Of Aging: Wistar Researchers Shed New Light on Getting Old

ocus F Summer 2008

The Science of Aging: Wistar researchers shed new light on getting old

Wistar Launches High-Tech Research Center

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

Wistar: Research at the Frontier

he Wistar Institute has a pioneering tradition. TCaspar Wistar, for whom the Institute is named, was a forward-thinking 18th-century physician who wrote the first American anatomy textbook and was an early proponent of vaccination. His great-nephew, Insti- tute founder Isaac J. Wistar, was a pioneer in his own right who trekked west by wagon train to spend winters as a trapper in the wilds of California. Isaac Wistar founded The Wistar Institute in 1892 with the stated intention of creating a center for “new

and original research” in the biological and medical sci- Peter Olson ences. In the ensuing century, Wistar lived up to that charge, and it continues to do so today. massive amounts of data and pinpoint disease-causing Wistar’s first scientific advisory board, convened in genes and proteins. The center supports work like that of 1905, declared research as the Institute’s principal objec- David W. Speicher, Ph.D., who is developing blood tests tive and specified three areas of focus: comparative for the early detection of the deadliest cancers. anatomy, embryology, and neurology—fields that repre- Likewise, the Institute’s new chemical screening facil- sented the leading edge of science and medicine at the ity, set to launch this fall, will allow investigators to turn of the century. screen vast numbers of compounds and identify those The Institute’s research focus has evolved over the years. that are the best candidates for development as drugs. Today, Wistar is best known for cancer research and The facility will enhance Wistar’s ability to do “transla- vaccine development. What hasn’t changed is that Wistar tional” research, transforming its basic research into remains at the forefront of biomedical research. therapies for patients. In this issue of Focus, you’ll read about how Wistar These resources will make the most of our scientists’ scientists are contributing to new knowledge about the creative ideas and dedicated efforts and help to ensure aging process and finding new hope for aging-related that Wistar stays where it belongs: at the frontier of sci- diseases such as cancer, Alzheimer’s, and diabetes. These entific knowledge, seeking the answers that will save lives advances build on Wistar’s longstanding legacy of and improve human health worldwide. achievement in aging research. You’ll also learn how Wistar is embracing emerging technologies that greatly expand our researchers’ capabilities. Our Center for Systems and Computational Biology, which opened its doors this spring, provides powerful, Russel E. Kaufman, M.D. cutting-edge instruments that help investigators analyze President and CEO

is published two times per year for donors, friends, faculty, and staff of The Wistar Institute is an equal opportunity/ Focus affirmative action employer. It is the policy of The Wistar Institute by the Office of Public Relations. To contact the The Wistar Institute to provide equal employ- editor, phone (215) 898-3943 or e-mail [email protected]. For general inquiries, contact ment opportunities to all individuals regardless The Wistar Institute at (215) 898-3700. Send address changes to: Development Office, of race, color, creed, religion, national origin, ancestry, sex, age, veteran status, disability, The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104-4265. sexual orientation, or gender identity for all terms and conditions of employment. ABBEY J. PORTER KARLYN ROSEN AIRES STOCK PHOTOGRAPHY Editor and Acting Director Designer Cover Image: of Public Relations Shuji Kobayashi/Getty Images JAMES E. HAYDEN LEE CHRISTINE SHURTZ FREDERICK S. KEENEY Pages 3 (bottom) and 4: Public Relations Assistant Photographers Frank Schwere/Getty Images

3601 SPRUCE S TREET • P HILADELPHIA, PA 19104-4265 • 215-898-3700 www.wistar.org

The Wistar Institute is a National Cancer Institute-designated Cancer Center. Focus CONTENTS : SUMMER 2008

New Center Opens Door to Future of Research page 8

4 The Science of Aging 12 Screening Facility to Open 18 Briefings Wistar researchers explore what A new facility will help Wistar News, honors, and events. happens when we age—and how to scientists identify promising combat the effects of getting old. drug candidates. 22 Behind the Science Wistar researcher Harold Riethman 8 Research Center Launches 13 Progress grew up wanting to understand how A hi-tech new center helps to keep The latest advances from Wistar labs. living things worked. the Institute at the forefront of biomedical research. 17 New Grants 24 Q&A Highlights of recent funding. A Wistar scientist answers 10 Federal Funding Woes questions on aging. Declining support from the National Institutes of Health means it’s harder than ever to get federal grants, and Wistar scientists are among Summer 2008 Summer those feeling the pinch. Studying : 11 Profile of Support How We Age Wistar champion Fran Tobin page 4 FOCUS works to bolster the Institute’s 3 brain tumor research. The Science of Aging Wistar researchers investigate what happens when we get old

BY THOMAS W. DURSO Summer 2008 Summer : FOCUS 4 mong life’s inevitabilities, mosomes that are added in developing telomeres reach a critically short length, aging is as absolute as embryos and in stem cells by an they trigger cells to stop dividing and they come, but no one enzyme called telomerase. In normal either enter a permanent arrested state has yet determined adult cells, telomerase is switched off, known as senescence, or commit cellu- why: That is, what halting the lengthening of telomere lar suicide. In both instances, aging exactly happens at strands and ending cell division. Inap- results. Riethman is researching DNA the cellular level propriate activation of telomerase can sequences located directly adjacent to that not only slows us down and even- lead to uncontrolled cell growth—and telomeres. These so-called subtelomeric Atually wears us out, but also leaves us cancer. sequences vary widely from person to more susceptible to diseases ranging Exploring these phenomena today person and seem to regulate the lengths from cancer to Alzheimer’s and at Wistar are Emmanuel Skordalakes, of their adjacent telomere sequences, a influenza? fact that could have Biomedical research significant biological into the causes and treat- “YOU HAVE TO THINK ABOUT consequences. ment of disease has helped the whole organism when you think “It only takes a sin- to extend life spans, and gle telomere or a very scientists at Wistar have about aging, because none of these small number of played important roles in telomeres to trigger those efforts. Less visible changes happen in isolation.” senescence,” says but equally significant, Riethman. “Certain Wistar research into the mechanisms of Ph.D., an assistant professor in the DNA segments may be able to predict aging has given investigators new leads Gene Expression and Regulation Pro- telomere length, which would in turn to pursue in the quest to extend the gram, and Harold C. Riethman, predict susceptibility to telomere- golden years and infuse them with a Ph.D., an associate professor in the related diseases—basically, aging-related greater quality of life. Molecular and Cellular Oncogenesis diseases, including cancer.” “The physiological changes with age Program. continued on page 6 are incredibly interesting,” says E. John Last year, Skordalakes and his team Wherry, Ph.D., an assistant professor deciphered the three-dimensional in Wistar’s Immunology Program. structure of an important region of AT A GLANCE “You have to think about the whole telomerase. He hopes this will lead organism when you think about aging, to the development of drugs to deac- ◗ because none of these changes happen tivate the enzyme and stop tumor THE MECHANICS OF AGING in isolation.” growth or, more pertinent to aging appear to play a role in numer- research, to activate it under con- ous diseases, including cancer, Building on a legacy trolled conditions to allow some cells influenza, and Alzheimer’s. The legacy of Wistar’s aging-related to begin dividing again, resulting in ◗ WISTAR RESEARCHERS are work extends back to the legendary healthier, younger-looking tissue that studying aging from numerous Leonard Hayflick, Ph.D., a former stays alive longer. and diverse angles, from DNA Wistar researcher who more than 40 “Telomerase, if it’s overactivated, replication to protein activa- years ago demonstrated that normal causes cancer, so it has to be a very tion to immunological human cell division ceases after about fine balance,” Skordalakes says. “We pathways. 50 splits. Discovery of what became believe that if we can decode the ◗ known as the Hayflick limit was three-dimensional structure of the WISTAR’S INFLUENCE in aging groundbreaking, providing both a refu- entire enzyme, we will be able to research extends back to the tation of existing theories of cell identify drugs that would both com- 1960s, when Wistar researcher division and the basis for a good deal bat cancer and activate the enzyme Leonard Hayflick, Ph.D., dis- covered that human cells in of modern cancer research. for the regeneration of tissue.” 2008 Summer : Scientists later tied the Hayflick Riethman’s focus is on under- culture replicate about 50 limit to the shortening of telomeres, standing the mechanisms of times before dying. small bits of DNA at the ends of chro- telomere loss and lengthening. Once FOCUS 5 “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?”

By gaining a more complete under- An anti-aging enzyme? and Regulation Program, are collabo- standing of subtelomeric sequences, he Elsewhere at the Institute, Ronen rating on research into a family of adds, scientists could detect early evi- Marmorstein, Ph.D., a professor in the enzymes called sirtuins. dence of telomere fusion, a signal of Gene Expression and Regulation Pro- Increased levels of sirtuins coincide cancer development, allowing them to gram, and Shelley L. Berger, Ph.D., the with a marked increase in lifespan for diagnose and treat cancer far sooner Hilary Koprowski Professor at Wistar flies, yeast, and worms. It isn’t clear than is currently possible. and a professor in the Gene Expression 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. Marmorstein’s team has determined the structure of a sirtuin called Sir2 and is imaging it in three-dimensional detail in hopes of figuring out how the protein works and identifying novel small-molecule compounds that might regulate it. “We’ve succeeded in identifying small-molecule regulators,” he reports. “In a rational way, we can now look at the molecules that bind the sirtuins and say, aha, we need to modify the molecules here to make them more effective. Then we can go ahead and prepare these modified molecules to make specific regulators of the sirtuin proteins.” Berger believes proteins that orga- nize each cell’s lengthy strand of DNA and pack it into the nucleus undergo epigenetic changes—inherited changes that don’t alter DNA sequence—that are related to aging. Using yeast molecules as a model, she is researching how Sir2 affects that process, possibly by becoming deactivated over time,

Summer 2008 Summer Wistar professors Shelley L. Berger, Ph.D., : and Ronen Marmorstein, Ph.D., are collaborating on research that aims to identify potential treatments for aging- FOCUS

Tommy Leonardi Tommy related diseases. 6 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. Photo Insolite Realite & V. Gremet / Photo Researchers, Inc. / Photo Researchers, Gremet Photo Insolite Realite & V.

allowing typically tightly wound DNA age. He notes that as people age, they fications that bypass the pathways that strands to start opening up, turning become less responsive to vaccines, so are ineffective,” he says. “T cells in old wrong genes on and causing cellular influenza and other viral illnesses, as mice might be subject to inhibitions— replication, which usually happens in a well as bacterial infections, show up they might have a pathway operating very regulated way, to go awry. more often. In addition, it takes longer that restrains them, or they might lack The scientists hope their work will for the elderly to bounce back from a pathway that should activate them. lead to the development of drugs that such illnesses, and their overall health is Either way, you should be able to regulate Sir2. decreased even after they have recovered. design a vaccine that supplements “Sir2 is a very important molecule Because T cells play an important what they’re missing or overcomes the to target for drug development,” role in the immune system’s response to inhibitory pathway that they’re Berger says. “As long as it remains intercellular infections, Wherry is trying expressing.” active, in principle the genome would to understand how their mechanisms His and the other scientists’ efforts stay tightly packed, and we wouldn’t change over time, in hopes of eventu- are helping to elucidate a mysterious get these wrong genes turned on. ally designing better vaccines for such process. “The direction of our work is to illnesses as flu, West Nile virus, and “It’s a phenomenally intriguing ques- investigate the range of all of the mech- herpes. The more robust response of tion: Why is there aging?” says Berger. anisms that regulate our genome younger T cells to immunization—and “Not just mechanistically, but evolu- epigenetically. We’re interested in the weaker response of older cells— tionarily speaking, why don’t organisms whether they are altered as we age so have given him some leads on live much longer or never die?” that we can possibly find new enzymes differences in immunological pathways. Science may never discover the 2008 Summer : to target for drug development.” “If we can understand which path- answer to that question, but thanks to Immunologist John Wherry studies ways control the failure to respond, we Wistar researchers, it is getting more how immunity to viruses changes with can design a vaccine with some modi- direction on where to look. ❖ FOCUS 7 FACILITY SUPPORTS NEW APPROACH TO RESEARCH Wistar Launches Center for Systems and Computational Biology

BY ABBEY J. PORTER

istar took a step into all the genes or proteins involved in a the future of biomed- particular function. ical research when it This approach depends more on opened its Center for technology and computation, which WSystems and Computational Biology in Wistar’s new center provides. The facil- March. The center, which includes ity will eventually provide computing high-powered computers and techno- and data storage capacity up to 100 logically advanced instruments, will times greater than the Institute’s previ- support Wistar scientists in developing ecule, or small group of molecules, ous capacity. The center’s computational new tests for the early diagnosis of can- sometimes throughout their entire resources support research efforts across cers and other diseases, as well as new careers. Now, there is greater emphasis the Institute. treatments. on systems biology, which focuses on The center is particularly valuable in The center’s technology allows sci- the large-scale analysis of complex bio- bolstering Wistar’s programs in genomics entists to produce and process vast logical systems and takes a more and proteomics—the study of genes amounts of data at an unprecedented open-ended approach to research. and proteins, respectively. The new rate—an ability crucial for today’s Instead of exhaustively studying the facility’s technologically advanced researcher, says Wistar president and function of one gene, for example, a equipment includes a gene sequencer CEO Russel E. Kaufman, M.D. systems biologist might seek to identity that can rapidly sequence an entire “Investigators used to ask narrowly focused questions and get very spe- TERMS DEFINED cific answers,” Kaufman says. “What we do now is ask a very big question, SYSTEMS BIOLOGY is a relatively new field of study that focuses on the large- cast a broad net, collect lots of data, scale analysis of complex biological systems. and sort it out with the computer. COMPUTATIONAL BIOLOGY uses techniques including computer science, applied Many people call it ‘discovery sci- mathematics, and statistics to process, manage, and interpret complex data sets. Summer 2008 Summer ence.’ You’re making discoveries rather : than following a hypothesis.” THE CENTER FOR SYSTEMS AND COMPUTATIONAL BIOLOGY allows Wistar scientists Historically, researchers have to produce and process vast amounts of data at an unprecedented rate, further- FOCUS tended to focus on a single gene, mol- ing their understanding of disease biology.

8 Photos by Scott H. Spitzer Right: John J. Rux, Ph.D., head of the bioinformatics facility at Wistar, discusses an image of a molecular structure on display in Wistar’s new Center for Systems and Computational Biology. Below: Wistar supporter Leroy E. Kean, right, takes in the center’s conference room with professor Frank J. Rauscher III, Ph.D. Opposite below left: Center director David W. Speicher, Ph.D., addresses attendees at the facility’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, perform the ribbon-cutting that officially launched the center.

genome, helping researchers to identify Advances in technology have medical research, as far forward as we genetic changes that play important enabled scientists to generate ever- can see,” Kaufman says. roles in the development of cancer, larger and more complex data sets, In addition to Speicher, the center’s HIV/AIDS, and cardiovascular disease. Speicher notes, and the center provides leadership includes Louise C. Showe, Center director David W. Speicher, the tools to analyze that data at a level Ph.D., associate director and director Ph.D., relies on the center’s computer previously unheard of. “It’s highly of genomics; and recent Wistar recruit resources, analytical tools, and faculty enabling,” he says. “With these Ramana V. Davuluri, Ph.D., associate expertise to analyze complex protein resources, we will accomplish things we director and director of computational data. He and his team are identifying couldn’t even conceive of doing a cou- biology. ❖ protein “biomarkers” shed by cancers ple of years ago.” into the blood in hopes of soon devel- By advancing Wistar’s work in sys- The Center for Systems and Compu- oping blood tests that could detect tems biology, the center supports a top tational Biology is supported by a cancer early. His team studies the five priority of Wistar’s strategic plan and grant from the Philadelphia Health Care Trust. Additional funding is tumor types responsible for most can- helps the Institute stay at the forefront provided by a Keystone Innovation cer deaths: lung, colon, ovarian, of scientific investigation. “This is Starter Kit grant from the Common- prostate, and pancreatic. going to be the leading edge of bio- wealth of Pennsylvania. Summer 2008 Summer : FOCUS 9 The Federal Funding Crunch: Scientists Feel Effect of Declining Support

BY THOMAS W. DURSO

iomedical research relies Challenging Times for Researchers heavily on financial support from the U.S. government, and Wistar is no exception. In 2007, OVERALL 32% federal grants supplied SUCCESS RATE FOR Bhalf of the Institute’s income. But five NIH R01* PROPOSALS 24% straight years of flat funding of the SUCCESS RATE ON National Institutes of Health— 29% Wistar’s primary research sponsor— FIRST SUBMISSION OF GRANT APPLICATION 12% has researchers worried that scientific advances will begin falling off and that 0% 5% 10% 15% 20% 25% 30% 35% younger investigators, their research curtailed, will leave academia. According to “A Broken Pipeline? grant applications Flat Funding of the NIH Puts a Gen- 1999 WITH ONLY ONE IN FOUR to the National Institutes of Health being funded, eration of Science at Risk,” a report 2007 released earlier this year by a consor- scientists say research is suffering. tium of seven academic research institutions, researchers nationwide are experiencing “a sense of despair” at the *R01 equivalents: R29, R37 Source: National Institute of Health opportunities lost due to the government’s failure to support research adequately. FEELING THE PRESSURE is felt most by junior investigators, “In competition for limited Between 1999 and 2007, the overall who must wait longer for their first resources, scientists at every point success rate of applications for R01 big grant. In 1990, the average age at along the academic research pipeline grants—the most common NIH grant which researchers received their first are feeling the destructive effects,” the for individual projects—fell from 32 R01 grant was 39; today, it’s 43. report notes. “Currently, only one in percent to 24 percent. The success rate Because of the government’s belt-tight- four original research applications to for first-time submissions fell even ening, the 12 new investigators Wistar the NIH are being funded, and many more sharply, from 29 to 12 percent. has hired over the past five years have of those are funded only after lengthy Those trends are reflected at Wistar, had to spend more time chasing delays and cumbersome reapplications. which received only 11 new NIH research dollars and less time working The system is backlogged with propos- grants in 2007, down from 22 in in their labs. als and too few are being funded— 2002. NIH grants provided $5.2 mil- “The fact that the funding is so bad impeding scientific progress.” lion in new funding to the Institute means that I have to spend much

Summer 2008 Summer The bottom line? last year, compared to $7 million in more time writing grants, which : “There is less research being done,” 2002. means I can focus less on actual sci- says Wistar Institute president and While researchers at all levels feel ence,” confirmed Joseph Kissil, Ph.D., FOCUS CEO Russel E. Kaufman, M.D. increased funding pressure, the crunch an assistant professor in Wistar’s Mole- 10 Profile of Support cular and Cellular Oncogenesis Pro- gram. “I’m spending more time writing grants than anything else. FRAN TOBIN: That means not keeping up with the Inspired by Research literature as much as I’d like to, and forget altogether about doing hands- or Fran Tobin, supporting Wistar research is a personal passion. “My on experiments.” husband Sylvan is a brain tumor survivor,” Tobin explains, “and he suf- Ffered effects from the radiation treatment. Too little is known about the A BUDGETARY SHORTFALL brain and how to treat patients without causing serious side effects.” From 1998 to 2003, Congress dou- Tobin has given both financial support and her time to Wistar. She has bled NIH funding, and the results made contributions to Wistar’s Albert R. Taxin Brain Tumor Research Center included the development of treat- as well as to the Institute’s unrestricted funds. And for the past three years, ments that reduced mother-to-child she has co-chaired the annual Albert R. Taxin Golf Clas- HIV infection in the United States sic, which raises funds for Wistar’s brain tumor research. Research from 25 percent to 1 percent, as (For more on this year’s tournament, see page 20.) “is really what well as new gene-based therapies for “Research is really what drives progress in health care,” such neurological disorders as Hunt- Tobin says. “It’s essential for creating better treatments for drives progress ington’s disease and amyotrophic the future. I find Wistar, where the focus is entirely on in health care.” lateral sclerosis, or Lou Gehrig’s research, very inspiring.” disease. Tobin got involved with Wistar through the Since then, though, annual encouragement of her friends, Wistar board of increases in NIH funding have failed trustees member Bob Fox and his wife to exceed inflation; the five consecu- Penny. She takes pride in honoring the tive years “of no real budgetary memory of Albert Taxin, the president growth” represents “a 13 percent of Old Original Bookbinder’s restau- drop in purchasing power since rant, who died of an inoperable 2003,” according to “Broken brain tumor at 53. Tobin’s family Pipeline.” That fact is not lost on and the Taxins have known each Kissil, who joined Wistar in 2004. other for years; her parents were “It was pretty bad when I started, friendly with Albert’s parents. and it’s just been declining,” he says. “Albert had such a dynamic per- “The money’s not keeping up with sonality,” Tobin says, “and enough expenses…Even when you get cannot be said about his wife Doris and funded, the money is short of what her sense of responsibility in raising aware- you actually need, just because of the ness and funds for brain tumor research.” rising costs.” According to Tobin, the Taxin Golf Classic Kaufman anticipates the situation plays an important role not only in raising improving but doesn’t believe a funds for brain tumor research but also in return to the flush funding of the late raising awareness of Wistar’s work. 1990s will happen anytime soon. “Because Wistar doesn’t treat “It can’t stay like this forever, but I patients, it’s not as well known to don’t think that over the next three the public,” she says. “The Taxin to five years we are going to see the Golf Classic is a chance to intro- heyday of a decade ago, when the duce Wistar and its important NIH’s budget doubled,” he says. “As work to a wider audience. a result, we’re going to be more Wistar is a wonderful place, dependent on foundations, philan- and the more people who 2008 Summer : thropy, technology transfer, and support us, the better the industry-sponsored research than we researchers can do in have been in the past.” ❖ curing disease.” ❖ FOCUS

Photo by Tommy Leonardi 11 NEW SCREENING FACILITY WILL EXPAND WISTAR’S CAPABILITIES

eflecting its commitment Wistar researchers adapt their investi- WISTAR’S NEW SCREENING to staying at the leading gations to the technology. FACILITY will allow scientists to edge of biomedical “One of the most important aspects quickly and accurately screen vast research, Wistar will open of the facility is how it will allow Wis- numbers of chemical compounds and a chemical screening facil- tar scientists to further explore poorly identify those that may be targets for ity this fall that will build defined disease biology,” Schultz says. development as drugs. An example of its capabilities in transla- “Specifically, implementation of this how the process works: Rtional research—the crucial bridge technology will allow investigators to A cancer-causing protein is placed into 1 between early-stage research and clini- identify new potential therapeutic tar- wells in hundreds of plastic plates. cal investigations. gets and classes of molecules that aren’t “The new facility will enable our even on the radar today.” scientists to identify compounds that Wistar professor Ronen Mar- may advance our understanding of morstein, Ph.D., has previously used cancer and, in some cases, be potential the technology when collaborating drug candidates,” with researchers at explains John Lucas, other institutes and is Ph.D., vice president “We can use looking forward to for academic affairs. using it in his ongoing 2 The plates are fed into sophisticated Understanding the screening studies related to can- robotic machinery, along with plates containing a “library” of thousands of chemi- protein function and facility to look cer and aging. cal compounds to be tested. The equipment then finding ways to “We can use the combines each compound with the protein affect it is important for inhibitors screening facility to and records the effect. in creating new treat- of a particular look for inhibitors of a ments. For example, cancer.” particular cancer, for scientists may dis- example,” he says. cover a protein that is “And when we find present in excess such inhibitors, we can quantities in a type of cancer. With use our understanding of molecular this knowledge, researchers can begin structure to modify the inhibitors and searching for small-molecule com- to make them more effective.” pounds to turn the protein The facility will allow Wistar to off—compounds that could be candi- collaborate on projects with other dates for drug development. research organizations, including the Searching for chemical compounds University of the Sciences in Philadel- with very specific functions, however, phia and Lankenau Institute for is a little like looking for a needle in a Medical Research ❖ 3 Compounds that inhibit the protein are haystack. The research demands the identified, letting scientists know where ability to process vast quantities of bio- to focus their research efforts. logical information efficiently and Wistar’s new chemical screening facility is supported by a Keystone Summer 2008 Summer accurately. Sophisticated robotic : Innovation Zone grant of $150,000 equipment has made it possible to do from the Commonwealth of just that, allowing scientists to screen Pennsylvania, as well as the F.M. FOCUS tens of thousands of chemical com- Kirby Foundation, the CLAWS Foundation, the Florence & Daniel 12 pounds for those that meet specific Green Foundation, and the McLean criteria. David Schultz, Ph.D., who Contributionship. will direct the new facility, will help PROGRESS The latest advances from Wistar labs

Virus Used to Create Experimental HIV Vaccines Directly Impairs Immune Response

eading efforts to create an HIV simply, they mean that AAV vaccines The research was supported by Lvaccine have hinged on the use of against HIV may potentially cause grants from the National Institutes of viruses as carriers for HIV genetic harm and that, without additional pre- Health and the Commonwealth Uni- material. Evidence has emerged that clinical studies, they should not be versal Research Enhancement Program some of these so-called viral vector used in humans.” of the Pennsylvania Department of systems may undermine the immune Taken together, the data partly out- Health. ❖ system and should not be used for vac- line a condition known as T-cell cine development. A study by Wistar exhaustion, seen in a number of scientists provides strong support for chronic infections, including HIV, the idea that some viral-vector vaccines hepatitis B, and hepatitis C, as well as may cause more harm than good. in some cancers, such as melanoma. The findings show that an HIV vac- “Why would you want to inject cine construct incorporating one of people with a vaccine that’s going to these viruses, called adeno-associated have a detrimental effect?” Ertl asks. virus, or AAV, directly interferes with “AAV vaccines against HIV may do the immune response to the HIV virus. more harm than good by robbing peo- AAV is a small virus that does not ple of their natural immune response cause disease and has been found to to HIV.” stimulate a mild immune response. The study appeared in November in Specifically, while AAV induces Journal of Clinical Investigation. The HIV-specific T cells—a type of white lead author is Shih-Wen Lin at Wistar. blood cell—those cells are functionally Wistar’s Nia Tatsis, Ph.D., Marcio O. impaired in important ways. Lasaro, Ph.D., and Scott E. Hensley “What do these results mean?” asks (now at the National Institute of Hildegund C.J. Ertl, M.D., director of Allergy and Infectious Diseases) were Leonardi Tommy Hildegund C.J. Ertl, M.D., has demonstrated the Wistar Institute Vaccine Center co-authors. Lin is also affiliated with that a type of HIV vaccine may do more and senior author on the study. “Put the University of Pennsylvania. harm than good.

Study Sheds Light on Body’s Cell-Making Process

he seemingly inefficient way our cells, which differentiate, or grow into Patterns Suppress Somatic Evolution,” Tbodies replace worn-out cells is a different types of cells. Some divide to in December in PLoS Computational defense against cancer, according to a make transient amplifying cells, or Biology. study co-authored by scientists at Wis- TACs—intermediate cells that in turn “Somatic evolution” refers to muta- tar. Having a neighboring cell split into divide to produce skin cells. The new tions that can occur in somatic cells, two identical daughter cells would seem skin cells are evolutionary dead ends; which are found throughout the body, to be the simplest way to keep bodies they cannot reproduce. over an organism’s lifetime. The from falling apart. However, that would Cells that self-renew, or make process of cellular differentiation be a recipe for the kind of genetic copies of themselves, instead of dif - flushes mutant cells from our bodies. mutation that leads to uncontrollable, ferentiating are more vulnerable to The researchers compared muta- 2008 Summer : rapid cell reproduction—and cancer. cancer, says Carlo C. Maley, Ph.D., an tions in different modes of cellular Instead, multicellular organisms use assistant professor in Wistar’s Molecu- reproduction. They found that if cells a seemingly inefficient process to lar and Cellular Oncogenesis Program reproduce by simply making carbon- FOCUS replace lost cells. When replacement and senior author of the study. Maley copies of themselves, their descendants 13 cells are needed, epithelial tissues such and his colleagues published their are more likely to accumulate muta- as those in the skin call upon stem paper, “Animal Cell Differentiation (continued on page 14) PROGRESS

Study Sheds Light on “and we’d like to understand the earli- Maley’s co-author at Wistar is Kath- Body’s Cell-Making Process est processes in carcinogenesis.” leen Sprouffske, who is also affiliated (continued from page 13) Additional studies will further with the University of Pennsylvania. explore the cellular mutations that give The National Institutes of Health, tions. In contrast, if cellular repro- rise to cancer and the dynamics of the the Pew Charitable Trusts, the duction is much more complicated, interactions between stem cells and Commonwealth Universal Research the cells’ descendants have fewer other cells. Enhancement Program of the mutations. John W. Pepper, Ph.D., of the Uni- Pennsylvania Department of Health, “It looks like it’s easier to prevent versity of Arizona and the Santa Fe and the Santa Fe Institute funded cancer than to cure it,” Maley says, Institute is lead author on the study. the research. ❖

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

he more scientists learn about two miRNAs transformed non-invasive Klein-Szanto is at Fox Chase Cancer TmicroRNAs—short strands of human breast cancer cells into cells that Center. Phyllis A. Gimotty, George RNA that can interfere with normal rapidly metastasized, or spread, in cell Coukos, and Lin Zhang are at the Uni- gene activity—the more obvious it cultures and laboratory mice. versity of Pennsylvania, and Dionyssios becomes how closely they are associ- “Of the 450 miRNAs we tested, we Katsaros is at the University of Turin. ated with cancer. Scientists at Wistar found two, miR-373 and miR-520c, The research was supported by and their colleagues have identified two that induced cell migration in MCF-7 the Breast Cancer Alliance, Pardee microRNAs (miRNAs) that promote cells—a line of human breast cancer Foundation, V Foundation, the tumors’ deadly spread, or metastasis. cells that normally does not metasta- Commonwealth Universal Research One of the miRNAs may provide an size,” says Qihong Huang, M.D., Enhancement Program of the Pennsyl- early warning of metastatic breast can- Ph.D., an assistant professor in Wistar’s vania Department of Health, the cer and the need for aggressive treatment. Wistar researchers have identified a molecule that may By blocking the translation of provide an early warning of metastatic breast cancer. tumor suppressor genes, miRNAs have been shown to facilitate the develop- Molecular and Cellular Oncogenesis Dutch Cancer Society, the Dr. Josef ment of many types of cancer. In a Program and lead author and co-corre- Steiner Cancer Research Foundation, study published in February in Nature sponding author on the study. the National Cancer Institute, Ovarian Cell Biology, researchers describe how Another intriguing characteristic of Cancer Research Fund and the Ameri- these two miRNAs is that they are not can Cancer Society. Agami was found in normal adult cells—only in supported by the European Young tumor cells. “They are not in normal Investigator Award and the EMBO testis, but are expressed in testicular Young Investigator Program. ❖ cancer,” Huang says. “We see them in breast cancer cells, especially metastatic DID YOU KNOW? cells, but not in normal breast cells.” Wistar’s Kiranmai Gumireddy, METASTASIS—the development Ph.D., is a co-lead author on the study. of additional malignant growths at Additional Wistar co-authors are Ellen a distance from a primary cancer Puré, Ph.D., Anping Li, and site—is the major cause of death Summer 2008 Summer Guanghua Huang (now at the Univer- : in cancer patients. Wistar scien- sity of Iowa). Co-lead author Mariette tists are working to better Schrier and senior author and co-corre-

FOCUS understand the metastatic process sponding author Reuven Agami are at so that new drugs can be the Netherlands Cancer Institute, as are 14 designed to stop it. Qihong Huang, M.D., Ph.D., studies micro- Carlos le Sage, Remco Nagel, Suresh RNAs, which are implicated in many cancers. Nair, and David A. Egan. Andres J. Protein from Wistar Welcomes Computational Biologist Herpes Virus Serves as Potent istar recently welcomed new the Ohio State University’s Compre- Wfaculty member Ramana hensive Cancer Center. He received his Vaccine Enhancer Davuluri, Ph.D., as an associate pro- doctorate from the Indian Agricultural fessor in the Molecular and Cellular Statistics Research Institute in New reating vaccines to protect people Oncogenesis Program. Davaluri, who Delhi and underwent postdoctoral Cagainst viral diseases like AIDS, holds the Philadelphia Health Care training at Cold Spring Harbor Labo- cervical cancer, and infectious hepatitis Trust Professorship, is also an associate ratory in New York. is a delicate balancing act: if the director of Wistar’s new Center for Computational biology involves the immune system’s response to the vac- Systems and Computational Biology use of techniques including computer cine is too strong, toxic side effects can (see story on page 8), as well as the cen- science, applied mathematics, and sta- kill the patient. If it’s not strong ter’s director of computational tistics to process, manage, and interpret enough, the virus will spread faster biology. In addition, he serves as sci- complex data sets. than the immune system can kill it. entific director of Wistar’s Cancer Davaluri’s research focuses on funda- A new vaccine design strategy devel- Center Bioinformatics Shared Facility. mental aspects of mammalian genomics oped by scientists at The Wistar Before coming to Wistar, Davuluri and cancer. His current research efforts Institute Vaccine Center could be the was an associate professor and head of include the identification of gene net- answer. The secret is using a herpes the bioinformatics consulting unit in works involved in promoting breast and simplex protein called glycoprotein D the human cancer genetics program at ovarian cancer. ❖ to block a specific receptor molecule on antigen-presenting cells, or APCs. New faculty member Ramana Davuluri, Ph.D., right, greets a guest at the opening of Wistar’s These sentinel cells monitor the body new Center for Systems and Computational Biology. Davuluri is an associate director of the for foreign antigens—molecules that center, as well as director of computational biology. Looking on is Carlo C. Maley, Ph.D. can stimulate an immune response— from invading viruses. When they detect viral antigens, APCs signal the body’s immune system to activate T cells to attack and destroy cells infected with the virus. At the same time, they also send inhibitory signals to prevent overreaction by the immune system. One of these inhibitory signals is blocked by glycoprotein D from herpes virus. In a study published in February in Nature Medicine, Wistar scientists showed that vectors, which are vaccine delivery systems, made by fusing the glycoprotein D with genes from target antigens increase the immune system’s response to those antigens in cell cultures and laboratory mice. The researchers used antigens from HIV,

the virus that causes AIDS, and from Scott H. Spitzer

HPV-16, a human papilloma virus 2008 Summer : that causes cervical cancer. vaccine approaches. “It allows us to effectiveness. If studies in research ani- Hildegund C.J. Ertl, M.D., director lower the dose but still get a stronger mals continue to be positive, they hope of The Wistar Institute Vaccine Center immune response,” she says. to conduct human clinical studies with FOCUS and senior author of the study, says Ertl and her colleagues are planning HIV and HPV vaccines under devel- 15 using glycoprotein D to deliver anti- future studies to further elucidate the opment at the Vaccine Center. gens has a major advantage over other mechanism behind the carrier protein’s (continued on page 16) PROGRESS

Protein from Herpes Scientists Solve Structure of Gene Virus Serves as Potent Vaccine Enhancer Regulator that Plays Key Role in Cancer (continued from page 15) cientists at Wistar have collaborated Ertl is corresponding author of the Son a major advance in understand- study. Lead author is Wistar’s Marcio ing a gene regulator implicated in some Lasaro, Ph.D. Wistar co-authors are of the deadliest cancers in humans. Nia Tatsis, Ph.D., Shih-Wen Lin, John The culmination of 10 years’ work, the J. Rux, Ph.D., E. John Wherry, Ph.D., research paves the way for the develop- and Scott E. Hensley (now at the ment of new cancer therapies. National Institute of Allergy and During much of its lifetime, the Infectious Diseases). Lin is also DNA that resides in each of our cells affiliated with the University of exists in an inactive form, stored inside Pennsylvania. Co-authors J. Charles densely knotted structures in the cell Whitbeck, Gary H. Cohen, and nucleus. There, the DNA is wound Roselyn J. Eisenberg are with the spool-like around proteins called his- University of Pennsylvania. tones, which bind the DNA and

The research was supported by the restrict its activity. For a cell to activate Robert H. Clink National Institute of Allergy and Infec- a gene, many proteins, called transcrip- Ronen Marmorstein, Ph.D., and his colleagues have revealed the structure and function of tious Diseases (NIAID) and the tion factors, work in concert to an enzyme implicated in pancreatic, colon, Commonwealth Universal Research separate DNA from the histones. One and lung cancer. Enhancement Program of the Pennsyl- family of transcription factors are vania Department of Health. ❖ enzymes known as HATs, or histone “It’s unusual to have a HAT that’s so acetyltransferases, which transfer implicated in cancer, and even more DID YOU KNOW? acetate groups onto the histones. unusual to have one that has both Wistar scientists, collaborating with tumor suppressor and oncoprotein researchers at the Johns Hopkins Uni- activities,” Marmorstein says. WITH THE EXCEPTION of clean versity School of Medicine, have made In a report published in February in water, vaccines are considered the a major advance in the understanding Nature, the scientists detail their eluci- greatest public health advance. of the structure and function of a key dation of the three-dimensional Prior to the vaccine developments HAT enzyme called p300/CBP. structure of a p300/CBP HAT domain, of the twentieth century, the Unlike most HATs, which regulate or segment, bound to a small molecule following occurred annually in the expression of only a few genes, that inhibits its activity. The study also the United States alone: p300/CBP is involved in the activation reveals how the binding site and chemi- ◆ 10,000 children were paralyzed of a wide variety of genes. In addition, cal mechanism of the enzyme enable it by polio. deviant p300/CBP activity contributes to regulate a variety of genes. ◆ 20,000 children were born with to pancreatic, colon, and lung cancer— The scientists plan to use the new birth defects from rubella, or among the deadliest cancers in information to develop inhibitors of German measles. (A Wistar vaccine humans—as well as gastric and thyroid p300/CBP—research that will pave the eradicated this disease in the cancer and some leukemias. Besides way for the development of new cancer United States by 2005). promoting tumors, p300/CBP also therapies, Marmorstein says. ◆ 15,000 children suffered brain can suppress them. Co-authors on the study are Xin Liu damage from Haemophilus These unusual properties have made and Kehao Zhao, Ph.D., at Wistar and influenzae type b (Hib). p300/CBP one of the most studied Ling Wang, Paul R. Thompson and ◆ 4 million measles infections HAT enzymes, and a target for develop- Yousang Hwang of Johns Hopkins. Summer 2008 Summer ing new cancer drugs, says Ronen The research was supported by

: resulted in 3,000 deaths. Marmorstein, Ph.D., a professor in Wis- grants from the National Institutes of ◆ Thousands of infants were killed tar’s Gene Expression and Regulation Health; the FAMRI, Kaufman, and

FOCUS by Pertussis, or whooping cough. Program and a senior author and corre- Keck foundations; and the Common- ◆ 16 Diphtheria was a common cause sponding author on the study. Philip A. wealth Universal Research Enhance- of death in school children. Cole, M.D., Ph.D., at Johns Hopkins is ment Program of the Pennsylvania also a senior and corresponding author. Department of Health. ❖ GRANT HIGHLIGHTS NEW GRANT AWARDS*

Predicting Tumor The Wistar Institute and its Progression scientists continue to compete successfully for grants to support arlo C. Maley, Ph.D., an assistant research and programs. Below is a Cprofessor in Wistar’s Molecular and Cellular Oncogenesis Program, is the first sampling of recent awards. recipient of the Landon Foundation-AACR INNOVATOR award for cancer prevention. PRIVATE GRANTS The $100,000, two-year grant from the new grants Landon Foundation and the American THE AMERICAN CANCER SOCIETY Association for Cancer Research was created Nadia Dahmane, Ph.D., brain cancer to fund promising early-career cancer research, four-year grant, $600,000. researchers. Maley’s project will measure genetic diversity in tumor cells as a way to THE EDWARD MALLINCKRODT, JR. FOUNDATION predict whether a tumor is likely to progress Susan Janicki, Ph.D., live-cell imaging of and respond to preventive therapy. Maley was Carlo C. Maley, Ph.D. chromatin, the material of chromosomes, recognized for the innovative, collaborative, $60,000. and multidisciplinary nature of his work. THE MCLEAN CONTRIBUTIONSHIP The Wistar Institute, laboratory Exploring Enzymes and equipment, $60,000. Gene Expression W.W. SMITH CHARITABLE TRUST usan M. Janicki, Ph.D., an assistant Nadia Dahmane, Ph.D., research on Sprofessor in Wistar’s Gene Expression and brain development and brain tumors, $105,000. Regulation Program, has received the Basil O’Connor Starter Scholar Research Award from the March of Dimes Foundation. GOVERNMENT GRANTS Janicki will receive a two-year grant of THE NATIONAL CANCER INSTITUTE $150,000 to further her work exploring Anthony Capobianco, Ph.D., the role how certain enzymes regulate gene expression. of cell-to-cell signaling in tumor development, five-year grant, $1.8 million. The award supports young scientists embark- Susan M. Janicki, Ph.D. ing on their independent research careers. NATIONAL INSTITUTE OF AGING Shelley L. Berger, Ph.D., regulation of Optimizing T-Cell aging in a yeast model, five-year grant, Response $8.9 million. NATIONAL INSTITUTE OF ALLERGY John Wherry, Ph.D., an assistant AND INFECTIOUS DISEASE E.professor in Wistar’s Immunology Hui Hu, Ph.D., gene expression and Program, has received a $168,000, three-year immune cell development, two-year grant from the Dana Foundation to study the grant, $270,000. optimization of T-cell responses in hopes of 2008 Summer preventing chronic viral infections. Under NATIONAL CENTER FOR RESEARCH : RESOURCES Wherry’s direction, W. Nicholas Haining, Louise C. Showe, Ph.D.,

equipment to FOCUS M.B., B.Ch., of the Dana-Farber Cancer support genomics research, $404,650. Institute and Georg M. Lauer, M.D., Ph.D., 17 of Massachusetts General Hospital will collaborate on the project. E. John Wherry, Ph.D. *List reflects grants of $50,000 and over. BRIEFINGS News, honors, and events

‘Date with a Plate’ Institute Welcomes Three New Board Members Event Benefits istar recently welcomed three new members to its Wboard of trustees: Dani Paul Bolognesi, Ph.D., Melanoma Research George J. Vergis, Ph.D., and Dan W. Matthias. Bolognesi is the CEO and chairman of B3Bio Inc., rom the Heart, a Philadelphia- a new biotech venture in the field of RNA therapeutics. based philanthropic group that F He participated in the discovery in the mid-1980s supports local organizations, held a of AZT, considered the first effective AIDS drug, and co- “Date with a Plate” fundraiser in May founded the biopharmaceutical company Trimeris, which to support melanoma research. Both also has focused on the development of anti-viral drugs. Wistar and the Noreen O’Neil Foun- Bolognesi is the James B. Duke Professor emeritus in the dation for Melanoma Research were Department of Surgery at Duke University Medical Center. Dani Paul Bolognesi, Ph.D. beneficiaries of the effort. He earned his doctorate from Duke University. The event featured a walking dinner Vergis is president and CEO of Neose Technologies tour through unique table set-ups. On Inc., a clinical-stage biopharmaceutical company in display were one-of-a-kind place set- Horsham, Pa., that focuses on the development of tings created by local designers, event therapeutic proteins. He is the former vice president of planners, florists, and private collectors. new product development and commercialization of The event, held in Philadelphia, drew BASF/Knoll Pharmaceutical Company and associate more than 500 visitors. ❖ director of medical and scientific affairs for the Warner- Event sponsors included Mr. and Mrs. Lambert/Parke-Davis division of Pfizer. Vergis also worked Richard Berman and family, Mr. and previously as a clinical research scientist for American Mrs. William Gabrose and family, Mr. Home Products: Wyeth-Ayerst Laboratories. He earned his George J. Vergis, Ph.D. and Mrs. Bruce Goodman and family, the Korman Family Foundation (Mr. doctorate from the Pennsylvania State University. and Mrs. Larry Altman, Mr. and Mrs. Matthias is the chairman, CEO, and co-founder of Marc Feldman, and Mr. and Mrs. Mothers Work Inc., a company that manufactures and sells Michael Schurr), Mr. and Mrs. Gary maternity apparel through 1,600 stores in the United States Lassin and family, Mr. and Mrs. Seymore and Canada. He also served as manager of ZaBeCor Phar- Rubin, Mr. and Mrs. Leonard Abramson, maceutical Company, LLC, a start-up company involved in and the Noreen O’Neill Foundation for the development of an asthma-control drug. Matthias Melanoma Research. served 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. ❖ Dan W. Matthias

Wistar Establishes Leadership Council

istar recently formed the Wistar co-chair Rick Horowitz, “and use their WInstitute Leadership Council, skills to raise the profile of this world- which held its inaugural meeting in class institution.” December. The group, comprised of Members, who act as ambassadors community leaders with an interest in for the Institute, help spread the word Wistar and the region’s life sciences about groundbreaking work at Wistar.

Summer 2008 Summer industry, was created to help the Insti- They also help to forge new relation- : tute achieve its goal of improving global ships with individuals, foundations,

John Armich health through research. and corporations interested in support- FOCUS “The Art of Style,” designed by Neiman “The Leadership Council provides ing Wistar’s research. In addition, they Marcus, was among the unique table set- an excellent opportunity for some of confer with board members and other 18 tings displayed at “Date with a Plate,” a fundraiser hosted by From the Heart to our region’s bright, energetic leaders to institutional leaders in planning for the benefit melanoma research. get involved with Wistar,” says council Institute’s future. ❖ Wistar Hosts Nikon ‘Small World’ Exhibit

istar hosted the 33rd annual judge of the competition. Almost 200 WNikon Small World exhibition students visited the exhibit at Wistar. in January and February. The traveling “Images like those on display in the exhibit featured the winners of the Small World exhibit are helping to Nikon Small World competition for stimulate and inspire a new genera- photos taken through the microscope. tion,” says Hayden, who is coordinator The 20 winning images, which were of the exhibition at Wistar. “At Wistar, selected for originality, informational we hope to play a part in motivating content, technical proficiency, and young minds as we advance the fron- visual impact, were on display at Wis- tiers of biomedical science.” tar for eight weeks. The tours included an overview of Nikon Small World The Institute invited Philadelphia- the role that microscopes play in A photo of a Papaver subporforme (corn area science teachers and their students research at Wistar and an explanation poppies) flower bud by Shamuel Silberman to tour the exhibit, guided by James E. of how select photographs were made, of Ramat Gan, Israel, captured ninth place in the Nikon Small World contest for photos Hayden, manager of Wistar’s micro- as well as the biological significance of taken through the microscope. Wistar hosted scopy facility and a previous winner and their subjects. ❖ an exhibit of winning photos this winter.

Technician Training Program Receives Funding Ruth Patrick Honored istar recently received the grant of $89,619 will partially fund WDelaware Valley Innovation the program for one year. Network’s first Innovation Investment Wistar partners with Temple Uni- Grant to support its Biomedical Tech- versity’s Fels Institute, as well as nician Training Program. The various industry labs, to provide labo- two-year “BTT Program” provides ratory training for the students. The Community College of Philadelphia initiative continues to expand; this students with instruction and hands- year, the University of the Sciences in on experience in preparing them for Philadelphia also became a training careers as biomedical technicians. The affiliate. “We see tremendous value in supporting a pipeline of talented students from the Community College of Philadelphia through real work experience at The Wistar Institute, various laboratories and the Fels Institute,” says Helen Groft, project director of DVIN. “These students will be able to jump- start their careers, and employers will Pioneering biologist Ruth Patrick, Ph.D., who have experienced candidates to hire.” has served on Wistar’s board of trustees for The award will support Wistar in pro- more than three decades, was honored and viding training for 17 first- and named a trustee emerita of the Institute when the board met in June. Celebrating second-year students. with her, from left to right, are Wistar The DVIN Innovation Investment president and CEO Russel E. Kaufman, M.D.;

Fund supports training and capacity- William Yancey Brown, Ph.D., president and 2008 Summer CEO of the Academy of Natural Sciences; and : building programs for the Delaware Brian H. Dovey, chair of Wistar’s board of Valley’s life science workforce. trustees. Patrick is honorary chair of the Oni Kolawole Olaiya, a student at Commu- Additional funding for the BTT board of trustees of the Academy of Natural FOCUS nity College of Philadelphia, works in the Program is provided by the National Sciences, where she has worked since the lab of Wistar researcher Harold C. Riethman, 1930s. Her many awards include the National 19 Ph.D., as part of Wistar’s Biomedical Techni- Cancer Institute’s CURE program and Medal of Science, America’s highest decora- cian Training Program. the Hassel Foundation. ❖ tion for scientific achievement. BRIEFINGS

Wistar Names High School Essay Contest Winners, Summer Fellows

istar honored winners of its high The 2007 summer fellows were Wschool biology essay contest and Manjima Dhar, Julia R. Masterman recipients of its summer fellowships for High School; Marcelina Garcia and high school students at a ceremony in Esteban Sanlate, Marianna Bracetti June. The event recognized essay con- Academy Charter; Eva Jiang and Khail test winners and summer fellows for Van, Northeast High School; Georgia both 2007 and 2008. The contest and Karmee, Motivation High School; fellowships aim to promote science Fatima Mohammed, George Washing- education and encourage the pursuit ton Carver; and Richard Stark, Lower of science careers by Philadelphia-area Merion High School. students. The fellowship program allows Michael Gorokhovsky, a sophomore at George The Honorable James R. Roebuck, students to become directly involved Washington High School, is presented with Pennsylvania Representative for the in biological research. It is supported an award by the Honorable James R. Roebuck, Pennsylvania Representative for 188th District, presided over a cere- by the Hassel Foundation and Glaxo- the 188th District, for winning Wistar’s mony at the Institute at which the Smith Kline. ❖ 2008 high school biology essay contest. first-place winners of the essay contest read their essays. The 2008 winner, Michael Gorokhovsky, a sophomore at Golf Tournament Supports Brain Tumor Research George Washington High School, read “HIV/AIDS,” while 2007 winner Dante Galzarano, a junior at Julia R. Masterman High School, read “Genetic Research on Autism.” The first-place winners each received $500, and their schools each received $500 for laboratory and teaching supplies. Additional 2008 winners are Alba Baze and Elizabeth Massele of Julia R. Masterman High School for second place and Gabrielle Sammartino of the Girard Music Academy and Sandy Weng of Central High School for third place. Additional 2007 winners were Allegra Black of Roxborough High School for second place and Georgia Karmee of Motivation High School for third place. The contest is supported by the Hassel Foundation. The 2008 Wistar Institute Summer Fellows are Eva Bugos, Julia R. Master- Cherry Hill Photo Golfers prepare to tackle the course at the 13th annual Albert R. Taxin Golf Classic, held man High School; Jessica Grier, in June at Green Valley Country Club in Lafayette Hill, Pa. The event raised more than George Washington Carver High $120,000 for brain tumor research at Wistar. Pictured, from left, are Wistar president and CEO Russel E. Kaufman, M.D.; event founder and honorary co-chair Doris Taxin; JoAnne Summer 2008 Summer School of Engineering & Science; Eva : Bagnell; and former NFL coach Dick Vermeil. Tournament highlights included a hole-in-one Jiang, Northeast High School; Georgia by Bob Alper, who won a new Lexus automobile for his feat, and an appearance by the Karmee, Motivation High School; “Phillies Fanatic” team mascot. This year’s event, co-chaired by Fran Tobin and Evie and FOCUS Thomas Madej, Saint Joseph Prepara- Ron Krancer, also featured a bridge tournament. Since its inception, the tournament has raised $1.25 million to support Wistar’s Albert R. Taxin Brain Tumor Research Center. Albert tory School; Yuwen Wang, Strath 20 R. Taxin, president of Old Original Bookbinders restaurant in Philadelphia, died of a brain Haven High School; and Ross D. tumor at 53. Wistar, Germantown Friends School. Wistar Family Fund Established SPECIAL LECTURES The Wistar Institute recently hosted istar recently launched fund will become part of its the following lectures by distinguished Wthe Wistar Family endowed principal; only the guest researchers. Fund for Cancer Research to fund’s earnings will be provide support for cancer applied toward research. The JONATHAN LAX MEMORIAL LECTURE research pilot projects at the earnings will support novel June 12, 2008 Co-sponsored by the AIDS service organization Institute. Created with a pilot projects that might oth- Philadelphia FIGHT and presented in memory of $100,000 gift from C. erwise go unfunded. Jonathan Lax, an activist and former FIGHT Cresson Wistar and his fam- Ailsa Wistar, a longtime president, who died of AIDS in 1996. Speaker: Lawrence Corey, M.D., Fred ily, the fund was established Ailsa Wistar friend of the Institute, served Hutchinson Cancer Research Center, University in honor of Cresson’s wife, as the first chairwoman of the of Washington, Seattle Ailsa Wistar, who died last year of Friends of The Wistar Institute, which Topic: “HIV Vaccine Development Post-STEP” breast cancer. helped provide funding for Wistar VINCENT J. CRISTOFALO LECTURE In making the initial gift, Cresson research for more than 30 years. December 5, 2007 says he hoped to establish a vehicle for For more information, contact Peter Established by The Wistar Institute in honor of Wistar professor emeritus Vincent J. Cristofalo, giving that is open to all Wistar family Corrado, Wistar’s director of institu- Ph.D., an internationally recognized expert on members who share an interest in sup- tional development, at (215) 898-3930 aging, who died in 2006. porting cancer research. Gifts to the or [email protected]. ❖ Speaker: Bruce Stillman, Ph.D., FRS, Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y. Topic: “Control of the Chromosome Cycle in Study Co-Authored by Wistar Researcher Human Cells by the Origin Recognition Named Top Scientific Breakthrough Complex” GEORGE KHOURY MEMORIAL LECTURE study co-authored by a former protection. When a pathogen attacks, October 16, 2007 Founded by the Hassel Foundation in memory AWistar researcher while he some CD8 T cells become short-lived of George Khoury, M.D., former head of the worked at the Institute was selected as “soldiers,” while others morph into Laboratory of Molecular Virology at the National one of the top scientific breakthroughs memory cells that linger for decades in Cancer Institute. Speaker: Douglas R. Lowy, M.D., Laboratory of of 2007 by Science magazine. The case the same pathogen attacks again. Cellular Oncology, National Cancer Institute, research by Wolfgang Weninger, The research might eventually be Bethesda, MD M.D., a former Wistar assistant pro- used to create more effective vaccines. Topic: “The Prevention of Cervical Cancer by HPV Vaccination and Other Interventions” fessor, illuminated how immune cells The study was published in Science in specialize for immediate or long-term March 2007. ❖

Wistar Hosts Author of Book on Diet, Health

ward-winning science writer Gary disease. Further, he maintains that the ATaubes discussed his new book, only healthy way to lose weight is to Good Calories, Bad Calories: Challeng- eat fewer carbohydrates—particularly ing the Conventional Wisdom on Diet, refined carbohydrates such as flour, Weight Control, and Disease, in May as sugar, and rice. part of Wistar’s Authors Series. In his talk at Wistar, Taubes focused In his book, Taubes challenges the on the growing obesity epidemic and widely held belief that a low-fat diet is disputed the popular belief that obesity the best approach to losing weight and results from eating too much and exer-

avoiding disease. Instead, he advocates cising too little. Instead, he explored 2008 Summer : carbohydrate restriction, arguing that the role of carbohydrates, and their the key to good health is the kind of effect on insulin, in weight gain. calories people take in, not the number. Taubes is a correspondent for Sci- FOCUS Taubes argues that there is no ence magazine. He has also written Author Gary Taubes signs copies of his book 21 after speaking at the Institute in May as compelling scientific evidence that sat- articles for Discover, New Scientist, and part of Wistar’s Author Series. urated fat and cholesterol cause heart The New York Times magazine. ❖ Behind the Science MEET HAROLD C. RIETHMAN, PH.D.

or Wistar associate professor Harold C. Riethman, Ph.D., an interest in the natural world came early. F “I grew up on a farm in Ohio, surrounded by plants and animals,” he says. “I wanted to understand how living things worked.” That interest continued through high school and college at the University of Cincinnati, where his experience in a biology lab confirmed science as his future career. “The idea that we could explore the building I wanted blocks of life and figure “ out how they work was to understand really exciting,” he says. how living Riethman joined Wis- tar in 1990 and has things worked.” focused on studies of telomeres, the tips of chromosomes. His lab played an essential role in extending the human genome sequence to include the telomere regions, a significant milestone in the Human Genome Project. Today, Riethman continues his investigations of telomeres, which are involved both in aging processes and cancer development. (See story on page 4.) He remains just as excited about going into his lab each morning as he did when he was a student. “The open-endedness and the adventure of finding something new is really appealing to me,” he says, “as is contributing to a larger effort in the scientific community to improve our quality of life. My wife has breast cancer, and my mother has Alzheimer’s disease. So I’m keenly aware of the importance of research to patients.” Since completing his training, Riethman has spent his entire research career at Wistar—and he says it’s been a great place to do his work. “You’re given a ✫ YEARS AT WISTAR: 18 great deal of freedom to pursue areas that you find interesting and exciting,” he says. “And ✫ CAREER HIGHLIGHT: Contributing the Institute’s small size allows you to get to to the human genome sequence know the other scientists and broaden your ✫ TV SHOW HE NEVER MISSES: research.” “The Colbert Report” Outside the lab, Riethman has an active ✫ BOOK HE RETURNS TO AGAIN family life that keeps him busy. He and his

Summer 2008 Summer AND AGAIN: Huckleberry Finn wife have five children, and his evenings and : ✫ FAVORITE SPORTS TEAM: The Sixers weekends are spent helping with homework, ✫ ON WEEKENDS YOU’LL FIND HIM: attending sports events and other school activi- FOCUS With his family, at baseball or soccer ties, and just having time together as a family. VITAL STATISTICS 22 games, taking long walks with his “They’re the focus of my life,” he says. ❖ dog, hiking or camping, attending a Unitarian church. Photo by Tommy Leonardi RECEIVE SECURE Fixed Annual Payments FOR LIFE While supporting Wistar research.

A CHARITABLE GIFT ANNUITY allows you to earn a lifetime income for yourself while supporting Wistar scientists in the fight against deadly diseases.

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WORRY-FREE MANAGEMENT: Reduce stress over investment responsibilities. For more information, GENEROUS SUPPORT: Your contribution helps Wistar researchers to contact Peter Corrado, develop new treatments for cancers including melanoma, lung cancer, Wistar’s director of and brain tumors and create new vaccines against flu and other diseases. institutional development, Minimum contribution is $10,000. Cash, stock, or other assets can be at 215-898-3930 or used to fund the annuity. This program is currently available only to [email protected]. Pennsylvania, Delaware, and New Jersey residents. A WISTAR SCIENTIST ANSWERS QUESTIONS ON AGING

Wistar professor Ronen Why do you think people are Marmorstein, Ph.D., Q: so fascinated with the topic of conducts research on aging and the prospect of developing aging and age-related anti-aging therapies? People don’t like to grow old, and the diseases, focusing on A: idea of living longer and doing more is enzymes called sirtuins. attractive. But I think a more important con- (See story on Wistar’s cern is age-associated diseases. My work aging-related research focuses on extending “healthspan”—the amount of time people can be healthy. on page 4.) Here, Marmorstein answers It has been reported that drinking questions about the Q: red wine can help you stay young. implications of this Is that true? Resveratrol, a component of red wine, research. A: has gotten a lot of press as being an activator of sirtuins, which are associated with increased lifespan in some organisms. But a person would have to drink about two cases of wine a day to get an effective dose.

Do you think we’ll see anti-aging Q: drugs in the next 25 years? I think it’s likely we’ll have new med- A: ications that can slow the aging process and inhibit age-associated diseases like cancer, type-II diabetes, obesity, and Alzheimer’s.

At the end of the day, what Q: do you hope to accomplish with your research? My team and I hope to identify small- A: molecule compounds with the potential to be developed as drugs that can treat age- associated diseases and extend the amount of Q time that people can be active and healthy. Tommy Leonardi &A

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