging engineering and nanomedicine. (Photo courtesy of Steve McCaw)

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New NTP atlas helps standardize nonneoplastic lesion diagnoses By Robin Mackar

InJanuary,NTPdebutedanewweb-basedresourcethatwillhelppathologistsworldwidebetterdiagnose,record,anddiscussnonneoplasticrodentlesions.Nonneoplasticlesions,ornoncancerlesions,canbeprecursorstocancerandcanalsobeassociatedwithlife-threatening,noncancerousdiseases,suchaspulmonaryfibrosis,andarethereforeimportantfindingsintoxicityandcarcinogenicitystudies.

Thisnewtool,theNTPNonneoplasticLesionAtlas,isavailableonlineandishighlightedinanewcommentarybyNTPstaffinthepeer-reviewedjournalToxicologicPathology.

Whencompleted,theAtlaswillconsistofthousandsofhigh-quality,zoomableimagesanddiagnosticguidelinesarrangedin56sectionsorganizedbyorgansystem,eachcoveringaparticularorganortissue.Thesubsectionsonbonemarrowinthehematopoieticsystem;liverandgallbladderinthehepatobiliarysystem;skinintheintegumentarysystem;brain,nerve,andspinalcordinthenervoussystem;andtheureterandurinarybladderintheurinarysystemsectionarealreadyavailable.

DeSimone’s team can produce nanoparticles with a variety of sizes and shapes using PRINT technology. (Graphic courtesy of Joseph DeSimone)

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Inadditiontothedigitalimages,eachlesionpageincludestheNTPrecommendedterminology,histopathologicdescriptions,andotherusefulinformationaboutthelesions,diagnosticguidelinerecommendations,andreferences.

An authoritative resource“HavingaresourcethattoxicologistsandpathologistsallovertheworldcanusetospeakthesamelanguagewhendiagnosingnonneoplasiclesionsinratsandmicewillbeinvaluabletotheNTPandtothefield,”saidRobertSills,D.V.M.,Ph.D.,headoftheNTPCellularandMolecularPathologyBranch.

Sillsconceivedtheatlasand,alongwithhisteam,helpedbringtheprojecttofruition.“Beingabletoactuallyzoominandsee,inexquisitedetail,whattheselesionslooklikeandknowingthepreferredNTPdiagnostictermforeachlesionwillleadtomorestandardizationofstudyresults,”heexplained.

TheimageshavebeencompiledmostlyfromtheNTParchives,astate-of-theartfacilitythattheNTPhasbeensupportingsince1984tohouseitsexpansivecollectionofresearchspecimensandsupportingdatafromNTPstudies.

“ThepathologycommunitylookstoNTPtodevelopthesekindsofresources,”Sillssaid.TheatlashelpsimprovetheorganizationanddiagnosticconsistencyoftheNTPdatabaseandcanalsobeusedbyotherlaboratoriestostandardizetheirdiagnosticstrategyandimprovetheirowndatabases.

Establishing the gold standard“TheNTPhaslongbeenknownforestablishingthediagnosticcriteriaandterminologyforneoplasticlesionsinrodentcancerbioassaysandwewantedtoestablishthesamestandardsfornonneoplasticlesions,”saidNTPpathologistMarkCesta,D.V.M.,Ph.D.,aneditorandauthoroftheToxicologicPathologypaperandtheatlas.Cestaaddsthatnonneoplasticdiseasesarealsoamajorcauseofmorbidityandmortalityinhumans,withsomeofthesediseasesthoughttobebroughtonbyenvironmentalcauses,makingthisresourcevaluabletomedicalresearchersworldwide,aswellastoNTPstudypathologists.

“WeknowthatmanylesionsseeninhumandiseaseshaverelevantcounterpartsinNTProdenttoxicityandcancerstudies,”Cestasaid.“Thiswillbealivingdocumentthatwewillkeepupdatingasnewinformationaboutdiagnosingnonneoplasticlesionsbecomesavailable,”Sillssaid.“Itwillbecomethemust-haveresourceforeverypathologistandagreattrainingtoolforthenextgenerationoftoxicologicpathologists.”

Collaborative effort“Thiswastrulyagroupeffort,”saidNTPAssociateDirectorJohnBucher,Ph.D.“Wecouldn’thaveaccomplishedthiswithoutdrawingupontheexpertiseofmany.”EachsectionoftheAtlaswasextensivelyreviewedbyNTPpathologistsandbyindependentpathologyexpertswhospecializeinspecificorgansystems.

The NTP Nonneoplastic Lesion Atlas was the brainchild of Sills. It will be used by NTP and its many pathology partners to standardize lesion diagnosis, terminology, and the way lesions are documented. It is expected to improve understanding, consistency, and accuracy between pathologists and laboratories. (Photo courtesy Steve McCaw)

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Additionally,expertsinweb-basedtechnologieswerealsocalledupontocreatetheonlinesearchabledatabase.TheAtlasalsowentthroughseveralfocusgroupsbeforelaunchingtoensureusability.“IthinktheAtlaswillbeatremendousresourcetotheNTPandmanyothers,”Bucheradded.

NTPisproactivelycreatingawarenessabouttheAtlasamongkeystakeholders.TheNTPwillhostanexhibitorsessionattheSocietyofToxicologyannualmeetinginMarch,offerdemonstrationsduringaNTPsatellitesymposiumattheSocietyofToxicologicPathologyannualsymposiuminJune,andprovideseveraldemonstrationsandwebinarsforNIEHSandNTPstaff,grantees,internationalusers,andpathologystudents,amongothers.

Citation:CestaMF,MalarkeyDE,HerbertR,BrixA,HamlinM,SingletaryE,SillsRC,BucherJR,BirnbaumLS.2014.TheNationalToxicologyProgramweb-basedNonneoplasticLesionAtlas:Aglobaltoxicologyandpathologyresource.ToxPath42:458-460.

(RobinMackaristhenewsdirectorintheNIEHSOfficeofCommunicationsandPublicLiaison,andafrequentcontributortotheEnvironmentalFactor.)

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Scientists begin to fill in the gaps in understanding about fracking By Eddy Ball

NIEHS-fundedscientistsarelookingmorecloselyattheimpactofhydraulicfracturingonairandwaterqualityindrilling-denseareasofOhioandColorado.

Offeringtheprospectofenergyindependenceandnewsourcesofincomeforlandowners,hydraulicfracturing,orfracking,hasspreadmanytimesfasterthanhasresearchintothepotentialhealtheffectsofthechemicalsusedinthepractice.AlongwithanupcomingseminarattheUniversityofPennsylvania(seetextbox),thesenewstudiesarehelpingraiseawarenessofthepotentialenvironmentalpublichealthimpactofthisunconventionalnaturalgasdrillingmethod.

New studies build on ongoing researchInastudypublishedDec.16,2013inthejournalEndocrinology,ateamofscientistsledbyUniversityofMissouriAssociateProfessorSusanNagel,Ph.D.,identified,forthefirsttime,dozensofchemicalsusedinhydraulicfracturingfornaturalgasthatmayhaveadverseeffectsonhumanhealth,bydisruptingestrogenandandrogenaction.

Cesta has been instrumental in reviewing and coordinating all the content for the new atlas, and has worked with a dedicated team of federal and contract staff to bring the atlas to fruition. When completed, the atlas will contain 56 sections and thousands of images. (Photo courtesy Steve McCaw)

Nagel, a reproductive biologist specializing in estrogenic actions, reported finding moderate levels of endocrine-disrupting chemicals in samples from the Colorado River, the basin where the Garfield County fracking sites drain. The county has more than 10,000 active wells. (Photo courtesy of the University of Missouri)

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WithanewgrantfromNIEHS,ateamofresearchersfromtheUniversityofCincinnatiandOregonStateUniversityislayingthefoundationforacommunity-basedparticipatoryresearchpilotstudyofairqualityandfrackinginCarrollCounty,Ohio(seestory).

Trying to answer nagging questions about safety“Withfrackingontherise,populationsmayfacegreaterhealthrisksfromincreasedendocrine-disruptingchemicalexposure,”NagelwasquotedassayinginaLosAngelesTimesarticle.“I’mnotanalarmistaboutthis,butitissomethingthecountryshouldtakeseriously.”

Theresearcherscompared39watersamples,fromknownincidentsites,thathadexperiencedsomesortofspilloraccidentrelatedtofrackinginadrilling-denseregionofGarfieldCounty,Colo.,withsamplesfromdrilling-sparseareasinMissouriandColoradowithoutspills.Theyfoundthatdrilling-denseregionwatersamplesshowedasmuchastwotimesgreaterestrogenic,anti-estrogenic,oranti-androgenicactivitythanwaterfromreferencesites,whereactivitywasdramaticallylower.

NagelreceivedNIEHSfundingin2011tostudytheDNAmethylationpatternintheendometriumofwomenwithendometriosis.Withapreviousgrant,sheexaminedtheeffectsofprenatalendocrine-disruptingchemicalexposureandalteredexpressionofendometriosisrelatedgenesinamousemodel.Shesaidherultimategoalistolinkthesetwostudies,byidentifyingmarkersofexposureinmiceandconnectthemwithmarkersinwomen.

AsNagelandhercolleaguesreadilyadmit,thekindofearly-stageresearchhergroupconductedinColoradocannotproduceconclusiveresults,andmorestudiesareneededtofullyunderstandtheimplicationsoftheirfindings.InaninterviewwithRTNewsfollowingpublicationofthestudy,shesaid,“Thereisarealdearthofinformationonthehealthimpactsofthisentireprocess.”

Theteamshowedstrongassociationsbetweenfrackingsitesandthepresenceofchemicalswithendocrine-disruptingeffectsinwater,butnotaclear-cut,cause-and-effectlink,ascriticswerequicktopointoutinastatementfromEnergyinDepth,oneofseveraldefensiveresponsesfromindustrygroups.

Others,suchaseditorsoftheRaleigh(N.C.)NewsandObserver,inaDec.19,2013editorial,havecitedNagel’sfindingsasonemorereasontoproceedwithcaution,inregardtoregulationsforproposedfrackingoperationsintheirstate.“Thestate’sMiningandEnergyCommissionshoulderronthesideofdisclosureandcaution,asitwritestherulesforNorthCarolina,”theyconcluded.

Linked video:Watch an RT news channel interview with Nagel on the implications of her new findings (04:13)

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Upcoming symposium on hydraulic fracturing

TheUniversityofPennsylvaniaCenterofExcellenceinEnvironmentalToxicology(CEET)andtheCenterforPublicHealthInitiativesareco-hostingasymposiumFeb.18attheSmilowCenterforTranslationalResearch,exploringtheimpactofunconventionalnaturalgasdrillingoperationsontheenvironmentandpublichealth.

CEETisanenvironmentalhealthsciencescorecenterfundedbyNIEHS.Thesymposiumisintendedtoengagemanydifferentstakeholdersconcerninghydraulicfracturing,andeducateparticipantsontheprocessandeffectsontheenvironmentandpublichealth.Themeetingwillalsoprofileongoingresearchonthistopic,andendwithapaneldiscussiononcitizens’concerns.InadditiontopresentationsbyNIEHSgranteesduringthesymposium,theprogramwillconcludewithremarksonfuturedirectionsbyNIEHSSeniorMedicalAdvisorAubreyMiller,M.D.

Registrationisfreebutrequired.

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Citation:KassotisCD,TillittDE,WadeDavisJ,HormannAM,NagelSC.2013.EstrogenandAndrogenReceptorActivitiesofHydraulicFracturingChemicalsandSurfaceandGroundWaterinaDrilling-DenseRegion.Endocrinology;doi.org/10.1210/en.2013-1697[Online16December2013].

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Community engagement drives new pilot study on fracking and air quality By Eddy Ball

AteamofNIEHS-fundedresearchersmetwithcitizensofCarrollCounty,Ohio,Jan.9markingoneofthefirststepsinthenewone-year,community-engagedpilotstudyoffrackingandairquality.

HostedbyCarrollConcernedCitizens,theteamismountingarecruitmenteffortforanewNIEHS-fundedpilotstudyoflandownerspotentiallyaffectedbyhydraulicfracturing(fracking)intheruralAppalachianOhiocounty.Theresearchersplantoplacepassiveairsamplingdevicesat4-6sitesonoradjacenttolandwheregasisbeingextractedbytheunconventionalnaturalgasdrilling(UNGD)method(seefactsheet).

TheresearchersfromtheUniversityofCincinnati(UC)andOregonStateUniversity(OSU),ledbyUCProfessorErinHaynes,Dr.P.H.,arealsorecruitingindividualstowearwristbandpersonalmonitorsthatcanmeasuretheirexposuretosome1,000chemicalsintheair,inwhathasrapidlybecomethemostshale-drilledareainthestate.

ThestudyisfundedbyagrantfromNIEHStotheUCCenterforEnvironmentalGeneticsledbyShuk-MeiHo,Ph.D.OSUresearchersKimAnderson,Ph.D.,andLaurelKincl,Ph.D.,arealsofundedbyNIEHSgrants.

The community as a research partnerHaynesexplainedthatthestudywilladdressthecommunity’sconcernsaboutthepotentialconsequencesoffrackingatthequicklygrowingnumberofsitesinthecounty.“AsOhio’sshalegasboomcontinues,thousandsofnewpadswillbeinstalled,manyofwhichwillbeincloseproximitytohomesandbusinesses,”shetoldreporterBobDowningforastoryintheAkronBeaconJournal.“Understandingifsignificantairqualitychangesoccurduringthevariousshalegasoperationsisimportanttounderstandinghealthrisksforhumansandlivestock.”

Haynes is also the director of the NIEHS-funded UC Center for Environmental Genetics Community Outreach and Engagement Core, and director of the Clinical and Translational Research training program. (Photo courtesy of the University of Cincinnati)

Linked audio:Listen as Carroll Concerned Citizens Chair Paul Freezel describes his group’s support for the new study (0:25)

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Inplanningthestudy,HaynesandherteamhaveworkedcloselywithresidentsofCarrollCounty.Summarydatawillbesharedfollowingthestudy’scompletion.Participantswillbeinformedabouttheirindividualmonitoringresults,whichwillbekeptconfidential.

“Byemphasizingcommunityparticipation,we’llbebringingcutting-edgesciencedirectlytothepublic,bridgingthegapbetweenscientistsandtheircommunities,”Haynessaid.“ItiscriticalthatresearchrelatedtoUNGD[fracking]involvekeycommunitystakeholdersattheoutset,asitistheirairandwaterthatwe’restudying.”

Looking aheadAccordingtoHaynes,thepilotstudyshouldbecompletedbysummer,andsheisalreadyworkingtowardfundingforalargerfollow-upstudy.“Wewanttoaddressthequestionveryrigorouslyandwithanopenmind,”shesaid.“We’renotcomingwithaconclusioninhand—weactuallywanttoseewhatthedatawillreveal.”Thestudywillalsoevaluatetheperformanceofthesamplersdeployed.

“AdditionalUNGDresearchisneeded,includingwaterquality,impactonruralroadwaysandcommunityinfrastructure,andUNGD-generatedwastetransportationandinjectionintowells,”Haynesexplained.

HaynessaidshehopestosharethedatawiththeOhioDepartmentofNaturalResources,whichregulatesoilandgasdrillinginthestate,aswellastheenergyindustry.“Ifwedofindsomething,wehopethatthey[theindustry]wouldmakeachange.”

(ThisstoryisbasedinpartonanarticlebyKeithHerrell,apublicinformationofficerwithhealthNEWS,theUCAcademicHealthCenterPublicRelationsandCommunicationspublication.)

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The passive air sampling devices, developed by Anderson’s team for monitoring air quality following the Deepwater Horizon oil spill in the Gulf, can be attached to trees, fence and utility posts, or structures, posing no danger to humans, livestock, or crops. The sampling box is in the shape of a T, weighs 3 pounds, and is 29 inches long by 12 inches wide at the T. (Photo courtesy of Kim Anderson)

The small, lightweight personal samplers are made of silicone, which absorbs chemicals in the air. Researchers can then extract and identify these chemicals. As the cartoons show, participants will wear their bracelets 24 hours a day. (Photo courtesy of Kim Anderson)

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Wastewater treatment offers a view into environmental chemicals’ risks By Carol Kelly

Wastewatertreatmentfacilitiesoffertremendousvalueasobservatoriesforwhatchemicalsarebeingproduced,consumed,andcirculatedinourenvironment,accordingtonewresearchfromNIEHSgranteesArjunVenkatesan,Ph.D.,andRolfHalden,Ph.D.,fromArizonaStateUniversity(ASU).

“Ourstudyhighlightstheuseofsewagetreatmentplantsasaresource,insteadoftreatingthemasameredecontaminationfactory,”saidVenkatesan,adoctoralresearchassociateinHalden’slabatASU.

Wastewatertreatmentfacilitiesarethecornerstoneefforttokeepthenation’swatersclean.Processedsolidwastematerialisaresidualofwastewatertreatment,andthebyproductslabeledbiosolidsarecharacterizedastreated,tested,anddeterminedsafeforlandapplication.Thesebiosolidscontainnutrientsusefulasfertilizers,aswellasheavymetals,toxicants,andpathogens.

Testing biosolidsTheresearchersanalyzedbiosolidsfrommunicipalwastewatertreatmentplantstoidentifycontaminantsofemergingconcern(CECs),whicharechemicalsknowntobeharmful,butwithunknownriskfromtheirpresence,frequencyofoccurrence,orsource.Ofparticularinteresttotheresearcherswerechemicalsthatstayintactduringtheirjourneythroughseveralphasesofwastewatertreatmenttothebiosolidsstage.Itwasimportanttoidentifythesechemicals,becausetheyarelikelytoalsopersistintheenvironment.UsinganationallyrepresentativesampleofbiosolidscollectedbytheU.S.EnvironmentalProtectionAgency(EPA),theresearchersdetected123CECs.Thequantitiesofthosechemicalsfoundinthesamplescanbeusedtoestimatetheamountofeachoriginallyproduced.

“Ourstudysendsapowerfulmessagethatthechlorinated,brominated,andfluorinatedchemicalcompoundsmassproducedtodaydonotbiodegradesafelyornaturally,”saidHalden.“Weprovideawaytoidentifytoxicprioritycompoundsuseddailyinlargequantitiesthatarepronetoaccumulationinorganismsandpeople.”

Rolf Halden, Ph.D., is director of the Biodesign Institute Center for Environmental Security; professor in the School of Sustainable Engineering and the Built Environment; and senior sustainability scientist at the Global Institute of Sustainability at ASU. (Photo courtesy of Arizona State University)

Arjun Venkatesan, Ph.D., is currently working on monitoring the occurrence and persistence of emerging contaminants in biosolids, soils, and sediments at ASU. (Photo courtesy of Arizona State University)

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Monitoring contaminantsCommonchemicalscreeningmethodstypicallydonotconsidertwoimportantriskstopeopleandecosystems—currentchemicalproductionratesandhowchemicalsbehaveinreal-worldbiologicalsystems.Theresearchersbelievethattheirapproach,usingbiosolidstoidentifyamountsandtypesofchemicalspresentintheenvironment,addressestheseshortcomings,andshouldbeawelcomeadditiontothetoolboxforriskassessorstaskedwithprioritizingandmanagingCECs.

“Onecouldbetterunderstand,orevenpredict,thefateanddistributionofmass-producedchemicalsinenvironmentalsystems,bystudyingtheamountandbehaviorofthosechemicalsinsewagetreatmentplants,”saidVenkatesan.

“Inadditiontomonitoringcompoundsasproduced,biosolidscanprovideestimatesoftheidentityandvolumeofchemicaltransformationproductsresultingfromtheirdegradation,”saidHalden.“Thischemicalprogenymaybeequally,ormore,harmfulthantheirparentcompounds.Oneexampleisnonylphenol,anendocrinedisruptor,whichisreleasedfromthebreakdownofalkylphenolethoxylatedetergents.”

Assessing biosolids riskIntheU.S.,morethan50percentofbiosolidsproducedbywastewatertreatmentareappliedtolandasanagriculturalamendment,accordingtotheEPA.Toreducetheamountthatmustbelandfilledorincinerated,theyareincreasinglyusedassoilconditionersorfertilizers,orforlandreclamation.Variouslandapplicationsofbiosolidstakeplaceinall50states.

In2002,theNationalResearchCouncilsaidthatEPAshouldconductstudiesofthepotentialhealthrisks,orlackthereof,toworkersandresidentialpopulationsexposedtobiosolidsfromlandapplications,butthisrecommendationhasnotbeenaddressedtodate.EPAregulationsrequireperiodicmonitoringofcertainheavymetalsandindicatorbacteriainsolidwastefromwastewatertreatment,butthereisnoroutinemonitoringofothertoxicants.ThefindingofCECsinthestudy’sbiosolidssamplesunderscorestheneedforimprovedassessments,accordingtotheresearchers.

The researchers’ diagram shows how chemicals move from production, then into and through people, to the wastewater treatment environment. (Courtesy of Arizona State University)

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“Weneedtotakestepsnowtoavoidhumanandecologicalhealthhazards,aswellasthecostly,long-termcontaminationofsoilandwaterresourcesnationwide,”saidHalden.“Thereturnoninvestmentcanbehuge.It’smuchmoreexpensivetocleanuportreatlarge-scaleenvironmentalcontaminationthantotreatcomparativelysmallerprocessstreamsatthesource.”

Citation:VenkatesanAK,HaldenRU.2014.Wastewatertreatmentplantsaschemicalobservatoriestoforecastecologicalandhumanhealthrisksofmanmadechemicals.SciRep4:3731.

(CarolKellyisasciencewriterwithMDBInc.,acontractorfortheNIEHSDivisionofExtramuralResearchandTraining.)

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High-throughput screening examines multiple effects of 1060 compounds on zebrafish By Nancy Lamontagne

ResearchersledbyOregonStateUniversitySuperfundResearchProgramgranteeRobertTanguay,Ph.D.,usedhigh-throughputscreeningtoanalyze1,060uniquecompoundsfor22possibleeffectsonzebrafishembryos.

Researcherssaidthisisoneofthelargestsystematicin vivotoxicologicalstudiestodate.Usingzebrafishtotestalargenumberofchemicalswithknownstructures,andlookatalargenumberofeffects,willallowtheidentificationofgroupsofchemicalsthatmaysharethesamemechanismoftoxicity.Chemicalsthatshowaresponseinzebrafishcanalsobefurtherstudiedusingothersystems,suchascell-basedtesting.

“Ourstudydemonstratesthatitisnowpossibletorapidlyevaluatethebioactivityofalargenumberofchemicalsinthewholeanimal,”Tanguaysaid.“Theabilitytoscreenmoreofthechemicalspacewillhelpthefieldmoveclosertorelevantwholeanimalchemicalstructure-responserelationshipsforpredictivetoxicology.”

ThehighlyautomatedandstreamlinedscreeningapproachdevelopedbytheresearchersisdetailedinapaperpublishedintheJanuaryissueofToxicologicalSciences.

A comprehensive screening approachUsingtheirnewapproach,theresearchersconducteddevelopmentalandneurotoxicityscreeningof1,060uniqueToxCastphase1andphase2chemicals.TheU.S.EnvironmentalProtectionAgency(EPA)NationalCenterforComputationalToxicologyToxCastprogramisassessingalargenumberofchemicals,

Tanguay said that the goal in screening chemicals with zebrafish is not simply to identify hazardous compounds, but to also generate data that will allow prediction of toxicity. (Photo courtesy of Robert Tanguay)

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usingadiversesetofin vitrotests,withthegoalofdevelopingcost-effectivewaystoprioritizethethousandsofchemicalsforwhichthereisnotoxicityinformation.ToxCastphase1chemicalsarewell-studiedchemicals,suchaspesticides.Phase2chemicalscomefromabroadrangeofsources,includingindustrialandconsumerproducts,foodadditives,greenproducts,cosmetics,andpharmaceuticaldrugs.

Usingautomationtostreamlinethescreeningprocess,investigatorsemployedanautomatedembryoplacementsystemtoload6-hour-oldzebrafishembryosinto96-wellplates.Thentheresearchersaddedonechemicalperwell,atsixconcentrations,with32embryosusedforeachconcentration.Theymonitoredvariousdevelopmental,behavioral,andmorphologicalendpoints,attimepointsupto120hoursafterfertilization.

Thediversityofthemeasuredendpoints,andthelargenumberofanimalspertest,increasedthescreening’ssensitivitytodetecthazardouschemicals.Also,bymeasuring18ofthe22endpointssimultaneouslyovertime,theresearcherscoulddeterminerelationshipsbetweentheendpointsandembryonicdevelopment.DavidReif,Ph.D.,astudycollaboratorfromNorthCarolinaStateUniversity,wasinstrumentalindevelopingnovelanalysisandvisualizationtools,suchasacustomphotomotorresponseassessmenttooltoquantifyanembryo’sresponsetopulsesoflight.

Biological responsesOfthe1,060uniquechemicalsevaluated,487showedsignificantbiologicalresponses.Thedatademonstratedthatmortalityalonewasnotagooddeterminantoftoxicity,becauseofthehighnumberoffalsenegatives.Globalpatternsofvariationacrossthetestedchemicalsrevealedhighcorrelationamongendpoints.However,somechemicals,suchasthepesticidesthiram,ziram,andsodiumdimethyldithiocarbamate,affectedonlyasingledevelopmentalendpointinthezebrafish.Theresearchersconcludedthattheirapproachdetectedadverseresponsesthatothermethodswouldmiss.

Thescientistscontinuetorefinetheirexperimentalapproachandtoexpandthenumberofchemicalstested.TheyareworkingwiththeEPA,theNationalToxicologyProgram,andotherstocomparetheirzebrafishfindingswithdatacollectedfrommammaliancellsandwholeanimalmodels.Theresultswillallowthemtodeterminethechemicalclassesforwhichthezebrafishmodelispredictive,andtoidentifythelimitationsofthemodel.

Citation:TruongL,ReifDM,StMaryL,GeierMC,TruongHD,TanguayRL.2014.Multidimensionalinvivohazardassessmentusingzebrafish.ToxicolSci137(1):212-233.

Zebrafish have several advantages as a model system for toxicology screening. They develop rapidly, have a short life cycle, and are clear for the first few days of life. Also, approximately 84 percent of human genes involved in disease are present in zebrafish. The zebrafish embryos above are 24 hours old. (Photo courtesy of Robert Tanguay)

Each well, above, contains a zebrafish embryo. “This was an enormous study that required a multidisciplinary team composed of mechanical engineers, software engineers, toxicologists, statisticians, and informatics specialists to complete,” Tanguay said. (Photo courtesy of Robert Tanguay)

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(NancyLamontagneisasciencewriterwithMDBInc.,acontractorfortheNIEHSDivisionofExtramuralResearchandTraining.)

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Study identifies novel compounds more mutagenic than parent PAHs By Sara Mishamandani

ResearchersatOregonStateUniversity(OSU)havediscoverednovelbreakdownproductsthatformwhenspecifichighmolecularweightpolycyclicaromatichydrocarbons(PAHs)chemicallyinteractwithnitrogen.Thesenitrated-PAHs(NPAHs),whichwerenotpreviouslyknowntoexist,aremoremutagenicthantheirparentPAHcompounds.

Mutagensarephysicalorchemicalagentsthatchangethegeneticmaterialofanorganism,increasingthefrequencyofmutations.Becausemanymutationscausecancer,mutagensarelikelytoalsobecarcinogens,oragentsdirectlyinvolvedincausingcancer.

Automation helped improve accuracy and streamline the high-throughput zebrafish screening. The researchers used this robot to load the embryos into 96-well plates. (Photo courtesy of Robert Tanguay)

NPAHs are produced by certain types of chemical reactions, such as those found in grilling meat. (Photo courtesy of Oregon State University)

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“Someofthecompoundsthatwe’vediscoveredarefarmoremutagenicthanwepreviouslyunderstoodandmayexistintheenvironmentasaresultofheavyairpollutionfromvehiclesorsometypesoffoodpreparation,”saidStaciSimonich,Ph.D.,professorofchemistryandtoxicologyintheOSUCollegeofAgriculturalSciencesandSuperfundResearchProgram(SRP)researcher.

Thestudy,ledbySimonich,waspublishedinJanuaryinthejournalEnvironmentalScienceandTechnology.

Understanding the formation of NPAHsPAHsarepresentinfossilfuelsandarealsoformedbyincompletecombustionofcarbon-containingfuels,suchaswood,coal,diesel,andtobacco.ManyPAHs,suchasbenzo[a]pyrene,areknowncarcinogens.

Researchersinvestigatedthereactionsoffivemutagenic,highmolecularweightPAHsinexperimentsthatmimickedconditionssimilartothosefoundintheEarth’satmosphere.TheyalsoconductedatheoreticalstudytounderstandtheformationofNPAHs.Theteamdiscoveredthatnitrogendioxide(NO2)andnitrate(NO3)/dinitrogenpentoxide(N2O5)wereeffectiveoxidizingagentsintransformingPAHstoNPAHS.

AccordingtotheOSUpressrelease,NPAHsraisefurtherconcernsaboutthehealthimpactsofheavily-pollutedurbanairanddietaryexposure,althoughithasnotyetbeendeterminedinwhatlevelthecompoundsmightbepresent,andnohealthstandardsnowexistforthecompounds.

Rising concerns on health effectsByperformingmutagenicityassays,researchersfoundthat,forallthePAHstested,theNO3/N2O5exposureresultedina6-foldto432-foldincreaseindirect-actingmutagenicity.

ThestudymeasuredthebreakdownofspecificPAHsbysubstitutingdeuteriumforhydrogeninthePAHs,causingNPAHstobeformed.ResearchersfoundthatthesubstitutionofdeuteriumloweredthemutagenicityoftheNPAHs,suggestingtheresultsfromthemutagenicityassaysmayactuallyunderstatetheincreaseintoxicity.

ThisstudygrewfromPAHpollutionworkofOSUSRP.AsSRPworkstoidentifyremediationtechnologiesthatbreakdownPAHsinsoilandsediment,SimonichisassessingthePAHbreakdownproducts,todeterminewhichremediationtechniquesminimizetheformationofthesepotentiallyhazardousproducts.

ThestudywassupportedbyNIEHSandtheNationalScienceFoundation.CollaboratorsonthestudyincludedresearchersfromOSU;theUniversityofCalifornia,Riverside;andTexasA&MUniversity.

(SaraMishamandaniisaresearchandcommunicationspecialistforMDBInc.,acontractorfortheNIEHSSuperfundResearchProgramandDivisionofExtramuralResearchandTraining.)

Citation:JariyasopitN,McIntoshM,ZimmermannK,AreyJ,AtkinsonR,CheongPH,CarterRG,YuTW,DashwoodRH,MasseySimonichSL.2014.Novelnitro-PAHformationfromheterogeneousreactionsofPAHswithNO2,NO3/N2O5,andOHradicals:prediction,laboratorystudies,andmutagenicity.EnvironSciTechnol48(1):412-419.

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Simonich has also done extensive work on urban air quality, specifically related to PAHs found in particulate matter, which is a concern for air pollution. (Photo courtesy of Narumol Jariyasopit)

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Using teeth to uncover developmental susceptibility to chemical mixtures By Sara Mishamandani

ManishArora,Ph.D.,fromtheIcahnSchoolofMedicineatMountSinai,presentedtheJan.13KeystoneScienceLectureSeminarSeriestalkatNIEHS.HostedbyWilliamSuk,Ph.D.,directoroftheNIEHSSuperfundResearchProgram(SRP),Aroradiscussedhisresearchon“UncoveringEarlyLifeExposuretoChemicalMixturesUsingMicro-spatialAnalysisofTeeth.”

“Agoodwaytothinkofthisresearchistoconsiderteethasanencryptedharddrive,”saidArora.“Wearetryingtobreakdownthatencryptionandlookatdifferentlayersofinformationoneachtooth.Somelayersgiveusinformationonenvironmentalpollutants,othersondiet.AndIbelievetherearemanymorelayersofinformationtouncover.”

Understanding critical developmental windowsAlthoughstudiesaremakingprogressinbetterunderstandingthetimingofexposures,Arorapointedoutthedifficultyofusingprospectivestudiestolinkexposurestooutcomes.

“Foranoutcomethataffectsonein100,youwouldneedabout10,000mother-childpairstogetasamplesizeofcloseto100inaprospectivestudy.Onewaytoavoidthisistomatchcasestocontrolsandlookretrospectively,butthenwehavetoreconstructexposuresleadinguptothehealthoutcome,”saidArora.“Usingmaternalbiologicalmarkersdoesn’talwaysaccuratelyreflectfetalexposure,sincedifferentchemicalscrosstheplacentaatdifferentlevels.Thisiswhereteethcomein.”

Teethstartdevelopingprenatallyandcarryanimprintofdailycircadianrhythm,thebody’sinternalclock.Duringdevelopmentofatooth,ringsareformed,muchliketheringsofatree.Arora’sresearchteamhasdevelopedmethodologythatcombinesdetailedanalysisofthelayersofteeththatcorrespondtospecificlifestages.Theycanusethisinformationtoreconstructexposuretoindividualchemicalsandchemicalmixtures,aswellascumulativeexposure,inthesecondandthirdtrimestersofprenataldevelopmentandearlychildhood.

Arora explained how mapping homeostatic disruption, the disruption of the body’s internal equilibrium, in teeth can provide insight into response to environmental exposures during different developmental windows. (Photo courtesy of Steve McCaw)

Arora is an assistant professor of preventive medicine and dentistry, and director of exposure biology at the Icahn School of Medicine at Mount Sinai. He is an NIEHS grantee and former postdoctoral trainee at the Harvard University SRP Center. (Photo courtesy of Steve McCaw)

Listen as Arora describes how much information can be found by analyzing teeth. (0:57)

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Samplesfortheseearly-lifeexposurestudiescanbecollectednon-invasively,becausemostchildrenlosetheirbabyteethbetweentheagesof6and13.

Linking innovative research to NIEHS prioritiesAroraisparticularlyinterestedinexploringhowwerespondtoenvironmentalmixtures,anNIEHSprioritydescribedina2013EnvironmentalHealthPerspectiveseditorial.

Inhisworkusingchildren’steethtomapearly-lifeexposureincohortsinMexicoandtheU.S.,Aroraisworkingtobetterunderstandhowchemicalmixturesaffectchildrendifferently.Lookingatmorethan10chemicalsacross50developmentaltimepointsperindividual,Arora’sresearchteamisrevealingpotentialcriticalwindowsofsusceptibilitytochemicalmixtures.

Theyarealsoinvestigatinghowdisruptiveconditions,suchasstress,canchangethewaychemicalexposuresaffectthebody,andworkingtowardunderstandingthepathwaysinvolvedindisruptionofnormalbodyfunctionsasaresultofchemical,physical,andpsychologicalstressors.

“Inthepast,thefieldofenvironmentalhealthhasfocusedonmeasuringexposuresandlinkingthattoanoutcome,butthatapproachmissesinformationabouthowdifferentpeoplerespondtodifferentexposures,”saidArora.“Wearelookingattoxicantinteractionsmoreclosely,byexaminingthedisruptionsofdifferentpathwaysafterexposure,basedonchemicalsignaturesinteeth.”

Aroratouchedonsomeofhisrecentinnovativefindingsrelatedtochemicaldistributionsinteeth,suchasaMay2013studypublishedinthejournalNature.

(SaraMishamandaniisaresearchandcommunicationspecialistforMDBInc.,acontractorfortheNIEHSSuperfundResearchProgramandDivisionofExtramuralResearchandTraining.)

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Webinar highlights new insights about childhood leukemia By Audrey Pinto

Inawebcastseminar(webinar)Jan.8,twoNIEHS-fundedscientistsfromtheUniversityofCalifornia,Berkeley—physicianepidemiologistCatherineMetayer,M.D.,Ph.D.,andexposurebiologistStephenRappaport,Ph.D.—presentednewfindingsfromtheirongoingresearchattheCenterforIntegrativeResearchonChildhoodLeukemiaandtheEnvironment(CIRCLE).

Metayeraddressed“PaternalandMaternalTobaccoSmokingandtheRiskofLeukemiainChildren,”andRappaportexplored“UsingNewbornDriedBloodSpotstoEstimateIn UteroExposurestoChemicals.”TheirpresentationswerepartoftheChildren’sCenters2014WebinarSeriessponsoredbyNIEHSandtheU.S.EnvironmentalProtectionAgency.

Linking father’s tobacco smoking and childhood leukemiaMetayer’sresearchfocusesonhowexposuretocontaminantsinthewombandinearlylifecontributetoacutelymphocyticleukemia(ALL),themostcommoncanceramongchildren.

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Toidentifythecausesofthisdisease,sheandherresearchteamareusingdataonalmost1,000childhoodleukemiacasesfromtheNIEHS-sponsoredCaliforniaChildhoodLeukemiaStudy(CCLS)toanalyzeassociationsbetweenhouseholdenvironmentalexposuresandchildhoodleukemia.Assheexplained,“AccesstothisextensivedatabaseplacestheresearchteamsattheCIRCLEinauniquepositiontodisentangletherelationshipsbetweenchemicalexposuresandchildhoodleukemia.”

UsingthisdatahasledMetayer’steamtotargetariskfactorthathasrecentlyattractedattentioninseveralstudiesworldwide—activetobaccosmokingbythefather.Tobaccosmokecontainsseveralcarcinogensandisknowntoalsodamagegermcellsinsperm.Referringtowhatisknownasthetwo-hitmodelhypothesisforleukemogenesis—theinductionorproductionofleukemia—Metayersaidthereisincreasingevidencethatexposurestothefather’sactivesmokingbeforeoraroundconception,andtosecondhandsmokeafterbirth,aretwonecessarystepsleadingtoanincreasedriskofspecifictypesofchildhoodALL.

Tobaccosmokingappearstoalsoincreasetheriskofacutemyeloidleukemiainchildren,arelationshipthatisalreadywellestablishedamongadults.Metayerreported,however,thattheCCLSandotherstudiesdonotfindanassociationbetweenreportedactivetobaccosmokingbythemotherduringpregnancy,andchildhoodleukemia.Thisobservationremainspoorlyunderstood.

Metayerconcludedherpresentationbycallingfortheadditionalresearchneededtoreplicatethefindings;identifycritical,time-specificwindowsofexposure;andinvestigatetheroleofgeneticsusceptibility.MoreanalysesareunderwaywithintheChildhoodLeukemiaInternationalConsortium,whichassemblesdataforthousandsofchildrenwithleukemiaaroundtheworld.

A new approach to measuring early life environmental exposures Rappaportisapioneerintheemergingfieldsofexposurebiologyandexposomics,andintheuseofbloodproteinadductsasbiomarkersofexposuretotoxicchemicals.

Inhispresentation,Rappaportdescribedhisanalysisofadductpopulationstoidentifypossiblebiomarkersofchildhoodleukemiaandchronicdiseases.Hisultimateobjectiveistodesignastableandconsistentprocessthatcancharacterizethetotalityofaperson’senvironmentalexposures,andidentifyevidenceofexposurestochemicalsbeforebirth.

“There are many reasons why we are interested in understanding the relationship between tobacco smoking and cancer in children,” Metayer said. (Photo courtesy of Catherine Metayer)

“We still have a lot to do,” Rappaport said of his untargeted and targeted omics studies. “This is really the first step.” (Photo courtesy of Stephen Rappaport)

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Measuring adducts in neonatal dried blood spotsUsingneonataldriedbloodspots(DBS),whichareavailabletotheCCLSfromtheStateofCalifornia,Rappaport’slaboratorydevelopedanassaytopurifythebloodprotein,humanserumalbumin(HSA),andmeasureadductsofHSAproducedbyparticularchemicals.SuchHSAadductsinDBSreflectexposuresduringthelastmonthofpregnancy.

TheadductsRappaportselectedforhispilotstudyarerelatedtochemicalsincigarettesmoke.Toidentifyevidenceofexposurestosmoke-relatedchemicalsbeforebirth,hemeasuredtheHSAadductsinDBSfromchildrenofsmokingandnonsmokingmothers.HispreliminaryfindingsindicatethatsomeofthetargetedHSAadductswerepresentathigherlevelsinchildrenofsmokingmothers.

Inhisconclusion,RappaportexplainedthatDBSofferavaluabletoolforidentifyingfetalexposures.HenotedthatDBSfromtheStateofCaliforniaareparticularlyvaluableforthispurpose,becausetheyarearchivedatminus20degreesCelsius,atemperaturethatprotectsHSAandtheassociatedadductsfromdegradation.

Unfortunately,mostotherstatesdonotpreserveneonatalDBSinthismanner.Whenstoredatroomtemperature,adductsmaynotbestableforlongerthanabout6months.

Citations:MetayerC,ZhangL,WiemelsJL,BartleyK,SchiffmanJ,MaX,AldrichMC,ChangJS,SelvinS,FuCH,DucoreJ,SmithMT,BufflerPA.2013.TobaccosmokeexposureandtheriskofchildhoodacutelymphoblasticandmyeloidleukemiasbycytogeneticsubtypeCancerEpidemiolBiomarkersPrev22(9):1600-1611.

MetayerC,MilneE,ClavelJ,Infante-RivardC,PetridouE,TaylorM,SchuzJ,SpectorLG,DockertyJD,MagnaniC,Pombo-de-OliveiraMS,SinnettD,MurphyM,RomanE,MongeP,EzzatS,MuellerBA,ScheurerME,ArmstrongBK,BirchJ,KaatschP,KoifmanS,LightfootT,BhattiP,BondyML,RudantJ,O’NeillK,MiligiL,DessyprisN,KangAY,BufflerPA.2013.TheChildhoodLeukemiaInternationalConsortium.CancerEpidemiol37(3):336-347.

RappaportSM,LiH,GrigoryanH,FunkWE,WilliamsER.2012.Adductomics:characterizingexposurestoreactiveelectrophiles.ToxicolLett.213(1):83-90.

(AudreyPinto,Ph.D.,istechnicaleditorforthejournalEnvironmentalHealthPerspectives.)

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Leukemia and children’s healthAccordingtoMetayerandRappaport,childhoodleukemiaisamajorpublichealthissuethatdeservesmuchmoreinterdisciplinaryresearchsupport.

Between1975and2004,theincidenceofALL,whichaccountsformostchildhoodleukemiasincountriesintheWesternHemisphere,rosesignificantlyintheUnitedStates,Europe,andJapan,yetthecausesof90percentofchildhoodleukemiasareunknown.

Formorethanfortyyears,studieshavedemonstratedthetoxicityoftobaccosmoking.Contrarytowhatonewouldexpect,however,mosthavefailedtofindadefinitivelinkbetweenmaternaltobaccosmokingbeforeandafterbirth,andtheriskofleukemiainchildren.Evenlessisknownaboutotherenvironmentalandgeneticfactorsthatmaycontributetothedisease.

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Talk explores link between endometriosis and the estrogen receptor By Monica Frazier

AmeetingoftheNIEHSReceptorMechanismsDiscussionGroupJan.7featuredaseminarbypostdoctoralfellowKatherineBurns,Ph.D.,oftheReceptorBiologyGroup(RBG)on“TheRoleofEstrogenReceptorSignalinginEndometriosis.”

SeminarhostKennethKorach,Ph.D.,leadresearcherinRBGandheadoftheNIEHSLaboratoryofReproductiveandDevelopmentalToxicology,openedthemeetingbydiscussingthehistoryoftheReceptorMechanismsDiscussionGroup,establishedmorethanthirtyyearsago,andthecontributionsBurnshasmadetoRBGthroughherpassionforendometriosisresearch.

Burnsbeganherpresentationbynotingsomeeye-openingfactsaboutendometriosis,whichaffectsapproximately5.5millionwomenintheU.S.andcoststhecountrysome$22billionannually.Inadditiontoitsprevalenceandcost,theneedtoestablishanunderstandingofendometriosisprogressionisdrivenbythelackofclinicalbiomarkers.Presently,endometriosiscanbediagnosedonlythroughlaparoscopicsurgery.

Burnsaddedthatformanyyearsthediseasehasbeenthoughttobeassociatedwithestrogenandpossiblyestrogen-likechemicalsintheenvironment,butthereislittleresearchtoprovetheconnection—somethingsheistryingtochange.

Developing an endometriosis disease modelAninitialhurdlethatBurnsovercamewastofindagoodmodelforstudyingendometriosis,aconditionwherecellsfromtheuterusflourishoutsidetheuterinecavity.Acondition,knownasretrogrademenstruation,allowsendometrialdebristoexittheuterusthroughthefallopiantubes.Thisbackwardmovementofmenstrualfluidthroughthefallopiantubesintotheabdominalcavityistheleadinghypothesisfortheformationofendometriosislesions.

Interestingly,althoughBurnsnotedthatretrogrademenstruationoccursingreaterthan90percentofwomen,onlyabout10percentdevelopendometriosis.However,shesaid,throughthedevelopmentofadiseasemodel,“Wemaybeabletostudytheearlyinitiationofthisdiseaseandpotentiallyunderstandhowandwhyitisforminginsomewomenandnotothers.”

Tostudythepotentialroleofestrogenreceptors(ER)inthedevelopmentofendometriosislesions,BurnsusedbothdonorandhostmicethathaveoneofthegenesforERalphaorbetaknocked-out.Fromhermousestudies,Burnsdevelopedaworking

Burns, a guest speaker at the January Receptor Mechanisms Discussion Group, explained her research on the estrogen receptor’s role in endometriosis to an audience of scientists involved in receptor signaling research. (Photo courtesy of Steve McCaw)

Hong Soon Kang, Ph.D., staff scientist in the NIEHS Cell Biology Group, listened during the question and answer session after Burn’s seminar. (Photo courtesy of Steve McCaw)

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endometriosismodel,torecapitulatehumandiseaseandfindlesionsthatareessentiallyindistinguishablefromhumanlesions,thatillustratestheroleofERalphaandbetainlesionestablishmentandprogression.

Environmental exposures and endometriosisNowthatBurnshasaworkingmodelofdiseaseinitiationandprogression,sheisbeginningtolookathowenvironmentaltoxicants,suchasbisphenolA(BPA),mayaffectendometriosis.SinceBPAandthefluorinatedvariantofBPA,BPAF,haveestrogenic-likeactivity,Burnssuspectstheyplayaroleinendometriosisandotherreproductiveconditions.

Burns’initialexperimentsshowthatBPAandBPAFhaveeffectsontheuterussimilartodosesofestrogen,buttheBPAFeffectisstronger.

“WepredictthatBPAFmaypotentiatethedevelopmentofendometriosis,”Burnscommented,notingthatsheintendstocontinuetostudythisrelationshipinfutureexperiments.

(MonicaFrazier,Ph.D.,isanIntramuralResearchTrainingAwardfellowintheNIEHSMechanismsofMutationGroup.)

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This month in EHPTheFebruaryissueofEnvironmentalHealthPerspectives(EHP)highlightsthehealthimpactsontheNavajopopulationofuraniummining,andradioactiveconsequencesoffracking.

Once Upon a Mine: The Legacy of Uranium on the Navajo NationTheNavajoNationishometohundredsofabandoneduraniummines,rangingfromsmallholesdugbyasingleprospectorintothesideofamesa,tolargecommercialminingoperations.Withindecadesofthearrivalofprospectorsinthe1940s,Navajominersweredevelopinglungcancer,arelativelyrarediseaseinthislargelynonsmokingpopulation.TodaytheNavajopopulationremainsathighriskforkidneydiseaseasaresultofuraniumexposure,aswellaspotentiallyassociatedhypertension,cardiovasculardisease,andautoimmunediseases.

Radionuclides in Fracking Wastewater: Managing a Toxic BlendExtractinggasfromthemulti-stateMarcellusShaleFormationusuallyentailsapracticeknownashydraulicfracturing(fracking).Frackingbringsupmorethangasfromthedepths—thewastewaterthatflowstothesurfacecontainsradioactivematerialsthatmustbemanagedanddisposedof.FrackingintheMarcellushasadvancedsoquicklythatpublicunderstandingandresearchonitsradioactiveconsequenceshavelaggedbehind,andtherearemanyquestionsabouttheextentandmagnitudeofthepotentialrisktohumanhealth.

http://twitter.com/ehponline

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Featured research and related news articles this month include:• F2RL3 Methylation as a Biomarker of Current and Lifetime Smoking Exposures —ASmokingGun?EpigeneticMarkersofTobaccoUseHistory

• Evaluating the Effectiveness of Fish Consumption Advisories: Modeling Prenatal, Postnatal, and Childhood Exposures to Persistent Organic Pollutants —FishConsumptionCaveat:AdvisoriesMayNotHelpWithLong-LivedContaminants

• Environmental Noise Pollution in the United States: Developing an Effective Public Health Response —FightingNoisePollution:APublicHealthStrategy

• Polyfluoroalkyl Chemicals and Menopause Among Women 20-65 Years of Age (NHANES) —PFCsandEarlyMenopause:AssociationRaisesQuestionsAboutCausality

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Myles Brown to give distinguished lecture By Shannon Whirledge

ThesecondNIEHSdistinguishedlectureof2014willbepresentedFeb.11byprominentphysicianscientistMylesBrown,M.D.,at11:00a.m.inRodbellAuditorium.NIEHSReproductiveandDevelopmentalToxicologyLaboratoryheadKennethKorach,Ph.D.,willhostBrown’stalk,“GeneticsandEpigeneticsofEndocrineResistance.”

BrownisaprofessorofmedicineatHarvardMedicalSchoolanddirectoroftheCenterforFunctionalCancerEpigeneticsattheDana-FarberCancerInstitute.TheBrownlaboratoryatHarvardMedicalSchoolfocusesonelucidatingtheepigeneticfactorsunderlyingsteroidhormoneaction,withimplicationsforbothnormalphysiologyandthetreatmentofhormone-dependentcancer.

Browniswidelyrecognizedforseveralimportantdiscoveriesinthesteroidreceptorfield.Hisgroup’sresearchhasshedlightonthecomplexnatureofsteroidreceptorcoregulators,includingthedynamicnatureofreceptorandcoregulatorinteractionswiththegenome.SomerecentfindingsfromBrown’sgrouphighlighttheabilityofepigeneticmodificationstodictatetranscriptionfactorbindingtodiscreteregulatoryregionsinthemammaliangenome.

Amonghismanyaccomplishments,Brownhaspublishedmorethan150peer-reviewedarticles,reviews,andbookchaptersthathavebeenhighlyquoted,andhehasbeeninvitedtopresentlecturesatconferencesworldwide.HismanyhonorsincludebeingelectedtotheAmericanSocietyforClinicalInvestigationin1997andtheAssociationofAmericanPhysiciansin2003,receivingtheTischFamilyOutstandingAchievementAwardin2006,andbeingpresentedtheEdwinB.AstwoodAwardbyTheEndocrineSocietyin2010.

Brown is a pioneer in the field of cancer research. His seminal discoveries include the first identification of the p160 class of steroid receptor coactivators and the description of the estrogen receptor cistrome, the targets of estrogen action across the genome. His work has important implications for understanding the actions of selective receptor modulators and endocrine disruptors. (Photo courtesy of Myles Brown)

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ResearchersatNIEHSandinthelocalcommunityareenthusiastictohaveBrownpresenthisstudiesonacurrentandrelevanttopic.AsKorachsaid,“Dr.Brown’sresearchinthefieldofhormoneactionandnuclearreceptormechanismsinbreastcancerishighlyrelevanttostudiesattheNIEHSinvolvingenvironmentalendocrine-disruptingchemicals.”

(ShannonWhirledge,Ph.D.,isanIntramuralResearchTrainingAwardfellowintheNIEHSMolecularEndocrinologyGroup.)

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Extramural papers of the month By Nancy Lamontagne

• Transcription factor influences codon choice and protein evolution

• Compound from mold linked to symptoms of Parkinson’s disease

• New tool for assessing ovarian cancer

• Partnership identifies chemical-gene-disease interactions for inclusion in database

Transcription factor influences codon choice and protein evolutionResearch,partiallysupportedbyanNIEHSgrantfundedbytheNationalInstitutesofHealthCommonFund,revealedthatcomplexgenomessimultaneouslycodeforaminoacidsandregulatoryinformation.Theworkaddsatranscriptionfactorbindingcodetothespectrumofotherregulatorycodesthatarebelievedtoinfluenceproteinevolutionbyinfluencingcodonchoice.

Genomescontainprotein-codingregions,aswellasregulatorycodethatinfluencesgeneexpressionbyspecifyingrecognitionsequencesfortranscriptionfactors.Scientistshaveassumedthatthegeneticcodeandregulatorycodeswerephysicallyandoperationallyindependent.Tofindoutifthesecodesintersect,theresearcherscreatedanucleotide-resolutionmapshowingwhereprotein-codingregionsofthehumangenomewereoccupiedbyatranscriptionfactor.Theylookedat81diversecelltypes,andfoundthatapproximately15percentofhumancodonssimultaneouslyspecifybothproteinsandtranscriptionfactorrecognitionsites.Thesedual-usecodons,orduons,arehighlyconserved,andconstraintfromthetranscriptionfactorsappearstobeamajordriverofcodonusagebias.Theresearchersfoundthatmorethan17percentofsingle-nucleotidevariantswithinduonsdirectlyalteredtranscriptionfactorbinding.

Theresearchersconcludedthatwidespreaddualencodingofaminoacidandregulatoryinformationappearstobeafundamentalfeatureofgenomeevolution.

Citation:StergachisAB,HaugenE,ShaferA,FuW,VernotB,ReynoldsA,RaubitschekA,ZieglerS,LeProustEM,AkeyJM,StamatoyannopoulosJA.2013.Exonictranscriptionfactorbindingdirectscodonchoiceandaffectsproteinevolution.Science342(6164):1367-1372.

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ReadthecurrentSuperfundResearchProgramResearchBrief.NewissuesarepublishedonthefirstWednesdayofeachmonth.

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Compound from mold linked to symptoms of Parkinson’s diseaseNIEHSgranteesreportthatanorganiccompoundemittedbymoldmightbelinkedtoParkinson’sandotherneurodegenerativediseasesinhumans.Studieshavefoundevidencethatseveralenvironmentalagents,especiallypesticides,arepossibleriskfactorsforParkinson’sdisease,butthisisthefirstnaturallyoccurringenvironmentalagentidentifiedasapotentialriskfactor.

Exposuretofungihasbeenlinkedtomovementdisorders,aswellaslossofbalanceandcoordination,butthemechanismsinvolvedinthesehealtheffectsareunknown.Tofindoutmoreaboutthepossibletoxicologicaleffectsoffungalvolatileorganiccompoundsassociatedwithindoorenvironments,theresearchersscreenedavarietyoffungaltoxicantsusingfruitflies.Thevolatilefungalsemiochemical1-octen-3-olemergedasoneofthemostpotentagentstheytested.1-octen-3-oliscommonlyemittedbymoldsandisresponsibleformuchofthemoldyodorassociatedwithfungalcolonization.

Parkinson’sdiseaseisassociatedwiththelossofneuronsthatproducetheneurotransmitterdopamine.Theresearchersfoundthatlowlevelsof1-octen-3-olreduceddopaminelevelsandcauseddopamineneurondegenerationinthefruitflies.Geneticandcellculturestudiesrevealedthat1-octen-3-olmostlikelyexertstoxicitybydisruptingdopaminehandling.Theagentalsoincreasedlossofdopaminergicneuronsthroughinteractionswithgeneticvariantsofthevesicularmonoaminetransporter,whichisinvolvedindopaminebiosynthesis.

Citation:InamdarAA,HossainMM,BernsteinAI,MillerGW,RichardsonJR,BennettJW.2013.Fungal-derivedsemiochemical1-octen-3-oldisruptsdopaminepackagingandcausesneurodegeneration.ProcNatlAcadSciUSA110(48):19561-19566.

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New tool for assessing ovarian cancerAnNIEHSgranteeandcolleaguesdevelopedanewtechniquethatmayhelppredictovariantreatmentresponse,cancerrecurrence,anddisease-freesurvivalearlierandmoreeffectivelythancurrentmethods.

Formanytypesofcancer,countingthenumberoftumor-attackingimmunecells(TILs)thathavemigratedintothetumoroffersawaytopredictapatient’ssurvival.ThenumberofTILsindicatethebody’simmuneresponsetothecancer,butcurrentmethodsforcountingTILsareeithertechnicallychallengingorexhibittoomuchvariabilitytobeusedforclinicaldecisions.Thenewapproach,whichtheresearcherscallQuanTILfy,usesdropletdigitalpolymerasechainreactiontechnologytocountTILsreliably,quickly,andcheaply.

TheresearcherstestedQuanTILfyontumorsamplesfrom30ovariancancerpatientswhohadsurvivaltimesrangingfromoneto22months.TheresultsshowedanassociationbetweenhigherTILcountsandimprovedsurvivalamongwomenwithovariancancer,whichwasconsistentwithotherstudiesthathadfoundthataperson’simmuneresponseagainstovariancancercanbeusedtoestimatesurvival.

TheabilitytoreproduciblycomputeTILsintumorswithsensitivitymayallowdoctorstostratifyandmoreeffectivelytreatpatientsbasedontumorTILcounts.

Citation:RobinsHS,EricsonNG,GuenthoerJ,O’BriantKC,TewariM,DrescherCW,BielasJH.2013.Digitalgenomicquantificationoftumor-infiltratinglymphocytes.SciTranslMed.5(214):214ra169.

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Partnership identifies chemical-gene-disease interactions for inclusion in databaseEnvironmentalhealthresearchersandpharmaceuticaldrugdeveloperssharethecommongoalofimprovingtheabilitytopredictchemicaltoxicity.Withthisgoalinmind,PfizersafetyscientistsandthebiocurationstaffattheComparativeToxicogenomicsDatabase(CTD)collaboratedintextminingandmanuallyreviewingmorethan88,000scientificarticles,todevelopadatasetofadverseeventsfromdrugs.FundedinpartbyNIEHS,thispartnershipdemonstratesthebenefitsofresourcesharingandcollaborationbetweenpublicandprivateentitieswithcomplementaryneeds.

CTDisapublicdatabasethatpromotesunderstandingabouthowthemolecularinteractionsbetweenenvironmentalchemicalsandgenesaffecthumanhealth.CTDcuratorsusetextminingandmanualcurationtoconvertknowledgefromscientificpapersintodataonchemical-gene,chemical-disease,andgene-diseaseinteractionsthatcanbemoreeasilymanaged,queried,explored,andanalyzed.Thecollaboratingresearcherstextminedandmanuallyreviewed88,629articleswithinformationonthepotentialinvolvementof1,200pharmaceuticaldrugsincardiovascular,neurological,renal,andhepatictoxicity.Inoneyear,thisprocessproduced254,173toxicogenomicinteractions,including152,173chemical-disease,58,572chemical-gene,5,345gene-disease,and38,083phenotypeinteractions.AlloftheseinteractionsarefullyintegratedintothepublicCTD.

Citation:DavisAP,WiegersTC,RobertsPM,KingBL,LayJM,Lennon-HopkinsK,SciakyD,JohnsonR,KeatingH,GreeneN,HernandezR,McConnellKJ,EnayetallahAE,MattinglyCJ.2013.ACTD-Pfizercollaboration:manualcurationof88,000scientificarticlestextminedfordrug-diseaseanddrug-phenotypeinteractions.Database(Oxford)2013:bat080.[Story]

(NancyLamontagneisasciencewriterwithMDBInc.,acontractorfortheNIEHSDivisionofExtramuralResearchandTraining.)

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Intramural papers of the month By Kelly Lenox, Kristin Lichti-Kaiser, Mallikarjuna Metukuri, and Zack McCaw

• Scientists closer to understanding stem cell self-renewal and differentiation

• Estrogen receptor alpha involved in DES-induced gene expression in male mice

• Identification of a novel mechanism that suppresses glucocorticoid signaling

• Factors critical during early stages of heart development clarified

Scientists closer to understanding stem cell self-renewal and differentiationAresearchteam,ledbyNIEHSscientists,determinedthatthemRNAexportcomplexTHO,presentinembryonicstemcells(ESCs),preferentiallyinteractswithandregulatespluripotencygeneexpression.

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Pluripotencyistheabilityofacelltodevelopintoanytypeofcell,andself-renewalistheabilityofacelltoproliferatewhilemaintainingitsdevelopmentalpotential.ESCsthatlackThoc5orThoc2,twocomponentsofTHO,losethisself-renewalcapacityanddifferentiateintovariouscelltypes.ThisresearchisvitallyimportanttobasicandclinicalresearchbecausescientistsuseESCstoderivecellsfordiseasemodeling,drugdiscovery,andthedevelopmentofcell-basedtherapies.

TheauthorsculturedESCsandtransfectedcellswitheitherThoc2orThoc5smallinterferingRNAs(siRNAs)in96-wellplates.Otherexperimentaltechniquesincludedimmunofluorescence,microarray,andRNAimmunoprecipitationandsequencing.

TheresearchersfoundthatTHO,viaThoc5,isneededforESCself-renewal.Furthermore,theydiscoveredthatadecreaseofTHOinhibitedsomaticcellreprogrammingandblastocystdevelopment,makingTHOarequiredcomplexintheestablishmentofpluripotency.ThefindingthatESCself-renewalanddifferentiationoccursatthepost-transcriptionallevelbringsscientistsclosertounderstandingthemechanismsinvolvedinstemcellfatespecification.(ZM)

Citation:WangL,MiaoYL,ZhengX,LackfordB,ZhouB,HanL,YaoC,WardJM,BurkholderA,LipchinaI,FargoDC,HochedlingerK,ShiY,WilliamsCJ,HuG.2013.TheTHOcomplexregulatespluripotencygenemRNAexportandcontrolsembryonicstemcellself-renewalandsomaticcellreprogramming.CellStemCell13(6):676-690.[Story]

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Estrogen receptor alpha involved in DES-induced gene expression in male miceInarecentissueofEnvironmentalHealthPerspectives,NIEHSresearchersarethefirsttoreportanovelestrogenreceptoralpha(ERalpha)dependentcorrelationbetweenDNAmethylationpatternsandlevelsoftheSvs4andLtfgenes,afterneonataldiethylstilbestrol(DES)exposureinmalemice.Thisworkprovidesmoredetailonthenegativeeffectsofendocrine-disruptingchemicalsonmammals.

ResearchersusedaneonatalDESexposuremousemodeltoexaminechangesinthemethylationpatternsofandrogen-dependentgeneSvs4andestrogen-dependentgeneLtfintheseminalvesiclesofmalemice.TheyfoundthatDNAmethylationoftheSvs4genepromoterchangedfrommethylatedtounmethylatedduringdevelopment,andthatDESexposurepreventedthischange.IntheLtfgenepromoter,DESexposurealteredthemethylationstatusfrommethylatedtounmethylatedattwospecificCpGs.AlterationsinmethylationstatuscorrelatedwithdecreasedlevelsofSvs4andincreasedlevelsofLtfgeneexpressioninanERalpha-dependentmanner.Inaddition,DESexposureincreasedexpressionofepigeneticmodifiers.(KLK)

Citation:LiY,HamiltonKJ,LaiAY,BurnsKA,LiL,WadePA,KorachKS.2013.Diethylstilbestrol(DES)-stimulatedhormonaltoxicityismediatedbyERalphaalterationoftargetgenemethylationpatternsandepigeneticmodifiers(DNMT3A,MBD2,andHDAC2)inthemouseseminalvesicle.EnvironHealthPerspect;doi:10.1289/ehp.1307351[Online6December2013].

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Identification of a novel mechanism that suppresses glucocorticoid signalingArecentstudyconductedbyresearchersatNIEHSidentifiedhairyandenhancerofsplit-1(HES1)asanovelregulatorofglucocorticoids,theprimarystresshormonesessentialforlife.HES1isakeyregulatorofdevelopmentandorganogenesis,andtheauthorssuggestabnormalexpressionofHES1maycontributetoformsofglucocorticoidresistanceseeninsomepatients.

TheauthorsdemonstratedthatglucocorticoidssilenceHES1geneandproteinexpressioninmultiplecelltypesandtissues.OverexpressionofHES1inhumancellsledtoreducedglucocorticoid-mediatedchangesingeneexpressionandviceversa.Inaddition,amutatedformofHES1couldnotimpairglucocorticoidsignaling.Toassesstheeffectsin vivo,theauthorsgeneratedHES1liverknockoutmice,whichdisplayedabnormalglucocorticoid-dependentsignalingprofilesthatresultedinimpairedglucosetolerance.Thismetabolicphenotypewascorrectedbytheremovalofendogenousglucocorticoidsbyadrenalectomy,whereasinjectionofexogenousglucocorticoidsrestoredit.

ThefindingssuggestthatthedismissalofHES1cooperateswiththeglucocorticoidreceptortoregulatealargecomponentofthetranscriptionaltargetsofglucocorticoidsthroughatranscriptionalderepressionmechanism.TheauthorsproposethatHES1isamasterregulatorofglucocorticoidsignalingprofileandsilencingofHES1isrequiredforproperglucocorticoidsignaling.(MM)

Citation:RevolloJR,OakleyRH,LuNZ,KadmielM,GandhavadiM,CidlowskiJA.2013.HES1isamasterregulatorofglucocorticoidreceptor-dependentgeneexpression.SciSignal6(304):ra103.

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Factors critical during early stages of heart development clarifiedNIEHSresearchersstudyingheartdevelopmentinmammalianembryosreportedseveralimportantfindingsthatrevealspecializedandnovelcardiac-enrichedSwitch/SucroseNonFermentable(SWI/SNF)chromatin-remodelingcomplexes.Becausethesecomplexesarerequiredforheartformationandcriticalforcardiacgeneexpressionregulationattheearlystagesofheartdevelopment,theresultswillbevaluableinimprovingcardiacreprogrammingstrategiesandelucidatingthemechanismsthatcontributetocongenitalheartdisease.

Studyingmouseembryosatdistinctdevelopmentalstages,researchersdemonstratedthattheSWI/SNFcomplexsubunitsexhibitdifferentialpatternsofexpressioninearlydevelopment,andthatspecificBRG1-associatedfactorswereelevatedintheearlyheartcomparedwithheadandtrunk.SubsequentstudiesrevealedthattheBAF250asubunitwasrequiredforfullyfunctionalcardiomyocytedifferentiationin vitro.ResultssuggestthatthesubunitBAF250aplaysaregulatoryroleinearlyheartformation,viathedirectrepressionofcardiac-specificgeneexpression.MolecularanalysessuggestthatBAF250aphysicallyinteractswithrepressorproteins,includingCHD4andHDAC1,toalterthechromatinarchitectureandepigeneticsignatureofcardiacrelatedgenes.

DefiningapreviouslyunknownSWI/SNFcomplexcompositionandspatiotemporalexpressionpattern,thesefindingsprovidenovelinsightintotheroleofthecomplexincardiaclineagedecisionandsubsequentheartformationduringearlydevelopment.(KL)

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Citation:SinghAP,ArcherTK.2013.AnalysisoftheSWI/SNFchromatin-remodelingcomplexduringearlyheartdevelopmentandBAF250arepressioncardiacgenetranscriptionduringP19celldifferentiation.NucleicAcidsRes;doi:10.1093/nar/gkt1232[Online13December2013].

(KellyLenoxiseditoroftheEnvironmentalFactor.KristinLichti-Kaiser,Ph.D.,isanIntramuralResearchTrainingAward(IRTA)fellowintheNIEHSCellBiologyGroup.MallikarjunaMetukuri,Ph.D.,isaresearchfellowintheNIEHSMetabolism,Genes,andEnvironmentGroup.ZacharyMcCawisapostbaccalaureateIRTAfellowintheNIEHSEnvironmentalGeneticsGroup.)

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Inside the InstituteNIEHS CFC raises more than $100,000 By Allison Eason

Since1961,thegoaloftheCombinedFederalCampaign(CFC)hasbeentoprovideanopportunityforfederalemployeestogivebacktotheircommunities.Thisyearwasnodifferent,asNIEHSemployeessteppeduptoraise$100,425.Thecharitabledrivewasbusierthanever,withatalentshow,bakeoff,bakesale,silentauction,funrun,andyogaclasses.

StafffromtheDivisionofExtramuralResearchandTrainingledtheNIEHScampaign.Thisyear’sco-chairswereElizabethRubenoftheProgramAnalysisBranch,BarbaraGittlemanoftheGrantsManagementBranch,andDanielleCarlin,Ph.D.,oftheHazardousSubstancesResearchBranch.

“Wereached87percentofourgoal,andwewerehonoredtoexperiencethegenerosityofNIEHSers,”saidRuben.“Thisyear’stalentshowwasverywellattendedandprovidedawayforNIEHSerstoconnectandenjoycommunityspirit.”

Drive extended due to shutdownTheCFCtakesplaceeveryyearfromOctobertoDecember.Duetothegovernmentshutdown,the2013campaignwasextendedtoJan.15.Withnearly3,000charitiesacceptingdonations,asimpleprocessmadepledgingeasyforemployees.Mostchosetodonatethroughonlinepayrolldeduction.

Aspartofthedrive,severalcharitiescametoNIEHSNov.19,2013,togive2-minutepresentationsontheirmissionsandgoals,sharinghowtheyhelpthelessfortunatebyprovidingsupporttothoseinneed.Thepresentationswerewebcastinordertoreachasmanyemployeesaspossible.

TheNationalInstitutesofHealth(NIH),ofwhichNIEHSispart,exceededitsoriginalgoalduringthisyear’scampaign.NIHDirectorFrancisCollins,M.D.,Ph.D.,wrote,“Withyourgenerosity,anddespitetheuniquechallengeofthegovernmentshutdown,wemetmorethat100percentofour$2.2milliongoal.”

Rising above economic challengesTheGreaterN.C.AreaCFCreportedthatdonationstotaledmorethan$1.3million.Eventhoughtherewerespendingcuts,agovernmentshutdown,andeconomicstresses,thecampaignstill

Ruben was proud to serve as a CFC co-chair. (Photo courtesy of Steve McCaw)

“Helping those less fortunate is a life-guiding principle,” said CFC co-chair Gittleman. (Photo courtesy of Steve McCaw)

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managedtofundraiseataremarkablelevel.Thestate’sCFCrepresentativesGinaMisasi-WoodandLindaMatichLangplayedakeyroleinleadingtheambitiousendeavor.

Inanall-handsemail,NIEHSandNTPDirectorLindaBirnbaum,Ph.D.,thankedemployeesforsupportingthemanyCFCevents,andforbeinggenerousandcaring.“Thecharitiesofyourchoicewillnowhaveresourcesin2014todeliverservicestothoseinneed.”Birnbaumalsothankedtheorganizersofthisyear’scampaignforgivingtheirtimetoplanthevariouspromotions,activities,andevents.

(AllisonEasonisaprogramspecialistintheNIEHSOfficeofCommunicationsandPublicLiaison.)

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NIEHS inaugurates new facilities for fitness, research, and training By Kelly Lenox

AlivelygatheringofNIEHSstaffkickedoffthenewyearataJan.8openhousefornewlyremodeledspaceinthemainbuilding.NIEHSandNTPDirectorLindaBirnbaum,Ph.D.,openedwithafewbriefwords.

“Thewholeobjective[oftheremodel]wastogetusmoreusable,morefunctionalspacethatwewouldallliveinandenjoy,”sheexplained.

Thenewareaincludesalibrary,expandedfitnesscenter,newtrainingroom,work/lifeoffice,andtheBioinformaticsTeam.

“Getting involved with the CFC lets you know that there’s a lot going on in our community,” Carlin added. (Photo courtesy of Steve McCaw)

Dick Sloane of the NIEHS Office of Management showcased his comical talents at the CFC talent show held Nov. 4, 2013. (Photo courtesy of Steve McCaw)

NIEHS Program Analyst Liam O’Fallon raced toward the finish line at this year’s popular CFC Fun Run. (Photo courtesy of Steve McCaw)

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Bigger and better — and still freeProgrammanagerStephanieBullock-Allenenthusiasticallyshowedoffthefitnessfacilities,encouragingemployeestosignupforaccess,registerforrecreationalsportsteams,andpickupacalendarofclasses.Arafflekeptthecuriousstreamingin.

Atmorethan21/2timesthesizeoftheoldspace,thefitnesscenter,bothconvenientandfree,hasavarietyoffitnessequipment,aswellasplentyofroomforexerciseclasses.

The best for work and lifeAnewwork/lifeofficeaccommodatesacareercounselor,GordonFolger,andtheNIHombudsman,whenonsite.Keepingwiththefitnesstheme,Folgerhandedoutsurveystodeterminewhetherstaffwerekeepingcareersfit,too.

Bioinformatics team unitedDavidFargo,Ph.D.,directorofIntegrativeBioinformatics,ispleasedthatthegroupisfinallygatheredinoneplace.Thenewworkspaceisdesignedtofacilitateteamwork,asthestaffprovidesbioinformaticsandcomputationalsupporttoNIEHSresearchers.

Top-notch training roomThoughnoonemindedthesunpouringinonthatfrigidday,RoyReteroftheComputerTechnologyBranchdemonstratedthelight-blockingblinds,designedtoeaseeyestrainonthelaptops.Besidestraining,theaudioandvideoequipmentintheroomalsosupportsvideoconferencing.

Partners in researchTheNIEHSlibraryteamusedtheroadmapthemeoftheirmotto(seesidebar)toeducatestaffabouttheirservices.

“Nowthatthereissomuchinformationoutthere,wecanhelpyounavigateit,byprovidinghelpfindingarticles.Or,ifyou’redoingaliteraturesearch,wecanhelpyoudecidewhichdatabasestouseorwhichkeywordstoselect,becausemanyscientificdatabasesuseveryspecificvocabularies,”explainedlibrarymanagerErinKnight.“Wecansaveyoutimeandfrustration.”

Smoothie samples — and recipes — were on hand, whetting the palate of many, including raffle winners April Parker, left, and Leslie Lynch. (Photo courtesy of Steve McCaw)

“To ask why we need libraries at all, when there is so much information available elsewhere, is about as sensible as asking if roadmaps are necessary now that there are so many roads.”

– Jon Bing, J.D., professor of information technology law, University of Oslo

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

Director of Communications: Christine Bruske FlowersEditor-in-Chief: Kelly Lenox | Managing Editor: Eddy Ball | Science Editor: Robin Arnette

Ming-Lang Zhao, M.D., didn’t let visitors keep him from his workout. (Photo courtesy of Steve McCaw)

Birnbaum, who minutes earlier told the crowd, “I look forward to seeing some of you down here, as one of my resolutions is to use this fitness center,” wasted no time signing up with Bullock-Allen. (Photo courtesy of Steve McCaw)

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