whitehead institute

a whitehead institute2008annualreport

2008 AnnuAl RepoRt. ayearinthelifeofascientificcommunity

empoweredtoexplorebiology’smostfundamentalquestions

forthebettermentofhumanhealth.

whitehead institute

b 1 whitehead institute2008annualreport

it’scustomaryinthisspacetorecountandreflect

ontheaccomplishmentsoftheyeargoneby.

i’llcertainlydosohere—proudly—butinmany

importantways,2008wasaboutpositioningthe

instituteforyearstocome.

manycolleges,universities,andindependent

researchinstitutionsfoundthemselvesindire

fiscalpositionsatthecloseof2008andentered

2009inoperationalcrisisreflectiveoftheglobal

economicenvironment.hiringfreezesandlarge-

scaleworkforcereductionshavebecomethenorm.

althoughwhiteheadinstituteiscertainlynot

insulatedfromtheimpactofthedownturn,iam

pleasedandsomewhathumbledtoreportthatthe

instituteremainsfinanciallystrongandnoless

committedtoscientificexcellence.

overthepasttwoyears,wehavebeenengagedinafocusedefforttoincreaseefficiencyand

reduceouradministrativecosts,withtheexplicitgoalofensuringthatasmuchoftheinstitute’s

revenueaspossibledirectlysupportswhiteheadresearch.ourapproach,whichhasresultedin

a10-percentreductioninoperationalexpense,hasbeencarefullyconsidered.everydecision

hasbeenevaluatednotjustforitspotentialeffectsonourscientificmission,butalsofor

possibleconsequencestothewhiteheadcommunityanditsuniqueculture.

insomecases,ourreductionsinoverheadhavealsoyieldedculturalbenefits.thispastyear,

wemovedadministrativedepartmentsthathadforthepastseveralyearsbeenhousedinoffsite

officespacebackintoourmainbuildingatninecambridgecenter.insodoing,wehave

eliminatedsignificantrentalexpensewhileexperiencingthekindsofgainsinproductivity,

communication,andideationthatresultfromwhatirefertoas“randomcollisions”between

scientificandadministrativestaff.thisreunionoffunctionsiscontributingtoamorecohesive

andvibrantenvironmentthatwillserveuswell.

ourattentiontofiscaldisciplinehasalsoenabledustotakebold,definitivestepstoward

ensuringtheinstitute’sscientificprowessforsuccessivegenerations.in2008,ourboardof

directorsapprovedthefirstphaseofamulti-yearplantorecruitnewfacultytowhitehead.

phaseoneanticipatesthehiringoftwojuniorfacultymembersandonemid-careerhire.

friendsoftheinstituteknowwellthatasdirector,ihavemadefacultyrecruitmentapriority.

ourabilitytorecruitactivelyduringaperiodofgreateconomicuncertaintyandstaffing

contractionelsewhereisanenormouscompetitiveadvantageforwhitehead.

Preserving the mission, facing the future

davidpage,director

1 preservingthemission,facingthefuture

5 scientificachievement

15 principalinvestigators

30 whiteheadfellows

34 communityevolution

40 honorrollofdonors

46 financialsummary

48 leadership

49 sitedforscience

contents

editor & direCtor

mattfearer

assoCiate editor

nicolegiese

offiCe of CommuniCation and PubliC affairs

617.258.5183

www.whitehead.mit.edu

design

hechtdesign

inside CovermatthewsaelzlerPage 1, 30JohnsoaresPage 4, 10 (left)©felice

frankel,from“envisioningscience,thedesignandcraftofthescienceimage

(mitpress)Page 6reprintedfromcell,133/4,samani,etal.,theepithelial-

mesenchymaltransitiongeneratescellswithpropertiesofstemcells,704-15,

copyright2008,withpermissionfromelsevier.Page 7Jinfectdis.emfrickel,

etal.universityofchicago,publisher.©2008bytheinfectiousdiseases

societyofamerica.allrightsreserved.Page 8 duennwaldml,etal.impaired

eradanderstressareearlyandspecificeventsinpolyglutaminetoxicity.

genesdev.2008dec1.copyrightc2008bycoldspringharborlaboratory

press.Page 9mwernig,etal.neuronsderivedfromreprogrammedfibroblasts

functionallyintegrateintothefetalbrainandimprovesymptomsofrats

withparkinson’sdisease.pnas.2008apr15.copyright©2008bythenational

academyofsciences.Page 10 (right)rtwheeler,etal.dynamic,morphotype-

specificcandidaalbicansbeta-glucanexposureduringinfectionanddrug

treatment.plospathog.2008dec;4(12).reprintedinaccordancewiththe

creativecommonsattributionlicense.page11fromylinetal.germcell-

intrinsicand-extrinsicfactorsgovernmeioticinitiationinmouseembryos.

science.2008dec12;322(5908):1685-7.reprintedwithpermissionfromaaas.

Page 14-29, 31-33kellylorenzPage 34-45 Justinknight

background imagetumorcellsinamousemodelofhumanbreast

cancerdevelopedinthelabofwhiteheadmemberrobertweinberg.

2 3 whitehead institute2008annualreport 3

thispastyear,wesaidfarewelltotwolong-servingmembersofthewhiteheadfaculty.after

23yearshere,paulmatsudairahastakenoverasheadofthedepartmentofbiologicalsciences

atthenationaluniversityofsingapore.wethankpaulforhiscontributionstowhiteheadand

wishhim,hiswifemaureen,andtheirtwochildrenwellinthisexcitingnewopportunity.in

september,thebroadinstitute,bornoutofthewhitehead/mitcenterforgenomeresearch,

becameanindependentorganization,andwhiteheadrelinquishedthegovernanceroleithad

heldsincethebroad’sinceptionin2004.atthesametime,broaddirectorericlanderformally

leftthewhiteheadfaculty.weviewtheestablishmentofthis“new”,independentbroadasthe

culminationofanaturalevolutionforthisneighboringinstitutionandareproudoftherole

whiteheadplayedinitscreation.whiteheadfacultycontinuetocollaboratewiththeirpeers

atbroadinthepursuitofscientificdiscovery,andbothinstitutionsarethebetterforit.

inthepagesthatfollow,you’lllearningreaterdetailwhy,despiteaglobaleconomicmalaise,

wehaveeveryreasonforoptimismaswemovethrough2009.oursciencehasneverbeen

strongerormoreimpactful.ourfacultyarecontinuallyrecognizedfortheirextraordinary

achievements.wearethebeneficiariesofremarkablephilanthropy,mostnotablyfromboard

memberlandonclayandboardvicechairsusanwhitehead.and,regardlessofone’spolitical

leanings,itwashearteningtohearournewpresidentdeclareduringhisinauguraladdress:

“wewillrestoresciencetoitsrightfulplaceandwieldtechnology’swonderstoraisehealth

care’squality.”

i’mextraordinarilygratefultoourfaculty,staff,friends,andsupportersforcontinuallyvalidating

thisoptimismandforhelpingusrealizeourpotentialonadailybasis.

sincerely,

davidc.page

director

attractingthebrightestyoungscientistsrequiresmorethansimplypostingjobopenings.

wemustconstantlyseekopportunitiesforimprovementifweintendtocontendforthe

best.lastyear,wesubstantiallyincreasedcompensationforourpostdoctoralscientists

throughinnovativeenhancementstooursalaryandbenefitsplans.postdocsplayacritical

roleatwhitehead,fuelingsomeofourmostcreativeandproductiveresearch.atthesame

time,theseyoungresearchersoftenfacethedualchallengeoftryingtolaunchtheircareers

andestablishfamilies.ourabilitytorewardthemfinancially,recognizetheirvaluetoour

community,andincreasetheinstitute’sappealasascientificworkplacemakethischange

incompensationoneofourmostimportantaccomplishmentsof2008.

Justbeforethisreportwenttopress,wereceivedwordthatoureffortstoimprovethe

postdocexperiencehavenotgoneunnoticed.The Scientist magazine,whichconductsan

annualrankingofeducationalandresearchinstitutions,namedwhiteheadinstitutethe

bestplaceinthecountryforpostdocstowork.theinstitute,unrankeduntil2008when

weplaced14th,surgedtothetopofthelistof85surveyedinstitutions.weviewthisnews

assolidaffirmationofourcommitmenttothefutureofbiomedicalresearch.

inanenvironmentasdynamicaswhitehead,changeandtransitionareinevitable.2008

delivereditsshareofboth.inJuly,wesufferedthelossofformerboardchairalex

d’arbeloff.wealltreasuredalexforhisboldleadership,profoundhonesty,andintellectual

rigor.alexservedasamentorformewhenifirstassumedthedirectorshiphere,andi

cametorelyonhimheavilyduringthosefirstfewyears.hispassingisablowsoftened

onlybythenewsthatalex’swife,brit,hasjoinedourboardofdirectors.brit’ssupport

ofandaffectionfortheinstitutearesostrongthatattimesitseemedtomethatshe

actuallysharedthepositionofboardchairwithalex.herwisdom,knowledge,experience,

andgoodhumormakeheranoutstandingaddition.

atthecloseof2008,wealsowelcomedmarklapmantotheboard.markisasuccessful

investmentprofessionalwithadvanceddegreesinthehumanities—perhapstheperfect

combinationforourtimes.mark’senergyandfreshperspectiveshouldinspireus.

Jonathangoldstein,anmitalumnuswhoasanundergraduatestudentworkedinthelab

ofwhiteheadfoundingdirectordavidbaltimore,becamechairoftheboardofassociates

(boa).Jono,whowillserveaconcurrenttermontheinstitute’sboardofdirectors,takes

overforoutgoingboachairellenpolaner.we’redelightedtohaveJonoaboard.wewill

certainlymissellen’senthusiasmforourmission.ipersonallywishtothankherforher

leadershipoftheboaduringatransitionaltimeforthatimportantgroup.

“ Our attention to fiscal discipline has enabled us to take bold, definitive steps toward ensuring the Institute’s scientific prowess for successive generations.”

preservingthemission,facingthefuture

4 5

imageofyeastcolonygrowninthelabofmembergeraldfink©felicefrankel,from“envisioningscience,thedesignandcraftofthescienceimage(mitpress)

whiteheadscience is institutionalbedrock. it isourverycore,acore

further strengthened by a host of significant research findings

emergingfrom institutelaboratories in2008.manyofthescientists

behindtheseadvances—andlargerbodiesofwork—wererecognized

accordinglyduringwhitehead’s26thyear.

scientific achievement

6 7 whitehead institute2008annualreport

immune system

novel technologies refined in the lab of whitehead member hidde Ploeghbroughtnewclarity

totheunderstandingofhowtheimmunesystemrespondstohostileinvaders.employinga

sophisticatedtargetingmethod,researchersstudyingtheparasiteToxoplasma gondii(which

cancausetheseriousdiseasetoxoplasmosis)wereabletoidentifytwospecificepitopes—small

portionsofinvadingpathogensthattriggerhostdefenses.aseparateteamofscientistsinthe

labpinpointed19suchepitopesinvolvedintheimmuneresponsetoaformofmouseherpesvirus,

whichbearssimilaritiestotheherpesvirusthatcausesmononucleosisinhumans.identification

ofspecificepitopescapableoftriggeringimmuneresponsescouldbringnewefficienciesto

vaccinedevelopmentstrategies.

micrornas—exceedingly small rnas that modulate genetic expression and protein-coding

—arecomingunderever-increasingscrutinyasscientistscontinuetolearnhowdiffuse,diverse,

andrelevanttheyaretomyriadbiologicalprocesses.in2008,researchersinthelabofwhitehead

fellowfernando Camargodiscoveredthatasinglemicrorna,knownasmicrorna-223,playsa

keyroleinregulatingthemammalianimmunesystem’sfirstlineofdefenseagainstinfection.it

turnsoutthatmicrorna-223,whichisexpressedonlyinaspecificbranchoftheimmunesystem,

controlsboththeproductionandfunctionofaclassofdefendingcellscalledgranulocytes.inmice

modifiedtolackmicrorna-223,researchersfoundexcessivelevelsofgranulocytesthatprovedto

beover-aggressiveinreactingtoforeignstimuli.moreover,thesegranulocytescontinuedtheir

attackintheabsenceofinfection,causingdestructiveinflammationinvitalorgans.thediscovery

ofmicrorna-223couldfurthertheunderstandingofavarietyofharmfulinflammatoryconditions.

on the defensive

atleftisathree-dimensionalrepre-

sentationofasmallmolecule,known

asanepitope,identifiedbyanew

methoddevelopedintheploegh

lab.thisepitopefromthedisease-

causingparasiteToxoplasma gondii

isenoughtotriggeratargeted

immuneresponse.

cAnceR

recent research in the lab of member robert weinberghasshownthatcancerstemcellsbestow

oncertaintumorstheabilitiestogrowandspreadtodistantsitesaroundthebody.suchcells,though

fewinnumberwithinatumor,havetheuniqueyetdevastatingcapabilitytoself-renewandformnew

tumorselsewhere.

in2008,scientistsinweinberg’slabdiscoveredthatsometumorcellsundergoashapechange

thatenablesthemtobreakfromtheprimarytumor,plantremotely,andseednewtumors.known

asanepithelial-mesenchymaltransition(emt),theprocessessentiallyproducescancerstemcells.

researchersrealizedtheycouldinduceemtincancercellsinthelaboratorysetting,allowingfor

creationofcancerstemcellstobescreenedforsusceptibilitytopotentialanti-cancerdrugs.

thencametheunexpected:inducingemtinnon-cancerouscellsconfersthedesirablepropertiesof

adultstemcells.thisremarkablefindingmayhavesignificantimplicationsforregenerativemedicine,

asitsuggestsarelativelysimpleroutetoproducingadultstemcellsfortherapeuticpurposes.

saysweinberg:“thisforusisaveryexcitingdiscovery,notonlybecauseofitsunexpectednessbut

becauseitoffersaroutebywhichonecouldinprinciplegenerateunlimitednumbersofstemcells

committedtocreateaspecificcelltype.onecouldimagine,forexample,thatifonetakesskincells

andinducesthemtoundergoanemt,theycouldbecomeskinstemcells.”

those afflicted with mixed-lineage leukemia (mll) typically face poor prognoses.infantsdiagnosed

withmllseldomreachtheirfirstbirthdays.themajorityofmllcasesarecausedbythefusionoftwo

specificgenes—MLLandAF4.thisfusionresultsinproductionofaso-calledfusionproteinknown

tobeintricatelyinvolvedinthediseaseprocess.whatwasunknown,untilnow,isexactlyhowthis

proteindisruptsnormalcellularfunction.researchersinthelabofwhiteheadmemberrichard Young

recentlydiscoveredthatthisfusionprotein,knownasmll-af4,bindstomorethan200genes.inso

doing,thetargetedsetofgenescorruptsbloodstemcellmachinery,essentiallyturningbloodcells

cancerous.geneswithinthisidentifiedsetmightonedaybecometherapeutictargets.

notesyoung:“wethinkwe’vefiguredoutakeypieceofhowthisleukemiaworks.”

stemming a cancerous tide

themulti-coloredstainingofhuman

mammarycellsthathaveundergone

anepithelial-mesenchymaltransition

denotesthebeginningsofmultiple

celltypes.theabilitytogiverise

todiversecelltypesisadefining

featureofcertainstemcells.

scientificachievement


stem cells

the lab of member rudolf Jaenisch maintained its leadership in cellular reprogramming—the

processofrevertingmature,fullydifferentiatedcellstoanembryonicstemcell-likestate.

embryonicstemcellsarepluripotent,havingtheabilitytobecomeanyoftheroughly200cell

typesinthebody.reprogrammedcells,knownasinducedpluripotentstemcellsoripscells,have

capturedconsiderableattention,astheyappeartoharborthetherapeuticpotentialofembryonic

stemcellswithouttheneedforembryos.in2008,Jaenisch’slabfueledtheexcitementbyusing

ipscellstotreatarodentmodelofparkinson’sdisease.saidJaenisch:“it’saproofofprinciple

experimentthatargues,yes,thesecellsmayhavethetherapeuticpromisethatpeopleascribe

tothem.”

sincethen,membersofhislabhaverefinedthereprogrammingprocess,which,asfirstdescribed,

wasproblematic.initialcreationofipscellsreliedonvirusestoinsertfourreprogramminggenes

intocellulardna.oneofthesefourgenesisknowntocausecancer,andviralinsertionsmayalso

triggervirally-inducedcancers.theoriginalmethodisalsoremarkablyinefficient,withroughly1in

1,000cellsreprogrammed.inaproductiveseriesofexperimentsinthelatterhalfof2008,Jaenisch

labmemberseliminateduseofthec-Myconcogene(oneoftheoriginalreprogramminggenes)in

creatingipscells;cutthenumberofvirusesusedinreprogrammingfromfourtoone;anddevised

amethodthatreliablyreprogramsnot1in1,000cellsbut1in20.

with all the focus on novel stem cell research,it’seasytoforgetthatstemcelltransplantation

hasbeeninclinicaluseformanyyears.bonemarrowtransplantsareinfactstemcelltransplants.

however,suchproceduresarecomplicatedandmayrequirelifelongimmunosuppressivetherapy

forrecipients.oneoftheimpedimentstosuccessfultransplantationisthatblood-formingstem

cellsinthebonemarrow—hematopoieticstemcells(hscs)—areextremelyrare.anestimated1

in10,000bloodcellsisanhsc,anditishscsthattransplantrecipientsrequire.

in2008,scientistsinthelabofmemberharvey lodishidentifiedacocktailofgrowthfactorsthat

increasesthenumberofhscsinculturebyafactorof20.sucharesultshouldintheoryimprove

theoddsforsuccessfultransplant.lodish’sworkisslatedforclinicaltestinginsingaporein2009.

unscheduled Programming

inanattempttotreatparkinson’s

diseaseinarodentmodel,whitehead

scientiststransplantedneuralprecursor

cells(stainedgreen)—derivedfrom

reprogrammedskincells—intothe

rodents’brains.cellsstainedyellow

atleftarethosethatmatured

successfullypost-transplant.

pRotein function

the work in the Camargo lab described earlier helped informaspectsofacomprehensive

micrornastudyundertakeninthelabofwhiteheadmemberdavid bartel.scientistsinbartel’s

labteamedupwithresearchersatharvardmedicalschooltolookattheproteinoutputofgenes

targetedbyspecificmicrornas.

“thisisthefirsttimealarge-scaledatasethasbeenusedtoobservetheeffectofmicrornas

ontheproductionofthousandsofproteins,”bartelsays.“previoustechnologyenabledustoonly

lookathowmicrornasaffectmessengerrnas.”thestudyconfirmedthat,ratherthanbehaving

asblunton–offswitches,micrornasactuallyfinetuneproteinexpression,ofteninexquisitely

delicatefashion.anindividualmicrornamayaffectthelevelsofhundredsofproteins,butonly

intinyamounts.

huntington’s disease, a devastating neurodegenerative disorder, isknowntobelinkedtoamis-

foldedcellularprotein.whatremainsamystery,however,ishowthisproteininflictsthedamage

thatleadstothedeathofneuronsinthebrain.innovember,scientistsinthelabofwhitehead

membersusan lindquistdiscoveredamechanismthatbeginstoexplainhowthemisfoldedprotein

canwreakneuronalhavoc.usingyeast,rat,andmousemodelsofnervetoxicityandhuntington’s

disease,researchersfoundthattheproteininquestiondisruptscells’normalproteindegradation

anddisposalsystems,leadingtoadestructiveaccumulationofotherproteinsthatsimplyaren’t

meanttoberetainedinsidethenervecells.thisfindingimplicatespreviouslyunsuspectedcellular

pathways,openingnewareasforinvestigation.

of folding and fine tuning

accordingtoresearchfromthe

lindquistlab,aprotein(stained

redinthecenterimage)thought

tocausehuntington’sdisease

clogsthecell’sproteinrecycling

system(stainedgreen),causinga

toxicbuilduplethaltonervecells.



arrowsintheimageontheleft

showcondensedchromosomesin

nucleiofnormalmouseovaries—an

indicatorthatmeiosisisbeginning.

ovariantissueontherightisfrom

micelackingtheDazl gene,with-

outwhichmeiosisdoesnotinitiate.

forreproductiveanddevelopmentalbiologists,fewprocessesaremoreintriguingthanthosethat

regulategermcellsandtheircomplexpathtosexualdifferentiation.possesseduniquelyamongall

cellswiththeabilitytohalvetheirgeneticmaterialinpreparationforthenextgeneration,germ

cellsresideatthecoreofsurvivalofsexuallyreproducingorganisms.

“fromthepointofviewofreproductivebiology,thisisasfundamentalajunctureinananimal’s

lifecycleasicanimagine,”saysinstitutedirectordavid Page,whoselaboratoryhasbeenfocused

intentlyonmeiosis;morespecifically,onthe initiationofmeiosis,whenthechromosomalhalving

commences.researchersinthepagelabhavebeenlookingtosettlealongstandingdebateover

whethermeiosisistriggeredbyintrinsicfactorswithinthegermcellsthemselvesorbyextrinsic

signalscomingfromthecellularenvironment.theycrackedthecasethispastyear,provingthrough

aseriesofexperimentsthatbothsetsofsignalsarerequiredtostartthemeioticprocess.

previousworkinthepagelabhadshownthatinfemalemice,extrinsicsignalingfromthevitamin

aderivativeretinoicacid(ra)inducesexpressionofthegeneStra8(stimulatedbyretinoicacid),

whichinturninducesmeiosis.itwasanimportantfinding,tobesure,butthescientistsrealized

thatbecauserasignalingisfairlyubiquitousinmammalsatmultiplephasesofdevelopment,it

alonecouldnotexplainsomethingasspecificasmeioticinitiation.

theyturnedtheirattentiontoageneknownasDazl,whichhadbeenshowntocodeforthegerm-

cell-specificproteindazl,anddiscoveredthatintrinsicsignalingfromdazlreadiesgermcellsto

respondtoextrinsicrasignaling,whichthentriggersthemtogomeiotic.twosetsofsignals,one

fewerdebate.

twice the signaling, half the chromosomes

atenuousdétenteexistsinthecoldwarbetweentheyeastCandida albicansanditshumanhosts.

ahealthyimmunesystemlargelykeeps C. albicansatbay,allowingoccasionalbreakthroughthrush

orvaginalyeastinfections.mostofthetime,theyeastresidescontentedlyonourskinandin

ourintestines.

butiftheimmunesystemisweakenedbydrugtherapyforcancerororgantransplantation,C. albicans

seizestheopportunity,invadesthebloodstream,andattacksvitalorgans.

C. albicanshastwoforms:around,yeastformandaninvasive,multi-celledfilamentousform.interest-

ingly,ahealthyimmunesystemlaunchesanattackwhenitdetectsaspecificmoleculeonthecell’s

surface.thismoleculeisß-glucan,astructuralmoleculethatholdstogetherthecellwallaroundthe

pathogenbutalsotagsitfordestructionbyimmunecells.

robertwheeler,thenapostdoctoralresearcherinthelabofmembergerald fink,wasperplexed

thatfungigrowninthelabcanmuteimmuneresponsesbymaintainingadensesugarcoatingover

ß-glucan.heaskedwhetherthisevasionmechanismfunctionsduringinfection—inthefaceofimmune

response.lookingatfungalinfectionsinmice,wheelerfoundthatß-glucanisinitiallycoveredbya

thinmaskthatpreventstheimmunesystemfromlaunchingafull-blownattack.laterduringinfection,

itlosesthatmaskandtheimmunesystemrecognizestheassailantasforeign.

“wedon’tknowwhyyeasttakesoffthatmask,”sayswheeler,whoisnowanassistantprofessorat

theuniversityofmaine.“maybeitdoesitonpurposeormaybetheimmunesystemdamagesthemask

toexposeß-glucan.thatquestionissomethingwe’refollowingupon.”

Yeast, unmasked

thefungusC. albicans,farleft,in

roundandfilamentousforms.in

earlyinfection(topimage),little

ofthefungus’sß-glucansurface

protein(stainedred)isexposed.

later,themaskoverß-glucanis

lost(bottomimage),prompting

animmuneresponse.


farleft:

©felicefrankel,from“envisioningscience,the

designandcraftofthescienceimage(mitpress)


TheScientist

BESTPLACESTO WORK

2009POSTDOCS

howardhughesmedical

institute(hhmi)investigator.

theappointmentisahighly

sought-afterpostthatrecog-

nizesthenation’stopbio-

medicalscientistsbyprovid-

inglong-term,flexiblefunding

insupportofcreativityand

intellectualdaring.sabatini,

whowasoneof56scientists

selectednationwidefroma

fieldofnearly1,100applicants,

remainsatwhiteheadinstitute

whilehhmisupportsalarge

percentageofhisresearch.

otherhhmiinvestigatorsat

whiteheadincludemembers

davidbartel,susanlindquist,

anddavidpage.

institutionAl HonoRs

indecember,Sciencemaga-

zinenamedcellularrepro-

gramming—theprocessof

turningadultcellsbackinto

anembryonicstemcell-like

state—asitsbreakthrough

oftheyearfor2008.aspart

ofitscoverage,themaga-

zine’seditorscompiledalist

of25ofthemostimportant

reprogrammingpapersfrom

laboratoriesaroundtheglobe

thatwerepublishedduring

theyear.fourofthesesemi-

nalpublicationscamefrom

whiteheadinstitute,whichis

clearlymaintainingitsleader-

shippositioninafieldthat,

accordingtoScience,is“mov-

ingfasterdownthehighway

ofdiscoverythanmanyhad

expectedordaredtohope.”

Justpriortopublication,

themagazineThe Scientist

namedwhiteheadinstitute

thebestplaceinthecountry

forpostdoctoralresearchers

towork.whiteheadclaimed

thenumberonepositionin

asurveyofpostdocsat85

researchinstitutionsacross

theunitedstates.in2008,the

firstyearinwhichwhitehead

appearedinThe Scientist’s

rankings,itplaced14th.white-

headdirectordavidpage,

uponhearingoftheinstitute’s

surgetothetopcommented,

“ourpostdocsareandalways

havebeenthebackboneof

thewhiteheadinstitute…they

deserveafirst-classenviron-

mentinwhichtowork,train,

andlearn,andwewilldoour

besttocontinuetoenhance

theirexperiencehere.”

althoughtechnicallya2009

honorforwhitehead,thistop

rankingislargelytheresult

ofa2008initiative,whenthe

institutebolsteredcompen-

sationforpostdocsthrough

innovativeimprovementsin

salaryandbenefitspackages.

inannouncingitsrankings,

editorsatThe Scientistcited

whitehead’srenewedfocuson

postdocs,includinggener-

ousbenefits,interactionswith

high-caliberseniorscientists,

andafamily-friendlyenvi-

ronmentthatsupportsgood

work–lifebalance.

whiteheadinstituteresearchon

reprogrammingcellswasheavily

citedinSciencemagazine’s

“breakthroughoftheyear”

coverage.The Scientistmagazine

namedwhiteheadthebestplace

inthecountryforpostdocsto

work—avalidationoftheinstitute’s

commitmenttoimprovingthe

postdocexperience.

iAin cHeesemAn

whiteheadmemberiain

cheesemanwasoneof11

scientistsstatewidetoreceive

acompetitivenewinvestigator

grantfromthemassachusetts

lifesciencescenter.thethree-

yeargrantsupportshisstudy

ofcoreproteinsinvolvedin

celldivision.

Rudolf JAeniscH

whiteheadmemberrudolf

Jaenischreceivedthe2008

meiraandshaulg.massry

prizerecognizinghiswork

increatingso-calledinduced

pluripotentstemcells,or

ipscells.themassryprizeis

givenannuallytothosemak-

ingoutstandingcontributions

tothebiomedicalsciencesand

theadvancementofhealth.

Jaenischsharedtheprizewith

twootherrenownedstemcell

scientists:shinyayamanakaof

kyotouniversity,andJames

thomsonoftheuniversityof

wisconsin-madisonschoolof

medicineandpublichealth.

susAn lindquist

researchintheareaofpro-

teinfoldingearnedwhitehead

membersusanlindquistthe

ottowarburgmedalfrom

thegermanassociationof

biochemistryandmolecular

biology.inawardinglindquist

themedal,theassociationpres-

identsaid,“susanlindquist’s

findingsinthefieldofprotein

foldingaregroundbreaking.”

lindquistalsoreceivedthe

geneticssocietyofamerica

medalinrecognitionofout-

standingcontributionstothe

fieldofgenetics.

harvarduniversitypresented

lindquistwithacentennial

medal,awardedtoalumniof

itsgraduateschoolofarts

andsciencesdeemedtohave

madeoutstandingcontribu-

tionstosociety.

atthecloseof2008,lindquist,

whoisalsoahowardhughes

medicalinstitute(hhmi)inves-

tigator,wonanhhmicollab-

orativeinnovationaward.hhmi

establishedtheawardprogram

tobroadenitscommunityof

supportedscientists.lindquist

leadsateamofresearchers,

includingwhitehead’srudolf

Jaenisch,investigatingthe

mechanismsofneurodegenera-

tivedisorders.

HARvey lodisH

themassachusettslifesci-

encescenter(mlsc)appoint-

edwhiteheadmemberharvey

lodishchairofitsscientific

advisoryboard.inthiscapac-

ity,lodishleadsagroupof

scientistschargedwithdevel-

opingatransparent,competi-

tive,peerreviewprocessfor

grantapplicationsandfunding

proposalstothemlsc.the

scientificadvisoryboardwill

alsomakefundingrecommen-

dationstothemlscboardof

directors.

dAvid pAge

whiteheaddirectordavid

pagewaselectedtotheinsti-

tuteofmedicine(iom)ofthe

nationalacademies.election

totheiomrecognizesindi-

vidualswhohavemademajor

contributionstotheadvance-

mentofthemedicalsciences,

healthcare,andpublichealth.

pageisthefifthwhitehead

memberintheiom,joining

geraldfink,rudolfJaensich,

susanlindquist,androbert

weinberg.

peteR Reddien

thew.m.keckfoundation

namedwhiteheadmember

peterreddienadistinguished

youngscholarinmedicalre-

search.reddienisoneoffive

scientistsacrossthecountry

sohonoredbythefounda-

tion.thedesignationincludes

afive-yeargrantsupporting

reddien’sresearchonthe

mechanismsofregeneration

inplanariaflatworms.

dAvid sAbAtini

whiteheadmemberdavid

sabatiniwasappointeda

honors and awards


14 15

itisanaugustcollective,whiteheadfaculty:14members,hand-picked,

accomplished,decorated.theyareworld-classscientistswhoalsoare

giftedteachers,mentors,andleaders.theirinfectiouspassionand

commitmenttotheircraftcontinuallydistinguishtheinstitute.

PrinciPal investigators


david bartelReseARcH focus

davidbartel’slabisdeterminedtodescribefullythe

rolesmicrornasplayinbiologicalprocessesandthe

profoundeffectsthesetinysnippetsofrnahavehad

ontheevolutionofmyriadspecies.thebartellabwas

amongthefirsttoidentifyhundredsofthesemicrornas

andtheireffectsonprotein-codinggenesinplantsand

animals.(itistheproteinsthatsuchgenescodeforthat

actuallycarryoutcellularfunctions.)

inthebartellab,it’sbecomingclearthatmicrornas

aremoreintegraltolifethanthoughtjustafewyears

ago.saysbartel:“wenowknowthatmorethanhalf

ofprotein-codinggenesaretargetsofmicrornas.”

2008 AccomplisHments

usingsophisticatedhigh-throughputdnasequencing,

bartel’slabdeterminedthatmicrornasarepresent

indiverseanimalspecies,includingsponge,whichis

thesimplestofallanimals.theseresultsindicatethat

micrornashavebeenshapinggeneexpressionfor

thepastbillionyears;thatis,throughoutanimalevolu-

tion.during2008,thelabalsousedimprovedtechnical

capabilitiestoexaminetheeffectsofamicrornaonthe

productionofmultipleproteins,discoveringthatasingle

micrornaalterslevelsofhundredsofcellularproteins,

butofteninamodestfashion,actingmoreasdimmer

thananon–offswitch.

tHe futuRe

thelabhasdiscoveredrnainterference—orrnai,a

processbywhichsmallrnasnaturallysilencecertain

genes—inacloserelativeofbaker’syeastandwillbe

usingthisyeastforthegeneticandbiochemicalstudy

ofrnai.

did you know… that David Bartel lived for three years in Mwamba, a small village in Zambia? Bartel was a volunteer in the African nation with a non-governmental development agency working to improve agricultural methods.


ReseARcH focus

iaincheeseman’slabstudiesthekinetochore,aspe-

cializedcomplexofanestimated80to100proteins

thatassemblesduringcelldivisionandcoupleschro-

mosomeswiththinproteinfilamentstermedmicrotu-

bules.withoutproperattachment,microtubulesare

unabletodragthelargechromosomesthroughthe

nucleus’sviscousfluidandaccuratelydividethechro-

mosomesbetweenthetwonewcells.thepenaltyfor

amistakeissevere:cellswiththewrongchromosomes

oftendieorbecomecancerous.


thekinetochore’sproteinsmustbindtomicrotubules

andalsoremainboundtothechromosome’scentrom-

ereregion.thecentromere,whereahumanchromo-

some’sarmspinchtogethertoformanxoryshape,

containshighlycompacteddnaintertwinedwith

centromere-specificproteins.accordingtocheeseman,

whilethemitosisfieldhasfocusedononlyoneofthese

centromereproteins,cenp-a,itwasunclearwhether

additionalproteinswerecentraltokinetochoreforma-

tionandattachmenttothechromosome.workingwith

collaboratorsinJapan,cheeseman’slabfoundthata

newgroupofhumankinetochoreproteins,thecenp-t/

cenp-wcomplex,isalsonecessaryforthekinetochore

toholdontothechromosome.

tHe futuRe

cheesemanisfascinatedbybothsidesofthekineto-

chore:thesidenestledagainstthechromosome’sdna

andthesidereceptivetoproteinmicrotubules.heis

especiallyinterestedinunderstandinghowtheseinter-

facesworkandhowsuchanincrediblycomplexand

dynamicstructureissotightlyregulatedbythecell.

iain cheeseman

did you know… that Iain Cheeseman often serenades the researchers in his lab? He has been known to croon impromptu ditties about microtubules and how he hopes his experiments will work.

17 whitehead institute2008annualreport

18 19 whitehead institute2008annualreport18 principalinvestigators

ReseARcH focus

geraldfink’slabanalyzeshowmicrobesaltertheircell

surfacestorecognizeeachotherbutavoiddetectionby

theimmunesystem.inyeastthiscamouflageinvolves

switchingfromonecellsurfaceproteintoanother.fink’s

workhasuncoveredapreviouslyinvisiblenetworkofnon-

codingrnasthattogglethecellsurfacegenesonand

off,providingvariationthatconfusestheimmunesystem.


ourimmunesystemrecognizesasignaturesurfacefea-

tureoffungalcells,ß-glucan,whichalertstheorganismto

theinvader’spresence.thefungalcellsmasktheß-glucan,

thusfoilingtheimmunesystem’srecognitionsystem.

eventually,theimmunesystemunmasksthefungalcells

andmountsanimmuneresponse,butasluggishresponse

canleadtoseveresystemicinfections.fink’slabshowed

thatanantifungalagentcanspeedtheunmaskingpro-

cess.thefinklabalsodemonstratedthatcertaincellwall

genesareunderthecontrolofnon-codingrnas.some

ofthesernasareantisense,eachwithasequencecom-

plementarytotheexpressedgene;othersarefoundin

thespacesbetweengenesandswitchtheadjacentgenes

onandoff.newsequencingmethodshaverevealedthat

thesenon-codingrnasaremuchmoreprevalentthan

previouslysuspected.

tHe futuRe

finkisfascinatedbynon-codingrnas.thesernascome

fromdnathatdoesnotcodeforproteins,butregulates

proteins.so,whatregulatesthesenon-codingrnas?

finkisworkingcloselywithdavidbartelandwhitehead

affiliatememberdavidgiffordtoanswerthisquestion.

gerald fink

did you know... that Gerald Fink discovered a super-secret fishing hole somewhere off Cape Cod? When Fink took David Bartel there, he and his son caught 30 striped bass and bluefish. The normally mild-mannered Bartel was so excited that he fumbled the handoff of Fink’s favorite fishing rod, which sank deep into the ocean.

rudolf jaenischReseARcH focus

apioneerincellularreprogramming—theprocess

ofturningmature,differentiatedcellsbacktoan

embryonicstem-cell-likestate,withouttheuseof

embryos—rudolfJaenischisfocusedondevelop-

inghighlyefficient,consistentlyreliablemethods

forcreatingso-calledinducedpluripotentstem

(ips)cells.


theJaenischlabgarneredconsiderableattention

forusingipscellstogenerateneuronscapable

oftreatingarodentmodelofparkinson’sdisease.

thiswasagroundbreaking,proof-of-principle

experimentshowingtheremarkabletherapeutic

potentialofipscells.cellsusedinthisresearch,

however,werecreatedusingviralvectorsto

insertfourreprogramminggenesintocellular

dna—anapproachthatcaneventuallyleadto

developmentofcanceroustumors.during2008,

thelabwasabletoimprovethereprogramming

processbyeliminatingtheuseofaknown-cancer

causinggene.researchersalsoshowedthatips

cellscanbecreatednotjustfromskincells,which

hadbecomeastandardapproach,butalsofrom

terminallydifferentiatedcellsintheimmunesys-

temandfromcellsofvariousothertissuetypes.

tHe futuRe

theadvancesof2008haveputthelabinposition

tostudyavarietyofdiseasesusinghumanips

cells.saysJaenisch:“we’veassembledthetools

toreallymaketheipssystemsreadyfordisease

studyandforthecreationofpatient-specificcell

types.thepossibilitiesaremuchmorerealnow.”

did you know… that Rudolf Jaenisch is an accomplished mountain climber who has trekked across a variety of peaks in Europe, Asia, and Africa? Although a fan of climbs in the Himalayas, he cites Mount Kenya as his favorite conquest.



ReseARcH focus

proteinsarelong,complexchainsofaminoacidsthat

mustfoldintoprecisethree-dimensionalstructuresto

performtheirvitalcellularfunctionsproperly.susan

lindquist’slabstudiesthemanyunexpectedwaysin

whichtheproteinfoldingprobleminterfaceswith

biologyinbothhealthanddisease.


inhuntington’sdisease,toxiclevelsofmisfoldedproteins

accumulateinbraincells.studyingproteinbehaviorin

yeastcells,lindquist’slabfoundthatamisfoldedprotein

(huntingtin)clogsthecells’proteinrecyclingsystem,

whichnormallyclearsoutmisshapenhuntingtin.re-

searchersobservedthesamephenomenoninmammalian

nervecellsofthekindaffectedinhuntington’sdisease,

confirmingthatcompromisedproteindisposalleadsto

neurotoxicity.cellscanpreventsomeproteinmisfolding.

heatshockproteins(hsps)steermisfoldedproteins

intoform,allowingtheproteinstofunctionnormally.

however,understress(extremetemperatureortoxin

exposure),hspsareoverwhelmed,allowingmutant

proteinsintoshapesthataltercellularandorganismal

function.instressedmustardplants,lindquist’s

researchersfoundthatsuppressingakeyhspaffects

traitslikefloweringandseedproduction.suchseemingly

spontaneouschangesinmultipletraitsmayexplainrapid

evolutioninresponsetoenvironmentalshifts.

tHe futuRe

studyingthemoleculargeneticsofyeast,lindquist

isexploringhowenvironmentalchangecouplestothe

evolutionofnewtraits.sheisalsoinvestigatingthe

numberofprionproteinsfoundinyeastandother

organisms,suspectingthattheyaremorecommon

andmorebeneficialthanresearcherscurrentlythink.

susan lindquist

did you know... that Susan Lindquist is a ballroom dancer? She and her husband picked it up eight years ago and now like to tango and swing dance at home or wherever they can find a band.


harveY lodishReseARcH focus

currentareasofinterestinthelodishlabinclude

redblood-celldevelopment,hematopoietic

(blood-forming)stemcells,andtheregulatory

rolesmicrornasplayindevelopmentandfunction

ofmusclecells,fatcells,andseveraltypesofblood

cells,includingthebcellsoftheimmunesystem.

muchofthelab’sworkliesattheinterfacebetween

molecularcellbiologyandmedicine.


researchersinthelabdevisedacocktailofgrowth

factorsthatincreasesthenumberofhumanhe-

matopoieticstemcellsinculturebyafactorof20.

it’safindingwiththepotentialtoimprovesuccess

ratesofbonemarrowtransplants.scientistsalso

identifiedmicrornasthataffectdrugresistance

incertaintypesofleukemia,notingthatwhen

thelevelofonemicrorna(mir-221)isincreased

intheseleukemiccells,theyrespondtodrug

therapy.otherworkhasbeguntoimplicatespecific

micrornaswhosedown-regulationisassociated

withobesity.

tHe futuRe

accordingtolodish,micrornaworkwillbefront

andcenter:“theexcitingthingaboutmicrornasis

thattheyreallydoplaykeyrolesindevelopmental

processes.theyhaveprofoundeffects.we’vebeen

studyingthesedevelopmentalsystemsforyears,

andnowallofasuddenwe’vediscoveredawhole

newlayerofregulation.”

did you know… that Harvey Lodish has twice officiated at marriage ceremonies of students in his lab? In fact, in February 2009, he presided at what is believed to be the first and only wedding ever held at the Institute itself. Says Lodish: “It’s an honor to be asked to serve at such important life events.”


22 23 whitehead institute2008annualreport22 principalinvestigators

terrY orr-weaverReseARcH focus

cellsmayundergocertainimportanttransitionsintheir

lifetimes:dividingfromonecellwithacompletechromo-

somesetintotwocells,eachwithcompletesets(mito-

sis);dividingfromonecellwithacompletechromosome

settoproduceeggsorspermwithhalfaset(meiosis);

andchangingfromunfertilizedeggtofertilizedeggto

embryo.terryorr-weaverstudiestheprecisecontrols

neededforthesestepstooccurproperly.


asafemalehumanembryodevelops,allitseggsare

createdandentermeiosis.buttheprocessstopshalf-

waythrough,andtheeggsawaitatriggeratpuberty

thatnudgesthemtoripenandmovetoasecondmeiotic

hiatus,awaitingfertilization.inmanyorganisms,theegg

isfilledwithtemplatesformeiosis-regulatingproteins,but

thesetemplatesmustnotproduceproteinsuntiltheright

developmentaltime.

infruitflies,theorr-weaverlabanalyzedatthemolecular

levelhowtheseproteintemplatesarestalledanddiscov-

eredaproteincomplexthatexquisitelyjumpstartsthem.

theorr-weaverlabisalsodecipheringthefirststepof

celldivision—thereplicationofacell’sdna.although

muchofthisprocessisunderstood,littleisknownabout

replicationregulationinanimals.insixdnareplication

sitesinfruitflyovaries,thelabfoundstrikinglydifferent

mechanismscontrollingeachsite.untilnow,researchers

hadthoughtonlyonemechanismregulatestheinitiation

ofdnareplication.

tHe futuRe

surprisedbythevarietyofdnareplicationcontrols,

orr-weaverisinvestigatinghowothercelltypesregulate

theprocess.sheisalsodelvingdeeperintotheprocesses

thatmanagemeiosis.

did you know... that Terry Orr-Weaver enjoys playing the piano? She is currently perfecting Beethoven’s Sonata #8 Rondo.

ReseARcH focus

institutedirectordavidpagehaslongbeenatthe

forefrontofresearchintomammaliansexchromo-

somes.whileperhapsbestknownforexposingthe

previouslyunappreciatedcomplexityofthehumany

chromosome,hisworkinelucidatinghowgermcells

halvetheirchromosomesandcommittobecoming

eithereggorspermmayprovenolessimportantin

thefieldofreproductivebiology.


thepagelabfoundanotherpieceofthepuzzleof

howgermcellsentermeiosis(thehalvingofchro-

mosomes)inpreparationforproductionofsperm

oregg.thelabhadpreviouslydiscoveredinmouse

studiesthatthegeneStra8(stimulatedbyretin-

oicacid)isrequiredtoinitiatemeiosis.in2008,

researchersdeterminedthatevenbeforeStra8

expressioncantriggermeiosis,anothergeneknown

asDazlmustproduceaproteinthatpavestheway

forStra8expression.theseresultsconfirmthat

meioticinitiationoccursthroughacomplexpath-

wayofsignalsthatisslowlybecomingclearer.

tHe futuRe

“ilookbackadecadeandrealizethatwenever

couldhaveguessedtheanswerswehavetoday,”

sayspage,whobelievestheDazl-Stra8storyhas

severalchaptersyettobetold.“they’rethetwo

centralplayers,andwe’reabouttogreatlyexpand

theirjobdescriptions.”

david Page

did you know… that David Page met his wife of 23 years while working at a hospital in Liberia? David and future spouse, Elizabeth, were medical students at the time. On her first day, Elizabeth encountered an active hornets’ nest while attempting to move into a hospital residence hall. A chivalrous Page cleared the hornets’ nest. Says Page, “That has not been a metaphor for our relationship!”



hidde PloeghReseARcH focus

forhiddeploegh,exploringtheintricaciesofthe

immunesystemhasbeenalifelongpursuit.alongthe

way,heandscientistsinhislabhavedevisednovel

methodstostudythevariouscellularandmolecular

mechanismsofthesystem’sresponsestoforeign

invasion.hisinterestindrawingfromotherscientific

disciplines,includingchemistryandchemicaland

mechanicalengineering,fuelsinnovationinhislab’s

immunologyresearch.


researchersdevelopedaunique“microengraving”

systemallowingthemtodepicthowindividualcells

intheimmunesystemrespondtovaccinations.the

systemquicklyandefficientlygeneratesimportant

dataonbcells,includingtheirnumber,whetherthey

areactivelyproducingantibodiestoavaccinechal-

lenge,andthespecificityofantibodiesproduced.

aseconddiscoveryconcernsthemannerinwhich

incomingpathogensarehandledbycertaintoll-like

receptors,whichareproteinsthatfocusonmicrobial

macromolecules.ploeghandcolleaguessolvedthe

longstandingmysteryofhowandwhylysosomes,

intracellularorganellesusuallychargedwithdisposal

ofunwantedmaterials,areinvolvedintheactivation

ofsomeofthesetoll-likereceptors.

did you know ...that Hidde Ploegh is an avid sport fisher-man? He co-owns a fishing boat named The Rampage, upon which he cruises the Atlantic on summer days in the hunt for striped bass, bluefish, and bluefin tuna.


tHe futuRe

beyondcontinuedinvestigationoftheimmuneresponse,

ploeghiscollaboratingwithwhiteheadmembers

rudolfJaenischandrichardyoungindevelopingnew

modelsforthestudyofinfectiousdiseases,makinguse

ofnucleartransplantationtechnologytogeneratemice

thatarebettersuitedtostudytheinterplaybetweena

hostanditspathogens.

Peter reddien


ReseARcH focus

howstemcellscanbeutilizedforregenerationisanis-

sueofgreatscientificinterest.gettingattherootofthis

problemrequiresunderstandinghowstemcellsfunction,

howcellularandtissueregenerationoccur,andhowa

bodypartregrowswithcorrectidentity.thereddien

labstudiesthesetopicsinplanarians,flatwormswiththe

amazingabilitytoregrowanyseveredbodypart—includ-

ingnervoussystem,muscles,skin,andintestine.


reddien’slabidentifiedmultiplegenesthatregulateneo-

blasts,theplanarianstemcellsresponsibleforregenera-

tion.becausestemcellregulationoccursinallanimals,

reddien’sworkinplanariamayultimatelyprovideinsight

intoregenerationandstemcellsinhigheranimals,includ-

inghumans.

reddien’slabfoundthatawntsignalingpathwaytrig-

gersatailtogrowonthebackendoftheworm.when

thispathwayisblocked,thebackendgrowsahead

instead.wntsignalingisimportanttothelifeofallani-

mals.thelabdeterminedthemechanismbywhichwnt

signalingmakestheregenerationpolaritydecision,

involvingactionofwntproteinsatwounds.thisrole

forwntsignalingprovidessomeofthefirstinsightinto

howtheprocessisregulatedatthemolecularlevel.

tHe futuRe

bystudyingplanarianstemcells,thereddienlabis

identifyingthemechanismsthatregulatethewnt

signalingpathwayandcontrolmultiplegenesthatare

turnedonspecificallyinthosestemcells.

did you know… that Peter Reddien was a remote-control racing car champion as a high school senior and college freshman? At the height of his remote racing career, he was on the U.S. team and placed first in Texas, 23rd in the country, and 45th in the world?


david sabatiniReseARcH focus

regulationofcellgrowthisessentialforproperde-

velopmentandtopreventcancer,whichresultsfrom

rampantovergrowthofcells.davidsabatinistudies

thecomponentsofacellularsystemthattriggers

growth(knownastor,ortargetofrapamycin)and

howthissystemiscontrolled.


sabatini’slabfoundapotentialdrugtargetforcan-

cerscausedbyamutationintheptengene.tumors

resultingfromptendeficiencydependonaparticu-

larproteincomplexinthetorsystem.whenthat

proteincomplexisdisabledinamousecancermodel,

tumorformationisblocked,butnormaltissuesarenot

affected—anidealresultforacancerdrug.

thetorsystemisalsoinvolvedinnormalcellgrowth.

thesabatinilabdiscoveredakeycomponentthat

linksnutritiontothe“grow”command,aconnection

thatgreatlypuzzlesresearchers.whentheso-called

ragfamilyofproteinssensesthepresenceofthenu-

trientsforprotein-building(aminoacids),ragalters

thelocationofpartofthetorsystemwithinthecell.

thisrelocationsignalsthecelltogrow.

tHe futuRe

despiteabetterunderstandingofhowgrowthsignals

aretransmittedthroughthecell,sabatinistilldoesnot

knowwhatactuallysensestheaminoacidnutrients.

also,similarpathwaysinvolvedincellgrowthhave

beendocumentedwithcancer-causingmutations.

althoughnosuchmutationshavebeenfoundinthis

nutrient-sensingpathway,sabatiniissearchingfor

connectionsbetweenthispathwayandcancer.


did you know... that David Sabatini’s garden is smaller than his office, but is home to several large, unusual trees, including a spiky monkey puzzle tree and a “Bigleaf Magnolia”, with 30-inch leaves?

haZelsiveReseARcH focus

inthesivelab,developingembryosoffrogsand

zebrafishserveastoolsforthestudyofearlybrain

andcraniofacialdevelopment.withinthecomplexity

ofbrainformationmayliecluestothegenesis

ofmentalhealthdisorders,includingschizophrenia

andautism.


scientistsinthesivelabidentifiedapreviouslyun-

describedbendingmechanismintheformationof

zebrafishbrains.asthebraindevelops,sheetsofcells

mustbendandfoldthebrainsothatitcan“pack”into

theskull.allcellsheetshavetwosides,theapicalside

andthebasalside.aconsiderablebodyofresearch

hascharacterizedthechangesthattakeplaceamong

thecellsoftheapicalsideofthesheet,butresearch-

ersinthesivelabhavediscoveredthatcellular

constrictiononthebasalside(“basalconstriction”)

occursactivelyandplaysacriticalroleinoneofthe

mostimportantearlybendsinthebrain.

tHe futuRe

“ourchallengenowistofigureouthowcellsknowto

basallyconstrictandwhatgenesarerequiredforthe

process,”sivesaysofthislatestdiscovery.“whatever

resultsweobtainwillbenovel,andthat’saveryexcit-

ingplacetobe.”

did you know... that Hazel Sive believes that biology has a soundtrack? In a recent interview on National Public Radio, Sive explained that the earliest embryonic cell divisions appear to her as though they’re moving to the beat of Pink Floyd’s “Another Brick in the Wall”, and that nerve cells seem to fire to the score of the Who’s rock opera “Tommy”.



ReseARcH focus

longattheforeofcancerresearch,robertweinberg

hasinrecentyearsturnedanintenseeyetothepro-

cessesbywhichcanceroustumorsinvadesurround-

ingtissueandmetastasizetodistantsitesinthebody.

muchofthisworkhasimplicatedso-calledcancer

stemcells,relativelyrarecellswithinatumorthat

havetheabilitytoself-renewandseednewtumors.


researchersintheweinberglabdeterminedthat

certaintumorcellsareabletotapintoanormal

embryonicpathwaythatallowsthemtoundergo

animportantmorphologicalchange.thischangein

shapenotonlyallowsthesecellstoseparatefrom

theirneighbors,italsoconfersonthemtheproperties

ofstemcells.thefindingaddsacrucialpiecetothe

metastasispuzzle.moreover,thesesameresearchers

soonrealizedthatthesamepathwaycanbeinduced

innon-cancerouscellstogeneratehealthystemcells.

saysweinberg:“perhapssurprisingly,studiesofthe

originsofhumancancersareleadingustowardnew

waysofcreatingnormalhumanstemcells.”

tHe futuRe

muchofthefocusinthelabnowisonexploitinglast

year’sunexpectedresults.“ihopewe’llfigureouta

formulabywhichwecanpropagateepithelialcellsin

culturetocreateepithelialstemcells,”weinbergsays,

addingthatthispursuitwilllikelyfurthertheunder-

standingoftheworkingsofcancerstemcells.

robert weinberg

did you know... that in addition to being an accomplished gardener and a passionate genealogist, Bob Weinberg physically built his own cabin in New Hampshire? He began work on his special hideaway in 1976, saying it became “habitable” in 1977. Over the years he’s expanded the place (himself, of course) and added a few creature comforts but insists the place retains its rustic charm.


richard YoungReseARcH focus

humansaremadeupofhundredsoftypesofcells,

eachwithaspecialjob.howcellsareprogrammedto

dothesejobsandstickwiththeprogramisunknown.

theyounglabhastakenonthechallengingtaskof

discoveringhowhundredsofregulatorygenescontrol

theseprogramsinclinicallyimportantcells.


thelabrecentlycompletedadraftmapofembryonic

stemcells’mainregulatorycircuitry.thisguidehelps

researcherspredicthowtokeepembryonicstemcells

intheirundevelopedstateortodevelopthemintoany

celltype.workingwiththeJaenischlab,youngalso

improvedtheefficiencyofconvertingadultcellsinto

embryonicstemcell-likecells,calledinducedpluripo-

tentstem(ips)cells.

workingwithmitbiologyprofessorphillipsharp,

youngfoundthatthemachinerythatnormallyslides

forwardalongdnatoproducernacanalsorun

backward.youngsaysthatrunningbackwardmay

allowthemachinerytosweepthednacleanof

proteinsthatpromoteorinhibitgeneexpression.

ortherecouldbeanotherreason—rightnow,it’s

anothermysteryfortheyounglabtoinvestigate.

tHe futuRe

inadditiontoextendingthemapofembryonicstem

cellcircuitry,theyounglabistryingtodiscoverwhat

keepsacellasaparticulartypeofcell,forexample,

whatkeepsaheartcellfromchangingintoabloodcell

oraneuron.

did you know... Richard Young is an adrenaline junkie? He was an award-winning giant slalom ski racer in high school, an accomplished marksman in later years, and continues today as a mountaineer who dreams of tackling the world’s highest peaks.



theyrepresentthefutureofbiomedicalresearch:asmallgroupof

promisingyoungscientistssupportedbytheinstituteandencouraged

topursuetheirresearchascreativelyastheydare.freefromteaching

responsibilities,theyexploreunderthetutelageoffaculty, inspiredby

theknowledgethatthewhiteheadfellowsprogramhaslaunchedanew

generationofscientificleaders.

whitehead fellows

30

thijn brummelkamP

thijnbrummelkampinvestigatesthehippopathway,a

chainofcellularsignalsthatregulatesorganandtissue

size.brummelkamphasfoundthatwhenanorgan’s

cellshavetoomuchofaspecifichippopathwaygene

(yap1),theorgancanquadrupleinsize.uncontrolled

cellgrowthandincreasedtissuesizearehallmarksof

cancer,andthehippopathwayisoveractiveinabout

one-thirdofcancers.althoughthehippopathway

appearstobeanimportantfactorintumorformation,

brummelkampisworkingtoclarifywhatremainsa

poorlyunderstoodrole.

brummelkamp’slabisalsostudyinggenesthathave

ahandinavarietyofhumandiseases.thisresearch

includesgeneticvariationsincanceraswellasalook

atcertaingenesthatinfectiousagentssuchasinfluenza

virusandtoxicbacteriausetoenteracell.bycharac-

terizinghowgenesfunctionindiseases,brummelkamp

isnarrowingdownhowandwhichtherapeuticsmight

bestexploitdisease-specificgenetictraits.

fernando camargo

likehiscolleaguethijnbrummelkamp,fernando

camargostudieshowthehipposignalingpathway

regulatestissuegrowth.camargoalsofocuseson

thedevelopmentofbloodcells.bothofhisareas

ofresearchhaveimportantlinkstocancer.when

atissueororgangrowsoutofcontrol,cancerous

tumorscanform.whenbloodcelldevelopment

goesawry,thebodyproducesinordinatenumbers

ofcertaincelltypes,resultinginvariousleukemias.

camargorecentlydeterminedthatinhealthycells,

thegenemef2cdirectscellstodevelopintobcells,

tcells,andnaturalkillercells,insteadofredblood

cellsorothertypesofwhitebloodcells.whentoo

littleortoomuchofthegeneisexpressed,thebal-

anceofbloodcellsisdisrupted,causingleukemia.

althoughtheconnectionbetweenmef2candleuke-

miawasknownpreviously,camargoidentifieditas

apivotalpointinbloodcelldevelopment.



Paul wiggins

lestyouthinkchemistsandgeneticistshaveallthefun,

paulwigginscombinesphysicswiththese“traditional”

techniquestoprobetheconnectionbetweenstructure

andfunctionatlargerscales.wigginsandcoworkers

havedevelopedanewtechniquetodeducetheforces

neededtomaintaintheshapeofcellularorganelles.

theseorganellesareenclosedintheirownmembranes,

someofwhichhavelabyrinthineshapesessentialto

organellefunction.toinvestigatetheconnectionbe-

tweenforcesandmembraneconformation,wigginsand

coworkersuseatoolcalledopticaltweezerstotugon

beadsboundtothemembrane.thesebeadsarethen

trappedandmanipulatedbyafocusedlaserbeam.by

recordingtheforceneededtoshapethemembranea

certainway,wigginscancalculatetheforceneededto

createsimilarconvolutionsinanorganelle’smembrane.

thelabisusingsimilartoolsandtechniquestoinvesti-

gatethemechanismofchromosomeorganization.

defne Yarar

sincegraduateschool,whiteheadspecialfellow

defneyararhasbeenfascinatedbyaubiquitous,

overachievingproteinknownasactin.thisprotein

comprisesakeypartofthecellulararchitecture

knownastheactincytoskeleton,whichplaysacen-

tralroleincellularmovementanddivision,aswellas

inmusclecellcontraction.foryarar,oneofactin’s

moreintriguingrolesisinendocytosis,aprocess

duringwhichacell’soutermembranefoldsinward

toengulfexternalmatterinamembrane-enclosed

pouch.endocytosisisimportantforprovidingcer-

tainnutrientstoacellandisakeyactivityamong

thecellsofthenervoussystem.yarardescribesher

examinationofendocytosisas“aglobal,systematic

lookatitsmechanisms.”yararsaysthisapproach

hasrecentlyuncoveredasurprisefinding,whichshe

hopestopublishin2009.atthiswriting,she’snot

sharingdetails,butit’sprobablyasafebetthatactin

isinvolved.staytuned…


andreas hochwagen

ourcellshaveremarkablequality-controlmechanisms

designedtoensurenormalfunction.despitesuch

mechanisms,thecomplexcellulardivisionprocessesof

mitosisand,inthecaseofgermcells,meiosis,maystill

goawry.improperchromosomalanddnabreaksoccur,

oftenwithdireconsequences.andreashochwagenhas

beenstudyingdouble-stranded(ds)dnabreaks,known

tobeamongthemostproblematicerrors.dsbreaks

aredifficultforacelltorepair,andflawedreparations

canleadtodeletionsofgeneticmaterialorimproper

sequencesuponrejoiningofthedna.theresults?

potentialgenemutations,chromosomalabnormalities,

andbirthdefects.mostrecently,thehochwagenlab

hasdiscoveredthata“checkpoint”kinaseknownasatr

playsakeyroleinblockinginappropriatedsbreaks.

hochwagenbelievesthatthisfunctionofatrwillshed

importantnewlightonthepossibleoriginsofdown

syndromeandrelatedbirthdefects.

kate rubins

therubinslabisbringingnoveltechnologyand

improvedfieldinfrastructureinafricatoitsinvestiga-

tionofmonkeypoxvirus.thevirus,whichkaterubins

describesasa“high-consequencehumanpathogen,”

causesinfectionwithepidemicpotential.tobet-

terunderstandthedynamicsofinfection,rubins

hasestablishedalabinthedemocraticrepublicof

congo,enablinghertocollectbloodsamplesduring

outbreaks.usingthesamples,she’sabletoidentify

viralgeneticvariationusingsophisticatedgenetic

sequencing.rubinsnotesthatmonkeypoxinfections

arecausednotbyasinglevirus,butbya“cloudof

viruses”withthousandsofindividualvirusgenomes.

eachgenomemayundergoaseriesofchangesto

eludeimmunesystemdefenses.thelab’slarge-scale

sequencingandmicroarrayanalysiswillprovidea

clearerpictureofwhat’sactuallyhappeninggeneti-

callyduringviraltransmissionandperhapsultimately

yieldcluestoepidemicprevention.

32 whiteheadfellows


theinstitutemovestorhythmsallitsown.asinthelifeofanyorganism,

the passage of time brings change—some expected, some unforeseen.

eachyeardeliversdiscoveries,events,andtransitionsthatshapethe

whiteheadcommunity.2008wasnoexception.

communitY evolution

34

fAculty depARtuRes

inhis23yearsattheinstitute,Paul matsudairaadvancedthe

studyofquantitativebiophysics,oftenthroughthedevelopment

orenhancementofmicroanalyticaltechnologies.hewasinte-

gralintheformationofmit’sbiologicalengineeringdepartment,

servedasfoundingdirectorofthekeckfacilityforbiological

imagingatwhitehead,andthenoversawthewhitehead/mit

bioimagingcenter.alongtheway,hebecameheavilyinvolvedin

thesingapore–mitalliance,aneducationalcollaborationamong

thenationaluniversityofsingapore(nus),nanyangtechnologi-

caluniversity,andmit.histiestosingaporestrengthenedatthe

closeof2008,whenheleftwhiteheadtorunthedepartmentof

biologicalsciencesatnusandtobecomefoundingdirectorofa

newbiologicalimagingcenterthere.

longtimemembereric lander formallyleftthewhiteheadfac-

ultyinseptember2008.lander’sdeparturecoincidedwiththe

announcementthatthebroadinstitute—whichspunofffromthe

whitehead/mitcenterforgenomeresearch—isbecomingan

independentorganization.whiteheadnolongerholdsagovern-

ingroleinbroad,whileharvarduniversityandmitstillhavea

handinitsgovernance.whiteheaddirectordavidpagedescribes

lander’stransitionandthebroad’sindependenceasappropriate

evolutionaryoutcomes.“thewhiteheadmodelhasalwaysbeen

toidentifyandattractexcellence,nurtureit,andallowittoflour-

ish,”pagesays.“this‘new’broadinstitutestandsasatestament

tothewisdomofthismodel.”lander,whohasservedasbroad’s

directorsinceitsinceptionin2004,hadbeenawhiteheadmem-

bersince1989.

atthecloseof2008,whiteheadfellowhui gejoinedcam-

bridgebiotechnologystart-upproteostasistherapeuticsas

thecompany’sheadofbioinformaticsandsystemsbiology.ge

saysofherfouryearsatwhitehead,“mytimeherereallyhelped

metobecomeanindependentscientist.”inwishinggeafond

farewell,institutedirectordavidpagelaudedher“extraordinary

intelligence,intellectualcuriosity,andcollaborativeapproachto

biologicalproblems.”

institute news


theinstituteengagesinanumberofprogramsdesignedtoedu-

catethepubliconthelatestadvancesinbiomedicalresearchand

toserveasacommunityresourceonscienceandsciencepolicy

issues.amongthemostpopularisthewhiteheadspringlecture

seriesforhighschoolstudents.thethree-dayevent,conducted

duringspringvacation,encouragesstudentstoexplorethefacts

behindscienceheadlinesandtoconsiderhowthelatestfindings

willaffecttheirownlives.

in2008,some100studentsattendedCell Wars: The Battle between

Infectious Agents and Their Hosts.theseriestookparticipantson

ajourneyintohowresearchersaretacklingsomeofbiology’smost

challengingissuesaroundinfectiousdisease,suchashowtheim-

munesystemdistinguishesfriendfromfoeandhowvirusesevade

normalimmuneresponse.theprogramfeaturedlecturesfrom

leadingscientificexpertsinthefieldsofimmunology,virology,and

yeastgenetics.studentswerealsotreatedtolabtoursatwhite-

headandneighboringfacilities,includingthosehousedatnearby

biotechnologycompanies.duringeachdayoftheprogram,stu-

dentslunchedwithyoungwhiteheadscientists,hearingfirsthand

aboutthediversepathsascientificcareermaytake.theprogram

concludedwithapaneldiscussionofpublichealthissuesassociated

withemerginginfections.

anotherimportantinitiativeisthewhiteheadseminarseriesfor

highschoolteachers,whichprovidesaframeworkforeducatorsto

incorporatenewideasintotheirclassrooms.in2008,morethan80

teachersparticipatedintheseriesentitledControlling Genes,anex-

aminationofdnapackaging,transcriptionfactors,micrornas,and

otherregulatorymechanisms.thestartoftheacademicyearinthe

fallbroughtwithitanewseriesforteachers,Pursuing the Promise:

Advances in Stem Cell Science.

innovember,whiteheadhostedthebostonstemcellscience

educationsymposium.thisinnovativeeventaimedathighschool

teachersandjuniorcollegeprofessorswasproducedincollabora-

tionwiththeharvardstemcellinstitute,thebroadinstitute,the

massachusettsbiotechnologycouncil,thebiotechnologyinstitute,

andthenationalacademyofsciences.

Public outreach(clockwisefromtop)

membergeraldfink

addressedagatheringof

studentswholatertook

tothelabsoftheinstitute

duringthewhitehead

springlectureseriesfor

highschoolstudents.

instituteoutreachextends

tohighschoolteachers,

whoattendanannualsem-

inarseriesand,inthefallof

2008,participatedinthe

bostonstemcellscience

educationsymposium.

communityevolution


inJuly2008,longtimeinstitutesupporterandformerboardchair

alex d’arbeloff passedawayafteralengthyillness.alex’spassing

hasbeenmournedthroughoutthewhiteheadcommunity.institute

directordavidpage,inpraisingalex’sintellect,leadership,and

legendarydirectnature,said,“whenheexaminedanissue,one

couldbecertainthatexaminationwouldbeathoroughone.the

boardandtheinstituteasawholearestrongerforhavingunder-

gonethekindofintrospectionalexdemanded.”

board and PhilanthroPY news

boARd And pHilAntHRopy neWs

atthecloseof2008,brit d’arbeloff,anardentandlongtime

whiteheadsupporter,acceptedaninvitationtojointheinsti-

tute’sboardofdirectors.brit,whoearnedamaster’sdegreein

mechanicalengineeringfrommit,holdsthedistinctionofbeing

thefirstwomantoreceiveabsinmechanicalengineeringfrom

stanforduniversity.brit’sformaltiestotheinstitutedateto

1997,whenshejoinedtheboardofassociates.

mitalumnus Jonathan goldstein, whoasanundergraduate

workedinthelabofwhiteheadfoundingdirectordavidbalti-

more,becamechairoftheboardofassociates—anappointment

thatcarrieswithitacorrespondingtermontheinstitute’sboard

ofdirectors.Jono,ashe’sknown,holdsanmbafromharvard

businessschoolandiscurrentlymanagingdirectorofthepri-

vateequityfirmtaassociates,whereheevaluateshealthcare,

technology,andservice-relatedbusinesses.

boston-basedinvestmentprofessionalmark C. lapmanwas

electedtotheboardindecember2008.markiscurrentlychief

executiveofficerofindependenceinvestments,wherehehas

workedsincethefirm’sincorporationin1982.heholdsanunder-

graduatedegreefromtheuniversityofmarylandandamaster’s

fromharvarduniversity,wherehealsoearnedhisphdinrussian

andeasteuropeanhistory.

theinstitute’srecentlylaunchedStem Cell and Regenerative

Biology initiativereceivedawelcomeinfusionindecember.

boardvicechairsusan whiteheadpledgedtodonate$500,000

tothecampaignoverthenextfiveyears.susan’sgenerositywill

helppropelstemcellresearchacrosstheinstitute.boardmem-

berlandon Clayannouncedanextraordinarygiftof$15million,

whichwillfundaresearchcollaborationamongthelaboratories

ofmembershiddeploegh,rudolfJaenisch,andrichardyoung.

“weareprofoundlygratefulfortheseremarkabledonations,

viewingthemasactsofwhatJackwhiteheadoncecalled

‘enlightenedphilanthropy’,”saysinstitutedirectordavidpage.

“clearly,thesearecommitmentstothepowerandpotentialof

basicbiomedicalresearchandthebeliefthatsuchresearch,as

performedhere,isamongthebestintheworld.”

Jonathangoldstein

britd’arbeloff

markc.lapman

communityevolution

40 41 whitehead institute2008annualreport40

whiteheadinstituterecognizeswithdeepestgratitudethoseindividuals,

organizations,foundations,andcorporationswholenttheirsupportso

generouslyinfiscalyear2008,betweenJuly1,2007andJune30,2008.

honor roll of donors

40

founder’s CirCle

$100,000 and above

landonandlaviniaclay

alex*andbritd’arbeloff

charlesellisandlindalorimer

thelevienfoundation

drs.Joanandhermansuit

direCtor’s CirCle

$50,000 and above

arthurandcarolbrill

peterhechtandkristinaJones

peters.andkathryns.kim

davidh.koch

harveyandpamelalodish

peterandrenéewhitehead

susanwhitehead

leader’s CirCle

$25,000 and above

anonymous

paulandandriaheafy

matthewd.nicholsandkatrinaburton-nichols

ellenandleonardpolaner

benefaCtor’s CirCle

$10,000 and above

endrea.balazsandJanetl.denlinger

philipandevecutterthroughthegoldhirshfoundation

mr.andmrs.robertg.dettmer

g.s.beckwithgilbertandkatharines.gilbert

amyandJimmyhaber

gregorye.mooreandwynnew.szeto

mattandmaunyplum

claytonandJuliannerose

mitchelsayare

dr.andmrs.danielvapnek

Johnl.andadelaidew.zabriskie

Patron’s CirCle

$5,000 and above

madeleinecondit

gareyv.ellisandtomora-lutreastellis

dr.orriem.friedman

ansbertgadicke,mpmcapital,lp

kaiaandJonathangoldstein

georgeanddaphnehatsopoulos

russellm.Jaffe

maryellenJohnsonandrichardgoeltz

dr.andmrs.lawrencec.pakula

Jamesw.andpatriciat.poitras

gabrielandsamanthaschlumberger

paulandfrancinetramontano

haroldandannas.ulliancharitablefoundation:stevena.meyer;robertsnider;eliotsnider,trustees

member’s CirCle

$2,500 and above

anonymous(2)

noubarafeyan,flagshipventures

alisonandrews

lucyaptekar

mr.andmrs.thomasr.armstrong

nealbaer,mdandgerrismith

lorraineandemanuelbalkin

dr.barrya.andmrs.barbaraberkowitz

davidandarlenebrook

Johnandsusanbrooks

georgeandJudithcarmany

neilandmarthachayet

alexanddorleencrutchfield

bobandwinniecurry

patriciaandrobertdenn

michaelandbarbaraeisenson

anthonyb.evnin

douglasm.fambrough

loraandcharlesfarkas

matthewandJacquelinefearer

peterfeinsteinandmiriamweinstein

r.Johnfletcher,fletcherspaght,inc.

kennethfong,kensonventures,llc

mr.andmrs.Jamesw.fordyce

richardandcatherinefoster

petera.glicklich

mr.andmrs.thomasgochberg

karlhandelsman

beverlyp.head

donandmargeryhetzel

Jamesheywood

bonnieandlesterhochberg

marianneandJameshoward

candaceandw.michaelhumphreys

evanandcindyJones


suPPorters

Other Gifts

giovannibosco

sheldonbuckler

davidchaoandJuliazeitlinger

dr.shoumendatta

roslyndaum

williamdietrichandrebeccamosher

dons.doering

davidandmarionellis

Johnandadrienneerickson

carlosandruthgimeno

rebeccahenderson

craigandheatherhill

rakeshk.Jain

victoriakaplan

ramunasandskirmaannakondratas

rosalindlichter

brigitted.linz

albertmeyerandirenegreif

Jillandtoddmilne

dr.georgem.milne

kenandlauramorse

mr.andmrs.edwardw.probert

williams.reardon

eliotandruthsnider

Joanandthomassteitz

mr.andmrs.richardd.stone

bobtalanian

laurieandpeterthomsen

lilaandbenedictwallis

stephanies.watowich

dr.dorothys.zinberg

in honor & memorY of gifts

inhonorandmemoryoffriendsandlovedones,arthurbrillandcaroltobin

Honorary Giftsinhonorofsusanlindquist,madeleinecondit

inhonorofcharlesl.meyer,adrienneandJackerickson

inhonorofwilliamnachtigal,adrienneandJackerickson

inhonorofJackkaufold,adrienneandJackerickson

inappreciationofarthurbrill,therodenfelsfamilyfoundation,inc.

inhonorofhusbandarthurbrill,carolr.tobin

In Honor of Samantha Schweitzer and Gabriel Schlumbergerbenjaminbrainard

mariondorer

paulaanddougeads

Janeandbillgrenawalt&family

zandyhillelandJanistaube,inmemoryofsandrameyerschweitzer

georgettelevis,inmemoryofsandrameyerschweitzer

tajleilevisandJonathancanter

markquinlan

reneeryan

christinewasserstein,inmemoryofsandrameyerschweitzer

Memorial Giftsinmemoryofhatsuyom.hayashida,adrienneandJackerickson

inmemoryofvivianhoward,richardandhelengates

inmemoryofmargaritasubotky,petera.glicklich

inmemoryofvivianhoward,Jameshowardandfamily

inmemoryoffranciss.levienandJanicec.levien,thelevienfoundation

In Memory of Norman Hascoeallanandnancybernard

arthurandcarolbrill

robertandpatriciadettmer

marioJ.gabelli

thegoergenfoundationinc.

landmarkcharitablefoundation,inc.

Jameslashands.deborahJones

oivindlorentzen,Jr.

susane.lynch

themoralesfamily

sallyswanson

arnoldn.andinget.weinberg

matChing gifts

americanexpress

capitalguardiantrust

goldmansachs&co.

robertwoodJohnsonfoundation

*deceased

paulJoskowandbarbarachasenJoskow

JeromeandJudithkoch

fanniee.rippelfoundation:lauralandy

earlandbarbaralewis

gordonn.litwin

monaiseandangusmacdonald

georgemccabe

thomasn.mccarter

terryandcarolynmcguire

davidandfrannymitchell

martina.mullins

Joeandkathyo’donnell

dorothyornitz

davidandelizabethpage

Joygailraywid

philipr.andnancyl.reilly

r.rudolphreinfrank

carlynring

scottandpattyrocklage

nealandsharonrodin

rogersametz,sametzblackstoneassociates,inc.

ruthscheuer,JdandJamesscheuer,md

arthurandyvetteschleifer

schoonerfoundation

paragshah

Jamesp.sherblom,seaflowerassociates

mr.andmrs.malcolml.sherman

mr.andmrs.r.greggstone

henritermeer,genzymecorporation

JohnandJeantravia

mr.*andmrs.Jepthah.wade

drs.barbarawallnerandrichardl.cate

roberta.weinbergandamyshulmanweinberg

iraandphylliswender

Justinwenderanddeborahgoldfrank

robertf.wright

friend’s CirCle

$1,000 and above

anonymous

Johne.abele

alchemyfoundation

edithandhenryallen

e.s.anderson

davidbartelandJanpreheim

paulberg

thomass.caldwell,caldwellassetmanagement

lawrenceandsusandaniels

paulw.douglas

richardgoldsbyandbarbaraosborne

lawrenceandtinahaut

Johnr.kennedy

allanandJoankleinman

kristines.langdon

samJ.lehr

frankandamylinde

maryandnelsonluria

eveandnicknichols

loispeerce

Jean-Jacquespierrat,frenchgovernment

hiddeploeghandannemahon

marciaradosevich

elisabetha.raleigh

davide.redlick

margaretsand

eugeniaandrobert*seamans,Jr.

stephenandbessieseiler

phillipandannsharp

christined’arctaylor

arnoldn.andinget.weinberg

honorrollofdonors


children’stumorfoundation

Janecoffinchildsmemorialfundformedicalresearch

deshpandecenterfortechnologicalinnovation

ellisonmedicalfoundation

fisherscientificinc.

annafullerfund

howardhughesmedicalinstitute

iscbioexpress

thew.m.keckfoundation

thesidneykimmelfoundationforcancerresearch

charlesa.kingtrust

susang.komenforthecure

thelamfoundation

leukemiaandlymphomasociety

lifesciencesresearchfoundation

lonzawalkersville,inc.

virginiaandd.k.ludwigfundforcancerresearchatmit

marchofdimes

massachusettsinstituteoftechnology

g.haroldandleilay.matherscharitablefoundation

themedicalfoundation

merckresearchlaboratories

milliporecorporation

novartisinstitutesforbiomedicalresearch

openbiosystems,inc.

perkinelmerlifesciences,inc.

pressurebiosciences,inc.

qiagen,inc.

rettsyndromeresearchfoun-dation

fanniee.rippelfoundation

rochediagnosticscorporation

damonrunyoncancerresearchfoundation

sagesciencecorporation

searlescholarsprogram

sigma-aldrichbiosciences

singapore/mitalliance

richardandsusansmithfamilyfoundation

stanleymedicalresearchinstitute

alexanderandmargaretstewarttrust

unionbiometrica,inc.

vwrinternational,inc.

helenhaywhitneyfoundation

bradleyzankelfoundation,inc

Each of our donors is impor-tant to us. Please notify us of any omissions or errors.

restriCted gifts

Liliana and Hillel Bachrach Fund for Stem Cell Research at Whitehead Institutelilianaandhillelbachrach

Clay Fellows Fundlandonandlaviniaclay

Genzyme Postdoctoral Fellowshipgenzymecorporation

RNAi Selection Web Serverambion,inc.

dharmacon,inc

CorPorate and foundation suPPort

anonymous

abcaminc.

advancedmedicalresearchfoundation

agencourtbiosciencecorporation

agilenttechnologies

ritaallenfoundation

americancancersociety

americandiabetesassociation

amgen,inc.

appliedbiosystemsinc.

battellenationalbiodefenseinstitute

bdbiosciences

thebeezfoundation

biogenidecfoundation,inc.

biolineinc.

thebreastcancerresearchfoundation

broadinstitute

canadianinstitutesofhealthresearch

honorrollofdonors


revenues & suPPort

exPenditures & disbursements

in millions in millions

2008

2008 2007 2006

2008 2007 2006

2008 2007 2006

2008 2007 2006

19% 34%

31% 55%

33%

17% 11%

$14 gifts&otherrevenue

$25.1 general&administrative

$24.3 whiteheadsupport

2008 total

$73.5

2008 total

$73.2

$12.3 nonfederalresearch

$8.4 capitalizedplant&other

$22.9 federalresearch

$39.7 research

2007

2007 total

$70.7

2007 total

$68

2008 2007 2006

2008 2007 2006

2008 2007 2006

2008 2007 2006

19% 35%

35%54%

29%

17% 11%

$13.7 gifts&otherrevenue

$23.9 general&administrative

$20.7 whiteheadsupport

$12 nonfederalresearch

$7.6 capitalizedplant&other

$24.3 federalresearch

$36.5 research

whitehead institute’s continued financial strength enables its

commitment to best-in-class science, even in the midst of an extra-

ordinarily difficult economic climate. the generous support of

individuals, corporations, and foundations remains an important

ingredient inwhitehead’srecipeforfiscalstability,whilethequality

ofwhiteheadresearchallowstheinstitute’sfacultyandassociated

scientiststocompetesuccessfullyforfederalandnon-federal

funding. at the same time, institute administration is paring operat-

ingcostsinanongoingefforttoallocateagreaterproportionof

everydollardirectlytoresearch.

financialsummarY


leadershiP

board of direCtors

alexv.d’arbeloff(deceased)

arthurw.brill

landont.clay

charlesd.ellis(chair)

Jonathanm.goldstein

peterm.hecht

barbaraimperiali

peters.kim

davidh.koch

roberts.langer

markc.lapman

davidc.page

ellens.polaner(throughseptember2008)

phillipa.sharp

JohnJ.whitehead

peterJ.whitehead

susane.whitehead(vicechair)

paull.Joskow(emeritus)

abrahamJ.siegel(emeritus)

offiCers of the CorPoration

charlesd.ellis,boardchair

susane.whitehead,boardvicechair

davidc.page,president

martina.mullins,vicepresident

Johnr.travia,treasurer

arthurw.brill,secretary

kimberlys.forness,assistantsecretary

board of advisorY sCientists

elainefuchs

andrewmurray

ericwieschaus

direCtor

davidc.page

whitehead members

davidbartel

iaincheeseman

geraldr.fink

rudolfJaenisch

erics.lander(throughaugust2008)

susanl.lindquist

harveyf.lodish

pault.matsudaira

terryl.orr-weaver

faculty and fellowswhiteheadprincipalinvestigatorsare

world-classscientistsworkingatthefrontiersofbiologicalre-

search.undertheinstitute’scloseaffiliationwithmassachusetts

instituteoftechnology,whiteheadmembersalsoaremembers

ofmit’sbiologydepartmentorothermitdepartments.

thewhiteheadfellowsprogramallowsexceptionallytalented

youngscientiststosetupindependentresearchprogramswith-

outundertakingthefullrangeofnormalfacultyduties.

faculty achievementswhiteheadfacultyincludestherecipi-

entofthe1997nationalmedalofscience(weinberg),seven

membersofthenationalacademyofsciences(fink,Jaenisch,

lindquist,lodish,orr-weaver,page,andweinberg),sixfellows

oftheamericanacademyofartsandsciences(fink,Jaenisch,

lindquist,lodish,ploegh,andweinberg),fivemembersof

theinstituteofmedicine(fink,Jaenisch,lindquist,page,and

weinberg),andfourhowardhughesmedicalinstituteinvestiga-

tors(bartel,lindquist,page,andsabatini).

hiddeploegh

peterreddien

davidsabatini

hazell.sive

roberta.weinberg

richarda.young

affiliatemember:davidgifford

whitehead fellows

thijnbrummelkamp

fernandocamargo

huige(throughnovember2008)

andreashochwagen

katerubins

paulwiggins

defneyarar(specialfellow)

viCe President

martina.mullins

assoCiate viCe President for administration

mariannehoward

board of assoCiates

Jonathanm.goldstein,chair

ellens.polaner,chair(throughnovember2008)

C H A R L E S R I V E R

49

mcgoverninstitute(mit)

novartisinstituteforbiomedicalresearch

genzyme

biogenidec

whiteheadinstitute

broadinstitute

thepicowerinstitute(mit)

thekochinstitute(mit)

mitdepartmentofbiology

(kochbiologybuilding)

whiteheadinstitutewasconstructedintheearly1980sonavacant

lotonthenorthernedgeofthemitcampus,strategicallyplaced

inproximitytothephysicalresourcesofmit’sdepartmentof

biology.today,theinstituteisatthenexusofavibrantbiomedical

“supercluster.”thebroadinstitute,alongwiththedavidh.koch

instituteforintegrativecancerresearchatmit,mcgoverninstitute

forbrainresearchatmit,andthepicowerinstituteforlearning

andmemoryatmit,haveemergedorexpandedsincewhitehead’s

founding,andpromisingbiotechstartupsnowsitalongsidesuch

industryleadersasbiogenidec,genzyme,andnovartis.itisan

unprecedentedconcentrationoftalent;aneighborhoodwhere

innovationanddiscoveryarethenorm.

sited for science

memo

riald

rive

mainstreet

massachusettsavenue

broadway

kendallst.

50 whiteheadinstituteforbiomedicalresearchninecambridgecentercambridge,massachusetts02142-1479

whitehead institute

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