Alfred North Whitehead Dialogues of Alfred North Whitehead 1954
whitehead institute
Transcript of 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
8 9 whitehead institute2008annualreport
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.
scientificachievement
10 11 whitehead institute2008annualreport
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.
scientificachievement
farleft:
©felicefrankel,from“envisioningscience,the
designandcraftofthescienceimage(mitpress)
12 13 whitehead institute2008annualreport
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
scientificachievement
14 15
itisanaugustcollective,whiteheadfaculty:14members,hand-picked,
accomplished,decorated.theyareworld-classscientistswhoalsoare
giftedteachers,mentors,andleaders.theirinfectiouspassionand
commitmenttotheircraftcontinuallydistinguishtheinstitute.
PrinciPal investigators
16 17 whitehead institute2008annualreport
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.
16 principalinvestigators
ReseARcH focus
iaincheeseman’slabstudiesthekinetochore,aspe-
cializedcomplexofanestimated80to100proteins
thatassemblesduringcelldivisionandcoupleschro-
mosomeswiththinproteinfilamentstermedmicrotu-
bules.withoutproperattachment,microtubulesare
unabletodragthelargechromosomesthroughthe
nucleus’sviscousfluidandaccuratelydividethechro-
mosomesbetweenthetwonewcells.thepenaltyfor
amistakeissevere:cellswiththewrongchromosomes
oftendieorbecomecancerous.
2008 AccomplisHments
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.
2008 AccomplisHments
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.
2008 AccomplisHments
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.
19 whitehead institute2008annualreport
20 21 whitehead institute2008annualreport
ReseARcH focus
proteinsarelong,complexchainsofaminoacidsthat
mustfoldintoprecisethree-dimensionalstructuresto
performtheirvitalcellularfunctionsproperly.susan
lindquist’slabstudiesthemanyunexpectedwaysin
whichtheproteinfoldingprobleminterfaceswith
biologyinbothhealthanddisease.
2008 AccomplisHments
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.
20 principalinvestigators
harveY lodishReseARcH focus
currentareasofinterestinthelodishlabinclude
redblood-celldevelopment,hematopoietic
(blood-forming)stemcells,andtheregulatory
rolesmicrornasplayindevelopmentandfunction
ofmusclecells,fatcells,andseveraltypesofblood
cells,includingthebcellsoftheimmunesystem.
muchofthelab’sworkliesattheinterfacebetween
molecularcellbiologyandmedicine.
2008 AccomplisHments
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.”
21 whitehead institute2008annualreport
22 23 whitehead institute2008annualreport22 principalinvestigators
terrY orr-weaverReseARcH focus
cellsmayundergocertainimportanttransitionsintheir
lifetimes:dividingfromonecellwithacompletechromo-
somesetintotwocells,eachwithcompletesets(mito-
sis);dividingfromonecellwithacompletechromosome
settoproduceeggsorspermwithhalfaset(meiosis);
andchangingfromunfertilizedeggtofertilizedeggto
embryo.terryorr-weaverstudiestheprecisecontrols
neededforthesestepstooccurproperly.
2008 AccomplisHments
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.
2008 AccomplisHments
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!”
23 whitehead institute2008annualreport
24 25 whitehead institute2008annualreport
hidde PloeghReseARcH focus
forhiddeploegh,exploringtheintricaciesofthe
immunesystemhasbeenalifelongpursuit.alongthe
way,heandscientistsinhislabhavedevisednovel
methodstostudythevariouscellularandmolecular
mechanismsofthesystem’sresponsestoforeign
invasion.hisinterestindrawingfromotherscientific
disciplines,includingchemistryandchemicaland
mechanicalengineering,fuelsinnovationinhislab’s
immunologyresearch.
2008 AccomplisHments
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.
24 principalinvestigators
tHe futuRe
beyondcontinuedinvestigationoftheimmuneresponse,
ploeghiscollaboratingwithwhiteheadmembers
rudolfJaenischandrichardyoungindevelopingnew
modelsforthestudyofinfectiousdiseases,makinguse
ofnucleartransplantationtechnologytogeneratemice
thatarebettersuitedtostudytheinterplaybetweena
hostanditspathogens.
Peter reddien
25 whitehead institute2008annualreport
ReseARcH focus
howstemcellscanbeutilizedforregenerationisanis-
sueofgreatscientificinterest.gettingattherootofthis
problemrequiresunderstandinghowstemcellsfunction,
howcellularandtissueregenerationoccur,andhowa
bodypartregrowswithcorrectidentity.thereddien
labstudiesthesetopicsinplanarians,flatwormswiththe
amazingabilitytoregrowanyseveredbodypart—includ-
ingnervoussystem,muscles,skin,andintestine.
2008 AccomplisHments
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?
26 27 whitehead institute2008annualreport
david sabatiniReseARcH focus
regulationofcellgrowthisessentialforproperde-
velopmentandtopreventcancer,whichresultsfrom
rampantovergrowthofcells.davidsabatinistudies
thecomponentsofacellularsystemthattriggers
growth(knownastor,ortargetofrapamycin)and
howthissystemiscontrolled.
2008 AccomplisHments
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.
26 principalinvestigators
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.
2008 AccomplisHments
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”.
27 whitehead institute2008annualreport
28 29 whitehead institute2008annualreport
ReseARcH focus
longattheforeofcancerresearch,robertweinberg
hasinrecentyearsturnedanintenseeyetothepro-
cessesbywhichcanceroustumorsinvadesurround-
ingtissueandmetastasizetodistantsitesinthebody.
muchofthisworkhasimplicatedso-calledcancer
stemcells,relativelyrarecellswithinatumorthat
havetheabilitytoself-renewandseednewtumors.
2008 AccomplisHments
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.
28 principalinvestigators
richard YoungReseARcH focus
humansaremadeupofhundredsoftypesofcells,
eachwithaspecialjob.howcellsareprogrammedto
dothesejobsandstickwiththeprogramisunknown.
theyounglabhastakenonthechallengingtaskof
discoveringhowhundredsofregulatorygenescontrol
theseprogramsinclinicallyimportantcells.
2008 AccomplisHments
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.
29 whitehead institute2008annualreport
30 31 whitehead institute2008annualreport
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.
31 whitehead institute2008annualreport
32 33 whitehead institute2008annualreport
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…
33 whitehead institute2008annualreport
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
34 35 whitehead institute2008annualreport
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
36 37 whitehead institute2008annualreport
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
38 39 whitehead institute2008annualreport
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
42 43 whitehead institute2008annualreport
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
44 45 whitehead institute2008annualreport
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
46 47 whitehead institute2008annualreport
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
48 49 whitehead institute2008annualreport
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