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Breaking The CyCle

J o h n s H o p k i n s M a l a r i a R e s e a r c h I n s t i t u t e

CONTENTS

1 ANEWAPPROACHTOMALARIA 3 SAVINGLIVESTHROUGHBASICSCIENCE 4 WINGEdMISERy:MALARIA’SESSENTIALVECTOR 6 WHENISAFEVERCAUSEdByMALARIA? 8 VACCINATINGAVILLAGE 9 WANTEd:AKNOCKOUTPUNCH 10 RxFORMALARIA 11 NURTURINGNEWIdEAS 12 ExECUTIVESUMMARy 14 MACHA:ALIVINGLABORATORyINZAMBIA 18 HUNTINGMOSqUITOESFROM126MILESUP 20 SAVINGFREdERICK 22 MEETTHENExTGENERATIONOFSCIENTISTS 23 FACULTy 24 INTOTHEFUTURE

Isabelle Coppens, phD,isresearchingwaystopreventthe Plasmodium parasitefromleavingtheliverandcausingclinicaldisease.

Cover: Avode Nawechi, 3, sits beneath a bed net at the Kalene Mission Hospital in Zambia as Endes Npompu (back cover) cares for her malaria- stricken grandson Paul Kangoma, 5. (John Stanmeyer / VII)

BREAKING THE CYCLE 1

The Johns Hopkins MalariaResearch Institute is one ofthe Bloomberg School’s great-estresearchendeavors.

Foundedin2001,theMalariaRe-searchInstituteconfrontsadifficultchallenge: toprovide thescientificbasis to eradicate one of human-ity’s most persistent and lethalfoes—the Plasmodium parasitethatcausesmalaria.

From quinine (derived from cin-chonabark)totoday’sartemisinin-combination therapy, antimalarialtreatmentshavesavedmanylives,but theparasitehasalways foundawaytoadapt,thriveandthreatenmore people. Today four of ev-ery tenpeople in theworld are atrisk. And more than one millionpeople—mostlychildren—diefrommalariaeachyear.

Newapproachesareneeded.

TheInstituteembodiestheBloom-bergSchool’sstrengths:world-classresearchers, community-based re-search in an international setting,and a spirit of interdisciplinary in-vestigationthatleadstotransforma-tivescientificinsights.

A N e w A p p r o a c h t o M a l a r i a

“Discoveries, insights

and achievements by

the Johns Hopkins Malaria

Research Institute signal

great hope.”

Since its inception, the Institutehasdonealltherightthings.Ithasdrawn together the best people,thebest technologyand thebestresearch to probe the Plasmo-dium parasite’scomplexlifecyclein Anopheles mosquitoes and inhumans.

Asyouwillsee,JohnsHopkinsMa-lariaResearchInstituteresearchershavealreadyexposedweakpointsin the parasite, proposed radicalnew ways of containing malariaanddeepenedbasicscientificun-derstanding essential to develop-ingnewstrategiesthatwillonedayeradicatetheparasite.

In epidemiology, we place greatemphasisonincidence—thenum-ber of new occurrences of a con-dition or disease over a period oftime. Measurement of incidenceovertimemakesusawareoftrendsthathelppredictthefuture.InthecaseoftheJohnsHopkinsMalariaResearchInstitute,theincidenceofdiscoveries, insights and achieve-mentssignalsgreathopefortheul-timatesuccessagainstourancientenemy,malaria.

MichaelJ.Klag,MD,MPHDeanJohnsHopkinsBloombergSchool

ofPublicHealth

2 Johns Hopkins Malaria Research Institute

every year, MaLarIa kILLs More than one MILLIon peopLe—MostLy chILdren


S a v i n g L i v e s T h r o u g h B a s i c S c i e n c e

Atthebeginningofanewcentury,wesurveyedthestateofmalariasci-enceandfoundgreatopportunitiestomakeadifference.Malariawaswidespread (it threatens 40 per-centof theworld’speople),widelyignored (at least by the fortunate,malaria-free developed countries)and extremely complex (the para-siteneedstoinfectbothAnopheles mosquitoesandhumans).

Thesmallcommunityof scientistswhohaddevotedthemselvestoma-lariawasresearchingmostlyfamil-iarapproaches.Themainfinancialresourcesdevotedtomalariawerelargelyspentonapplyingtraditionalsolutions such as bed nets andantimalarial drugs discovered 50yearsago.Thoseeffortsarestillim-portant,butwefoundedtheJohnsHopkinsMalariaResearchInstitute(JHMRI)in2001withadifferentvi-sion. In 10 years or 20 years, wewanted to live inaworld thathadrid itself ofmalaria.Weknew thatwouldrequirenewknowledgeandnew tools. We believed—and stillbelieve—ourgreatestcontributionsto malaria research would be ad-vancesinbasicsciencethatwouldshedlightonallaspectsofthedis-easeandprovidenewapproachesforcontrol.

WelaunchedJHMRIatapropitioustime. With the sequencing of thegenomes of humans, the Anoph-eles mosquitoandthePlasmodium parasite,sciencehadacompletelynewbasefromwhichtoforgenoveldiscoveries. The human immune

system might be primed againsttheparasite,orthemosquito’sowngenes might be tweaked to makeit less hospitable to Plasmodium.New molecular approaches mightspeed diagnosis of malaria in thefield.

Toachieveourparadigm-changingdiscoveries,weestablishedstate-of-the-artcorelaboratoryandcomput-ingfacilities,andwerecruitednewfaculty in a wide variety of areas.(Youwillseemanyoftheirstoriesinthepagesthatfollow).Webelievedit was critically important to bringtogethermorescientistsfromdiffer-ent fields towork onmalaria.Ourpilot grant program has attractedmanyinvestigatorswithnopreviousmalariaexperience.Ourmostillus-triouspilotgrant recipient isPeterAgre,whoextendedtomalariahisNobel Prize-winning insights intoaquaporins and earned his firstNIHmalariagrantbeforesucceed-ingmeas JHMRI’sdirector.Petershareshis story andhis vision fortheInstitute’sfutureonpage24.

We also founded JHMRI with theconviction that malaria researchcould not be done exclusively inBaltimore.Wecommittedourselvestostudyingandcombatingthedis-ease inanendemiccountry.Asaresult,wehavebuilt anadvancedresearchfacilityinMacha,Zambia,where we can pursue promisinginvestigationsandapplynewdiag-nostic tools, treatments and inter-ventions.

I am pleased to report that ourbroad-based, basic science ap-proachtomalariaisalreadyhavingrealimpacts.Fromapowerful,newartemisinin-derivative treatment toapromising,easy-to-usediagnostictest,toadvancesinatransmission-blockingvaccineandthedevelop-ment of transgenic mosquitoes,JHMRI is capitalizing on its earlyinvestmentsinpeopleandtechno-logical resources. Life-saving dis-coverieshavebeenmadeandwillcontinuetobemade.

We have known since the begin-ning that therewouldneverbeonesolution to malaria. Controlling thisdiseasewillrequireacombinationofapproaches.AsJHMRIentersanewera,wewillpersevereinourgoaltodiscoverentirelynewsolutions.

DianeE.Griffin,MD,PhDFoundingDirector,JohnsHopkinsMalariaResearchInstituteAlfredandJillSommerProfessorandChairinMolecularMicrobiologyandImmunologyJohnsHopkinsBloombergSchoolofPublicHealth


By genetically modifying the mosquito, Marcelo Jacobs-lorena, PhD, and his team investigate multiple approaches to thwarting the Plasmodium parasite’s reproduction.

GeorGe DiMoPoulos, PhD, researches ways to use the mosquito’s immune system to resist the malaria parasite more efficiently.

By studying local mosquito populations, DouGlas norris, PhD, provides data that can help officials to gauge the most effective measures for specific regions.

Jason rasGon, PhD, and his team search for genetic markers in mosquitoes with the goal of creating mosquito populations less likely to transmit malaria to humans.


quito’sexposuretobacteriathatcanboostitsimmunesystem’sabilitytoresistparasites.Butsinceparasitescanalsouseevasivetacticsagainstthemosquito’sdefenses,theteamisexploringwaysthatthemosquitocanmountmultipleandmoreeffi-cient immuneattacks, saysDimo-poulos,PhD.Preventingtheparasitefromrepro-ducing. Plasmodium reproducesinside the mosquito’s midgut. Inorder to reproduce successfully, itmust lock onto a receptor on themidgutwalland thenpenetrate it.But now MMI Professor MarceloJacobs-Lorenaandhisgrouphavefoundanantibody thatblocks theparasite from making that crucialconnection. This offers two possi-bilities: one, developing a vaccinethat might keep Plasmodium outof the midgut, and, two, alteringexpression of the receptor to pre-ventinfection,saysJacobs-Lorena,PhD. But, he adds, defeating theclever parasite most likely will re-quiremultipleapproaches.Asan-otherpossiblemeansofeliminatingtheparasite,histeamisdevelopingawaytomodify themicrobesthatoccurnaturallyinthemidgut.

Mappingthebehaviorandgenet-ics of Macha-area mosquitoes. Malaria specialists often say “allmalaria is local,” since the hab-itsandgeneticsoflocalmosquitopopulations vary greatly anddra-matically affect the infection riskin a given area. Around Macha,

Six legs. Two wings. And a tastefor blood. The female Anophelesmosquito is theessentialvectorofmalaria. Without it, the Plasmodi-umparasitewouldlanguishinonevictim, unable to infect the nextperson. Its complicated life cyclewould stall. Disabling the wingedtransporter of Plasmodium wouldscore a great victory in the waragainst malaria. Yet, for the mostpart, the mosquito has proved aswilyasurvivalistastheparasite.SoJHMRIscientistsarescrutinizingthe mosquito—from its life in thefieldtothegenesofitsimmunesys-tem—tofindwaysofinterruptingoreliminatingitsparasiticpassenger’stravels. “The key to controlling isunderstanding,”saysDouglasNor-ris, a Molecular Microbiology andImmunology (MMI) assistant pro-fessorwhodoesresearchinMachaandBaltimore.Thisquestleadsre-searchers down several promisingavenuesofresearch:

Turning the mosquito’s immunesystem against the malaria para-site. Some strains of Anopheles completely resist infection by themalaria parasite, while others be-come infected.Whatever theirde-gree of resistance, however, themosquitoesusethesameimmunefactorsagainstPlasmodium astheydo against bacteria, according torecent research by MMI assistantprofessor George Dimopoulos andhis team. That knowledge createsopportunitiestomanipulateamos-

W i n g e d M i s e r y : M a l a r i a ’s E s s e n t i a l V e c t o r

the risk can differ by a factor of18 between villages just 10 kilo-metersapart,saysDouglasNorris,PhD.Sohisteamisconductingadetailedinvestigationofwhereandhow the area’s mosquitoes live,howoftentheybite,howmanyareinfectedwiththeparasite,andsoon.Atthesametime,theyarealsostudying mosquito genetics, withan emphasis on finding out howlocal mosquito populations differ.Combining the information fromthese studies may explain bothwhy some mosquitoes are moresusceptible to parasite infectionandwhichcontrolmeasurescouldworkbestinaspecificarea.

Discoveringhowgeneticvariationinmosquitoesisrelatedtotheirabilityto transmitpathogens.JasonRas-gon, an MMI assistant professor,issearchingforgeneticmarkersinmosquitoesthatarecorrelatedwiththeirabilitytobecomeinfectedwith,and transmit, malaria parasites.Some mosquitoes have geneticfactors that give rise to resistancetomalaria,saysRasgon,PhD.Histeamisalsoworkingontechniquesto introduce genes into mosquitopopulationsthatinhibittheirabilitytotransmitmalariatohumans.Theteam is studying abacteriumanda virus that infect mosquitoes inordertodetermineif,oncesuitablymodified,theseagentscanbeusedtointerrupttransmission.


Imagineyou’reamotherinaniso-latedAfricanvillage,andyourchildis sick.Maybe the fever andmal-aisearecausedbyavirusandwillpass in aday or two.Or, perhapsthey are early signs ofmalaria re-quiring prompt medical attention.Shouldyouandyourchildstartthetwo-hourwalktothenearestclinic,orgamblethatshe’llsoonbefeel-ingbetter?

Now, imagine that you can avoidthedilemmaaltogether.Fromyourcupboard, you take a cardboardstrip anddip it in a tablespoonofyour child’s urine. If a line on thestrip changes color, you know in-stantlythattheinfectionverylikelyis malaria and you need to startwalking.

MMIassociateprofessorDavidSul-livan,abiochemistandphysician,haspursued the ideaofa reliablehomediagnostictestforyears.Thegoalisnottoreplacethegold-stan-dard diagnostic (blood smear mi-croscopy), but to make diagnosismore accessible, he says. Today,onlyalaboratorybloodtestcandi-agnose malaria, and that requiresclean needles to draw the bloodandequipmentandtrainedperson-neltodotheanalysis—all inshortsupply in many malaria-affectedareas.Thearduousexaminationofabloodsmearformalariacantakeupto20minutes.Inmanyplaces,clinicianstreatfirstformalariaand

then see what happens—wastingprecious time if thepatient’s feverisactuallyduetopneumonia,bac-terialmeningitisorotherinfection.Sullivan,MD,hasdevelopedadip-stick that indicates the presenceofaproteinspecifictothemalariaparasiteand found in theurineofinfectedpeople.He’soptimisticthatthetechnique,nowinearlyclinicalexperimentation, will prove usefulasafirst-linescreening test.Suchlow-techtests,saysSullivan,couldlet people know earlier that theyhavemalaria,helpingthemtohavebothbetteraccesstomalariatreat-mentandgreaterpeaceofmind.

Sullivan is also collaborating withSungano Mharakurwa, PhD, sci-entific director of JHMRI’s fieldresearchsite inZambia,onaverydifferent diagnostic test. They areexploring whether it’s possible touse polymerase chain reactiontechnology todetect thepresenceofa fragmentof themalariapara-site’sDNAinaperson’ssaliva.

W h e n i s a F e v e r C a u s e d b y M a l a r i a ?

Low-tech

tests would

let people

know earlier

that they have

malaria.

DaviD sullivan, MD, hopes that a new dipstick test for malaria will prove useful as a first-line screening test.


Foreons, the Plasmodium parasitehas exploited the female Anoph-eles mosquito’sappetiteforhumanblood, infecting one person andthen the next with the mosquito’shelp. But molecular parasitologistand immunologist Nirbhay Kumarhasanovelplan forstoppingma-lariatransmission.During each bite, the femaleAnopheles injects her anticoagu-lant-rich saliva into her victim’sbloodtokeep it fromclotting.Anyparasitesinthemosquito’ssalivaryglandsgoalongfortheride.Andasthe mosquito sucks out blood forhermeal,sheingestsanyparasitespresent in the victim as well. ButKumar, an MMI professor, hopesthat mosquitoes will soon pick upsomethingextraaswell.

Kumar, PhD, is developing a ma-lariatransmission-blockingvaccinethatcouldprotectentirecommuni-ties.Insteadofpreventingvaccinat-edindividualsfrombeinginfected,itblocks transmissionof thepara-sitebythemosquito.

Traditional vaccines induce im-munesystemstoproduceasub-stanceknownasanantibody.But

in Kumar’s transmission-block-ingvaccine,theantibodydoesn’thaveaneffectinhumans.WhenanAnophelesmosquitobitesthevaccinated person, she slurpsup the antibody along with theblood.Onceinsidethemosquito,the antibody goes into action,blockingaprocessthatisessen-tialtotheparasite’ssexualrepro-duction.Ifasignificantnumberofpeopleinacommunityhadthisvaccine—eventhose already infected with malar-ia—diseasetransmissioncouldnotoccur. Trials in baboons will soontest the vaccine’s efficacy. Kumarhopes thathuman trialseventuallywillfollow.Efforts to eradicate malaria-bear-ingmosquitoeshavethusfarfailed,Kumarsays,buthehopesthatthis“community-basedapproach”canturnaformerinsectenemyintoanunwitting ally in the fight againstmalaria.

V a c c i n a t i n g a V i l l a g e

A new

vaccine

brings a

community-

based

approach.

nirbhay KuMar, PhD, is developing a malaria transmission-blocking vaccine that could protect entire communities.


W a n t e d : A K n o c k o u t P u n c h

Astealthyinvader,thePlasmodium parasite survives in people by at-tractinglittleattentionfromthehu-manimmunesystem.

With each bite from a malaria-in-fected mosquito, a few hundredparasitesfindtheirwayintothevic-tim’sbloodstream.Theindividual’simmunesystemspotstheunwant-edparasitesandmountsadefense,butnotonestrongenoughtodefeatthe invaders. Turning that feebleresponse into a knockout punchisthegoalofMMIprofessorsFidelZavalaandRichardMarkham.

Zavala, MD, wants to improve onthe effective but temporary im-munedefense thathadbeen trig-gered experimentally by injectingpeople with large numbers of ir-radiated parasites. But procuringand irradiating the quantities ofparasites needed to immunize ahuman population at risk for ma-lariamaybelogisticallyunmanage-able,Zavalasays.Soheisworkingonanothermethodtoproducetheresponsewithoutsuchhugenum-bersofparasites,andalsoonwaystokeeptheresultingimmunecellsactiveoverthelongterm.

He’salreadyseenprogress.Anan-tigen—a part of the malaria para-site thatalertsaperson’s immunesystem—has been identified, andZavalaisworkingonavaccinethatwillcombinethatantigenwitheithera synthetic protein or a harmlessvirus to trick the immune systemintoseeingamassivePlasmodium invasion.Ifthatworks,andawayisalso found tokeep largenumbersoftheimmunecellsactiveoverthelong term, vaccines could protectpeople by producing large armiesof “constantly surveilling” CD8+immunecells,Zavalasays.Meanwhile, Markham, MD, is re-searchinghowtoboosttheimmuneresponse to malaria with a DNAvaccine thathasalreadysucceed-ed insparkingagreatlyenhancedresponseinmice.Thistypeofvac-cine uses genetically engineeredDNA from the malaria parasite astheantigenthatcanberecognizedbytheimmunesystem,whichthentriggersthedefense.Markhamwillsoon test thevaccine inmonkeys,acriticalsteponthepathtowardavaccineforhumans.

FiDel Zavala, MD, is workingon a vaccine that will trick the immune system into seeing a massive Plasmodium invasion.

A new DNA

vaccine

could

trigger an

enhanced

immune

response.



R x f o r M a l a r i a

Repurposing

existing

drugs to

fight

malaria

slashes

costs by

40 percent.

Gary Posner, PhD, and Theresa shaPiro, MD, PhD, are developing improved versions of the antimalarial drug artemisinin.

Inrecentdecades,pharmaceuticalcompanies have had few incen-tives to invest research funds innew antimalarial drugs. They canmakeagreater returnon their in-vestment by rolling out therapeu-tics for chronic illnesses commoninwealthycountries.

JHMRI researchers, however, arefillingthiscriticalgap.

Gary Posner, Scowe Professorof Chemistry in Hopkins’ KriegerSchool of Arts & Sciences, andTheresaA.Shapiro,WellcomePro-fessorofMedicine,andofPharma-cology and Molecular Sciences atHopkinsSchoolofMedicine,havecuredmalariainmicewithasingledoseofanewversionofanancientmalariaremedy.

For centuries, Chinese herbalistshave treatedmalariawithartemis-inin, derived from the wormwoodshrub Artemisia annua. Posner,PhD,andShapiro,MD,PhD,devel-opedanimprovedversionthatlastslonger and acts more quickly tocuremalariainmice.Theycreatedthedrug throughaprocesscalledrational design, using a chemicalprocess suitable for large-scalemanufacture.

AlsostrivingtoexpandthearsenalofantimalarialtherapeuticsisMMIassociateprofessorDavidSullivan.Butheistakingaverydifferentap-proach.

Sullivanandhisteamarenottryingtodevelopnewdrugs,butrathertoexploit theantimalarialpotentialofexistingones.Bringinganewdrugtomarketcostsupto$800million,butgettingapprovalforanewusefor an existing drug slashes costsby40percent,hesays.

“Repurposing is an old idea,” ex-plains Sullivan, MD. “Viagra wasoriginallydesignedtotreatangina,butdoctorsnoticedanothereffect.”Sullivan’s teamhasalready identi-fied an antihistamine that showsantimalarialactivityandapinwormmedicine that is effective againstmalaria’s close cousin, Cryptospo-ridium,aparasitethatcausesdiar-rhealdisease.

There are probably only a limitednumber of drug compounds thatarebothsafeandcapableofeffec-tiveactioninhumans.Noneshouldgotowasteinthefightagainstma-laria,saysSullivan.


N u r t u r i n g N e w I d e a s

isabelle coPPens, PhD, is studying ways to block the delivery of host nutrients to the parasite in order to starve it.

Pilot

grants

support

creative

ideas

with the

greatest

potential

benefits.

New methods to battle malariamust be bolder and more originalthanthoseofthepast.

After all, many treatments andpreventions—from witchcraft toquinine—havebeen triedover theyears,butnonehasenjoyed long-termsuccess.

Sadly,themostcreativeideaswiththe greatest potential benefits areoften considered too risky for re-searchgrants.Evenscientistssuc-cessfulinotherfieldsfinditdifficulttosecuremalariafunding.

To spawn innovation, JHMRI hasawardedpilotgrantsforpreliminaryworkthatmightleadtofruitfullinesofinvestigation.AnyJohnsHopkinsresearcher,withorwithoutpreviousexperienceinmalaria,cancompetefor awards ofup to$100,000an-nuallyforuptotwoyears.Thepilotgrantmoneycouldallowthesesci-entiststodiscovernewapproachesandgarnersufficientdatatoapplyfor long-termsupport fromNIHorotherfundingagencies.

“Thishasbeenanexcellentwayto increase thenumbers of peo-ple studying malaria and to en-courage new types of projects,”says Diane E. Griffin, MD, PhD,JHMRI’s founding director. “Theprogramhasmadeitpossiblefor25newinvestigatorstostartworkonmalaria. Therehavebeen33publicationsfrompilotgrantworkand 9 extramural grants fundedsofar.”

Recentpilotgrantsinclude:

Using “jumping genes” to modifythe Anopheles genome. Nancy L.Craig,PhD,aprofessorofMolecu-lar Biology and Genetics at Hop-kins School of Medicine, is usingmobile genetic elements calledtransposons found in the genomeof the Aedes aegypti mosquito tomodify thegenomeof twospeciesof Anopheles inanattempttointer-ruptmalariatransmission.

Producinganewanti-parasiteanti-biotic.JunLiu,PhD,aprofessorofPharmacology and Molecular Sci-ences at the School of Medicine,isworkingonanewfumagillin—anantibioticfirstusedtocontrolinfec-tions in honeybees—designed toattackthePlasmodium parasitebyinterferingwiththeactionofanen-zymeitneedsforcellgrowth.

Targetingtheparasite.CarenFreelMeyers, PhD, an assistant profes-sorofPharmacologyandMolecularSciences,isdevelopingnewmeth-odsforinhibitingametabolicpath-way important to many processesinthePlasmodiumparasite’scells.

Finding targets in the mosquitomidgut.AkhileshPandey,PhD,anassociateprofessorat the InstituteofGeneticMedicineof theSchoolofMedicine,islookingforproteinsinthe Anopheles midgutthatmightserve as targets that can be usedto block the mosquito’s ability totransmittheparasitetopeople.

Pilot Grants by the numbers

59 Pilotgrantsawarded

25 Investigatorsnewto

malaria

$9,219,935 Awardedforpilotgrants

33 Publicationsgenerated

9 Extramuralgrants generated


A c h i e v e m e n t s

Field site MachaBuilt the first permanent field research station for clinical, laboratory and epidemiologic research in Macha, Zambia, a malaria-endemic area

Malaria-Free MosquitoDeveloped transgenic mosquitoes and demonstrated they have a “fitness ad-vantage” over unaltered Anopheles when feeding on Plasmodium-infected blood

Quick DiagnosisDeveloped a simple urine-dipstick test for diagnosing malaria

stronger, better cureDeveloped a faster-acting, longer-lasting artemisinin-based drug treatment that is effective in mice and is promising in humans

a library of DrugsDeveloped a library of approved drugs to be screened as effective antimalarials and later identified an existing allergy medication as a potential antimalarial

attracting new investigatorsEstablished a successful system of pilot grants and fellowship opportunities that is drawing new scientists from many disciplines to malaria research

new vistas in vaccines Demonstrated that immune responses against Plasmodium are induced in specialized tissues and earlier than previously known, opening new options for vaccine development

Malaria-hiv connectionDemonstrated that placental malaria increases mother-to-child transmission of HIV

Tools for blocking TransmissionReported several breakthroughs in research of the mosquito’s anti-Plasmo-dium defense system, providing several new tools for transmission-blocking interventions

Gene chip Provided intellectual leadership and financial support to develop the first gene chip to contain genes from the Plasmodium parasite and Anopheles mosquito

E x e c u t i v e S u m m a r y

B r e a k i n g t h e C y c l e

JHMRI researchers are investigat-ing each stage of the lifecycle for innovative strategies that will yield new preventive or therapeutic methods to stop malaria.


international Malaria research conference A biennial, two-day conference that attracts more than 300 of the world’s top malaria experts, including many from Europe and Africa

Malaria Day A biennial one-day conference focusing on JHMRI projects that draws more than 200 area researchers

baltimore-Washington Quarterly Meeting A meeting of scientists from NIH, Walter Reed Army Medical Center, Naval Medical Research Center and area universities

J H M R I : A N e x u s o f K n o w l e d g e

Malaria interest Group MeetingA biweekly meeting of JHMRI faculty, pilot grant recipients and students through the academic year

award-Winning Malariology course A free, not-for-credit, online course on malaria is available on the Johns Hopkins Bloomberg School of Public Health’s OpenCourseWare site (http://ocw.jhsph.edu)

PublicationsFor a list of peer-reviewed publications, go to http://malaria.jhsph.edu/publications

J H M R I b y t h e N u m b e r s

J H M R I ’s N e w “ P i l o t ”

Nobel laureate Peter Agre received a JHMRI pilot grant in 2004 to extend his aquaporin research to malaria. His promising work later received NIH funding and inspired him to join JHMRI as its director in January 2008.

19 JhMrI faculty, including 9 hired since JhMrI’s founding 8, 7 and

3 post-docs, pre-docs and endemic-area fellows supported 171 peer-re-

viewed publications 7 years that JhMrI was led by founding director diane

e. Griffin 7,270,948 registered U.s. patent awarded to JhMrI and

other researchers for their novel technique that uses a mass spectrometer to

quickly diagnose malaria in multiple blood samples

E x e c u t i v e S u m m a r y

h t t p : / / m a l a r i a . j h s p h . e d u


M a c h a : A L i v i n g L a b o r a t o r y i n Z a m b i a

In southwestern Zambia, malariahaslongbeenaninescapablefactoflife…anddeath.

In the small rural community ofMacha, people live in scatteredclusters of huts connectedby dirtroads.Insomeyears,the208-bedMacha Mission Hospital wouldtreat more than 5,000 outpatientsand admit up to 1,000 childrenwithmalaria.Theyoungestpatientsmay suffer the disease’s cruelesttorments—severe anemia, convul-sions and coma—and sometimesdeath.But a new neighbor, the MalariaInstituteatMacha(MIAM),intendstochangethispicturewithmodernmalariacontrolmethodsandstate-of-the-art research. A partnershipof JHMRI, the Zambian govern-ment, the Macha Hospital and itsMachaMalariaResearch Institute,MIAMopenedinJanuary2005as“theonlycenterofitstypeincen-tralorsouthernAfrica,”saysCliveShiff, JHMRI chief investigator forMIAM. The malaria parasite hasadaptedsoexquisitelytobothmos-quitoesandhumansthattounder-stand the parasite, we first mustunderstand how the people andinsectsliveandinteractdaytodayandseasontoseason.“Malariaisadiseaseoftropicalareas.Itisnotadiseaseofivorytowers,”saysShiff,an MMI associate professor, ex-

plaining JHMRI’s mission to bringitsresearchandtrainingresourcestoanendemiccountry.The campus has clinical and re-search laboratories, satellite com-munications, a permanent staffof about a dozen, and living ac-commodations and lab space forvisiting researchers. In additionto providing research and trainingopportunitiesforscientistsandstu-dentsfromHopkinsandotheruni-versities,Shiffsays,“oneofourbigobjectivesistotrainZambians.”Essential to any success againstmalariaisadeepunderstandingoflocal conditions, says Shiff, PhD,anative ofneighboringZimbabwe(thenSouthernRhodesia).Hebe-gan his career as a malaria-con-trol officer in Zambia. MIAM’s ex-ecutiveandadministrativedirector,Philip Thuma, MD, is a Hopkins-trained pediatrician with decadesof experience living and workingatMacha.(Hisparentsweremedi-cal missionaries who founded theMachahospital.)ScientificdirectorSunganoMharakurwa,PhD,MSc,wasborninZimbabweandalsore-sidesatMacha.OtherkeymedicalandtechnicalstaffmemberscometoMIAMfromZambiaorotherAf-ricancountries.Students fromtheUniversity of Zambia’s graduateparasitology program regularly dopracticumsatMIAM.

To fight

malaria

we need a

deep under-

standing

of local

conditions.

MIAM’s executive director, Hopkins-trained pediatri-cian PhiliP ThuMa, MD, has lived and worked in Macha for decades.

WilliaM Moss, MD, MPh, gathers vital baseline information on malaria in the local population.


M a c h a : V i t a l R e s e a r c h i n a n E n d e m i c A r e a

ResearchdoneinjustthepastfewyearsinMachahasalreadybeenre-portedtotheinternationalscientificcommunity via 15 peer-reviewedpublications.EntomologistandMMIassistant professor Douglas Norris,PhD, is studying the biology, be-havior and genetics of Anopheles arabiensis, the dominant vector ofmalariainthearea,tobetterunder-stand its populationdynamics anddevise better ways to control themosquito.Amongtheotherprojectsunderwayisamajorresearchinitia-tive,ledbyWilliamMoss,anassoci-ateprofessorofEpidemiology,withassistance fromSnehalShah,MD,MPH, an MMI research associate.They are gathering vital baselineinformationonmalaria in the localpopulation. The hospital has dataontreatmentofactivecasesbutnotonmalariaintheentirecommunity.Thesurveywillprovide informationon unanswered questions such aswheretheparasiteexistsduringthedry season when case numbersdrop. Ifwecan identify thepeopleharboringparasitesatthattimeandtreat them, malaria transmissioncouldbereducedintherainysea-son,saysMoss,MD,MPH.

“Ourgrandmission is to identifyaset of interventions to eliminate orgreatly reduce malaria transmis-sion.MIAMcancontributesophis-ticatedmethods formonitoring theinterventions,”Mossadds.

Thus,saysCliveShiff,MIAM“servesthe needs of the endemic area aswellasJohnsHopkins.”

MIAM’s scientific director sunGano MharaKurWa, PhD, Msc, is a Zimbabwean scien-tist who lives in Macha.

JHMRI chief investigator for MIAM, clive shiFF, PhD, be-gan his career as a malaria-control officer in Zambia.

DouGlas norris, PhD, is studying the biology, behavior and genetics of Anopheles arabiensis mosquitoes.

Malaria

is not a

disease

of ivory

towers.

Macha by the numbers

6 Majorstudiesunderway

(molecularbiologyof

malariaparasites;molecular

drugresistancemarkersin

malaria;epidemiologyof

communitymalariawith

emphasisongametocyte

carriage;immuneresponse

tomalarialsexualstage

antigens;pharmacokineticsof

antimalarialdrugsin

pregnancy;newdiagnostic

methodsformalaria)

3,000 Squarefeetoflabspace

120 Squarefeetofinsectary space

34 Numberoflocalpeople employed

7 NumberofAfricanfellows/ scientists

1,400 Averagenumberof pediatricadmissionsfor malariaperyearatMacha Hospitaluntilrecentyears

300 – 500 Rangeofpediatricadmissions formalariaperyearatMacha Hospitalinrecentyears(The declineinadmissionsismost likelyduetodrought,fewer mosquitoesandnewdrugs usedtotreatinfection.)


H u n t i n g M o s q u i t o e s f r o m 1 2 6 M i l e s U p

“Actually, we do do rocket sci-ence,”saysGregoryGlass,anen-vironmental scientist who is usingimages from the space shuttle tosolvealong-standingmalariamys-tery:WheredoAfricanmosquitoes(soubiquitousduringtherainysea-son)spendthedryseason?Some species survive the annual“tough time”as eggs,butnot themalaria-bearing Anopheles mos-quito,whichspendsthedryseasonas an adult, says Glass, an MMIprofessor. “They must be hidingsomewhere, but nobody knowswhere.”Findingwhere the insectsclusterwhen theirpopulationsaresmallestcouldhelptocontrolthemandtoprotectvulnerablepeopleintheseasonswhenAnophelesnum-bersexpand.An expert in using geographicalinformation systems to analyzerisk factors for malaria and otherdiseases, Glass approaches themysteryofthemissingmosquitoesfrom a slightly different viewpointthan other researchers—from analtitude of 126 nautical miles viathe orbiting eye of Space ShuttleEndeavour.

In2002,theShuttleRadarTopog-raphy Mission (SRTM) producedthe most extensive and detailedtopographic maps of planet Earthever created. Combining SRTMdatawithother informationonhy-drology,topographyandvegetation,Glass’s team has mapped wherewater collects at various seasonsin specific African locations—andnotjustanywater,butthespecifictypesofclearpoolswithsandybot-toms and overhanging trees thatAnophelesprefers.Latelytheteamhasbeencheckingthe accuracy of their predictions.“We’rereallygoodatfindingwherethisparticularspeciesofmosquitolives,” says Glass, PhD. And, be-cause those favored dry-seasonspotsturnouttobenearparticularhouses,Glassalreadyforeseestheresearchproducingadown-to-earthresult:pinpointingthefamiliesthatneed extra help in controlling themosquitoes and thereby reducingtheirexposuretomalaria.

GreGory Glass, PhD, is using images from the space shuttle to solve the mystery of where the mos-quitoes go when the rainy season ends.

Where do

African

mosquitoes

spend the

dry

season?


S a v i n g F r e d e r i c k

One morning last April, I was ridingshotguninatruckinsouthernZambia.Two Dixie cups of Anopheles mosqui-toesinmyhandsandadyingboyinthebackseat.MycolleaguesandIhadbeeninMuf-wafwi village collecting mosquitoes aspartofmydissertationresearchonthedynamicsofmalariatransmission.Com-plex and minute, anopheline mosqui-toesarefascinatingcreatures.TheyalsocarrythemalariaparasitethatkillsonemillionchildreneachyearinAfrica.Aswewerejoviallypilingintothetruckto leave the village after a successfulmorning hunting monzenyas, a mancamerunninguptouswithalimpchildin his arms. A distraught woman fol-lowed close behind. Frederick lookedabout three years old and was com-pletelycomatose;onlythewhitesofhiseyes showed throughpartially crackedlids. None of us present was a physi-cian,but theseriousnessofhiscondi-tionwasclear.Ifhewasgoingtohaveachanceofsurviving,heneededadoctorassoonaspossible.“Getin,”wesaid.“Let’sgo.”April is the tail end of malaria seasonin southern Zambia. I’d seen manychildrensickwithmalariaintheMachaMission Hospital, which is adjacent tothe Johns Hopkins Malaria ResearchInstitute’s field station where my ento-mologicalresearchwasbased.WhetherFrederickhadmalariaorsomeotherin-fectiousdisease,wewereclearlyracingagainsttime.Reachingthehospitalisabigdealoutthere.Wewereagood45-minutedriveaway,including3kilome-tersofbushpaths leadingtothemainroad.Themotherheldhersickchildinthebackseat.Hisbreathingwasraspy.Iwasterrifiedforhim.Thetruckbouncedasquicklyassafe-ty permitted down eroded footpathsthroughtallgrass.Inmylap,Icradledtheenemy.Toppedbymeshheldwithrubber bands, each cup contained a

dozen or so blood-laden anophelinemosquitoes thatwehad justcollected.Somewerefromtheveryhouseinwhichlittle Frederick lived. With each bumpthe mosquitoes were jostled off theirresting place on the side of the cup.Their threadlike hind legs arched upgracefullybehindtheirbodies,andtheirfine, black and white dappled wingsbecamegrayblursastheystruggledtoregain their footing. I tried to cushionthemasmuchaspossible.Behindme,IheardFrederickalternatefromunevengaspstonosoundatall.Igazedoutthewindowandtriedtoconcentrateonthepretty yellow and orange flowers thatlinedtheroadside,onthebrightsunlightthathadjustbrokenloosefromanop-pressivecloudcover.Icaughtaglimpseoftheanguishedfatherintherearviewmirrorandclenchedmyjawandswal-lowedhardtokeepfromcrying.Please,letusgetthereontime.I lookedbackdownat themosquitoesinmylapandmarveledthatthesetiny,delicate creatures could be the men-acesresponsibleforsomeoftheworld’sdeadliest scourges. Any one of thesemosquitoes I held in my hands couldbe harboring thousands of wriggling,microscopic parasites. When a mos-quito takes an infectious blood meal,theparasiteburrowsintothemosquito’smidgut,whereitencystsitselfforaboutaweek.Seeminglyinert insidethisoo-cyst, theparasite is rapidlymultiplyingintotensofthousandsofminuteinfec-tiousstageparasitescalledsporozoites.If the oocyst survives attack from themosquito’s immune defenses, it rup-turesandreleases thesporozoites intothemosquito’sbodycavity,wheretheypenetrate the salivary glands. Fromthere,theyareinjectedintoahostuponthenextbloodfeeding.Mathematically, it is amazing thatma-laria transmission happens at all. As-suming themosquito’s very first bloodmealwasinfected,shemustliveabout16 to18days inorder to transmit theparasites.(Mosquitoesluckyenoughto

escapepredationbybirds,batsorrap-torial insectsmay liveaboutamonth.)InthecaseofAnopheles arabiensis,thecritical transmission time is the fourthorfifthbloodmeal. If thiscriticalmealistakenonacow,dogorchicken,thetransmissioncycleisbroken.Likewise,if the first blood meal is taken fromtheseanimalsoranuninfectedperson,themosquitomightnotlivelongenoughto become infectious. But, as JeffGoldblum’s character puts it in Juras-sic Park,“Naturewillfindaway.”Andnaturehadfounditswayintothebackseatofour4x4ToyotaHilux.Please, please,letusgetthereontime.The roadseemedendless. Ino longerheard breathing behind me. Finally,we pulled into Macha and stopped atthehospital’s frontdoor.Later,Dr.PhilThuma, a pediatrician and the execu-tive director of the Malaria Institute atMacha,toldusthatFrederickhadcere-bralmalariaanda+4malariasmear—alethal level.“I’mnotsurehe’sgoingtomakeit,”Thumatoldus.Over the next few days, Frederick re-spondedwelltointravenousquinine.Herecovered,evenmanagingtoavoidthedeafness and blindness often causedby cerebral malaria. To my relief andjoy, theeyesthatwereoncewhiteslitsgazedbackatme,suffusingmeintheirdeepbrown,captivatingwarmth.MyhappinessoverFrederick’srecoverywas tempered,however,bymyknowl-edgeofmalaria’sgrimreality inAfrica.On that sameApril day that Frederickrecovered,3,000otherAfricanchildrenweren’t as lucky. The malaria parasitefounditswaytothem,andtheydied.Wejustdidn’tgettothemintime.

Rebekah Kent, PhD, is a former pre-doctoral fellow with the Johns Hopkins Malaria Research Institute and is now a postdoctoral investigator with the Centers for Disease Control and Prevention.

Entomologist Rebekah Kent’s tale of death and life at the end of malaria season

rebeKah KenT, PhD, joins Frederick after his recovery.


M e e t t h e N e x t G e n e r a t i o n o f S c i e n t i s t s

Along with a steady stream of re-searchbreakthroughs,JHMRIlabsareproducingsomethingelsevitaltosuccessagainstmalaria:thenextgenerationofmalariaresearchers.

Graduate students and postdoc-toralfellowsworkingalongsideemi-nentscientistsaremakingoriginalcontributionstomalariascienceviaawiderangeofstudiesofthePlas-modium parasite, the Anopheles mosquitoandhumans:

Examining immune response toparasite infection. Ian Cockburn,PhD, a postdoctoral fellow in thelabofMMIProfessorFidelZavala,MD,isexamininghowtheimmunesystemgivesthefirstwarningsignaloftheparasiteinvasion.

Michael Overstreet, a PhD stu-dent also in Zavala’s laboratory, is“eavesdropping on the crosstalk”betweentwotypesofimmunecells(CD8+ and CD4+) to learn aboutthe human response to malariainfection, and he is studying howthesecells interact in thedefenseagainsttheparasite.

Understanding Plasmodium me-tabolism. Maroya D. Spalding, aPhDstudent, inBiochemistry andMolecularBiologyinthelaboratoryof Sean Prigge, PhD, an MMI as-sistant professor, is investigatingtheroleofaproteinessentialtotheparasite’s metabolism in the hopeoffindingtargetsforfutureantima-larialdrugs.

Stopping the parasite in the mos-quito.RhoelDinglasan,PhD,MPH,a postdoctoral fellow in the labo-ratory of MMI Professor MarceloJacobs-Lorena,PhD,isturningre-centdiscoveries (thatasugarandapreviouslyunknownantigenbothhelp theparasitegainentry to themosquito’s midgut) into strategiesforblockingdiseasetransmission.

Sung-JaeCha,PhD,apostdoctoralfellow in Jacobs-Lorena’s labora-tory, is studyingamoleculeandagenethatbothplayimportantrolesintheinsect’sresponsetoparasiteinfection.

Studyingtransmission-blockingvaccines. Debabani Roy Chowd-hury,PhD,apostdoctoralfellowinthe lab of MMI professor NirbhayKumar, is examining the effectsof worm infestation on the effec-tiveness of experimental vaccinesdesigned to block malaria trans-mission and immunological mem-ory. Worm infections are commonamong children in the developingworld and are known to suppressimmuneresponse.

Ralph LeBlanc, MD, a PhD stu-dent in the labofNirbhayKumar,is studying malaria antigens ex-pressed in mosquito-stage para-sitesastargetantigensforvaccinesthatblockmalariatransmissionbyinterferingwithmosquitoinfection.

Students

and post-

docs work

alongside

eminent

scientists

to make

original

contributions

to malaria

science.

rhoel DinGlasan, PhD, MPh, is turning recent discoveries into strategies for blocking disease trans-mission.

Diagnosis

Nirbhay Kumar, PhD* ProfessorMolecular Microbiology and Immunology (MMI)Bloomberg School of Public Health (JHSPH)

Sungano Mharakurwa, PhD* Research Associate MMI, JHSPH

David Sullivan, MD*Associate ProfessorMMI, JHSPH

Ernesto Freire, PhD

Drug Development

David Sullivan, MD*

Ernesto Freire, PhD*ProfessorBiology, Zanvyl Krieger School of Arts and Sciences

Gary Posner, PhD*ProfessorChemistry, Krieger School

Sean Prigge, PhD*Assistant ProfessorMMI, JHSPH

Theresa Shapiro, MD, PhD*ProfessorClinical Pharmacology, School of Medicine (SOM)

Jun Liu, PhDProfessorPharmacology, SOM

immunology and vaccine Development

Nirbhay Kumar, PhD*

George Dimopoulos, PhD*Assistant ProfessorMMI, JHSPH

Susan Kraemer, PhD*Assistant ProfessorMMI, JHSPH

Fidel Zavala, MD*ProfessorMMI, JHSPH

Donald Burke, MDFormer JHSPH faculty

Gary Ketner, PhDProfessorMMI, JHSPH

Richard Markham, MDProfessorMMI, JHSPH

Mathias Oelke, PhDAssistant ProfessorPathology, SOM

Scheheraza Sadegh-Nasseri, PhDAssociate ProfessorPathology, SOM

Malaria institute at Macha – Facility and Program Development

Sungano Mharakurwa, PhD*

Philip Thuma, MD*DirectorMalaria Institute at Macha

Clive Shiff, PhD*Associate ProfessorMMI, JHSPH

William Moss, MD, MPH*Associate ProfessorEpidemiology, JHSPH

Snehal Shah, MD, MPH*Research AssociateMMI, JHSPH

Fidel Zavala, MD

Molecular Parasitology / cell biology

Nirbhay Kumar, PhD*

Sungano Mharakurwa, PhD*

Sean Prigge, PhD*

Isabelle Coppens, PhD*Assistant ProfessorMMI, JHSPH

Marcelo Jacobs-Lorena, PhD*ProfessorMMI, JHSPH

Fernando Pineda, PhD*Associate ProfessorMMI, JHSPH

Brendan Cormack, PhDAssociate ProfessorMolecular Biology and Genetics, SOM

Robert Gilman, MDProfessorInternational Health, JHSPH

Sabra Klein, PhDAssistant ProfessorMMI, JHSPH

Michael McDevitt, MD, PhDAssistant ProfessorHematology, SOM

Caren Meyers, PhDAssistant ProfessorPharmacology, SOM

Sinisa Urban, PhDAssistant ProfessorMolecular Biology and Genetics, SOM

Pathogenesis / clinical studies

David Sullivan, MD*

Philip Thuma, MD*

Fidel Zavala, MD*

Peter Agre, MDProfessorMMI, JHSPH

Heena Brahmbhatt, PhDAssistant ProfessorPopulation, Family and Reproductive Health, JHSPH

Katherine Conant, MDAssociate ProfessorNeurology, SOM

Ronald Gray, MBBSProfessorPopulation, Family and Reproductive Health, JHSPH

Landon King, MDAssociate ProfessorPulmonary and Critical Care Medicine, SOM

Yukari Manabe, MDAssistant ProfessorInfectious Disease, SOM

Andre Levchenko, PhDAssistant ProfessorBiomedical Engineering, Whiting School of Engineering

Monique Stins, PhDVisiting FacultyNeurology, SOM

structural biology

Ernesto Freire, PhD*

Marcelo Jacobs-Lorena, PhD*

Nirbhay Kumar, PhD*

Sean Prigge, PhD*

Clara Kielkopf, PhD*Former JHSPH faculty

vector biology

Nirbhay Kumar, PhD*

George Dimopoulos, PhD*

Douglas Norris, PhD*Assistant ProfessorMMI, JHSPH

Jason Rasgon, PhD*Assistant ProfessorMMI, JHSPH

Nancy Craig, PhDProfessorMolecular Biology and Genetics, SOM

Marie Hardwick, PhDProfessorMMI, JHSPH

Michael Matunis, PhDAssociate ProfessorBiochemistry and Molecular Biology, JHSPH

Akhilesh Pandey, MD, PhDAssociate ProfessorBiological Chemistry, SOM

core Facilities

bioinformatics coreFernando Pineda, PhD*

environmental surveillance coreGregory Glass, PhD* ProfessorMMI, JHSPH

Gene array and Proteomics coreAlan Scott, PhD*ProfessorMMI, JHSPH

insectaryMarcelo Jacobs-Lorena, PhD*

Parasite coreNirbhay Kumar, PhD*

* JHMRI faculty

Susan Kraemer, PhD

F a c u l t y


Fernando Pineda, PhD

Alan Scott, PhD


Curiosity—thatbasicqualityofsci-ence—drivesusinnewdirections.Research isnotaboutplowingthesamerowrepeatedlyor restingonyour laurels. Research is aboutlookingaheadfornewwaystoad-vancesciencewiththegoalofim-provingthewell-beingofhumanity.

In2004,theJohnsHopkinsMalar-iaResearch Instituteprovidedourlab an opportunity todo just that.ApilotgrantfromtheInstitutehaschangedourlab’sdirection.Wehadneverworkedinmalariabefore,butthe Institute saw that our exper-tise in aquaporin research mightoffer an innovative way to attackthe Plasmodium parasite. (Aqua-porinsareproteinsthatformsmallwaterchannelsincellmembranesthroughoutnature, includingPlas-modium.) Our initial research re-vealed an interesting functionalroleforaquaporinsduringmalarialinfection.

Everyscientistislookingforanewadventure, and it’s a new day forus. We have secured a new five-yearNIHgranttostudyaquaporinsinmalaria.Scienceisneverpredict-able, and we are not guaranteedsuccess.ButIreallythinkthatourlabcannowcontributetobasicsci-ence,whichishumanity’sgreatesthopeforeradicatingmalaria.

ItisaheartwarminghonorformetobeaskedtodirecttheJohnsHop-kins Malaria Research Institute.Diane Griffin and her colleagueshavebuiltupatop-tiermalariapro-gramwithaglobalreach.Iamnotalifelongmalariologist,andIdonotcometothiswithgreatmalariaex-pertise.SometimesIevenfeel likeafanwho’sbeenaskedtoplaywiththeband.Nevertheless, I feel thatIhavepotentially importantexper-tise.Themalariaparasitespendsasignificantpartofitslifecycleinredblood cells, and my backgroundas a Johns Hopkins hematologistandred-blood-cellmembranebio-chemist will be very useful. I alsofeelthatIhaveavisionforthesci-enceandcancontributeinspecialways,usingthebullypulpit Ihavebeengiventoadvancethepreven-tionandtreatmentofmalaria.

My priorities are to increase thevisibility of the Institute and ma-laria science in general, and tocoordinate activities with othermalaria research centers. I hopetheseeffortswillleadtonewmeth-odsofpreventingmalariainfectionandnewapproachestotreatmentofmalaria.

Onanotherlevel,Istronglyfeelitistimeformetogivesomethingbacktoscienceandtosociety.Programscannotrunthemselves.Someone

I n t o t h e F u t u r e

hastogotobatfortheyoungersci-entistswhomwehopewillsoonbemakingthebigadvances.Iwanttodoall Icantohelpthem.Forme,that is what leadership is about. Ihavebeennameddirector,butmyjob is to serve, not to command.I’mjustanotherscientist—albeitata senior level—who still hopes tomakenewdiscoveriesbutwhoalsowantstocontributeinanorganiza-tionalwaytoJohnsHopkins,averyspecial institution that has alwaysbeenfirstinmyheart.

To achieve something genuinelysignificantinmedicalscience,youneed that rare constellation of re-sources, people and good ideas.The Johns Hopkins Malaria Re-searchInstitutehasthemall.Icon-sidermyselfextremelyfortunatetohave been given this opportunity.Now, my job is to make sure thebright people here have the re-sources needed to develop ideasthatwillonedayhelpuscontroloneoftheworld’sworstscourges.

PeterAgre,MDDirector, Johns Hopkins MalariaResearchInstitute,2008–Professor, Molecular MicrobiologyandImmunologyJohns Hopkins Bloomberg SchoolofPublicHealth

sean prIgge, phD,investigatestheroleofaproteinessentialtothemalariaparasite’smetabolism.

Phot

ogra

pher

s: D

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Col

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l, Pe

ter

How

ard,

She

zhad

Noo

rani

, Pho

to R

esea

rche

rs, I

nc.,

John

Sta

nmey

er /

VII;

Illu

stra

tor:

Joe

Cep

eda;

JH

MR

I Coo

rdin

ator

: Sus

an V

iles

Boo

ker;

Wri

ter:

Ber

yl B

ende

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Edi

tor:

Bri

an W

. Sim

pson

; Art

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ecto

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esig

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200

6-11

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00

Cover: Avode Nawechi, 3, sits beneath a bed net at the Kalene Mission Hospital in Zambia as Endes Npompu (back cover) cares for her malaria- stricken grandson Paul Kangoma, 5. (John Stanmeyer / VII)

Johns Hopkins Malaria Research Institute

615 N. Wolfe Street, E5132

Baltimore, MD 21205

[email protected]

410-502-3377

http://malaria.jhsph.edu

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