Launches Tackling the Top Cancer Killer a Melanoma Patient’S Legacy CONTENTS : FALL 2007

Focus Fall 2007 Vaccine Center Launches Tackling the Top Cancer Killer A Melanoma Patient’s Legacy CONTENTS : FALL 2007

PRESIDENT’S MESSAGE

Wistar’s Leadership in ‘New Economy’ ocus Fulfills Institute’s Mission F ’m often invited to give talks to community groups interested in Ithe research conducted at The Wistar Institute. One talk may be 4 The Wistar Institute to a group weighing the ethics of stem cell research, while another Vaccine Center Launches may be to a gathering interested in Philadelphia’s history as the Wistar’s new research effort focuses on birthplace of American medicine. More and more frequently, how- developing vaccines for some of the ever, I am asked to discuss the driving role played by biomedical world’s deadliest diseases. research in regional economic development. 8 A Melanoma Patient’s Legacy Robert H. Clink The life sciences represent one of the fastest-growing sectors of the still-emerging “knowledge-based” economy, seen as the successor to the area’s his- Melanoma patient Noreen O’Neill made a lasting impression on Wistar torical industrial strengths. The field is responsible for important new drugs, researcher Meenhard Herlyn—and vaccines, and other products coming to market from the major pharmaceutical com- established a foundation that supports panies headquartered in the Philadelphia area, and it spurs the creation of dozens of Institute research. new biotechnology enterprises throughout the region each year. For Wistar, as a non- profit organization, commercialization is also the path by which discoveries become 10 Tackling the Top treatments, preventions, and cures for the people who need them, a crucial step in Cancer Killer fulfilling our mission of advancing human health through research. Four Wistar investigators are making The importance of this subject is underscored by a recent report from the CEO significant progress against lung cancer. Council for Growth, an affiliate of the Greater Philadelphia Chamber of Commerce. 12 Wistar Gala “Accelerating Technology Transfer in Greater Philadelphia” concludes that technology Wistar honored longtime supporter transfer, the process by which discoveries move into commercial development, is key Hal Davis at a black-tie event. to Philadelphia realizing its potential as a center of economic development. I chaired the committee that commissioned the study, which has garnered significant attention 14 Progress including coverage in The Philadelphia Inquirer. My leadership in this area stems The latest from Wistar labs, additions from Wistar’s history of commercial successes: for example, its vaccines against to the faculty, and recent grants. rubella, rabies (in humans and wildlife), and rotavirus are available around the globe, 18 Briefings and monoclonal antibodies developed at Wistar helped launch Centocor, one of the Honors, news, and notes. world’s most successful biotechnology companies. Wistar leadership in biomedical research will surprise few who know about our 22 Former Director Honored accomplishments, past and present. That we have long been leaders in building Hilary Koprowski, M.D., won bridges from the laboratory to the marketplace is less well known but equally true. the Sabin Gold Medal. This is important work that provides a vital revenue stream to help Wistar maintain On the cover: A collaborative research and expand its research. More importantly, however, engagement with the commer- initiative, the Wistar Institute Vaccine Center cial sector ensures that Wistar science intended to save lives achieves that high is dedicated to improving global public health purpose. by taking on such threats as AIDS, influenza, and rabies. Top Wistar immunologists lead the effort, building on Wistar’s history of vaccine success. Full story on page 4. Russel E. Kaufman, M.D. President and CEO Focus Fall 2007 Vaccine Center Focus is published two times per year for donors, friends, faculty, and staff of The Wistar Institute by the Launches Office of Public Relations, 3601 Spruce Street, Philadelphia, PA, 19104-4265. To contact the editor, Tackling the Top Cancer Killer phone (215) 898-3943 or e-mail [email protected]. For general inquiries, contact The Wistar Institute at (215) 898-3700. A Melanoma Patient’s Legacy Send address changes to: Development Office, The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104-4265.

ABBEY J. PORTER LEE CHRISTINE SHURTZ JAMES E. HAYDEN Editor and Assistant Director of Public Relations Public Relations Intern FREDERICK S. KEENEY FRANKLIN HOKE KARLYN ROSEN AIRES Photographers Director of Public Relations Designer The Wistar Institute is an equal opportunity/affirmative action employer. It is the policy of The Wistar Institute to provide equal employment opportunities to all individuals regardless of race, color, creed, religion, national origin, ancestry, sex,

age, veteran status, disability, sexual orientation, or gender identity for all terms and conditions of employment. African girl: Gavriel Jecan/Danita Delimont.com

The Wistar Institute is a National Cancer Institute-designated Cancer Center. Portrait Purchase Celebrates Wistar Heritage By Abbey J. Porter

he Wistar Institute has sake, painted by a significant American of renowned portraitist John Wesley purchased a painting of its artist, belongs at The Wistar Institute, Jarvis. Otis’s best-known sitters namesake, prominent where we will be able to care for it in included Thomas Jefferson, Dolly Philadelphia physician perpetuity. We’re delighted to have the Madison, James Fenimore Cooper, and Caspar Wistar, created by opportunity to acquire the painting at William Henry Harrison, but most of Ta celebrated artist and inventor with this time.” his subjects were prominent members ties to the Philadelphia area. The Insti- Dr. Wistar’s great-nephew, Civil of the local middle class. He also tute acquired the oil portrait by Bass War general Isaac Wistar, founded The designed flags and engraved handbills Otis, who lived and worked in Wistar Institute in 1892 in his great- and is credited with being the first Philadelphia in the 1800s, from the uncle’s honor to preserve the doctor’s American lithographer. Schwarz Gallery. It was part of the collection of anatomical specimens Otis exhibited at the Pennsylvania collection of the Mutual Academy of the Fine Arts, Assurance Co. was a member of the Widely respected as a Franklin Institute of Science, physician and man of and was elected an academi- learning, Dr. Wistar cian of the Pennsylvania became professor of chem- Academy in 1824. Although istry at the medical school active in several East Coast of the College of Philadel- cities, he often returned to phia, now the University Philadelphia and died there of Pennsylvania, in 1789 in 1861 at age 77. and became chair of Penn’s The Mutual Assurance department of anatomy in Co. acquired the painting 1808. He wrote the first when it moved into the American anatomy text- house formerly occupied book and was an early by Dr. Wistar. The portrait advocate of vaccination. joins a number of other Learned in the humani- Wistar president Russel E. Kaufman, M.D., admires the Institute’s newly historically significant works acquired portrait of Caspar Wistar with Janet and Lew Klein, who made ties, he succeeded his a generous ‘challenge’ gift of $10,000 towards the painting’s purchase. of art in the Institute’s col- friend Thomas Jefferson Contributions from members of Wistar’s board of trustees and the lection. as president of the Ameri- Wistar family also helped to make the acquisition possible. Wistar archivist Nina can Philosophical Society Long views the portrait of and hosted “Wistar parties” for leading used as teaching aids and further Dr. Wistar as an appropriate reflection intellectuals at his home at Fourth and knowledge in the biological sciences. of the Institute’s mission. Describing Locust streets. The portrait was painted in 1816 by Dr. Wistar as a “compassionate” man “We’re very proud of our history artist and inventor Bass Otis, a Massa- who was “devoted to science and medi- and the active role we have played in chusetts native and physician’s son who cine,” Long notes also his dedication to the scientific and cultural life of moved to Philadelphia in 1812 and teaching and civic involvement—tradi-

Philadelphia, reaching back to Caspar established a studio at Third and tions carried on by the Institute today. Fall 2007 : Wistar’s contributions to teaching and Chestnut streets. There, Otis conceived “We’re part of the city, we have this knowledge in the post-Colonial era,” his most famous invention, a drawing long history, and our archival collec- says Russel E. Kaufman, M.D., Wistar aid called the perspective protractor. tions relate to our involvement with all FOCUS president and CEO. “Our feeling is A master of portraiture, Otis is of these areas,” she says. “Our past tells 3 that this exquisite portrait of our name- thought to have worked in the studio us who we are.” WISTAR LAUNCHES Research to Benefit Global Public Health

n May, Wistar celebrated the Also present at the inauguration Wistar is poised to make vital contri- launch of a collaborative were members of the state government, butions to this exciting and critically research effort aimed at saving donors to Wistar, media representa- important area of medicine.” countless lives across the tives, and key figures in education, Vaccines may be the greatest public globe. The Wistar Institute biomedical research, and public health. health success story of all time, but Vaccine Center will focus on Highlighting the event was an appear- that story remains unfinished. There Ithe development of new or improved ance by Pennsylvania Secretary of are many infectious diseases for which vaccines for some of the world’s dead- Health Calvin B. Johnson, M.D., no vaccine exists and others for which liest diseases: HIV, influenza, rabies, M.P.H., who congratulated Wistar on current vaccines could be more effec- hepatitis C, malaria, and others. its contributions to the nation’s public tive. Through the Vaccine Center, “The new vaccines we are working health accomplishments. Wistar scientists are responding to to develop have important implications The Institute has several important these needs by working to create vac- for public health because they can vaccines to its credit, including the cines for the following diseases: reduce disease and death from very standard-of-care protections against HIV/AIDS: Wistar researchers are common infections,” says Vaccine rubella, rabies, and rotavirus. Extend- developing a vaccine against HIV, Center director Hildegund C.J. Ertl, ing Wistar’s history of accomplishment responsible for the growing AIDS M.D., professor and Immunology Pro- in vaccine development, the Vaccine epidemic that affects some 40 million gram leader at Wistar. “We also are Center will draw upon and creating vaccines that will be effective focus the Institute’s strengths not only in the United States and in immunology, virology, and Europe, but in developing areas such as other research disciplines. Africa and Asia as well.” “Science offers us the abil- Ertl, who has 20 years’ experience ity to deliver a whole wave of in vaccine research and oversees major new life-saving vaccines in projects to develop vaccines against coming years,” notes HIV, influenza, rabies, and human Wistar president and CEO papillomavirus, was among the Wistar Russel E. Kaufman, M.D. leaders who gathered to mark the cen- “With its history of success ter’s launch May 31 at the Institute. in vaccine development,

From left, Wistar president and CEO Russel E. Kaufman, M.D., with Vaccine Center faculty member E. John Wherry, Ph.D; center director Hildegund C.J. Ertl, M.D.; Kenoye K. Eke, Ph.D., Cheyney University provost and vice president for academic and

Fall 2007 student affairs; and center

: faculty member Jan Erikson, Ph.D. FOCUS 4 VACCINE CENTER By Abbey J. Porter

people worldwide. The scientists are RABIES: Building on the success of and human papillomavirus, which pursuing human clinical trials for existing Wistar rabies vaccines for causes cervical cancer. Institute scien- a vaccine that has shown promise humans and wildlife, Wistar scientists tists’ autoimmune expertise also in animal studies. (See sidebar on are pursuing an improved human informs their development of novel page 7.) rabies vaccine for developing countries, new therapies for autoimmune diseases INFLUENZA: Institute scientists are where the disease still takes the lives of such as lupus and rheumatoid arthritis. working to create a universal influenza thousands of children each year. HEPATITIS C, MALARIA, AND OTHERS: vaccine that is effective against all CANCER AND AUTOIMMUNE DISEASES: Wistar researchers are collaborating strains of the flu, including avian flu, Wistar’s wide-ranging vaccine devel- with scientists at leading institutions eliminating the need for annual vacci- opment program encompasses worldwide to develop vaccines for nation programs and protecting against experimental treatment vaccines pandemics. (See sidebar on page 7.) against colorectal cancer, melanoma, continued on page 6

“SCIENCE OFFERS US THE ABILITY TO DELIVER A WHOLE WAVE OF NEW LIFE-SAVING VACCINES IN COMING YEARS.”

Left: Penny M. Heaton, M.D., vice Wistar Vaccine Successes president and chief medical officer Vaccines developed or co-developed by scientists at The Wistar Institute of Novavax, Inc., with Wistar adjunct professor Paul A. Offit, M.D., chief include: of infectious diseases at Children’s RUBELLA: The Wistar vaccine for rubella, also known as German measles, Hospital of Philadelphia. has eradicated this disease in the United States, according to the Centers for Below: Meryle Melnicoff, Wistar’s Disease Control. Rubella infections during pregnancy were once greatly feared director of business development, as a cause of devastating birth defects, including deafness and blindness. with Pakshirajan Sundaraparipooranan, chairman and director of Green Signal RABIES: Two vaccines for rabies developed at the Institute prevent this Bio Pharma Ltd., Chennai, India; disease in humans and wildlife. Wistar’s human rabies vaccine is a critical Wistar professor emeritus Stanley component of the treatment of choice for protecting people from rabies in A. Plotkin, M.D.; and B. Dhakshayani Lingamoorthy, director of Green the developed world. As long as the vaccine is given promptly as part of Signal Bio Pharma Ltd. post-exposure treatment, it is nearly 100 percent effective in preventing fatal infection. ROTAVIRUS: A new vaccine against rotavirus co-developed at Wistar became part of the recommended vaccine schedule for all U.S. babies in 2006. Rotavirus is the most common cause of severe dehydration disease in infants and young children. Rotavirus infections are responsible for tens of thousands of hospitalizations of U.S. children annually and an estimated 600,000 child- Fall 2007

hood deaths worldwide each year. : CYTOMEGALOVIRUS: Wistar researchers have developed a prototype vaccine

to protect against this widespread infection, which can cause severe disabili- FOCUS ties in infants. Wistar is now seeking a commercial partner to further develop this vaccine for the clinic. 5 Above: Wistar President and CEO Russel E. Kaufman, M.D., left, with Pennsylvania Secretary of Health Calvin B. Johnson, M.D., M.P.H. At right: Anthony P. Green, Ph.D., vice president of regional technology initiatives at Ben Franklin Technology Partners of Southeastern Pennsylvania, with, from left, Barbara S. Schilberg, Esq., managing director and CEO of BioAdvance, and RoseAnn B. Rosenthal, president and CEO of Ben Franklin Technology Partners of Southeastern Pennsylvania

hepatitis C, malaria, and other poten- Allergy and Infectious Diseases aimed effectively. The Vaccine Center also tially deadly diseases. at moving a promising new HIV vac- provides shared laboratory facilities at Reflecting Wistar’s outstanding rep- cine into human clinical trials. the Institute to support the work of all utation for vaccine research, Vaccine Wistar scientists lead the center, center researchers. These laboratories Center scientists have attracted strong working in collaboration with top include viral vector and human support from federal and state agencies Philadelphia-area organizations includ- immunology core facilities. and private grant makers. Center fac- ing the University of Pennsylvania, The center benefits from the exper- ulty members are supported by major Children’s Hospital of Philadelphia, tise of an external scientific advisory funding, including a $10.1 million and Temple University, as well as other board made up of leading researchers National Institutes of Health contract major research institutes around the and clinicians in immunology and vac- and a $4.2 million Pennsylvania country and the world. cine development. Wistar professor Department of Health grant to develop Vaccine Center faculty members emeritus Stanley A. Plotkin, M.D., a universal influenza vaccine and $13.3 maintain laboratories at the Institute, serves as board chair. A winner of the million from the National Institute of where they can collaborate easily and Sabin Gold Medal, Plotkin created the

Distinguished Researchers Lead Center

he following distinguished mem- the immune system regulates its immune responses to the influenza bers of the Wistar Institute responses to infecting agents and to virus. His expertise in immunology will T Immunology Program serve as the body’s own tissues and cells. He support his work on the development founding members of the Vaccine Cen- has extensive experience analyzing of a universal influenza vaccine, as ter. They bring a wide range of well as other projects. immunological expertise to the work of Professor Jan Erik- vaccine development. son, Ph.D., spearheads Professor Hildegund C.J. Ertl, M.D., efforts to better under- Vaccine Center director and leader of stand immune cell Wistar’s Immunology Program, is devel- activation and regula- oping preventive and therapeutic tion. Her lab has been vaccines for an array of infectious and studying the signals that

Fall 2007 noninfectious diseases, including HIV/ guide immune cells : AIDS and some forms of cancer. She down distinct develop- leads center efforts, including the devel- mental paths that result FOCUS opment of a universal influenza vaccine. in short-term immunity 6 Professor Andrew J. Caton, Ph.D., or long-lasting researches the mechanisms by which Hildegund C.J. Ertl, M.D. Andrew J. Caton, Ph.D. responses and memory Vaccine Center Garners State, Federal Funding Support rubella vaccine used in the United States and worldwide. He also devel- ince the Vaccine Center’s inauguration, its faculty members have earned two sig- oped experimental vaccines against nificant grants to support their research: $4.2 million from the Pennsylvania cytomegalovirus and polio and collab- SDepartment of Health to develop a universal influenza vaccine and $13.3 million orated with former Wistar scientists from the National Institute of Allergy and Infectious Diseases to move a promising Hilary Koprowski, M.D., also a Sabin new HIV vaccine into human clinical trials. Gold Medal winner, and Tadeusz The universal influenza project is being conducted in partnership with organiza- Wiktor, D.V.M., on a human vaccine tions including the University of Pennsylvania, Children’s Hospital of Philadelphia, and against rabies and with Paul A. Offit, Temple University. Project funding, which began June 1 and will extend for four years, M.D., and H. Fred Clark, D.V.M., also enables Wistar to partner with Lincoln University and Cheyney University to pro- Ph.D., on another against rotavirus. vide research training to undergraduate minority students and their instructors. More information on the Wistar “A universal influenza vaccine would allow us to guard against evolving strains, Institute Vaccine Center, including including the avian flu,” says project leader and center director Hildegund C.J. Ertl, inauguration highlights and podcast M.D. “It would also provide better protection for vulnerable populations, such as the interviews with center faculty mem- elderly.” bers, is available at www.wistar.org/ A universal vaccine would eliminate the need for annual vaccination campaigns and vaccinecenter. protect against flu pandemics, which occur when a new strain of flu emerges that is both deadly and highly contagious. Ertl also is principal investigator for the newly funded HIV vaccine project. With $13.3 million in funding over five years, the planned clinical trials will be conducted under the auspices of the Integrated Preclinical/Clinical AIDS Vaccine Development Program of the National Institute of Allergy and Infectious Diseases. Wistar Institute scientists will collaborate with researchers at Emory University, the University of Pennsylvania, Harvard School of Public Health, MRC/UVRI Uganda Research Unit, and the National Institute for Communicable Diseases in South Africa on the project, which began September 1. “We believe our vaccine, which is built on a novel chimpanzee virus backbone, has unique immunological advantages over other HIV vaccines currently in testing,” Ertl says. “In preclinical studies, the vaccine induced a vigorous immune response in mon- keys, and we are hopeful it will do the same in humans.”

formation. Her detailed understanding Professor Luis J. Montaner, D.V.M., and strategies for understanding and of immune cells and their interaction D.Phil., works with HIV/AIDS patients strengthening the immune system’s will inform her work on the develop- in the Philadelphia area and in South response to HIV. His expertise will ment of a universal influenza vaccine. Africa, researching novel treatments support the Vaccine Center’s development of vaccines for HIV/AIDS and other diseases. Assistant professor E. John Wherry, III, Ph.D., focuses on the failure of immune system response in cases of chronic infection and in the elderly. His insights and experience in this area promise to contribute to the develop-

ment of new and improved vaccines for Fall 2007 : conditions such as hepatitis C and influenza. Additional scientists will join the FOCUS center’s faculty as the initiative devel- 7 Jan Erikson, Ph.D. Luis J. Montaner, D.V.M., D.Phil. E. John Wherry, III, Ph.D. ops further. Melanoma Patient Creates Legacy of Understanding

By Abbey J. Porter

eenhard Herlyn, D.V.M., conscious or unconscious?—that I D.Sc., is one of the shied away from getting involved with world’s preeminent melanoma patients, but after I met melanoma researchers, Noreen, I realized that there’s more to but he hadn’t put a research than studying the basic mecha- Mhuman face on the disease until he met nism of the disease,” says Herlyn, who Noreen O’Neill. Prior to encountering leads Wistar’s Molecular and Cellular the vivacious woman in 1998, Herlyn, Oncogenesis Program. “I wanted to do who had been researching the disease something for the patient.” for more than two decades, had never Having been diagnosed with met a melanoma patient. melanoma, O’Neill sought out Herlyn “I don’t know the reason—was it because she was determined to make an impact on the disease that was affecting her. She wanted to raise money for

melanoma research and O’Neill Family Photo couldn’t find a Philadel- Noreen O’Neill phia-area organization that shared her goals. So, with long road even if it didn’t help her,” Herlyn’s help, O’Neill set Herlyn recalls. out to create her own The research she supported would, foundation. Her vision indeed, come too late to help O’Neill, would become the Noreen who died of melanoma in 2000 at O’Neill Foundation for age 48. Melanoma Research. Her vision lives on through her O’Neill knew that foundation, led by her sister Kate 60,000 people are diag- O’Neill. In addition to raising aware- nosed with melanoma ness about the disease, the organization each year and that 8,000 donates the money it raises to support of them will eventually die the melanoma research performed at of the disease. Among Wistar by Herlyn and his colleagues. patients whose melanoma (See sidebar at right.) In doing so, metastasizes, about 85 per- Herlyn believes, the foundation reflects cent die within five years. O’Neill’s visionary thinking and belief Like a scientist, she held a in the critical importance of research.

Fall 2007 long-term view, and she That support is being rewarded : knew that research holds with progress in the lab. Herlyn has the answer to creating developed unique artificial skin models FOCUS more effective treatments. that are aiding him in studying skin “Noreen was saying cell division and proliferation in 8 Leonardi Tommy Meenhard Herlyn, D.V.M., D.Sc. that she wanted to see the melanoma, and he is also working with federally approved stem-cell lines to understand what role melanoma stem ‘Running For Cover’ Benefits cells may play in the disease. “In the near future, meaning in Wistar Melanoma Research the next five years, we can start to unning for Cover, the annual race organized by the Noreen O’Neill think about saving the lives of most Foundation for Melanoma Research, raises funds to support melanoma patients with advanced melanoma,” R research at Wistar. The event, which expanded beyond Philadelphia this Herlyn says. year to include a site in Atlanta, netted total proceeds of $60,000. On a personal level, the charismatic O’Neill, who Herlyn remembers as “a people person” who could “get people “HER LEGACY IS TO BUILD BRIDGES between basic researchers and patients.“

engaged,” changed the way the

researcher approaches his work. Herlyn Joseph Zajaczkowski acknowledges that keeping distance PHILADELPHIA: TWO YEARS RUNNING—Wistar community members who participated in the from patients can serve a purpose in June 24 Running for Cover event at the Wachovia Center in Philadelphia pose for a team allowing scientists to dissect the com- photo. Nearly 600 people, including 95 Wistar employees and their friends and family members, turned out for the second annual five-kilometer run and one-mile walk. More plexity of a disease into relatively simple than twice as many runners, walkers, and volunteers participated this year as last year. models. However, he says “sometimes scientists go so far into a reductionist mode that they lose the association with human disease.” Meeting O’Neill helped Herlyn focus on the human aspects of the disease—and treatment—instead of merely examining a biological question. “Her greatest legacy, for me, is to motivate me to be involved in patients’ pressing issues, to become involved in therapy,” Herlyn says. “Her legacy is to build bridges between basic researchers and patients. You have to do that at a personal level and bring people together.” Fall 2007 Rick Hight : The Noreen O’Neill Foundation for ATLANTA: OFF WITH A BANG—Volunteers at Atlanta’s first annual Running for Cover event Melanoma Research was posthumously take time out from their duties June 23 at South Forsyth High School. The event drew named in Noreen O’Neill’s honor. For 150 participants and up to 40 volunteers and raised more than $15,000. At center in FOCUS more information on the foundation, visit white T-shirts are organizer Angie Bowbliss and her husband, Pete, a melanoma survivor in whose honor the event was held. 9 www.foundationformelanomaresearch.org. E. John Wherry, Ph.D., and Joseph Kissil, Ph.D., are exploring ways to harness the immune system to join the [ fight against lung cancer.

according to the Centers for Disease Control and Prevention. Four laboratories at The Wistar Institute are aiming to change this, and they can boast remarkable progress in just the past year. One set of researchers is developing an early detection blood test for lung cancer, while another is exploring how the immune system might be brought into the fight against the disease. Two of the laboratories are working with support from the Leroy E. Kean Family Foundation. Kean, whose wife Lois died of lung cancer in 2002, has as his primary goal to support research that may lead to a cure for lung cancer. He also has a secondary goal of raising the profile of lung cancer research at Wistar to attract more scientists to study this deadly disease. The other two Wistar labs studying lung cancer have received funding from the Commonwealth of Pennsyl- vania through the Tobacco Master Settlement Agreement, which directs tobacco-company payments to the

Tommy Leonardi Tommy states to compensate for smoking- related medical costs. Pennsylvania targets a percentage of the funds it receives through the agreement for bio- Tackling the No. 1 medical research. “There are roughly 40 million smokers and ex-smokers in the United States,” says Louise C. Showe, Ph.D., Cancer Killer a professor in Wistar’s Molecular and Cellular Oncogenesis Program and one P ROMISING P ROGRESS A GAINST L UNG C ANCER of the Wistar scientists researching lung cancer. “Approximately 15 FROM F OUR W ISTAR L ABORATORIES percent of those people will get By Franklin Hoke lung cancer. That’s 6 million people.” Showe has been supported by tobacco- settlement funds.

Fall 2007 The main reason that so many peo- : More people die from lung cancer each year ple die from lung cancer is that the than from any other form of cancer. In fact, the disease is often detected too late for FOCUS disease accounts for more deaths than breast cancer, effective treatment. Perhaps a quarter 10 of people with advanced lung cancer prostate cancer, and colon cancer combined, have no clinical symptoms. Many of the rest have non-specific symptoms A BLOOD TEST TO DETECT EARLY-STAGE LUNG CANCER, CURRENTLY IN DEVELOPMENT AT WISTAR, COULD SAVE MILLIONS OF LIVES. such as shortness of breath or a persis- ing an early detection lung-cancer test against other cancers, including tent cough. A simple and accurate test that also focuses on the blood. He too melanoma, the deadliest skin cancer. for early detection of the disease would has seen promising results. The first step in their efforts has save millions of lives. Speicher uses advanced analytic tools been to develop a strain of mice that This is the area in which Showe has to search for signature proteins shed by will enable closer study of the molecu- focused the efforts of her laboratory. different cancers into the blood. To lar mechanisms involved in the She and her colleagues compared the date, he has identified dozens of lung progression of the disease. For several activity of 25,000 genes in blood sam- tumor proteins in the blood, and he years, Kissil has been investigating the ples from lung cancer patients to the expects that some of these proteins will role of a gene called K-ras in the most activity of the same genes in samples form the basis of improved tests for common form of lung cancer. The from people with other lung diseases. cancer detection. These proteins are newly developed mice incorporate a They succeeded in identifying a group referred to as biomarkers, and Speicher mutant version of this gene that, when of only 15 genes that she believes could is now conducting additional studies to activated, results in tumors that closely be the basis for a new diagnostic test. determine which of the proteins have mimic human lung cancer. “In the laboratory, we can now diag- the most value as diagnostic markers for Already, experiments in the mice are nose early stage lung cancer using the early detection of lung cancer. producing significant results. In Sep- blood samples with something like 92 Support from donor Kean is allow- tember, Kissil published a study in the percent accuracy,” Showe reports. ing assistant professor Joseph Kissil, journal Cancer Research showing that “This is exciting, because the disease is Ph.D., in the Molecular and Cellular the activity of another gene called often curable when treated aggressively Oncogenesis Program, and E. John Rac1 is required for K-ras-induced in the earliest stages of development.” Wherry, Ph.D., an assistant professor lung cancers, illuminating an impor- David Speicher, Ph.D., a professor in the Immunology Program, to collab- tant step on the biochemical pathway in and co-leader of the Molecular and orate to investigate how the immune in lung-cancer development. Cellular Oncogenesis Program, heads system might be harnessed to recognize Wherry’s research focuses on under- the lung-cancer research project on and combat lung cancer. The pair of standing the immune response to which Showe works. He is using a scientists is encouraged by the fact that chronic infections. A study from his complementary approach to develop- this strategy is proving successful laboratory, published in the journal Immunity in October, showed that critical immune cells called T cells become exhausted by the fight against disease in specific ways, undergoing profound genetic changes that make them pro- gressively less effective over time. “The problem of T-cell exhaustion is seen not only in chronic infections, but also in cancer,” Wherry says. “As we come to understand the process better, we expect to find ways to turn the immune system back on when this happens. Interventions of this kind could be used to fight chronic infections but might also be applied to treating lung cancer and other cancers.”

On the strength of their initial Fall 2007 :

Tommy Leonardi Tommy work, Kissil and Wherry plan to apply to the federal government for sustain- ing funds to carry the research forward. FOCUS With funding from the Commonwealth of Pennsylvania, Louise C. Showe, Ph.D., and Micheal K. Showe, Ph.D., “There are a lot of opportunities 11 have identified genes that may form the basis for that will evolve out of this project,” [ an early detection blood test for lung cancer. Wherry says. W ISTAR A WARD P RESENTED TO L ONGTIME S UPPORTER H AL D AVIS

he Wistar Institute D AVIS AND W IFE E LEANOR H AVE honored real-estate C LIMBED M OUNTAINS FOR C ANCER R ESEARCH developer Hal Davis at a black-tie gala By Franklin Hoke October 27 at the T Four Seasons Hotel program by thanking the honorary Herbert Lotman Foundation. Addi- Philadelphia. Davis members of the committee: Governor tionally, she acknowledged the time has been a member of the Wistar Edward G. Rendell, Sen. Arlen Specter, and efforts of her fellow gala commit- board of trustees for 20 years and cur- Sen. Robert P. Casey Jr., Philadelphia tee members: Ira Brind, Robert A. Fox, rently serves as co-vice chair of the mayoral candidate Michael Nutter Russel E. Kaufman, M.D., Faye board. He and his wife, Eleanor, have (now mayor-elect), former NFL coach Kozich, Herbert Lotman, Nicholas supported breast cancer research at the Dick Vermeil, ABC News correspon- Martell, Helen P. Pudlin, Esq., Edward Institute for many years, and the event dent Sam Donaldson, and Gen. H. Sickles, and Kevin M. Tucker. in his honor raised more than Norman Schwarzkopf. On behalf of Wistar board chair Brian H. Dovey $100,000 for research at Wistar. Wistar, she also expressed her gratitude also offered remarks at the gala, outlin- At the gala, Davis was presented to the major sponsors of the event: ing some of the significant progress with the Wistar Award, which the Insti- RAF Industries, Realen Properties, being made at the Institute: the launch tute presents periodically to an PNC Financial Services Group, Betty of the Wistar Institute Vaccine Center individual who demonstrates compas- and Brian H. Dovey, Maureen and in May to create new vaccines against sion, integrity, generosity, commitment, Brian Harrison, and the Karen and HIV, influenza, and other major dis- and vision in service to Wistar. To date, only three other people have received the award: Robert A. Fox, Doris Taxin, and Kevin M. Tucker. “Hal has always been a person I could go to for advice and counsel,” says Russel E. Kaufman, M.D., president and CEO of The Wistar Institute. “And at the end of the day, he believes in what we do at Wistar and has been extremely supportive of our efforts.” Adele K. Schaeffer, chair of the Wistar gala committee, opened the Fall 2007 : HONORING A

FOCUS FRIEND OF WISTAR Wistar chair of the board Brian H. Dovey, left, honoree Hal Davis, and 12 Wistar president and CEO Russel E. Kaufman, M.D., following presentation of the Wistar Award to Davis eases; the anticipated opening of the Western Hemisphere at 22,831 feet— Center for Systems and Computational to raise awareness of breast cancer. Her Biology, which will extend Wistar’s climb also raised $50,000 for cancer 35-year history of accomplishment in research at Wistar. WISTAR cancer research; and the recruitment in Davis co-founded Realen Homes in SUPPORTERS just the past few years of 12 talented 1967. The company was named CELEBRATE scientists to join the Institute’s faculty. National Home Builder of the Year in Clockwise from top: Gala chair Kaufman spoke warmly about 1998. Davis sold the company in 2000 Adele K. Schaeffer; Dennis Davis and praised him for his intelli- but continues to serve as a founding Maloomian, a business partner of honoree Hal Davis, with gence and, particularly, his steadfast partner with Realen Properties, a com- Davis; Frank and Suzanne loyalty, not only to friends and family mercial real estate developer with Binswanger; Adele and Al but also to any cause to which he dedi- properties in Pennsylvania, New Jersey, Goldman; Judy Lieb, left, with Eleanor Davis, wife of honoree cates himself, including The Wistar California, and Florida. Hal Davis, and Maureen Institute. Wistar has long been Davis’s Harrison; Betty Dovey, wife of leading philanthropic commitment. Wistar chair of the board Brian The Davises’ interest in cancer H. Dovey, left, with Dick Gwinn, Brian Dovey, and Brita Gwinn; research—one of Wistar’s two primary Jerry Johnson, left, chair of areas of focus, along with vaccines— Radnor Trust Co., with Tony stems from personal experience. Hal lost Nichols and Raye Johnson a brother to cancer, and Eleanor sur- vived breast cancer. She recalls: “When I was diagnosed with breast cancer in 1979 at a young age and Hal became involved at Wistar, I thought it was a perfect opportunity for us to invest in basic biomedical research—to help find a cause, and eventually a cure.” After the couple’s son Christopher died in an automobile accident in 1995, they established the Christopher M. Davis Memorial Fund at Wistar in his memory. The fund created a fellowship that allows Wistar to recognize a postdoctoral fellow who excels in breast-cancer research. Most recently, the Davises also endowed an associate professorship at the Institute that will help Wistar to remain competitive in recruiting outstanding young scientists for cancer research. The Davises have climbed to great heights—literally—in their efforts to support cancer research. In 1992, the couple set off with family members to climb Mount Kilimanjaro in Kenya, an ascent of 19,340 feet. Wistar Insti- tute researchers supplied them with a Fall 2007 : Wistar flag, which they planted when they reached the summit. In 1995, Photos by Tommy Leonardi Photos by Tommy Eleanor also participated in Expedition FOCUS Inspiration, in which breast-cancer sur- 13 vivors climbed Aconcagua in Argentina—the highest point in the ■ PROGRESS

Regulation of Vital Tumor Small Gene-Silencing Suppressor Gene p53 Molecules Subject to Redirection by Editing o vital is the p53 tumor suppressor Sgene in controlling cancer that its iny molecules called microRNAs dysfunction is linked to more than half Tare able to effectively silence some- of human cancers. At the same time, times large sets of genes. Most often, the gene’s capacity for shutting down they do this by specifically binding to cell growth, even causing cells to com- and neutralizing another form of RNA mit suicide if necessary, is so absolute called messenger RNA, responsible for that it must be tightly regulated to conveying the information from genes maintain the optimal balance between to the cellular machinery that uses that protecting against cancer and permit- information to create proteins, the ting normal growth. building blocks of the body. Several Robert H. Clink A study by scientists at The Wistar Shelley L. Berger, Ph.D. hundred species of microRNAs have Institute revealed new levels of subtlety been identified to date, and increas- in the body’s management of this all- mutated or otherwise disabled in a ingly they are being seen as vitally important tumor suppressor gene and majority of human cancers. When important players in regulating the the protein it produces. The experi- working properly, the protein produced genome. ments showed that, while the addition by the p53 gene acts by binding to A study led by Wistar researchers of a specific molecule at a particular site DNA to activate other genes that direct showed that these microRNAs can on the p53 protein prevents it from act- cells with damaged DNA to cease undergo a kind of molecular editing ing, the addition of a second copy of the dividing until the damage can be with significant physiological conse- same molecule at the same site reverses repaired. Cells with such damage quences. A single substitution in their sequence can redirect these microRNAs All cancers track to genetic flaws to target and silence entirely different of one kind or another, sets of genes from their unedited coun- whether inherited or acquired. terparts. Further, errors in the editing can lead to serious health problems. the effect, sending p53 into action. Fur- include cancer cells, since all cancers The team’s findings appeared in Science ther, removal of the second copy returns track to genetic flaws of one kind or in February and were reported on the the protein to its repressed state. another, whether inherited or acquired. front page of the Philadelphia Inquirer A report on the study appeared in If repairs cannot be made, p53 com- and in other publications. September in Nature. mands the cells with damaged DNA to “What we found was that, in cer- “The p53 tumor suppressor is self-destruct so they are no longer a tain cases, edited versions of these extremely potent in halting cell danger to the body. microRNAs are being produced that growth,” says Shelley L. Berger, Ph.D., Jing Huang, Ph.D., was lead differ from the unedited versions by the Hilary Koprowski Professor at Wis- author on the study. The other Wistar- only a single nucleotide change,” says tar and senior author on the study. “So, based co-authors were Min Gyu Lee, Kazuko Nishikura, Ph.D., a professor as critical as p53 is in protecting Jean A. Dorsey, and professor Ramin in the Gene Expression and Regulation against the unchecked growth of can- Shiekhattar, Ph.D. The remaining co- Program at Wistar and senior author cer, you don’t want it constantly on. If authors were Roopsha Sengupta, Mario on the study. “These edited micro- it were always on, your cells wouldn’t Richter, Susanne Opravil, and Thomas RNAs are not encoded in the DNA, be able to grow normally. Yet it needs Jenuwein at The Vienna Biocenter in which means that at least two versions to be constantly on call for activation Austria, and Alexsandra B. Espejo are being produced by one gene. This against cancer and other aberrant cellu- and Mark T. Bedford at the M.D. was not anticipated—it was something

Fall 2007 lar developments. Our study shows one Anderson Cancer Center in Houston. really new.” : way that cells, working at one particu- Funding for the research was pro- The two lead researchers on the lar location on the p53 protein, vided by the National Institutes of Science study were Yukio Kawahara, FOCUS maintain a nuanced but firm control Health and the Commonwealth Uni- Ph.D., and Boris Zinshteyn, both in 14 over the gene’s activity.” versal Research Enhancement Program Nishikura’s laboratory at Wistar. Responsible for tumor suppression of the Pennsylvania Department of Co-authors included Hisashi Iizasa, throughout the body, the p53 gene is Health. also based at Wistar, and Praveen Component of Niacin WISTAR WELCOMES NEW FACULTY MEMBERS May Point the Way to Anti-Aging Drugs wo new scientists joined Wistar’s Tfaculty in September, bringing the n recent years, scientists have discov- Institute’s faculty complement to 31. Iered that a family of enzymes called Hui Hu, Ph.D., is an assistant pro- sirtuins can dramatically extend life in fessor in Wistar’s Immunology organisms as diverse as yeast, worms, Program. Hu was formly a postdoc- and flies. They may also be able to con- toral associate at the CBR Institute for trol age-associated metabolic disorders, Biomedical Research at Harvard Med- including obesity and type II diabetes. ical School, where he investigated Naturally occurring substances have immune cell genetics, development, been shown to activate sirtuins, includ- and function in the laboratory of ing a constituent of red wine called Anjana Rao, Ph.D. He also served as resveratrol—although an individual an instructor in the department of Kenichi Noma, Ph.D. would need to drink about two cases of pediatrics at Harvard’s Children’s Hos- wine a day to derive a clinically effec- pital Boston. in B cell development. He plans to elu- tive dose of resveratrol. Still, the Hu attended the Shanghai Medical cidate the molecular mechanisms of findings have energized a number of University and received his doctorate the factor’s regulation and participation scientific groups and biotechnology from Stockholm University. Prior to in transcriptional control of this companies, all of which are now joining Harvard in 2002, he served as process, as well as its role in mature B eagerly searching for drug candidates director of immunobiology for Synta and T cell functions. able to boost sirtuin activity. The Pharmaceuticals Corp. He also served Kenichi Noma, Ph.D., is an assis- public-health benefits of such an “anti- as a postdoctoral associate at the Cen- tant professor in Wistar’s Gene aging” drug would be substantial—as ter for Cancer Research at MIT and as Expression and Regulation Program. would the economic returns. a postdoctoral fellow at the Trudeau Noma was formerly a staff scientist at A study from Wistar scientists Institute. the National Cancer Institute’s Labora- points to another strategy for activating After initiating research on the tory of Biochemistry and Molecular sirtuins to unleash their anti-aging novel transcription factor Foxp1, Hu Biology, where he investigated the powers. A report on the research discovered that it plays an essential role mechanisms controlling the assembly appeared in February in Molecular Cell. of chromatin, the material that makes Using the techniques of structural up chromosomes, in fission yeast in the biology, the Wistar team demonstrated lab of Shiv Grewal, Ph.D. that a component of the common vita- Noma earned his doctorate from min B3, also known as niacin, binds to the University of Tokyo. He served as a a specific site on the sirtuin molecule postdoctoral fellow at Cold Spring to inhibit its activity. This observation Harbor Laboratory before moving to suggests that drugs designed to prevent the National Cancer Institute. the vitamin B3 component, nicotina- Noma’s long-term research goals mide, from binding at this site could include exploring the role of higher- have the effect of activating sirtuins. order chromatin organization in Any such drug would, in essence, various cellular processes, eventually inhibit the inhibitory effect of nicoti- extending his research in fission yeast namide. As in mathematics, the two Hui Hu, Ph.D. to mammalian systems. negatives would create a positive result —activation of sirtuins.

“Our findings suggest a new avenue Fall 2007 : Sethupathy at the University of Penn- Health, the National Science Founda- for designing sirtuin-activating drugs,” sylvania. Artemis G. Hatzigeorgiou, tion, the Juvenile Diabetes Research says senior author Ronen Marmorstein, Ph.D., at Penn was a collaborator on Foundation, and the Commonwealth Ph.D., a professor in Wistar’s Gene FOCUS the study. Universal Research Enhancement Pro- Expression and Regulation Program. 15 The research was supported by gram of the Pennsylvania Department “The jury is still out as to whether a grants from the National Institutes of of Health. drug of this kind might result in longer ■ PROGRESS

life in humans, but I’m equally excited the experiments involving human cells, by the possibility that such interven- are affiliated with the University of tions might help counteract age-related Pennsylvania. Kenneth J. Finn, Ph.D., health problems like obesity and type is with the University of California, II diabetes.” San Diego, as is study collaborator The lead author on the Molecular Amy E. Pasquinelli, Ph.D. Cell study was Brandi D. Sanders at The research was supported by the Wistar. Kehao Zhao, Ph.D., formerly at National Institutes of Health, the Searle Wistar and now at the Novartis Insti- Foundation, the V Foundation for tutes for Biomedical Research Inc. in Cancer Research, the Mathers Founda- Cambridge, Massachusetts, was also a tion, the Cooley’s Anemia Foundation, coauthor, as was James T. Slama, Ph.D., and the Commonwealth Universal with the College of Pharmacy at the Research Enhancement Program of the University of Toledo, Ohio. Funding to Pennsylvania Department of Health. support the research was provided by

Peter Olson ‘Insulator’ Helps Silence the National Institutes of Health and Ramin Shiekhattar, Ph.D. the Commonwealth Universal Research Genes in Dormant Herpes Enhancement Program of the Pennsyl- genes from producing proteins. vania Department of Health. MicroRNAs have been implicated in a y adulthood, most people have number of cancers, and the newly out- Bsuffered at least one bout of Newly Identified lined gene-silencing mechanism offers painful cold sores brought on by the Mechanism for promising potential targets for anti- herpes simplex virus 1, also known as Silencing Genes cancer interventions. HSV-1. After the initial infection, the “Some microRNAs closely match virus usually remains in the body, hid- enes provide the instructions used their sequences against particular mes- ing out in nearby nerve cells where the Gby individual cells to produce the senger RNA sequences to target them victim’s immune defenses cannot reach many different proteins that make up for destruction,” explains Ramin it, causing no symptoms at all between the body. Scientists are only beginning Shiekhattar, Ph.D., a professor in the periodic outbreaks. to appreciate, however, the extraordi- Gene Expression and Regulation Pro- In order to escape detection by the nary degree of control exercised over gram and the Molecular and Cellular body’s immune system, the latent virus every step of the production process. Oncogenesis Program at Wistar and works to silence genes that would cause Only about 10 percent of human senior author on the study. “That’s one it to replicate. In this dormant state, genes, for example, are actively produc- way we know that microRNAs can only a tiny fragment of the virus ing proteins in a given cell at a given silence genes. genome—a single gene called the time. The remaining 90 percent are “That mechanism requires extraor- Latency-Associated Transcript gene silenced by various mechanisms that dinary specificity, however, and we (LAT)—remains active. Scientists have act to interfere with gene transcription suspected that microRNAs were also into messenger RNA or translation of acting in some other way to inhibit messenger RNA into the final protein. gene translation into protein.” In a study published in May in the By tracking the associations between journal Nature, a team of scientists at molecules involved in generating Wistar and the University of Califor- microRNAs and other molecules in the nia, San Diego, reported identification cell, the researchers uncovered an of an important new gene-silencing entirely new mechanism that blocks mechanism, one that blocks the cellular the cellular machinery that produces machinery responsible for translating protein from messenger RNA.

Fall 2007 the messenger RNA associated with The lead author on the study was : specific genes into proteins. Thimmaiah P. Chendrimada, Ph.D., The findings suggest that small bits at Wistar. The additional Wistar FOCUS of RNA known as microRNAs, known co-authors were David Baillat, Ph.D., 16 to help regulate genes but not used for and Richard I. Gregory, Ph.D. protein production, may be operating Co-authors Xinjun Ji, Ph.D., and Steve Addison Geary in a completely novel way to prevent A. Liebhaber, M.D., who conducted Jumin Zhou, Ph.D. long puzzled over the mechanism used infected cells to survive,” says study a similarity that may work to the to keep this small region of the senior author Jumin Zhou, Ph.D., a virus’s advantage, says Shelley L. genome going while nearby genes Wistar associate professor. Berger, Ph.D., the Hilary Koprowski remain quiescent. The findings, which appeared in the Professor at The Wistar Institute and Now, scientists at Wistar have dis- May issue of the Journal of Virology, co-author on the study. covered a molecular mechanism that mark the first time such an insulator In addition to senior author Zhou keeps HSV-1 activation restricted to a has been identified in a virus and may and co-author Berger, the additional single gene for months or even years. lead to new strategies to manipulate coauthors on the study are Qi Chen, The researchers have identified an the virus to control infection. M.D., Lan Lin, Sheryl Smith, Ph.D., “insulator”—a stretch of DNA about Insulators, also known as boundary and Jing Huang, Ph.D., all at Wistar. 800 base pairs long—that serves as a elements, are DNA segments that The research was supported by grants physical barrier between active and work to prevent a gene from being from the National Institutes of Health inactive regions of the virus genome. influenced by the activation or repres- and the Commonwealth Universal Base pairs are the nucleotides on each sion of its neighbors. About a dozen Research Enhancement Program of side of the rungs that connect the different insulator elements have been the Pennsylvania Department of strands of the DNA ladder. identified in organisms as varied as Health. “By establishing an insulator in yeast, fruit flies, and humans. early latency, the herpes virus can pro- The study also showed that HSV-1 Information on Wistar technologies available for tect this one small region of the chromatin is organized in a manner licensing can be found at www.wistar.org under genome from silencing, allowing very similar to the host chromatin, “Technology Transfer.”

New Grant Awards The Wistar Institute and its scientists continue to compete successfully for grants to support research and programs. Below is a list of recent awards.

PRIVATE GRANTS INNISFREE FOUNDATION OF BRYN MAWR SAMUEL WAXMAN CANCER RESEARCH The Wistar Institute, Investing in Leadership FOUNDATION ACCELERATE BRAIN CANCER CURE Campaign, $20,000 Frank J. Rauscher, III, Ph.D., research on regulation Qihong Huang, M.D., Ph.D., development of new of chromatin, the material of chromosomes, $230,000 treatments for brain tumors, $140,000 KEYSTONE MERCY HEALTH PLAN The Wistar Institute, prostate cancer research, $2,500 ALPHA OFFICE SUPPLIES GOVERNMENT GRANTS The Wistar Institute, prostate cancer research, $2,500 LEUKEMIA & LYMPHOMA SOCIETY COMMONWEALTH OF PENNSYLVANIA Shelley L. Berger, Ph.D., research on regulation of Hildegund C.J. Ertl, M.D., development of univer- AMERICAN ASSOCIATION p53 tumor suppressor protein, $180,000 sal influenza vaccine, four-year grant of $4.2 million FOR CANCER RESEARCH Shelley L. Berger, Ph.D., research on regulation of LYMPHOMA RESEARCH FOUNDATION NATIONAL CANCER INSTITUTE p53 tumor suppressor protein, $36,000 Jing Zhou, M.D., Ph.D., laboratory of Paul M. Frank J. Rauscher III, Ph.D., investigation of links Lieberman, Ph.D., fellowship, $105,000 between gene-regulation and DNA-damage- AMERICAN HEART ASSOCIATION response mechanisms, three-year grant of $154,000 Vilma Decman, Ph.D., laboratory of E. John Wherry, EDWARD MALLINCKRODT, JR. FOUNDATION Ph.D., investigation of deficits in immune responses Susan M. Janicki, Ph.D., living-cell research on reg- NATIONAL CENTER FOR RESEARCH in the aged, $76,000 ulation of chromatin, the material of chromosomes, RESOURCES $60,000 David W. Speicher, Ph.D., laboratory equipment, AMERICAN SKIN ASSOCIATION $500,000 Brijal Desai, laboratory of Meenhard Herlyn, D.V.M, SAMUEL P. MANDELL FOUNDATION melanoma research, $7,000 Nadia Dahmane, Ph.D., cancer research, $1,000 NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES G. HAROLD AND LEILA Y. MATHERS MORRIS S. & FLORENCE H. BENDER Hildegund C.J. Ertl, M.D., clinical development FOUNDATION FOUNDATION, INC. of HIV-1 vaccine based on chimpanzee serotypes Gerd Maul, Ph.D., David W. Speicher, Ph.D., ovarian cancer research, research on regulation of cell of adenovirus, five-year grant of $13.3 million $1,250 stress responses, $255,000 NATIONAL INSTITUTE OF GENERAL CITIZEN’S BANK MERCK & CO., INC. MEDICAL SCIENCES William H. Wunner, Ph.D., Biomedical Technician The Wistar Institute, prostate cancer research, $5,000 Shelley L. Berger, Ph.D., research on gene-regulation Training Program, $2,500 THE PEW CHARITABLE TRUSTS mechanisms in yeast, four-year grant of $1.4 million ELLISON MEDICAL FOUNDATION The Wistar Institute, recruitment and provision of NATIONAL INSTITUTE OF NEUROLOGICAL Emmanuel Skordalakes, Ph.D., New Scholar Award equipment to three new investigators, three-year DISORDERS AND STROKE in Aging, research on replication of telomeres, grant, $1 million Shelley L. Berger, Ph.D., subcontract from genetic elements associated with aging, $200,000 THE PHILADELPHIA FOUNDATION University of Pennsylvania, studies of mechanisms governing herpes simplex virus latency, four-year, Fall 2007 The Wistar Institute, prostate cancer research, $5,000 : FIDELITY CHARITABLE GIFT FUND ten-month grant of $1.2 million The Wistar Institute, President’s Fund, $2,000 PHRMA FOUNDATION Qihong Huang, M.D., Ph.D., screening for drugs to Carlo Maley, Ph.D., bioinformatics research, $60,000 MARIE AND JOSEPH FIELD FUND modulate microRNAs, molecules associated with The Wistar Institute, biomedical research, $10,000 PRWT SERVICES multiple forms of cancer, one-year grant of $95,000 FOCUS The Wistar Institute, prostate cancer research, $5,000 GLAXOSMITHKLINE UNITED STATES ARMY William H. Wunner, Ph.D., 2007 Wistar Institute RADNOR TRUST David W. Speicher, Ph.D., prostate cancer research, 17 High School Fellowship Program, $9,640 The Wistar Institute, prostate cancer research, $5,000 one-year grant of $117,745 ■ BRIEFINGS

Cell Line Shows Promise from the cells of a child with a rare patients with breast cancer at the Uni- as Cancer Therapy form of T-cell leukemia, TALL-104 versity of Pennsylvania, and in patients has demonstrated potential for treat- with a variety of pediatric tumors at the he Italian biopharmaceutical coming cancers in both humans and Children’s Hospital of Philadelphia. Tpany Abiogen Pharma SpA animals. Santoli used the cell line suc- After Wistar granted Abiogen a limited recently obtained from Wistar a world- cessfully to treat dogs with license to TALL-104 in 1999, the com- wide license to TALL-104, a cell line osteosarcoma, a type of bone cancer, pany conducted a Phase I cancer trial that shows promise in combating a and malignant histiocytosis, a blood in Italy. Together these tests demon- variety of cancers. cancer. strated the safety of the therapy, which Developed by former Wistar In the late 1990s, TALL-104 was is the aim of Phase I trials. researcher Daniela Santoli, Ph.D., evaluated in Phase I clinical trials in Based on this early success, Wistar and Abiogen worked together to expand the company’s license and grant 2007 Journalism Award Winner Named Abiogen exclusive worldwide rights. Winner Discusses ‘Bioterror Threat’ on Wistar Panel “Abiogen has been encouraged by our early studies demonstrating the eter Aldhous, San Francisco bureau chief safety of TALL-104,” says Sergio Pfor New Scientist magazine, won the 2007 Rosini, Ph.D., director of research and Wistar Institute Science Journalism Award for a development at Abiogen Pharma SpA. set of articles that investigated important areas of “We look forward to the opportunity current biomedicine, including bioterror and to develop a novel and effective cancer stem cell research. For his work, Aldhous received treatment using these cells.” a certificate of award and cash prize of $5,000. The cell line is now entering addi- The judges praised Aldhous for his meticulous tional testing. Phase I/II clinical trials reporting, particularly on two major issues in bio- began this year at M.D. Anderson medical research. His original reporting on Cancer Center, Houston, with “dual-use” biomedical research made use of public leukemia patients who relapsed after databases to reveal little-known projects that pose treatment with the cutting-edge cancer potential risks to the public. He also conducted an therapy Gleevec. This level of testing insightful exploration of the limitations of stem cell research and pointed out will begin to assess the cell line’s effi- the hype put forth by many researchers in the field. In addition, he reported cacy, as well as its safety. A preclinical on a vital but poorly understood aspect of early HIV infection. research program also is under way Alhous received his award and was featured as part of a panel discussion on with the Cleveland Clinic to determine “The Bioteror Threat: Preventing the Misuse of Biomedical Research” Novem- whether TALL-104 can pass the blood- ber 1 at Wistar. Also featured were: brain barrier and treat brain cancer. • Joe Palca: senior science correspondent, National Public Radio; co-chair, “We believe TALL-104 may be Wistar Institute Science Journalism Award Judging Committee useful to treat a variety of cancers,” • Stanley Plotkin, M.D.: professor emeritus, The Wistar Institute; chair, Wis- notes Meryle J. Melnicoff, Wistar’s tar Institute Vaccine Center Scientific Advisory Board; developer of vaccines director of business development. against rubella and rotavirus; expert on anthrax “The early tests in dogs show that • Harvey Rubin, M.D., Ph.D.: director, Institute for Strategic Threat Analysis these cells have the potential to be a and Response, University of Pennsylvania; member, National Science Advi- completely different approach to sory Board for Biosecurity treating cancer.” The Wistar Institute Science Journalism Award honors annually the most insightful and enterprising reporting on the basic biomedical sciences in print Institute Recognized or broadcast journalism. Established in 2004, the prize has established itself as with Historical Marker

Fall 2007 a major award in professional journalism. Submissions for the contest were very : competitive this year, as in years past, with strong entries received from top istar unveiled a historical marker journalists reporting for print and broadcast outlets across the country. Wfrom the Pennsylvania Historical FOCUS Entries are judged by an independent panel of science journalists co-chaired and Museum Commission at a dedica- 18 by Pulitzer Prize winner Deborah Blum, a professor at University of Wisconsin- tion ceremony November 14. The blue Madison, and Joe Palca, senior science correspondent for NPR. marker outside the Institute indicates Wistar as a historic site. The ceremony also commemorated the 180th birth- Walter Gerhard day of Wistar founder Isaac Jones Retires Wistar. “This historical marker honors and Walter Gerhard, M.D., a professor celebrates Wistar’s rich history in the in Wistar’s Immunology Program, acknowledges colleagues in June region,” says Wistar president and at a reception marking his retire- CEO Russel E. Kaufman, M.D. “The ment after 33 years at the Institute has been an integral part of Institute. Using his extensive Philadelphia’s medical and scientific knowledge of influenza, Gerhard developed a prototype vaccine community for more than a century.” against the virus—a project that Kaufman made remarks at the cere- will continue under the leadership mony, as did Janet Klein, a PHMC of Jan Erikson, Ph.D., at the Wistar Institute Vaccine Center. member and Wistar supporter. Descen- A symposium featuring Nobel dants of the Wistar family, as well as Prize winner Peter C. Doherty, friends of the Institute, attended the Ph.D., a former Wistar faculty member, along with a number of event, which was followed by a cham- Gerhard’s former students, will pagne reception. be held in Gerhard’s honor Nov. 30 The text of the marker recognizes at the Institute. Wistar as the nation’s first independent biomedical research institution.

Skordalakes Wins New Authors of Vaccine Books Quest to Defeat the World’s Deadliest Scholar in Aging Award Speak at Wistar Diseases at the Institute in September. He focused on the man responsible mmanuel Skordalakes, Ph.D., accines have played a tremendous for nine of the “big fourteen” vaccines Eassistant professor in the Gene Vrole in the nation’s fight against recommended for all children: Maurice Expression and Regulation Program, infectious diseases, and they continue Hilleman, Ph.D., D.Sc. In Vaccinated, has won a New Scholar Award in Aging to occupy a prominent place in the Offit recounts Hilleman’s many contri- public’s consciousness. The two authors butions to worldwide public health and featured in Wistar’s 2007 Authors explores recent debates about vaccines Series wrote about aspects of vaccines’ and what science has to say about vac- development and current use. cine safety. Freelance journalist Arthur Allen, author of Vaccine: The Controversial Story of Medicine’s Greatest Lifesaver, spoke at the Institute in May. His book and talk focused on the tumultuous history of vaccines in the United States over the past 200 years, touching on vaccine safety, effectiveness, and public acceptance. Discussion topics included contem- porary vaccine

Tommy Leonardi Tommy controversies and the Emmanuel Skordalakes, Ph.D efforts made by the research community to from the Ellison Medical Foundation. ensure public confidence in Fall 2007 : The four-year award will provide vaccines and their ability to $200,000 to support his research into protect human health. the relationships among cell mortality Internationally known FOCUS and immortality, cancer, and aging in vaccine expert Paul A. Offit, 19 pursuit of anti-aging and anti-cancer M.D., discussed his new therapies. book Vaccinated: One Man’s Albert R. Taxin Golf Classic Sets Fundraising Record

Celebrating the success of the 12th Annual Albert R. Taxin Golf Classic to support brain tumor research are, from left, event co- chair Fran Tobin; Wistar Institute president and CEO Russel E. Kaufman, M.D.; former NFL football coach Dick Vermeil; event founder Doris Taxin; and event co-chairs Billy Cunningham of NBA fame and Electric Factory Concerts president Larry Magid. The tournament, held June 18 at the Green Valley Country Club in Lafayette Hill, raised more than $140,000 for brain tumor research at the Wistar Institute in its most successful year to date. Established in honor of Albert R. Taxin, who died of a brain tumor in 1993 at age 53, the event has raised nearly $1.25 million since its inception. Jim Rakowski, Cherry Hill Photo

Future Biomedical skills to make them excellent hires The BTT Program is one of sev- Technicians Graduate for institutions like Wistar or com- eral summer training initiatives for from Wistar Program panies in the pharmaceutical or college and high school students biotechnology sector. Some students offered by Wistar. The Institute also wo years of hard work was also plan to continue with further provides internships for college stu- Trewarded when students in the academic study. dents nationwide through the Biomedical Technician Training Pro- “You’re learning how to learn,” Summer Undergraduate Research Fel- gram were honored at a graduation keynote speaker Chad Womack, lows Program; research training for ceremony in August at The Wistar Ph.D., told the graduates. “Opening students from Cheyney University as Institute. A project of Wistar, Commu- doors is about asking the right ques- part of a state grant to support the nity College of Philadelphia, and the tions. With the training received in this Wistar Institute Vaccine Center; and Fels Institute for Cancer Research and program, you’ll be prepared to ask the internships for Philadelphia high Molecular Biology at Temple Univer- next question.” Womack, who is vice school students through the Wistar sity, the program combines classroom president for educational and training Institute High School Fellowship learning with hands-on lab experience initiatives at the Science Center in Program. over a two-year course of study. Philadelphia, received some of his early “Today is about opening doors,” training in the laboratory of former Assistant Professor said Wistar’s William H. Wunner, Wistar researcher Carlo M. Croce, Receives Grant Ph.D., administrative coordinator of M.D., now director of the human can- to Support Brain the BTT Program. He noted that the cer genetics program at Ohio State Tumor Research program equips students with the University Comprehensive Cancer technical, communication, and team Center. ihong Huang, M.D., Ph.D., an Qassistant professor in Wistar’s Molecular and Cellular Oncogenesis Program, has been selected to receive a $140,000 grant from Accelerate Brain Cancer Cure Inc. The funding supports his work in screening large numbers of microRNAs, molecules that appear to play a role in cancer genetics, for their possible activity in

Fall 2007 the treatment of brain tumors. : Huang’s research, which advances the goals of the Albert R. Taxin Brain FOCUS Tumor Research Center at Wistar, Graduates of the Biomedical Technician Training Program display certificates at a ceremony uses the tools of systems biology, 20 in August at Wistar. Pictured, from left, are Dr. Michael Byler of Community College of Philadelphia; graduates Hajime Yamagata, Don’te Carlos Beachem, Nicole Dannette Smith, one of the Institute’s areas of strategic Carin D. Upchurch, Stuart Stevens, and Erin Fisher; and William H. Wunner, Ph.D., of Wistar. focus. Wine Event Provides Taste of Research Training News >Jing Huang, Ph.D., has won the Ching Jer Chern Memorial Award, ed Wine and Eternal Youth,” which honors the postdoctoral fellow who writes the best scientific paper of an event held in April at “R the year. Huang, whose paper on cancer genetics was published in the journal Moore Brothers Wine Co. in New Nature, works in the laboratory of Shelley L. Berger, Ph.D. The award was York City, featured an opportunity to established in memory of Dr. Ching Jer Chern, a Wistar scientist. hear from Ronen Marmorstein, Ph.D., a professor in Wistar’s Gene Expression >Troy Messick, Ph.D., has received the Christopher M. Davis Memorial Fellowship, which recognizes a postdoctoral fellow who excels in breast-cancer research. Messick works in the laboratory of Ronen Marmorstein, Ph.D. The fellowship was established in memory of Christopher Davis, son of board of trustees co-vice chair Harold M. Davis and his wife, Eleanor Davis. >Brandi Sanders has been named winner of the Monica H.M. Shander Memorial Fellowship, given to predoctoral fellows conducting outstanding research. Sanders, who investigates structure-based design of drugs to modulate Sir2, a molecule involved in metabolism and longevity, works in the laboratory of Ronen Marmorstein, Ph.D. The fellowship honors trainees who demonstrate excellence in scholastics and aptitude and diligence in the laboratory. Lucy Provost Wistar director of development Peter Corrado Brandi Sanders, winner of the Monica H.M. Shander Memorial Fellowship, and Troy Messick, with Alice Koeth, left, and Emily Brown Ph.D., right, winner of the Christopher M. Davis Memorial Fellowship. Both work in the Shields, a member of the Wistar family. laboratory of Ronen Marmorstein, Ph.D., center. and Regulation program, and to sam- ple a selection of wines. Insights from Marmorstein’s work may lead to new drugs to activate or inhibit molecules called sirtuins, which play a critical role in life processes including metabolism, physiology, and aging. Wistar president and CEO Russel E. Kaufman, M.D., hosted guests including foundation representatives and members of the Wistar family who gathered to hear what Marmorstein and his colleagues have discovered about sirtuin-regulating compounds, such as one found in red wine, that are linked to improved health and longevity.

Professor Receives Funding, Joins ‘Institute Without Walls’

rofessor Frank J. Rauscher III, of chromosomes. The Waxman foun- PPh.D., leader of Wistar’s Gene dation is distinctive in that it requires Expression and Regulation Program researchers to collaborate with their Fall 2007 : and deputy director of the Wistar peers on funded research projects. The Institute Cancer Center, has received foundation refers to this collaborative a grant for $230,000 from the Samuel effort as its “Institute Without Walls.” FOCUS Waxman Cancer Research Founda- Rauscher is one of just 60 researchers 21 tion to support his research on the worldwide to have received funding regulation of chromatin, the material under the initiative. Frank J. Rauscher III, Ph.D. FORMER WISTAR DIRECTOR HILARY KOPROWSKI, M.D., WINS SABIN GOLD MEDAL

ilary Koprowski, M.D., known as the developer of the rubella colorectal cancer is used throughout one of the world’s out- vaccine responsible for eradicating that the world for diagnosis of pancreatic standing biomedical disease in the United States, also co- cancer by detection of the antigen in researchers over the past developed a vaccine against rotavirus blood. half-century, was named approved in 2006. A native of Warsaw, Poland, the 2007 winner of the Koprowski’s groundbreaking work Koprowski initially received a degree in HSabin Gold Medal. Koprowski was the in polio and rabies greatly advanced piano from the Warsaw Conservatory. director of The Wistar Institute from vaccine research. In the late 1950s, his He then received his M.D. from the 1957 to 1991 and is today a professor efforts resulted in production of the University of Warsaw in 1939 and in emeritus and board member at Wistar. first oral polio vaccine used in clinical 1940 graduated from the National Koprowski is the 15th Academy of Santa Cecilia in recipient of the medal, which Rome, a world-renowned is awarded annually to recog- institute for the study of nize the extraordinary music. accomplishments of those He moved to Brazil and who make vaccine discover- then soon relocated to the ies or employ vaccines to United States, where he even- combat vaccine-preventable tually became director of the diseases. He was presented Wistar Institute. At Wistar, he with the award by Stanley recruited top biologists from Prusiner, M.D., winner of throughout the world, and he the 1997 Nobel Prize in is credited with major growth Physiology or Medicine, in of the Institute. May in Baltimore in con- Koprowski is the author of junction with the National more than 850 scientific Foundation for Infectious papers and is a member of Diseases Annual Conference Former Wistar director Hilary Koprowski, M.D., left, 2007 winner of many of the world’s most the Sabin Gold Medal, with fellow Wistar professor emeritus Stanley on Vaccine Research. A. Plotkin, M.D., who won the medal in 2002. prestigious scientific societies. “Any serious discussion of He has received honorary the giants of 20th century biomedical trials to immunize people on four con- degrees from numerous universities research must include Hilary tinents. In the 1970s, his passionate and is the recipient of honors includ- Koprowski as one of the most promi- interest in rabies led him to co-develop ing the Philadelphia Award, the Scott nent,” said H.R. Shepherd, D.Sc., the a new tissue-culture-based vaccine that Award, and the French Legion of Sabin Vaccine Institute’s founding is more effective, less painful, and safer Honor. He is a member of the chairman. than the traditional Pasteur technique. National Academy of Sciences and the Sabin president Peter Hotez, M.D., He was a pioneer in the develop- American Academy of Arts and Sci- Ph.D., added: “The scope of his ment of monoclonal antibodies used ences. He was both a Fulbright achievements is simply remarkable, to detect cancer antigens and in can- Scholar and a Rockefeller University ranging from polio to rabies and to cer immunotherapy. And he has Fellow. He has been a continuous monoclonal antibodies that are a key successfully used plants to produce grantee of the National Institutes of

Fall 2007 to effective cancer immunotherapy.” experimental vaccines and antibodies. Health for more than 50 years. : In winning the medal, Koprowski Koprowski and his associates devel- Currently, Koprowski is director of joins former colleague and fellow Wis- oped the first functional monoclonal The Biotechnology Foundation Labo- FOCUS tar professor emeritus Stanley A. antibody against a colorectal cancer ratories, as well as the Center for 22 Plotkin, M.D., who was honored with antigen and rabies. The monoclonal Neurovirology at Thomas Jefferson the award in 2002. Plotkin, best antibody recognizing the antigen of University. JOIN US. BECOME A PARTNER IN THE SEARCH FOR CURES. Support Wistar’s innovative medical research—while earning a lifetime income for yourself—through a charitable gift annuity.

hrough a charitable gift annuity, you can CURRENT RATES FOR Tjoin Wistar scientists in the fight against CHARITABLE GIFT ANNUITIES disease while earning a lifetime income for AGE RATE AGE RATE yourself. Support Wistar’s researchers as they 55 ...... 5.5% 73 ...... 6.8% work to develop new treatments for melanoma, 56...... 5.6 74...... 6.9 57...... 5.6 75...... 7.1 lung cancer, and brain tumors and create new 58...... 5.7 76...... 7.2 vaccines for flu and other diseases. 59...... 5.7 77...... 7.4 60...... 5.7 78...... 7.6 You can earn a return of up to 11.3 percent 61...... 5.8 79...... 7.8 62...... 5.9 80...... 8.0 on your gift, depending on your age. You will 63...... 5.9 81...... 8.3 receive an income tax deduction at the time of 64...... 6.0 82...... 8.5 the gift, and a portion of your income will be 65...... 6.0 83...... 8.8 66...... 6.1 84...... 9.2 deductible in the future.The minimum contribu- 67...... 6.2 85...... 9.5 tion is $10,000. Cash, stock, or other assets 68...... 6.3 86...... 9.9 can be used to fund the annuity.This program is 69...... 6.4 87...... 10.2 70...... 6.5 88...... 10.6 currently offered only to Pennsylvania and 71...... 6.6 89...... 11.0 New Jersey residents. 72...... 6.7 90+ ...... 11.3

For more information, call Peter Corrado in Wistar Development at 215-898-3930. HAL DAVIS, co-vice chair of Wistar’s board of trustees, was presented with the Wistar Award at a gala in his honor October 27. Davis and his wife, Eleanor, have long supported breast cancer research at the Institute and once planted a Wistar flag on the summit of Mount Kilimanjaro. Below, Wistar president and CEO Russel E. Kaufman, M.D., right, and board chair Brian H. Dovey acknowledge Davis at the Four Seasons Hotel Philadelphia. Full story on page 12.

Photo by Tommy Leonardi

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