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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’ capabili- ties. 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.
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