FocusSummer 2008

The Scienceof Aging:

Wistar researchersshed new lighton getting old

Wistar Launches High-TechResearch Center

The Federal Funding Crunch:What Does It Mean for Wistar?

The Wistar Institute has a pioneering tradition.Caspar Wistar, for whom the Institute is named,

was a forward-thinking 18th-century physician whowrote the first American anatomy textbook and was anearly proponent of vaccination. His great-nephew, Insti-tute founder Isaac J. Wistar, was a pioneer in his ownright who trekked west by wagon train to spend wintersas a trapper in the wilds of California.

Isaac Wistar founded The Wistar Institute in 1892with the stated intention of creating a center for “newand original research” in the biological and medical sci-ences. In the ensuing century, Wistar lived up to thatcharge, and it continues to do so today.

Wistar’s first scientific advisory board, convened in1905, declared research as the Institute’s principal objec-tive and specified three areas of focus: comparativeanatomy, embryology, and neurology—fields that repre-sented the leading edge of science and medicine at theturn of the century.

The Institute’s research focus has evolved over the years.Today, Wistar is best known for cancer research andvaccine development. What hasn’t changed is that Wistarremains at the forefront of biomedical research.

In this issue of Focus, you’ll read about how Wistarscientists are contributing to new knowledge about theaging process and finding new hope for aging-relateddiseases such as cancer, Alzheimer’s, and diabetes. Theseadvances build on Wistar’s longstanding legacy ofachievement in aging research.

You’ll also learn how Wistar is embracing emergingtechnologies that greatly expand our researchers’ capabili-ties. Our Center for Systems and Computational Biology,which opened its doors this spring, provides powerful,cutting-edge instruments that help investigators analyze

massive amounts of data and pinpoint disease-causinggenes and proteins. The center supports work like that ofDavid W. Speicher, Ph.D., who is developing blood testsfor the early detection of the deadliest cancers.

Likewise, the Institute’s new chemical screening facil-ity, set to launch this fall, will allow investigators toscreen vast numbers of compounds and identify thosethat are the best candidates for development as drugs.The facility will enhance Wistar’s ability to do “transla-tional” research, transforming its basic research intotherapies for patients.

These resources will make the most of our scientists’creative ideas and dedicated efforts and help to ensurethat Wistar stays where it belongs: at the frontier of sci-entific knowledge, seeking the answers that will save livesand improve human health worldwide.

Russel E. Kaufman, M.D.President and CEO

Focus is published two times per year for donors, friends, faculty, and staff ofThe Wistar Institute by the Office of Public Relations. To contact the

editor, phone (215) 898-3943 or e-mail aporter@wistar.org. For general inquiries, contactThe Wistar Institute at (215) 898-3700. Send address changes to: Development Office,The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104-4265.

F R O M T H E P R E S I D E N T

Pete

r O

lson

ABBEY J. PORTEREditor and Acting Directorof Public Relations

LEE CHRISTINE SHURTZPublic Relations Assistant

KARLYN ROSEN AIRESDesigner

JAMES E. HAYDENFREDERICK S. KEENEYPhotographers

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The Wistar Institute is an equal opportunity/affirmative action employer. It is the policy ofThe Wistar Institute to provide equal employ -ment opportunities to all individuals regardlessof race, color, creed, religion, national origin,ancestry, sex, age, veteran status, disability,sexual orientation, or gender identity for allterms and conditions of employment.

The Wistar Inst i tute i s a National Cancer Inst i tute-des ignated Cancer Center.

STOCK PHOTOGRAPHYCover Image:Shuji Kobayashi/Getty Images

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C O N T E N T S : S U M M E R 2 0 0 8

4 The Science of AgingWistar researchers explore whathappens when we age—and how tocombat the effects of getting old.

8 Research Center LaunchesA hi-tech new center helps to keepthe Institute at the forefront ofbiomedical research.

10 Federal Funding WoesDeclining support from the NationalInstitutes of Health means it’s harderthan ever to get federal grants,and Wistar scientists are amongthose feeling the pinch.

11 Profile of SupportWistar champion Fran Tobinworks to bolster the Institute’sbrain tumor research.

12 Screening Facility to OpenA new facility will help Wistarscientists identify promisingdrug candidates.

13 ProgressThe latest advances from Wistar labs.

17 New GrantsHighlights of recent funding.

18 BriefingsNews, honors, and events.

22 Behind the ScienceWistar researcher Harold Riethmangrew up wanting to understand howliving things worked.

24 Q&AA Wistar scientist answersquestions on aging.

Focus

StudyingHow We Age

page 4

New CenterOpens Door

to Futureof Research

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The Scienceof Aging

Wistarresearchersinvest igatewhathappenswhen weget old

BY THOMAS W. DURSO

mong life’s inevitabilities,aging is as absolute asthey come, but no onehas yet determinedwhy: That is, whatexactly happens atthe cellular level

that not only slows us down and even-tually wears us out, but also leaves usmore susceptible to diseases rangingfrom cancer to Alzheimer’s andinfluenza?

Biomedical researchinto the causes and treat-ment of disease has helpedto extend life spans, andscientists at Wistar haveplayed important roles inthose efforts. Less visiblebut equally significant,Wistar research into the mechanisms ofaging has given investigators new leadsto pursue in the quest to extend thegolden years and infuse them with agreater quality of life.

“The physiological changes with ageare incredibly interesting,” says E. JohnWherry, Ph.D., an assistant professorin Wistar’s Immunology Program.“You have to think about the wholeorganism when you think about aging,because none of these changes happenin isolation.”

Building on a legacyThe legacy of Wistar’s aging-relatedwork extends back to the legendaryLeonard Hayflick, Ph.D., a formerWistar researcher who more than 40years ago demonstrated that normalhuman cell division ceases after about50 splits. Discovery of what becameknown as the Hayflick limit wasgroundbreaking, providing both a refu-tation of existing theories of celldivision and the basis for a good dealof modern cancer research.

Scientists later tied the Hayflicklimit to the shortening of telomeres,small bits of DNA at the ends of chro-

mosomes that are added in developingembryos and in stem cells by anenzyme called telomerase. In normaladult cells, telomerase is switched off,halting the lengthening of telomerestrands and ending cell division. Inap-propriate activation of telomerase canlead to uncontrolled cell growth—andcancer.

Exploring these phenomena todayat Wistar are Emmanuel Skordalakes,

Ph.D., an assistant professor in theGene Expression and Regulation Pro-gram, and Harold C. Riethman,Ph.D., an associate professor in theMolecular and Cellular OncogenesisProgram.

Last year, Skordalakes and his teamdeciphered the three-dimensionalstructure of an important region oftelomerase. He hopes this will leadto the development of drugs to deac-tivate the enzyme and stop tumorgrowth or, more pertinent to agingresearch, to activate it under con-trolled conditions to allow some cellsto begin dividing again, resulting inhealthier, younger-looking tissue thatstays alive longer.

“Telomerase, if it’s overactivated,causes cancer, so it has to be a veryfine balance,” Skordalakes says. “Webelieve that if we can decode thethree-dimensional structure of theentire enzyme, we will be able toidentify drugs that would both com-bat cancer and activate the enzymefor the regeneration of tissue.”

Riethman’s focus is on under-standing the mechanisms oftelomere loss and lengthening. Once

telomeres reach a critically short length,they trigger cells to stop dividing andeither enter a permanent arrested stateknown as senescence, or commit cellu-lar suicide. In both instances, agingresults. Riethman is researching DNAsequences located directly adjacent totelomeres. These so-called subtelomericsequences vary widely from person toperson and seem to regulate the lengthsof their adjacent telomere sequences, a

fact that could havesignificant biologicalconsequences.

“It only takes a sin-gle telomere or a verysmall number oftelomeres to triggersenescence,” saysRiethman. “Certain

DNA segments may be able to predicttelomere length, which would in turnpredict susceptibility to telomere-related diseases—basically, aging-relateddiseases, including cancer.”

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c o n t i nu e d o n p a ge 6

“YOU HAVE TO THINK ABOUT the whole organism when you thinkabout aging, because none of these

changes happen in isolation.”

A

A T A G L A N C E

◗ THE MECHANICS OF AGINGappear to play a role in numer-ous diseases, including cancer,influenza, and Alzheimer’s.

◗ WISTAR RESEARCHERS arestudying aging from numerousand diverse angles, from DNAreplication to protein activa-tion to immunologicalpathways.

◗ WISTAR’S INFLUENCE in agingresearch extends back to the1960s, when Wistar researcherLeonard Hayflick, Ph.D., dis-covered that human cells inculture replicate about 50times before dying.

By gaining a more complete under-standing of subtelomeric sequences, headds, scientists could detect early evi-dence of telomere fusion, a signal ofcancer development, allowing them todiagnose and treat cancer far soonerthan is currently possible.

An anti-aging enzyme?Elsewhere at the Institute, Ronen Marmorstein, Ph.D., a professor in theGene Expression and Regulation Pro-gram, and Shelley L. Berger, Ph.D., theHilary Koprowski Professor at Wistarand a professor in the Gene Expression

and Regulation Program, are collabo-rating on research into a family ofenzymes called sirtuins.

Increased levels of sirtuins coincidewith a marked increase in lifespan forflies, yeast, and worms. It isn’t clearwhether activating sirtuins in humanswould lead to similar longevity, butthe misfiring of certain sirtuins in people has been linked to such aging-related disorders as obesity, diabetes,and cancer.

Marmorstein’s team has determinedthe structure of a sirtuin called Sir2and is imaging it in three-dimensionaldetail in hopes of figuring out how theprotein works and identifying novelsmall-molecule compounds that mightregulate it.

“We’ve succeeded in identifyingsmall-molecule regulators,” he reports.“In a rational way, we can now look atthe molecules that bind the sirtuinsand say, aha, we need to modify themolecules here to make them moreeffective. Then we can go ahead andprepare these modified molecules tomake specific regulators of the sirtuinproteins.”

Berger believes proteins that orga-nize each cell’s lengthy strand of DNAand pack it into the nucleus undergoepigenetic changes—inherited changesthat don’t alter DNA sequence—thatare related to aging. Using yeast mole-cules as a model, she is researchinghow Sir2 affects that process, possiblyby becoming deactivated over time,

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Wistar professors Shelley L. Berger, Ph.D.,and Ronen Marmorstein, Ph.D., are collaborating on research that aims to identify potential treatments for aging-related diseases.

“IT’S A PHENOMENALLY INTRIGUING QUESTION: Why is there aging? Not just mechanistically, but evolutionarily speaking, why don’t organisms live much longer or never die?”

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allowing typically tightly wound DNAstrands to start opening up, turningwrong genes on and causing cellularreplication, which usually happens in avery regulated way, to go awry.

The scientists hope their work willlead to the development of drugs thatregulate Sir2.

“Sir2 is a very important moleculeto target for drug development,”Berger says. “As long as it remainsactive, in principle the genome wouldstay tightly packed, and we wouldn’tget these wrong genes turned on.

“The direction of our work is toinvestigate the range of all of the mech-anisms that regulate our genomeepigenetically. We’re interested inwhether they are altered as we age sothat we can possibly find new enzymesto target for drug development.”

Immunologist John Wherry studieshow immunity to viruses changes with

age. He notes that as people age, theybecome less responsive to vaccines, soinfluenza and other viral illnesses, aswell as bacterial infections, show upmore often. In addition, it takes longerfor the elderly to bounce back fromsuch illnesses, and their overall health isdecreased even after they have recovered.

Because T cells play an importantrole in the immune system’s response tointercellular infections, Wherry is tryingto understand how their mechanismschange over time, in hopes of eventu-ally designing better vaccines for suchillnesses as flu, West Nile virus, andherpes. The more robust response ofyounger T cells to immunization—andthe weaker response of older cells—have given him some leads ondifferences in immunological pathways.

“If we can understand which path-ways control the failure to respond, wecan design a vaccine with some modi-

fications that bypass the pathways thatare ineffective,” he says. “T cells in oldmice might be subject to inhibitions—they might have a pathway operatingthat restrains them, or they might lacka pathway that should activate them.Either way, you should be able todesign a vaccine that supplementswhat they’re missing or overcomes theinhibitory pathway that they’reexpressing.”

His and the other scientists’ effortsare helping to elucidate a mysteriousprocess.

“It’s a phenomenally intriguing ques-tion: Why is there aging?” says Berger.“Not just mechanistically, but evolu-tionarily speaking, why don’t organismslive much longer or never die?”

Science may never discover theanswer to that question, but thanks toWistar researchers, it is getting moredirection on where to look. ❖

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INCREASED LEVELS OF ENZYMES

called sirtuins coincide with a

marked increase in lifespan for flies,

yeast, and worms. It isn’t yet clear

whether activating sirtuins

in humans would lead to similar

longevity, but the misfiring of

certain sirtuins in people has

been linked to such aging-related

disorders as obesity, diabetes,

and cancer. Wistar researchers have

deciphered the structure of a

sirtuin called Sir2 and are working

to find methods of regulating it.

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istar took a step intothe future of biomed-ical research when itopened its Center for

Systems and Computational Biology inMarch. The center, which includeshigh-powered computers and techno-logically advanced instruments, willsupport Wistar scientists in developingnew tests for the early diagnosis of can-cers and other diseases, as well as newtreatments.

The center’s technology allows sci-entists to produce and process vastamounts of data at an unprecedentedrate—an ability crucial for today’sresearcher, says Wistar president andCEO Russel E. Kaufman, M.D.

“Investigators used to ask narrowlyfocused questions and get very spe-cific answers,” Kaufman says. “Whatwe do now is ask a very big question,cast a broad net, collect lots of data,and sort it out with the computer.Many people call it ‘discovery sci-ence.’ You’re making discoveries ratherthan following a hypothesis.”

Historically, researchers havetended to focus on a single gene, mol-

ecule, or small group of molecules,sometimes throughout their entirecareers. Now, there is greater emphasison systems biology, which focuses onthe large-scale analysis of complex bio-logical systems and takes a moreopen-ended approach to research.Instead of exhaustively studying thefunction of one gene, for example, asystems biologist might seek to identity

all the genes or proteins involved in aparticular function.

This approach depends more ontechnology and computation, whichWistar’s new center provides. The facil-ity will eventually provide computingand data storage capacity up to 100times greater than the Institute’s previ-ous capacity. The center’s computationalresources support research efforts acrossthe Institute.

The center is particularly valuable inbolstering Wistar’s programs in genomicsand proteomics—the study of genesand proteins, respectively. The newfacility’s technologically advancedequipment includes a gene sequencerthat can rapidly sequence an entire

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FACILITY SUPPORTS NEW APPROACH TO RESEARCH

T E R M S D E F I N E D

SYSTEMS BIOLOGY is a relatively new field of study that focuses on the large-scale analysis of complex biological systems.

COMPUTATIONAL BIOLOGY uses techniques including computer science, appliedmathematics, and statistics to process, manage, and interpret complex data sets.

THE CENTER FOR SYSTEMS AND COMPUTATIONAL BIOLOGY allows Wistar scientiststo produce and process vast amounts of data at an unprecedented rate, further-ing their understanding of disease biology.

Wistar Launches Center for Systems and Computational Biology

BY ABBEY J. PORTER

W

Photos by Scott H. Spitzer

genome, helping researchers to identifygenetic changes that play importantroles in the development of cancer,HIV/AIDS, and cardiovascular disease.

Center director David W. Speicher,Ph.D., relies on the center’s computerresources, analytical tools, and facultyexpertise to analyze complex proteindata. He and his team are identifyingprotein “biomarkers” shed by cancersinto the blood in hopes of soon devel-oping blood tests that could detectcancer early. His team studies the fivetumor types responsible for most can-cer deaths: lung, colon, ovarian,prostate, and pancreatic.

Advances in technology haveenabled scientists to generate ever-larger and more complex data sets,Speicher notes, and the center providesthe tools to analyze that data at a levelpreviously unheard of. “It’s highlyenabling,” he says. “With theseresources, we will accomplish things wecouldn’t even conceive of doing a cou-ple of years ago.”

By advancing Wistar’s work in sys-tems biology, the center supports a toppriority of Wistar’s strategic plan andhelps the Institute stay at the forefrontof scientific investigation. “This isgoing to be the leading edge of bio-

medical research, as far forward as wecan see,” Kaufman says.

In addition to Speicher, the center’sleadership includes Louise C. Showe,Ph.D., associate director and directorof genomics; and recent Wistar recruitRamana V. Davuluri, Ph.D., associatedirector and director of computationalbiology. ❖

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The Center for Systems and Compu-tational Biology is supported by agrant from the Philadelphia HealthCare Trust. Additional funding is provided by a Keystone InnovationStarter Kit grant from the Common-wealth of Pennsylvania.

Right: John J. Rux, Ph.D., head of the bioinformatics facility at Wistar, discussesan image of a molecular structure on dis-play in Wistar’s new Center for Systems andComputational Biology.

Below: Wistar supporter Leroy E. Kean,right, takes in the center’s conference roomwith professor Frank J. Rauscher III, Ph.D.

Opposite below left: Center director David W.Speicher, Ph.D., addresses attendees at thefacility’s opening in March.

Opposite left: Wistar president and CEO Russel E. Kaufman, M.D., left, and Bernard J.Korman, chairman of the board of trustees of Philadelphia Health Care Trust, performthe ribbon-cutting that officially launchedthe center.

iomedical research reliesheavily on financial sup-port from the U.S.government, and Wistaris no exception. In 2007,federal grants supplied

half of the Institute’s income. But fivestraight years of flat funding of theNational Institutes of Health—Wistar’s primary research sponsor—has researchers worried that scientificadvances will begin falling off and thatyounger investigators, their researchcurtailed, will leave academia.

According to “A Broken Pipeline?Flat Funding of the NIH Puts a Gen-eration of Science at Risk,” a reportreleased earlier this year by a consor-tium of seven academic researchinstitutions, researchers nationwide areexperiencing “a sense of despair” at theopportunities lost due to the govern-ment’s failure to support researchadequately.

“In competition for limitedresources, scientists at every pointalong the academic research pipelineare feeling the destructive effects,” thereport notes. “Currently, only one infour original research applications tothe NIH are being funded, and manyof those are funded only after lengthydelays and cumbersome reapplications.The system is backlogged with propos-als and too few are being funded—impeding scientific progress.”

The bottom line?“There is less research being done,”

says Wistar Institute president andCEO Russel E. Kaufman, M.D.

FEELING THE PRESSUREBetween 1999 and 2007, the overallsuccess rate of applications for R01grants—the most common NIH grantfor individual projects—fell from 32percent to 24 percent. The success ratefor first-time submissions fell evenmore sharply, from 29 to 12 percent.Those trends are reflected at Wistar,which received only 11 new NIHgrants in 2007, down from 22 in2002. NIH grants provided $5.2 mil-lion in new funding to the Institutelast year, compared to $7 million in2002.

While researchers at all levels feelincreased funding pressure, the crunch

is felt most by junior investigators,who must wait longer for their firstbig grant. In 1990, the average age atwhich researchers received their firstR01 grant was 39; today, it’s 43.Because of the government’s belt-tight-ening, the 12 new investigators Wistarhas hired over the past five years havehad to spend more time chasingresearch dollars and less time workingin their labs.

“The fact that the funding is so badmeans that I have to spend muchmore time writing grants, whichmeans I can focus less on actual sci-ence,” confirmed Joseph Kissil, Ph.D.,an assistant professor in Wistar’s Mole-

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B Challenging Times for Researchers

OVERALLSUCCESS RATE FOR

NIH R01* PROPOSALS

SUCCESS RATE ONFIRST SUBMISSION OF

GRANT APPLICATION

*R01 equivalents: R29, R37

0% 5% 10% 15% 20% 25%

32%

24%

29%

30% 35%

Source: National Institute of Health

WITH ONLY ONE IN FOUR grant applicationsto the National Institutes of Health being funded,scientists say research is suffering.

12%

1999

2007

The Federal Funding Crunch:Scientists Feel Effect of Declining Support

BY THOMAS W. DURSO

cular and Cellular Oncogenesis Pro-gram. “I’m spending more timewriting grants than anything else.That means not keeping up with theliterature as much as I’d like to, andforget altogether about doing hands-on experiments.”

A BUDGETARY SHORTFALLFrom 1998 to 2003, Congress dou-bled NIH funding, and the resultsincluded the development of treat-ments that reduced mother-to-childHIV infection in the United Statesfrom 25 percent to 1 percent, aswell as new gene-based therapies forsuch neurological disorders as Hunt-ington’s disease and amyotrophiclateral sclerosis, or Lou Gehrig’s disease.

Since then, though, annualincreases in NIH funding have failedto exceed inflation; the five consecu-tive years “of no real budgetarygrowth” represents “a 13 percentdrop in purchasing power since2003,” according to “BrokenPipeline.” That fact is not lost onKissil, who joined Wistar in 2004.

“It was pretty bad when I started,and it’s just been declining,” he says.“The money’s not keeping up withexpenses…Even when you getfunded, the money is short of whatyou actually need, just because of therising costs.”

Kaufman anticipates the situationimproving but doesn’t believe areturn to the flush funding of the late1990s will happen anytime soon.

“It can’t stay like this forever, but Idon’t think that over the next threeto five years we are going to see theheyday of a decade ago, when theNIH’s budget doubled,” he says. “Asa result, we’re going to be moredependent on foundations, philan-thropy, technology transfer, andindustry-sponsored research than wehave been in the past.” ❖

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For Fran Tobin, supporting Wistar research is a personal passion. “Myhusband Sylvan is a brain tumor survivor,” Tobin explains, “and he suf-fered effects from the radiation treatment. Too little is known about the

brain and how to treat patients without causing serious side effects.”Tobin has given both financial support and her time to Wistar. She has

made contributions to Wistar’s Albert R. Taxin Brain Tumor Research Centeras well as to the Institute’s unrestricted funds. And for the past three years,she has co-chaired the annual Albert R. Taxin Golf Clas-sic, which raises funds for Wistar’s brain tumor research.(For more on this year’s tournament, see page 20.)

“Research is really what drives progress in health care,”Tobin says. “It’s essential for creating better treatments forthe future. I find Wistar, where the focus is entirely onresearch, very inspiring.”

Tobin got involved with Wistar through theencouragement of her friends, Wistar board of

trustees member Bob Fox and his wifePenny. She takes pride in honoring the

memory of Albert Taxin, the presidentof Old Original Bookbinder’s restau-rant, who died of an inoperablebrain tumor at 53. Tobin’s familyand the Taxins have known eachother for years; her parents were

friendly with Albert’s parents. “Albert had such a dynamic per-

sonality,” Tobin says, “and enoughcannot be said about his wife Doris and

her sense of responsibility in raising aware-ness and funds for brain tumor research.”

According to Tobin, the Taxin Golf Classicplays an important role not only in raising

funds for brain tumor research but also inraising awareness of Wistar’s work.

“Because Wistar doesn’t treatpatients, it’s not as well known to

the public,” she says. “The TaxinGolf Classic is a chance to intro-

duce Wistar and its importantwork to a wider audience.

Wistar is a wonderful place,and the more people whosupport us, the better theresearchers can do incuring disease.” ❖

“Research is really what drives progress in health care.”

FRAN TOBIN:Inspired by Research

P r o f i l eo f S u p p o r t

Photo by Tommy Leonardi

eflecting its commitmentto staying at the leadingedge of biomedicalresearch, Wistar will opena chemical screening facil-ity this fall that will buildits capabilities in transla-

tional research—the crucial bridgebetween early-stage research and clini-cal investigations.

“The new facility will enable ourscientists to identify compounds thatmay advance our understanding ofcancer and, in some cases, be potentialdrug candidates,”explains John Lucas,Ph.D., vice presidentfor academic affairs.

Understandingprotein function andthen finding ways toaffect it is importantin creating new treat-ments. For example,scientists may dis-cover a protein that ispresent in excessquantities in a type of cancer. Withthis knowledge, researchers can beginsearching for small-molecule com-pounds to turn the proteinoff—compounds that could be candi-dates for drug development.

Searching for chemical compoundswith very specific functions, however,is a little like looking for a needle in ahaystack. The research demands theability to process vast quantities of bio-logical information efficiently andaccurately. Sophisticated roboticequipment has made it possible to dojust that, allowing scientists to screentens of thousands of chemical com-pounds for those that meet specificcriteria. David Schultz, Ph.D., whowill direct the new facility, will help

Wistar researchers adapt their investi-gations to the technology.

“One of the most important aspectsof the facility is how it will allow Wis-tar scientists to further explore poorlydefined disease biology,” Schultz says.“Specifically, implementation of thistechnology will allow investigators toidentify new potential therapeutic tar-gets and classes of molecules that aren’teven on the radar today.”

Wistar professor Ronen Mar-morstein, Ph.D., has previously usedthe technology when collaborating

with researchers atother institutes and islooking forward tousing it in his ongoingstudies related to can-cer and aging.

“We can use thescreening facility tolook for inhibitors of aparticular cancer, forexample,” he says.“And when we findsuch inhibitors, we can

use our understanding of molecularstructure to modify the inhibitors andto make them more effective.”

The facility will allow Wistar tocollaborate on projects with otherresearch organizations, including theUniversity of the Sciences in Philadel-phia and Lankenau Institute forMedical Research ❖

WISTAR’S NEW SCREENINGFACILITY will allow scientists toquickly and accurately screen vastnumbers of chemical compounds andidentify those that may be targets fordevelopment as drugs. An example ofhow the process works:

A cancer-causing protein is placed intowells in hundreds of plastic plates.

The plates are fed into sophisticatedrobotic machinery, along with plates

containing a “library” of thousands of chemi-cal compounds to be tested. The equipmentcombines each compound with the proteinand records the effect.

Compounds that inhibit the protein areidentified, letting scientists know where

to focus their research efforts.

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Wistar’s new chemical screeningfacility is supported by a KeystoneInnovation Zone grant of $150,000from the Commonwealth ofPennsylvania, as well as the F.M.Kirby Foundation, the CLAWSFoundation, the Florence & DanielGreen Foundation, and the McLeanContributionship.

“We can usethe screeningfacility to lookfor inhibitorsof a particular

cancer.”

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NEW SCREENING FACILITYWILL EXPAND WISTAR’S CAPABILITIES

Leading efforts to create an HIVvaccine have hinged on the use of

viruses as carriers for HIV geneticmaterial. Evidence has emerged thatsome of these so-called viral vector systems may undermine the immunesystem and should not be used for vac-cine development. A study by Wistarscientists provides strong support forthe idea that some viral-vector vaccinesmay cause more harm than good.

The findings show that an HIV vac-cine construct incorporating one ofthese viruses, called adeno-associatedvirus, or AAV, directly interferes withthe immune response to the HIV virus.AAV is a small virus that does notcause disease and has been found tostimulate a mild immune response.

Specifically, while AAV inducesHIV-specific T cells—a type of whiteblood cell—those cells are functionallyimpaired in important ways.

“What do these results mean?” asksHildegund C.J. Ertl, M.D., director ofthe Wistar Institute Vaccine Centerand senior author on the study. “Put

simply, they mean that AAV vaccinesagainst HIV may potentially causeharm and that, without additional pre-clinical studies, they should not beused in humans.”

Taken together, the data partly out-line a condition known as T-cellexhaustion, seen in a number ofchronic infections, including HIV,hepatitis B, and hepatitis C, as well asin some cancers, such as melanoma.

“Why would you want to injectpeople with a vaccine that’s going tohave a detrimental effect?” Ertl asks.“AAV vaccines against HIV may domore harm than good by robbing peo-ple of their natural immune responseto HIV.”

The study appeared in November inJournal of Clinical Investigation. Thelead author is Shih-Wen Lin at Wistar.Wistar’s Nia Tatsis, Ph.D., Marcio O.Lasaro, Ph.D., and Scott E. Hensley(now at the National Institute ofAllergy and Infectious Diseases) wereco-authors. Lin is also affiliated withthe University of Pennsylvania.

The research was supported bygrants from the National Institutes ofHealth and the Commonwealth Uni-versal Research Enhancement Programof the Pennsylvania Department ofHealth. ❖

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The seemingly inefficient way ourbodies replace worn-out cells is a

defense against cancer, according to astudy co-authored by scientists at Wis-tar. Having a neighboring cell split intotwo identical daughter cells would seemto be the simplest way to keep bodiesfrom falling apart. However, that wouldbe a recipe for the kind of geneticmutation that leads to uncontrollable,rapid cell reproduction—and cancer.

Instead, multicellular organisms usea seemingly inefficient process toreplace lost cells. When replacementcells are needed, epithelial tissues suchas those in the skin call upon stem

cells, which differentiate, or grow intodifferent types of cells. Some divide tomake transient amplifying cells, orTACs—intermediate cells that in turndivide to produce skin cells. The newskin cells are evolutionary dead ends;they cannot reproduce.

Cells that self-renew, or makecopies of themselves, instead of dif -ferentiating are more vulnerable tocancer, says Carlo C. Maley, Ph.D., anassistant professor in Wistar’s Molecu-lar and Cellular Oncogenesis Programand senior author of the study. Maleyand his colleagues published theirpaper, “Animal Cell Differentiation

Patterns Suppress Somatic Evolution,”in December in PLoS ComputationalBiology.

“Somatic evolution” refers to muta-tions that can occur in somatic cells,which are found throughout the body,over an organism’s lifetime. Theprocess of cellular differentiationflushes mutant cells from our bodies.

The researchers compared muta-tions in different modes of cellularreproduction. They found that if cellsreproduce by simply making carbon-copies of themselves, their descendantsare more likely to accumulate muta-

P R O G R E S ST h e l a t e s t a d v a n c e s f r o m W i s t a r l a b s

Virus Used to Create Experimental HIV Vaccines Directly Impairs Immune Response

Study Sheds Light on Body’s Cell-Making Process

(continued on page 14)

Hildegund C.J. Ertl, M.D., has demonstratedthat a type of HIV vaccine may do moreharm than good.

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tions. In contrast, if cellular repro-duction is much more complicated,the cells’ descendants have fewer mutations.

“It looks like it’s easier to preventcancer than to cure it,” Maley says,

“and we’d like to understand the earli-est processes in carcinogenesis.”

Additional studies will furtherexplore the cellular mutations that giverise to cancer and the dynamics of theinteractions between stem cells andother cells.

John W. Pepper, Ph.D., of the Uni-versity of Arizona and the Santa FeInstitute is lead author on the study.

Maley’s co-author at Wistar is Kath-leen Sprouffske, who is also affiliatedwith the University of Pennsylvania.

The National Institutes of Health,the Pew Charitable Trusts, the Commonwealth Universal ResearchEnhancement Program of the Pennsylvania Department of Health,and the Santa Fe Institute funded the research. ❖

The more scientists learn aboutmicroRNAs—short strands of

RNA that can interfere with normalgene activity—the more obvious itbecomes how closely they are associ-ated with cancer. Scientists at Wistarand their colleagues have identified twomicroRNAs (miRNAs) that promotetumors’ deadly spread, or metastasis.One of the miRNAs may provide anearly warning of metastatic breast can-cer and the need for aggressivetreatment.

By blocking the translation oftumor suppressor genes, miRNAs havebeen shown to facilitate the develop-ment of many types of cancer. In astudy published in February in NatureCell Biology, researchers describe how

two miRNAs transformed non-invasivehuman breast cancer cells into cells thatrapidly metastasized, or spread, in cellcultures and laboratory mice.

“Of the 450 miRNAs we tested, wefound two, miR-373 and miR-520c,that induced cell migration in MCF-7cells—a line of human breast cancercells that normally does not metasta-size,” says Qihong Huang, M.D.,Ph.D., an assistant professor in Wistar’s

Molecular and Cellular OncogenesisProgram and lead author and co-corre-sponding author on the study.

Another intriguing characteristic ofthese two miRNAs is that they are notfound in normal adult cells—only intumor cells. “They are not in normaltestis, but are expressed in testicularcancer,” Huang says. “We see them inbreast cancer cells, especially metastaticcells, but not in normal breast cells.”

Wistar’s Kiranmai Gumireddy,Ph.D., is a co-lead author on the study.Additional Wistar co-authors are EllenPuré, Ph.D., Anping Li, andGuanghua Huang (now at the Univer-sity of Iowa). Co-lead author MarietteSchrier and senior author and co-corre-sponding author Reuven Agami are atthe Netherlands Cancer Institute, as areCarlos le Sage, Remco Nagel, SureshNair, and David A. Egan. Andres J.

Klein-Szanto is at Fox Chase CancerCenter. Phyllis A. Gimotty, GeorgeCoukos, and Lin Zhang are at the Uni-versity of Pennsylvania, and DionyssiosKatsaros is at the University of Turin.

The research was supported by the Breast Cancer Alliance, Pardee Foundation, V Foundation, the Commonwealth Universal ResearchEnhancement Program of the Pennsyl-vania Department of Health, the

Dutch Cancer Society, the Dr. JosefSteiner Cancer Research Foundation,the National Cancer Institute, OvarianCancer Research Fund and the Ameri-can Cancer Society. Agami wassupported by the European YoungInvestigator Award and the EMBOYoung Investigator Program. ❖

P R O G R E S S

Qihong Huang, M.D., Ph.D., studies micro-RNAs, which are implicated in many cancers.

Study Sheds Light on Body’s Cell-Making Process(continued from page 13)

Two MicroRNAs Promote Spread of Tumor Cells: MiR-373 Could Be Indicator of Breast Cancer Metastasis

METASTASIS—the developmentof additional malignant growths ata distance from a primary cancersite—is the major cause of deathin cancer patients. Wistar scien-tists are working to betterunderstand the metastatic processso that new drugs can bedesigned to stop it.

D I D YO U K N OW ?

Wistar researchers have identified a molecule that mayprovide an early warning of metastatic breast cancer.

C reating vaccines to protect peopleagainst viral diseases like AIDS,

cervical cancer, and infectious hepatitisis a delicate balancing act: if theimmune system’s response to the vac-cine is too strong, toxic side effects cankill the patient. If it’s not strongenough, the virus will spread fasterthan the immune system can kill it.

A new vaccine design strategy devel-oped by scientists at The WistarInstitute Vaccine Center could be theanswer. The secret is using a herpessimplex protein called glycoprotein Dto block a specific receptor moleculeon antigen-presenting cells, or APCs.These sentinel cells monitor the bodyfor foreign antigens—molecules thatcan stimulate an immune response—from invading viruses.

When they detect viral antigens,APCs signal the body’s immune systemto activate T cells to attack and destroycells infected with the virus. At thesame time, they also send inhibitorysignals to prevent overreaction by theimmune system. One of theseinhibitory signals is blocked by glyco-protein D from herpes virus.

In a study published in February inNature Medicine, Wistar scientistsshowed that vectors, which are vaccinedelivery systems, made by fusing theglycoprotein D with genes from targetantigens increase the immune system’sresponse to those antigens in cell cul-tures and laboratory mice. Theresearchers used antigens from HIV,the virus that causes AIDS, and fromHPV-16, a human papilloma virusthat causes cervical cancer.

Hildegund C.J. Ertl, M.D., directorof The Wistar Institute Vaccine Centerand senior author of the study, saysusing glycoprotein D to deliver anti-gens has a major advantage over other

vaccine approaches. “It allows us tolower the dose but still get a strongerimmune response,” she says.

Ertl and her colleagues are planningfuture studies to further elucidate themechanism behind the carrier protein’s

effectiveness. If studies in research ani-mals continue to be positive, they hopeto conduct human clinical studies withHIV and HPV vaccines under devel-opment at the Vaccine Center.

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Protein fromHerpes VirusServes as PotentVaccine Enhancer

W istar recently welcomed newfaculty member Ramana

Davuluri, Ph.D., as an associate pro-fessor in the Molecular and CellularOncogenesis Program. Davaluri, whoholds the Philadelphia Health CareTrust Professorship, is also an associatedirector of Wistar’s new Center forSystems and Computational Biology(see story on page 8), as well as the cen-ter’s director of computationalbiology. In addition, he serves as sci-entific director of Wistar’s CancerCenter Bioinformatics Shared Facility.

Before coming to Wistar, Davuluriwas an associate professor and head ofthe bioinformatics consulting unit inthe human cancer genetics program at

the Ohio State University’s Compre-hensive Cancer Center. He received hisdoctorate from the Indian AgriculturalStatistics Research Institute in NewDelhi and underwent postdoctoraltraining at Cold Spring Harbor Labo-ratory in New York.

Computational biology involves theuse of techniques including computerscience, applied mathematics, and sta-tistics to process, manage, and interpretcomplex data sets.

Davaluri’s research focuses on funda-mental aspects of mammalian genomicsand cancer. His current research effortsinclude the identification of gene net-works involved in promoting breast andovarian cancer. ❖

(continued on page 16)

Wistar Welcomes Computational Biologist

New faculty member Ramana Davuluri, Ph.D., right, greets a guest at the opening of Wistar’snew Center for Systems and Computational Biology. Davuluri is an associate director of thecenter, as well as director of computational biology. Looking on is Carlo C. Maley, Ph.D.

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Scientists at Wistar have collaboratedon a major advance in understand-

ing a gene regulator implicated in someof the deadliest cancers in humans. The culmination of 10 years’ work, theresearch paves the way for the develop-ment of new cancer therapies.

During much of its lifetime, theDNA that resides in each of our cellsexists in an inactive form, stored insidedensely knotted structures in the cellnucleus. There, the DNA is woundspool-like around proteins called his-tones, which bind the DNA andrestrict its activity. For a cell to activatea gene, many proteins, called transcrip-tion factors, work in concert toseparate DNA from the histones. Onefamily of transcription factors areenzymes known as HATs, or histoneacetyltransferases, which transferacetate groups onto the histones.

Wistar scientists, collaborating withresearchers at the Johns Hopkins Uni-versity School of Medicine, have madea major advance in the understandingof the structure and function of a keyHAT enzyme called p300/CBP.

Unlike most HATs, which regulatethe expression of only a few genes,p300/CBP is involved in the activationof a wide variety of genes. In addition,deviant p300/CBP activity contributesto pancreatic, colon, and lung cancer—among the deadliest cancers inhumans—as well as gastric and thyroidcancer and some leukemias. Besidespromoting tumors, p300/CBP also can suppress them.

These unusual properties have madep300/CBP one of the most studiedHAT enzymes, and a target for develop-ing new cancer drugs, says RonenMarmorstein, Ph.D., a professor in Wis-tar’s Gene Expression and RegulationProgram and a senior author and corre-sponding author on the study. Philip A.Cole, M.D., Ph.D., at Johns Hopkins isalso a senior and corresponding author.

“It’s unusual to have a HAT that’s soimplicated in cancer, and even moreunusual to have one that has bothtumor suppressor and oncoproteinactivities,” Marmorstein says.

In a report published in February inNature, the scientists detail their eluci-dation of the three-dimensionalstructure of a p300/CBP HAT domain,or segment, bound to a small moleculethat inhibits its activity. The study alsoreveals how the binding site and chemi-cal mechanism of the enzyme enable itto regulate a variety of genes.

The scientists plan to use the newinformation to develop inhibitors ofp300/CBP—research that will pave theway for the development of new cancertherapies, Marmorstein says.

Co-authors on the study are Xin Liuand Kehao Zhao, Ph.D., at Wistar andLing Wang, Paul R. Thompson andYousang Hwang of Johns Hopkins.

The research was supported bygrants from the National Institutes ofHealth; the FAMRI, Kaufman, andKeck foundations; and the Common-wealth Universal Research Enhance-ment Program of the PennsylvaniaDepartment of Health. ❖

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P R O G R E S S

Ertl is corresponding author of thestudy. Lead author is Wistar’s MarcioLasaro, Ph.D. Wistar co-authors areNia Tatsis, Ph.D., Shih-Wen Lin, JohnJ. Rux, Ph.D., E. John Wherry, Ph.D.,and Scott E. Hensley (now at theNational Institute of Allergy andInfectious Diseases). Lin is also affiliated with the University ofPennsylvania. Co-authors J. CharlesWhitbeck, Gary H. Cohen, and Roselyn J. Eisenberg are with the University of Pennsylvania.

The research was supported by theNational Institute of Allergy and Infec-tious Diseases (NIAID) and theCommonwealth Universal ResearchEnhancement Program of the Pennsyl-vania Department of Health. ❖

Protein from Herpes Virus Serves as PotentVaccine Enhancer(continued from page 15)

WITH THE EXCEPTION of cleanwater, vaccines are considered thegreatest public health advance.Prior to the vaccine developmentsof the twentieth century, the following occurred annually in the United States alone:

◆ 10,000 children were paralyzed by polio.

◆ 20,000 children were born withbirth defects from rubella, or German measles. (A Wistar vaccineeradicated this disease in theUnited States by 2005).

◆ 15,000 children suffered braindamage from Haemophilus influenzae type b (Hib).

◆ 4 million measles infectionsresulted in 3,000 deaths.

◆ Thousands of infants were killedby Pertussis, or whooping cough.

◆ Diphtheria was a common cause of death in school children.

Scientists Solve Structure of GeneRegulator that Plays Key Role in Cancer

Ronen Marmorstein, Ph.D., and his colleagueshave revealed the structure and function ofan enzyme implicated in pancreatic, colon,and lung cancer.

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NEW GRANTAWARDS*

The Wistar Institute and itsscientists continue to competesuccessfully for grants to supportresearch and programs. Below is asampling of recent awards.

P R I V A T E G R A N T S

THE AMERICAN CANCER SOCIETYNadia Dahmane, Ph.D., brain cancerresearch, four-year grant, $600,000.

THE EDWARD MALLINCKRODT, JR.FOUNDATIONSusan Janicki, Ph.D., live-cell imaging ofchromatin, the material of chromosomes,$60,000.

THE MCLEAN CONTRIBUTIONSHIPThe Wistar Institute, laboratoryequipment, $60,000.

W.W. SMITH CHARITABLE TRUSTNadia Dahmane, Ph.D., research onbrain development and brain tumors,$105,000.

G O V E R N M E N T G R A N T S

THE NATIONAL CANCER INSTITUTEAnthony Capobianco, Ph.D., the roleof cell-to-cell signaling in tumor devel-opment, five-year grant, $1.8 million.

NATIONAL INSTITUTE OF AGINGShelley L. Berger, Ph.D., regulation ofaging in a yeast model, five-year grant,$8.9 million.

NATIONAL INSTITUTE OF ALLERGYAND INFECTIOUS DISEASEHui Hu, Ph.D., gene expression andimmune cell development, two-yeargrant, $270,000.

NATIONAL CENTER FOR RESEARCHRESOURCESLouise C. Showe, Ph.D., equipment tosupport genomics research, $404,650.

*List reflects grants of $50,000 and over.

GRANT HIGHLIGHTS

Predicting TumorProgression

Carlo C. Maley, Ph.D., an assistantprofessor in Wistar’s Molecular and

Cellular Oncogenesis Program, is the firstrecipient of the Landon Foundation-AACRINNOVATOR award for cancer prevention.The $100,000, two-year grant from theLandon Foundation and the AmericanAssociation for Cancer Research was createdto fund promising early-career cancerresearchers. Maley’s project will measuregenetic diversity in tumor cells as a way topredict whether a tumor is likely to progressand respond to preventive therapy. Maley wasrecognized for the innovative, collaborative,and multidisciplinary nature of his work.

Exploring Enzymes andGene Expression

Susan M. Janicki, Ph.D., an assistantprofessor in Wistar’s Gene Expression and

Regulation Program, has received the BasilO’Connor Starter Scholar Research Awardfrom the March of Dimes Foundation.Janicki will receive a two-year grant of$150,000 to further her work exploringhow certain enzymes regulate gene expression.The award supports young scientists embark-ing on their independent research careers.

Optimizing T-CellResponse

E.John Wherry, Ph.D., an assistantprofessor in Wistar’s Immunology

Program, has received a $168,000, three-yeargrant from the Dana Foundation to study theoptimization of T-cell responses in hopes ofpreventing chronic viral infections. UnderWherry’s direction, W. Nicholas Haining,M.B., B.Ch., of the Dana-Farber CancerInstitute and Georg M. Lauer, M.D., Ph.D.,of Massachusetts General Hospital willcollaborate on the project.

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B R I E F I N G SN e w s , h o n o r s , a n d e v e n t s

‘Date with a Plate’Event BenefitsMelanoma Research

F rom the Heart, a Philadelphia-based philanthropic group that

supports local organizations, held a“Date with a Plate” fundraiser in Mayto support melanoma research. BothWistar and the Noreen O’Neil Foun-dation for Melanoma Research werebeneficiaries of the effort.

The event featured a walking dinnertour through unique table set-ups. Ondisplay were one-of-a-kind place set-tings created by local designers, eventplanners, florists, and private collectors.The event, held in Philadelphia, drewmore than 500 visitors. ❖

Event sponsors included Mr. and Mrs.Richard Berman and family, Mr. andMrs. William Gabrose and family, Mr.and Mrs. Bruce Goodman and family,the Korman Family Foundation (Mr.and Mrs. Larry Altman, Mr. and Mrs.Marc Feldman, and Mr. and Mrs.Michael Schurr), Mr. and Mrs. GaryLassin and family, Mr. and Mrs. SeymoreRubin, Mr. and Mrs. Leonard Abramson,and the Noreen O’Neill Foundation forMelanoma Research.

“The Art of Style,” designed by NeimanMarcus, was among the unique table set-tings displayed at “Date with a Plate,” afundraiser hosted by From the Heart tobenefit melanoma research.

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Institute Welcomes Three New Board Members

W istar recently welcomed three new members to itsboard of trustees: Dani Paul Bolognesi, Ph.D.,

George J. Vergis, Ph.D., and Dan W. Matthias.Bolognesi is the CEO and chairman of B3Bio Inc.,

a new biotech venture in the field of RNA therapeutics.He participated in the discovery in the mid-1980sof AZT, considered the first effective AIDS drug, and co-founded the biopharmaceutical company Trimeris, whichalso has focused on the development of anti-viral drugs.Bolognesi is the James B. Duke Professor emeritus in theDepartment of Surgery at Duke University Medical Center.He earned his doctorate from Duke University.

Vergis is president and CEO of Neose TechnologiesInc., a clinical-stage biopharmaceutical company inHorsham, Pa., that focuses on the development oftherapeutic proteins. He is the former vice president ofnew product development and commercialization ofBASF/Knoll Pharmaceutical Company and associatedirector of medical and scientific affairs for the Warner-Lambert/Parke-Davis division of Pfizer. Vergis also workedpreviously as a clinical research scientist for AmericanHome Products: Wyeth-Ayerst Laboratories. He earned hisdoctorate from the Pennsylvania State University.

Matthias is the chairman, CEO, and co-founder ofMothers Work Inc., a company that manufactures and sellsmaternity apparel through 1,600 stores in the United Statesand Canada. He also served as manager of ZaBeCor Phar-maceutical Company, LLC, a start-up company involved inthe development of an asthma-control drug. Matthiasserved as a founding director of Zilog, Inc., an early micro-computer company, and as founder and president of Qyx,where he developed the first editing electronic typewriter.He received an MBA from Harvard Business School. ❖

Dani Paul Bolognesi, Ph.D.

George J. Vergis, Ph.D.

Dan W. Matthias

Wistar recently formed the WistarInstitute Leadership Council,

which held its inaugural meeting inDecember. The group, comprised ofcommunity leaders with an interest inWistar and the region’s life sciencesindustry, was created to help the Insti-tute achieve its goal of improving globalhealth through research.

“The Leadership Council providesan excellent opportunity for some ofour region’s bright, energetic leaders toget involved with Wistar,” says council

co-chair Rick Horowitz, “and use theirskills to raise the profile of this world-class institution.”

Members, who act as ambassadorsfor the Institute, help spread the wordabout groundbreaking work at Wistar.They also help to forge new relation-ships with individuals, foundations,and corporations interested in support-ing Wistar’s research. In addition, theyconfer with board members and otherinstitutional leaders in planning for theInstitute’s future. ❖

Wistar Establishes Leadership Council

Wistar recently received theDelaware Valley Innovation

Network’s first Innovation InvestmentGrant to support its Biomedical Tech-nician Training Program. Thetwo-year “BTT Program” providesCommunity College of Philadelphiastudents with instruction and hands-on experience in preparing them forcareers as biomedical technicians. The

grant of $89,619 will partially fundthe program for one year.

Wistar partners with Temple Uni-versity’s Fels Institute, as well asvarious industry labs, to provide labo-ratory training for the students. Theinitiative continues to expand; thisyear, the University of the Sciences inPhiladelphia also became a trainingaffiliate.

“We see tremendous value in sup-porting a pipeline of talented studentsfrom the Community College ofPhiladelphia through real work experi-ence at The Wistar Institute, variouslaboratories and the Fels Institute,” saysHelen Groft, project director of DVIN.“These students will be able to jump-start their careers, and employers willhave experienced candidates to hire.”The award will support Wistar in pro-viding training for 17 first- andsecond-year students.

The DVIN Innovation InvestmentFund supports training and capacity-building programs for the DelawareValley’s life science workforce.

Additional funding for the BTTProgram is provided by the NationalCancer Institute’s CURE program andthe Hassel Foundation. ❖

Technician Training Program Receives Funding

Oni Kolawole Olaiya, a student at Commu-nity College of Philadelphia, works in thelab of Wistar researcher Harold C. Riethman,Ph.D., as part of Wistar’s Biomedical Techni-cian Training Program.

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Pioneering biologist Ruth Patrick, Ph.D., whohas served on Wistar’s board of trustees formore than three decades, was honored andnamed a trustee emerita of the Institutewhen the board met in June. Celebratingwith her, from left to right, are Wistar president and CEO Russel E. Kaufman, M.D.;William Yancey Brown, Ph.D., president andCEO of the Academy of Natural Sciences; andBrian H. Dovey, chair of Wistar’s board oftrustees. Patrick is honorary chair of theboard of trustees of the Academy of NaturalSciences, where she has worked since the1930s. Her many awards include the NationalMedal of Science, America’s highest decora-tion for scientific achievement.

Ruth Patrick Honored

Wistar hosted the 33rd annualNikon Small World exhibition

in January and February. The travelingexhibit featured the winners of theNikon Small World competition forphotos taken through the microscope.The 20 winning images, which wereselected for originality, informationalcontent, technical proficiency, andvisual impact, were on display at Wis-tar for eight weeks.

The Institute invited Philadelphia-area science teachers and their studentsto tour the exhibit, guided by James E.Hayden, manager of Wistar’s micro-scopy facility and a previous winner and

judge of the competition. Almost 200students visited the exhibit at Wistar.

“Images like those on display in theSmall World exhibit are helping tostimulate and inspire a new genera-tion,” says Hayden, who is coordinatorof the exhibition at Wistar. “At Wistar,we hope to play a part in motivatingyoung minds as we advance the fron-tiers of biomedical science.”

The tours included an overview ofthe role that microscopes play inresearch at Wistar and an explanationof how select photographs were made,as well as the biological significance oftheir subjects. ❖

Wistar Hosts Nikon ‘Small World’ Exhibit

A photo of a Papaver subporforme (cornpoppies) flower bud by Shamuel Silbermanof Ramat Gan, Israel, captured ninth placein the Nikon Small World contest for photostaken through the microscope. Wistar hostedan exhibit of winning photos this winter.

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Wistar honored winners of its highschool biology essay contest and

recipients of its summer fellowships forhigh school students at a ceremony inJune. The event recognized essay con-test winners and summer fellows forboth 2007 and 2008. The contest andfellowships aim to promote scienceeducation and encourage the pursuit of science careers by Philadelphia-areastudents.

The Honorable James R. Roebuck,Pennsylvania Representative for the188th District, presided over a cere-mony at the Institute at which thefirst-place winners of the essay contestread their essays. The 2008 winner,Michael Gorokhovsky, a sophomore atGeorge Washington High School, read“HIV/AIDS,” while 2007 winnerDante Galzarano, a junior at Julia R.Masterman High School, read“Genetic Research on Autism.” Thefirst-place winners each received $500,and their schools each received $500for laboratory and teaching supplies.

Additional 2008 winners are AlbaBaze and Elizabeth Massele of Julia R.Masterman High School for secondplace and Gabrielle Sammartino of theGirard Music Academy and SandyWeng of Central High School for thirdplace. Additional 2007 winners wereAllegra Black of Roxborough HighSchool for second place and GeorgiaKarmee of Motivation High School forthird place. The contest is supportedby the Hassel Foundation.

The 2008 Wistar Institute SummerFellows are Eva Bugos, Julia R. Master-man High School; Jessica Grier,George Washington Carver HighSchool of Engineering & Science; EvaJiang, Northeast High School; GeorgiaKarmee, Motivation High School;Thomas Madej, Saint Joseph Prepara-tory School; Yuwen Wang, StrathHaven High School; and Ross D. Wistar, Germantown Friends School.

The 2007 summer fellows wereManjima Dhar, Julia R. MastermanHigh School; Marcelina Garcia andEsteban Sanlate, Marianna BracettiAcademy Charter; Eva Jiang and KhailVan, Northeast High School; GeorgiaKarmee, Motivation High School;Fatima Mohammed, George Washing-ton Carver; and Richard Stark, LowerMerion High School.

The fellowship program allows students to become directly involved in biological research. It is supported by the Hassel Foundation and Glaxo-Smith Kline. ❖

Golfers prepare to tackle the course at the 13th annual Albert R. Taxin Golf Classic, held in June at Green Valley Country Club in Lafayette Hill, Pa. The event raised more than$120,000 for brain tumor research at Wistar. Pictured, from left, are Wistar president andCEO Russel E. Kaufman, M.D.; event founder and honorary co-chair Doris Taxin; JoAnne Bagnell; and former NFL coach Dick Vermeil. Tournament highlights included a hole-in-oneby Bob Alper, who won a new Lexus automobile for his feat, and an appearance by the“Phillies Fanatic” team mascot. This year’s event, co-chaired by Fran Tobin and Evie andRon Krancer, also featured a bridge tournament. Since its inception, the tournament hasraised $1.25 million to support Wistar’s Albert R. Taxin Brain Tumor Research Center. AlbertR. Taxin, president of Old Original Bookbinders restaurant in Philadelphia, died of a braintumor at 53.

Golf Tournament Supports Brain Tumor Research

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Michael Gorokhovsky, a sophomore at GeorgeWashington High School, is presented withan award by the Honorable James R. Roebuck, Pennsylvania Representative forthe 188th District, for winning Wistar’s 2008 high school biology essay contest.

Wistar Names High School EssayContest Winners, Summer Fellows

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Award-winning science writer GaryTaubes discussed his new book,

Good Calories, Bad Calories: Challeng-ing the Conventional Wisdom on Diet,Weight Control, and Disease, in May aspart of Wistar’s Authors Series.

In his book, Taubes challenges thewidely held belief that a low-fat diet isthe best approach to losing weight andavoiding disease. Instead, he advocatescarbohydrate restriction, arguing thatthe key to good health is the kind ofcalories people take in, not the number.

Taubes argues that there is nocompelling scientific evidence that sat-urated fat and cholesterol cause heart

disease. Further, he maintains that theonly healthy way to lose weight is toeat fewer carbohydrates—particularlyrefined carbohydrates such as flour,sugar, and rice.

In his talk at Wistar, Taubes focusedon the growing obesity epidemic anddisputed the popular belief that obesityresults from eating too much and exer-cising too little. Instead, he exploredthe role of carbohydrates, and theireffect on insulin, in weight gain.

Taubes is a correspondent for Sci-ence magazine. He has also writtenarticles for Discover, New Scientist, andThe New York Times magazine. ❖

Wistar Hosts Author of Book on Diet, Health

Author Gary Taubes signs copies of his bookafter speaking at the Institute in May aspart of Wistar’s Author Series.

SPECIAL LECTURESThe Wistar Institute recently hostedthe following lectures by distinguishedguest researchers.

JONATHAN LAX MEMORIAL LECTUREJune 12, 2008Co-sponsored by the AIDS service organizationPhiladelphia FIGHT and presented in memory ofJonathan Lax, an activist and former FIGHTpresident, who died of AIDS in 1996.Speaker: Lawrence Corey, M.D., FredHutchinson Cancer Research Center, Universityof Washington, SeattleTopic: “HIV Vaccine Development Post-STEP”

VINCENT J. CRISTOFALO LECTUREDecember 5, 2007Established by The Wistar Institute in honor ofWistar professor emeritus Vincent J. Cristofalo,Ph.D., an internationally recognized expert onaging, who died in 2006.Speaker: Bruce Stillman, Ph.D., FRS,Cold Spring Harbor Laboratory, Cold SpringHarbor, N.Y.Topic: “Control of the Chromosome Cycle inHuman Cells by the Origin RecognitionComplex”

GEORGE KHOURY MEMORIAL LECTUREOctober 16, 2007Founded by the Hassel Foundation in memoryof George Khoury, M.D., former head of theLaboratory of Molecular Virology at the NationalCancer Institute.Speaker: Douglas R. Lowy, M.D., Laboratory ofCellular Oncology, National Cancer Institute,Bethesda, MDTopic: “The Prevention of Cervical Cancer byHPV Vaccination and Other Interventions”

Wistar recently launchedthe Wistar Family

Fund for Cancer Research toprovide support for cancerresearch pilot projects at theInstitute. Created with a$100,000 gift from C.Cresson Wistar and his fam-ily, the fund was establishedin honor of Cresson’s wife,Ailsa Wistar, who died last year ofbreast cancer.

In making the initial gift, Cressonsays he hoped to establish a vehicle forgiving that is open to all Wistar familymembers who share an interest in sup-porting cancer research. Gifts to the

fund will become part of itsendowed principal; only thefund’s earnings will beapplied toward research. Theearnings will support novelpilot projects that might oth-erwise go unfunded.

Ailsa Wistar, a longtimefriend of the Institute, servedas the first chairwoman of the

Friends of The Wistar Institute, whichhelped provide funding for Wistarresearch for more than 30 years.

For more information, contact PeterCorrado, Wistar’s director of institu-tional development, at (215) 898-3930or corrado@wistar.org. ❖

Wistar Family Fund Established

A study co-authored by a formerWistar researcher while he

worked at the Institute was selected asone of the top scientific breakthroughsof 2007 by Science magazine. Theresearch by Wolfgang Weninger,M.D., a former Wistar assistant pro-fessor, illuminated how immune cellsspecialize for immediate or long-term

protection. When a pathogen attacks,some CD8 T cells become short-lived“soldiers,” while others morph intomemory cells that linger for decades incase the same pathogen attacks again.

The research might eventually beused to create more effective vaccines.The study was published in Science inMarch 2007. ❖

Study Co-Authored by Wistar ResearcherNamed Top Scientific Breakthrough

Ailsa Wistar

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F or Wistar associate professor Harold C. Riethman,Ph.D., an interest in the natural world came early.“I grew up on a farm in Ohio, surrounded by

plants and animals,” he says. “I wanted to understandhow living things worked.”

That interest continued through high school and col-lege at the University of Cincinnati, where his experiencein a biology lab confirmed science as his future career.“The idea that we couldexplore the buildingblocks of life and figureout how they work wasreally exciting,” he says.

Riethman joined Wis-tar in 1990 and hasfocused on studies oftelomeres, the tips of chromosomes. His lab played anessential role in extending the human genome sequenceto include the telomere regions, a significant milestone inthe Human Genome Project.

Today, Riethman continues his investigations oftelomeres, which are involved both in aging processesand cancer development. (See story on page 4.) Heremains just as excited about going into his lab eachmorning as he did when he was a student.

“The open-endedness and the adventure of findingsomething new is really appealing to me,” he says, “as iscontributing to a larger effort in the scientific commu-nity to improve our quality of life. My wife has breastcancer, and my mother has Alzheimer’s disease. So I’mkeenly aware of the importance of research to patients.”

Since completing his training, Riethman has spent hisentire research career at Wistar—and he says it’s been a

great place to do his work. “You’re given agreat deal of freedom to pursue areas that youfind interesting and exciting,” he says. “Andthe Institute’s small size allows you to get toknow the other scientists and broaden yourresearch.”

Outside the lab, Riethman has an activefamily life that keeps him busy. He and hiswife have five children, and his evenings andweekends are spent helping with homework,attending sports events and other school activi-ties, and just having time together as a family.“They’re the focus of my life,” he says. ❖

MEETHAROLD C. RIETHMAN, PH.D.

“I wantedto understandhow livingthings worked.”

B e h i n dt h e S c i e n c e

✫ YEARS AT WISTAR: 18

✫ CAREER HIGHLIGHT: Contributingto the human genome sequence

✫ TV SHOW HE NEVER MISSES:“The Colbert Report”

✫ BOOK HE RETURNS TO AGAINAND AGAIN: Huckleberry Finn

✫ FAVORITE SPORTS TEAM: The Sixers

✫ ON WEEKENDS YOU’LL FIND HIM:With his family, at baseball or soccergames, taking long walks with hisdog, hiking or camping, attending aUnitarian church.

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Photo by Tommy Leonardi

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A W I S TA R S C I E N T I S T A N S W E R S Q U E S T I O N S O N A G I N G

Q:Why do you think people are so fascinated with the topic of

aging and the prospect of developinganti-aging therapies?

A: People don’t like to grow old, and theidea of living longer and doing more is

attractive. But I think a more important con-cern is age-associated diseases. My workfocuses on extending “healthspan”—theamount of time people can be healthy.

Q: It has been reported that drinkingred wine can help you stay young.

Is that true?

A: Resveratrol, a component of red wine,has gotten a lot of press as being an

activator of sirtuins, which are associated withincreased lifespan in some organisms. But aperson would have to drink about two casesof wine a day to get an effective dose.

Q:Do you think we’ll see anti-agingdrugs in the next 25 years?

A: I think it’s likely we’ll have new med-ications that can slow the aging

process and inhibit age-associated diseaseslike cancer, type-II diabetes, obesity, andAlzheimer’s.

Q:At the end of the day, what do you hope to accomplish with

your research?

A: My team and I hope to identify small-molecule compounds with the potential

to be developed as drugs that can treat age-associated diseases and extend the amount oftime that people can be active and healthy.

Wistar professor RonenMarmorstein, Ph.D.,conducts research onaging and age-relateddiseases, focusing onenzymes called sirtuins.(See story on Wistar’saging-related researchon page 4.) Here, Marmorstein answersquestions about theimplications of thisresearch.

Q&A

Tommy Leonardi