Through an ambitious scientific effort called EIF's Biomarker Discovery Project, world-class scientists are collaborating to develop a blood test that will detect breast cancer in its beginning stages, when it can be cured. World-class scientists funded by Women's Cancer Research Fund include:
EIF's Biomarker Discovery Project Oversight Committee
Richard D. Klausner, M.D.
The Column Group
Co-Chair
Dr. Richard Klausner was formerly the global-health executive director of the Bill & Melinda Gates Foundation's Global Health program, whose overarching goal is to improve global-health equity. Dr. Klausner previously served as director of the National Cancer Institute (NCI), where he led one of the world's largest research and health agencies, creating successful national and international programs aimed at applying science and technology to improving public health. In addition, Dr. Klausner is currently engaged as an independent consultant for biotech and global health and is a managing director of The Column Group, a strategy-based venture fund. Dr. Klausner is well-known for his work in cell and molecular biology. He has served as chief of the cell biology and metabolism branch of the National Institute of Child Health and Human Development. He has served on numerous advisory committees and is the past president of the American Society for Clinical Investigation. He is the author of more than 300 scientific articles and several books, and he has received numerous awards and honors. Dr. Klausner has served as a senior fellow at the National Academy of Sciences, advisor to the presidents of the Academies for Counter-terrorism, and liaison to the White House Office of Science and Technology Policy. In addition, Dr. Klausner led the efforts of the National Academies of Sciences to write standards for U.S. science education. He is a member of the National Academy of Sciences and the Institute of Medicine and the American Academy of Arts and Sciences.
David Baltimore, Ph. D., Nobel Laureate
California Institute of Technology
Dr. David Baltimore, who has been the president of California Institute of Technology since 1997, is one of the world's most influential biologists. Awarded the Nobel Prize at the age of 37 for research in virology, Baltimore has profoundly influenced national science policy on such issues as recombinant DNA research and the AIDS epidemic. Before coming to Caltech, Dr. Baltimore was an institute professor at the Massachusetts Institute of Technology. He was founding director of the Whitehead Institute for Biomedical Research at MIT, and served from the institute's creation in 1982 to 1990, when he became president of Rockefeller University. His career has been distinguished by his dual contribution to biological research and to national science policy. Dr. Baltimore helped pioneer the molecular study of animal viruses, and his research in this field had profound implications for understanding cancer and, later, AIDS. In the mid-1970's, along with several other eminent biologists, he played a pivotal role in creating a consensus on national science policy regarding recombinant DNA research and also established standards that are followed by the genetics community to this day. Dr. Baltimore has been a major figure in Washington as head of the National Institutes of Health AIDS Vaccine Research Committee from 1996-2002, and also in 1986 as co-chair of the National Academy of Sciences and Institute of Medicine's committee on a National Strategy for AIDS. In 2004 he was appointed to the Independent Citizen's Oversight Committee to the California Institute for Regenerative Medicine, and in 2006 he will serve as president-elect of the American Association for the Advancement of Science. He is a member of the National Academy of Sciences, the Pontifical Academy of Sciences, the American Academy of Arts and Sciences, and the Royal Society of London. He was awarded the 1999 National Medal of Science; he was a co-recipient of the 2000 Warren Alpert Foundation Prize and was awarded the 2002 AMA Scientific Achievement Award.
Joe W. Gray, Ph. D.
Lawrence Berkeley National Laboratory
Dr. Joe Gray received undergraduate training in Engineering Physics from the Colorado School of Mines and a Ph.D. in Nuclear Physics from Kansas State University in 1972. He then joined the Biomedical Sciences Division of the Lawrence Livermore National Laboratory, where he became increasingly active in cancer research, specifically in the development of a broad range of analytic techniques useful in the study of human and model cancers. Dr. Gray moved to the University of California, San Francisco (UCSF) as Professor of Laboratory Medicine and Radiation Oncology in 1991 to pursue his interest in clinical applications of these tools. He established and headed the Division of Molecular Cytometry in the Department of Laboratory Medicine until 1997, when this unit merged with the UCSF Comprehensive Cancer Center. He was Interim Director of the UCSF Cancer Center from 1995 to 1997 and became Program Leader for Cancer Genetics and Breast Oncology in the Cancer Center. He has been Principal Investigator of the Bay Area Breast Cancer Specialized Projects of Research Excellence (SPORE) since 1996. Dr. Gray accepted a position as Division Director of Life Sciences and Associate Director of Life and Environmental Sciences at the Lawrence Berkeley National Laboratory in April 2003. He continues as a member of the UCSF Comprehensive Cancer Center and as Program Leader for Breast Oncology and Principal Investigator of the Bay Area Breast Cancer SPORE with an appointment as Adj. Professor of Laboratory Medicine.
Dr. Gray has pursued several aspects of cancer research during his ~30-year career. He developed several new approaches for cell cycle analysis including the BrdUrd/DNA procedure for analysis of cell cycle progression. He pioneered flow karyotyping and chromosome sorting and used these technologies to produce chromosome-specific recombinant DNA libraries. He has developed mathematical models of cell cycle traverse and used these to explore the possibility of improving cancer therapy by optimally timing administration of cell cycle-specific therapeutic agents. He collaborated with Dr. Pinkel, on the development of several aspects of Fluorescence In Situ Hybridization (FISH) and with Drs. Anna and Olli Kallioniemi, Pinkel, Albertson and Waldman on the development and application of Comparative Genomic Hybridization (CGH) to analysis of relative DNA sequence copy number abnormalities. An array version of CGH developed with Drs. Pinkel and Albertson has proved particularly useful for study of cancer evolution and for identification of the involved genes. Most recently, he has collaborated with Dr. Colin Collins on the development of End Sequence Profiling (ESP) for identification and DNA sequence analysis of structural aberrations.
Dr Gray's current research program involves analysis of the genetic progression of human breast and ovarian cancer. His work falls into three general areas: 1) Development of quantitative systems biology approaches to identify genomic, genetic and biological aberrations that influence response to pathway targeted cancer therapeutics. Current work focuses on developing strategies that predict individual responses to agents that target EGFR family signaling. 2) Identification and functional elucidation of genes in regions of recurrent genomic abnormality associated with poor outcome including EPHA2, PVT1, ADAM9, and PFDN4. 3) Development of therapeutic strategies to attack drug-resistance-associated genes.
Dr. Gray's work is described in >317 publications and 48 patents. Major awards include the Radiation Research Society Research Award (1985); USDOE. E.O. Lawrence Award (1986); Election as a Fellow of the American Association for the Advancement of Science (1996), an Exceptional Service Award from the USDOE (1997); the Schiffer Award from the Cell Proliferation Society (1999); Boerhave Professor, Leiden University, the Netherlands (2000); the Curt Stern Award from the American Society for Human Genetics (2001), a Leadership Award from the National SPORE Program (2003), an Alumni Fellow award from Kansas State University (2005), a Distinguished Achievement Award from the Colorado School of Mines (2005) and an Honorary Doctorate from the University of Tampere, Tampere, Finland (2005). Dr. Gray was appointed as a Member of the Board of Scientific Advisors of the National Cancer Institute in 2004.
C. Kent Osborne, M.D.
Breast Center Baylor College of Medicine
Dr. C. Kent Osborne was born in 1946 in St. Louis, Missouri. He received his AB and MD degrees from the University of Missouri, both with honors. He completed his internship and residency at Johns Hopkins Hospital in 1974, and then spent three years as a clinical associate at the Medicine Branch, Breast Cancer Section of the National Cancer Institute in Bethesda, Maryland. In 1977 he took his first faculty position at The University of Texas Health Science Center at San Antonio, where he rose to the rank of Professor and became Director of the Division of Medical Oncology in 1992. In 1999 Dr. Osborne and his team moved to Baylor College of Medicine to develop a new multidisciplinary Breast Center.
Dr. Osborne is a physician as well as a research investigator. He has focused on breast cancer his entire career. His research interests include understanding the biology of breast cancer and then developing new treatment approaches for the disease. He has published extensively on the mechanisms by which hormonal therapies such as tamoxifen inhibit breast cancer growth and how breast cancers become resistant to these therapies. He has also studied the role of various growth factors in breast cancer development and progression, and more recently how these other growth factors can interact with estrogen to stimulate tumor growth. For more than a decade Dr. Osborne was Chairman of the Breast Cancer Committee for the Southwest Oncology Group, where he directed numerous nationwide clinical trials investigating new treatment strategies for breast cancer patients. He is currently the Principal Investigator of the Baylor Breast Cancer Specialized Program of Research Excellence grant, one of only nine such grants nationwide and the only one in Texas.
He also directs a large program project grant from the National Cancer Institute, the goal of which is to identify the gene pathways important in breast cancer growth and then to block these pathways for therapeutic purposes.
Among his previous awards are the Komen Foundation Award and the Brinker International Award for Breast Cancer Research. He recently received the European Institute of Oncology Annual Breast Cancer Award for 2004 and the Jacqueline Seroussi Award in Israel in 2005. In the Baylor College of Medicine, he is Professor of Medicine and Molecular and Cellular Biology, and Director of the Breast Center. He is also the Director of the Dan L. Duncan Cancer Center that is under development at the College. He currently holds the Tina and Dudley Sharp Chair in Oncology at Baylor College of Medicine.
Lawrence D. Platt, M.D.
Center for Fetal Medicine and Women's Ultrasound
Dr. Larry Platt is a professor of obstetrics and gynecology at the David Geffen School of Medicine at UCLA and is the director of the Center for Fetal Medicine and Women's Ultrasound in Los Angeles. He is the current president of the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG). He has authored more than 270 peer-reviewed publications, 52 chapters in medical books, and has four books to his credit. He is the current commissioning editor of Ultrasound in Obstetrics and Gynecology, the official journal of ISUOG. In addition, he is on the editorial board of several other prestigious medical journals. Dr. Platt has been elected to numerous prestigious professional organizations and has served in many leadership roles for such professional societies. He is a past president the American Institute of Ultrasound in Medicine (AIUM) and continues to serve on the organization's numerous committees. He also currently serves as the AIUM's administrative councilor to the World Federation for Ultrasound in Medicine and Biology. He is past president of the Los Angeles OB-GYN Society and is the current and founding treasurer of the Maternal-Fetal Medicine Foundation. His research interests include ultrasound in prenatal diagnosis, 2-, 3-, and 4-dimensional ultrasound in obstetrics and gynecology, and the biophysical assessment of fetal condition. Dr. Platt is a sought-after speaker and has participated in more than 350 educational symposia. He has received numerous honors and awards and has been recognized in America's Best Doctors for the last 12 years. He serves on numerous community charitable and education organizations. He serves on the oversight committee for the Entertainment Industry Foundation Breast Cancer Biomarker Discovery Project. He is chairman of the Breast Ultrasound Foundation of the American Registry for Diagnostic Medical Sonography and is a member of the board of trustees for Touro College.
Phillip A. Sharp, Ph.D., Nobel Laureate
Center for Cancer Research, Massachusetts Institute of Technology
Dr. Phillip Sharp, currently Institute Professor, joined the Center for Cancer Research at the Massachusetts Institute of Technology in 1974 and served as director of the center for six years, from 1985 to 1991, before taking over as head of the Department of Biology, a position he held for the next eight years. More recently, he was founding director of the McGovern Institute, a position he held from 2000 to 2004. Dr. Sharp's research interests have centered on the molecular biology of gene expression relevant to cancer and the mechanisms of RNA splicing. His landmark work (1977) provided one of the first indications of the startling phenomenon of "discontinuous genes" in mammalian cells. This discovery, which fundamentally changed scientists' understanding of the structure of genes, earned Dr. Sharp the 1993 Nobel Prize in physiology or medicine. His lab has now turned its attention to understanding how RNA molecules act as switches to turn genes on and off (RNA interference). These newly discovered processes have revolutionized cell biology and could potentially generate a new class of therapeutics. Dr. Sharp has authored more than 300 scientific papers. His work has earned him numerous cancer-research awards and presidential and national scientific-board appointments. He is an elected member of the National Academy of Sciences, the Institute of Medicine, and the American Academy of Arts and Sciences. He is also the recipient of the 2004 National Medal of Science. Dr. Sharp earned a B.A. degree from Union College, Ky., and a Ph.D. in chemistry from the University of Illinois. In 1978 he co-founded Biogen (now Biogen Idec), and in 2002he co-founded Alnylam Pharmaceuticals, an early stage therapeutics company. He serves on the boards of both companies.
Ellen V. Sigal, Ph.D.
Friends of Cancer Research
Dr. Ellen V. Sigal is the founder and chairperson of Friends of Cancer Research ("Friends"), a Washington, D.C.,-based nonprofit organization. Friends is dedicated to accelerating the nation's progress toward prevention and treatment of cancer by mobilizing public support for cancer-research funding and providing education on key public-policy issues. Dr. Sigal serves on the National Cancer Institute Board of Scientific Advisors, the National Institutes of Health Foundation Board (she chairs its Public Private Initiatives Committee), and the American Association for Cancer Research Foundation Board. Dr. Sigal holds leadership positions with a broad range of cancer-advocacy and public-policy organizations, and leadership positions with academic health centers including Duke University Comprehensive Cancer Center, the Johns Hopkins Cancer Center Advisory Council and the Howard University Cancer Center Board of Visitors. She serves on the C-Change (formerly the National Dialogue on Cancer Research) Research Committee, and is a member of the Entertainment Industry Foundation Oversight Committee for the Biomarker Discovery Project. During her more than 20-year commitment to cancer research, Dr. Sigal has served in a number of critical public positions. She served on the National Institutes of Health prestigious Director's Council of Public Representatives from 2003?2006. She was a presidential appointee to the National Cancer Advisory Board from 1992-1998, where she chaired the Budget and Planning Committee that oversees the federal cancer budget. In 1998, Dr. Sigal was named vice chairman of the board of the March, a national grass-roots advocacy group that brought thousands of volunteers to Washington to liaise with Congress and to set a new advocacy agenda for cancer research and treatment. She is a past member of the American Society of Clinical Oncology Foundation Board. Dr. Sigal has also been instrumental in harnessing the energies of Hollywood on behalf of cancer research, serving as president of The Creative Community Task Force for Cancer Research. For her efforts on behalf of cancer research advocacy, Dr. Sigal was awarded the Association of American Cancer Institutes' 2004 Public Service Award and was honored by Washingtonian magazine as a 2004 Washingtonian of the Year. In 2004 she was also honored by Research! America, the George Washington University Cancer Institute, and the International Spirit of Life Foundation. Dr. Sigal was awarded the 2002 American Society of Clinical Oncology Special Recognition Award, the 1999 Sidney Kimmel Cancer Center National Leadership Award, and the 1998 American Association for Cancer Research National Leadership Award.
EIF's Biomarker Discovery Project Steering Committee
Lee H. Hartwell, Ph.D., Nobel Laureate
Fred Hutchinson Cancer Research Center
Dr. Lee Hartwell is president and director of Seattle's Fred Hutchinson Cancer Research Center and professor of genome sciences at the University of Washington. Dr. Hartwell's primary research contributions were in identifying genes that control cell division in yeast including those necessary for the division process as well as those necessary for the fidelity of genome reproduction. Subsequently many of these same genes have been found to control cell division in humans and often to be the site of alteration in cancer. Recently his interests have turned to how we can use the enormous knowledge that has been gained about biology to improve health care. He believes that the most efficient path is to improve molecular diagnostics to identify individuals at high risk for disease, detect cancer and other disease at an early stage when they can be cured, provide prognostic information and monitor therapeutic response. Proteins will likely provide the best diagnostic information because of their greater diversity and because their state reflects biological function. He has directed his efforts recently to national and international projects to increase the number of laboratories working in protein diagnostics, develop more team science, improve the availability of informatics for data sharing, provide standardized reagents, and stimulate new technology development. Dr. Hartwell is a member of the National Academy of Sciences and received the Albert Lasker Basic Medical Research Award, the Gairdner Foundation International Award, the Alfred P. Sloan Award in Cancer Research and the 2001 Nobel Prize in physiology or medicine.
Gabriel N. Hortobagyi, M.D., FACP
University of Texas
M. D. Anderson Cancer Center
As a member of the M. D. Anderson faculty since 1976, Dr. Gabriel Hortobagyi has been instrumental in developing combination chemotherapy for previously inoperable breast tumors and for improving multidisciplinary treatment for patients with all stages of breast cancer, including advanced disease. He and his colleagues have conducted extensive clinical trials that have been widely incorporated into standard practices for managing breast cancer and have contributed to increased survival for many patients. His research studies have been supported by The Breast Cancer Research Foundation since 1993. Dr. Hortobagyi is widely known for a landmark study he initiated in 1974 as a fellow in developmental therapeutics at M. D. Anderson. His research involved giving presurgical chemotherapy to patients whose breast tumors had already spread to other parts of the body and concluded that many large tumors could be reduced as much as 50 percent, then removed surgically. In 1988, he published a 10-year study that showed a three-drug regimen administered before surgery and radiation therapy after surgery produced promising results for breast-cancer patients with advanced disease. Among major honors for his breast-cancer research, Dr. Hortobagyi has received the 1999 Vermeille Medal from the City of Paris and the 1997 Brinker International Award for Clinical Research. In 1997 he also received the Japanese Surgical Society Medal and the Sir Peter Freyer Medal in Galway, Ireland. Dr. Hortobagyi has contributed more than 500 articles to scientific journals and 80 textbooks. He was co-founder of the World Summit Against Cancer, an international group of scientists, health-care professionals, patient advocates, economists, lawmakers and celebrities who are campaigning to ensure all people worldwide receive the most advanced treatment for cancer. He also is a past president of the International Society of Breast Diseases.
Eric S. Lander, Ph.D.
Broad Institute of Massachusetts Institute of Technology and Harvard
Dr. Eric Lander is founding director of the Broad Institute. As one of the principal leaders of the Human Genome Project, Lander and colleagues are using these findings to explore the molecular mechanisms underlying the basis of human disease. Lander is also professor of biology at MIT, professor of systems biology at Harvard Medical School and member of the Whitehead Institute for Biomedical Research. He founded the Whitehead Institute/MIT Center for Genome Research in 1990. This Center became part of the newly founded Broad Institute in 2003. Over the past 15 years, Lander and colleagues have developed many of the key tools and generated many of the key information resources of modern mammalian genomics. They have also applied these tools and data to pioneer new ways to understand the basis of disease. Their work includes: mapping and sequencing of the human, mouse and other genomes; understanding the functional elements encoded in genomes through comparative analysis; understanding the genetic variation in the human population and its relationship to disease susceptibility; understanding the distinctive cellular signatures of diseases and of response to drugs; and understanding the mutations underlying cancer. They have also developed new analytical and laboratory techniques for genomics, which have been applied to a wide range of common diseases, including cancer, diabetes, inflammatory diseases and many other genetic illnesses. Lander's honors and awards include the MacArthur Foundation Prize Fellowship in 1987, the Woodrow Wilson Prize for Public Service from Princeton University in 1998, the City of Medicine Award in 2001, the Gairdner Foundation International Award of Canada in 2002, and the AAAS Award for Public Understanding of Science and Technology in 2004. He was elected a member of the U.S. National Academy of Sciences in 1997 and the U.S. Institute of Medicine in 1999. He has served on governing and advisory boards for various government agencies, academic institutions, scientific societies and corporations. Lander earned his B.A. in mathematics from Princeton University in 1978 and Ph.D. in mathematics from Oxford University in 1981 as a Rhodes Scholar. He was an assistant and associate professor of managerial economics at the Harvard Business School from 1981-1990.
EIF's Biomarker Discovery Project Scientists
Ruedi H. Aebersold, Ph.D.
Institute for Systems Biology
Dr. Ruedi Aebersold's research focuses on developing new methods and technologies for quantitative proteomics and for applying this emerging technology to enhance our understanding of the structure, function and control of complex biological systems. Current applications of quantitative proteomics technology are directed toward discovering protein markers that differentiate cancer cells from their normal counterparts, investigating the mechanisms of fundamental cellular processes by the comparative analysis of the gene and protein expression profiles in cells at different states, and studying medical microbiology. Dr. Aebersold is a member of the editorial advisory boards of Molecular and Cellular Proteomics, Molecular Systems Biology, Journal of Proteome Research and Molecular BioSystems. He is the 2002 recipient of the Widmer Award, the ASMS Biemann Medal, and the World Technology Network Award in the biotechnology category. In November 2004, he assumed an appointment as professor of Systems Biology, Institute of Biotechnology, ETH-Zürich and faculty of natural sciences, University of Zürich. He is a professor and founding member of the Institute for Systems Biology, Seattle, Wash.
Steven Carr, Ph. D.
Broad Institute of Massachusetts Institute of Technology and Harvard
Steven Carr, a senior scientific leader in protein biochemistry and proteomics leads the
Proteomics platform at the Broad Institute. In this capacity, Steven and his group work with biologists to systematically identify proteins and their modifications - such as phosphorylation, whose abundance or form is modulated by disease or drug action - as well as define physical and functional associations of protein constituents of regulatory and signaling pathways involved in health and disease. These studies involve analysis of complex biological specimens, such as tumor tissues or patient blood, using protein chemistry and advanced separation methods together with state-of-the-art mass spectrometry. For the last 25 years, Steven's research has focused on applying and developing proteomics methods in order to understand the mechanism of action of drug candidates and build an understanding of protein targets and their roles in disease. In particular, he is noted for developing methods for selective enrichment, detection and quantitation of posttranslational modifications, such as phosphorylation and glycosylation, in the proteome. He has over 125 publications on development and use of proteomics and biological mass spectrometry. Steven received his B.S. in 1976 from Union College and Ph.D. from MIT in 1980. After four years of postdoctoral training at Harvard Medical School and MIT, he joined SmithKline Pharmaceuticals (now GlaxoSmithKline), becoming director of Computational and Structural Sciences in 1997. Most recently he led protein science and proteomics groups at Millennium Pharmaceuticals in Cambridge, MA, prior to joining the Broad in 2004.
Todd Golub, M.D.
Broad Institute of Massachusetts Institute of Technology and Harvard
Todd Golub is a founding member of the Broad Institute of Harvard and MIT and serves as director of its Cancer program. Todd is a world leader in applying genomic tools to the classification and study of cancers. His work focuses on using the human genome to understand the biological and clinical challenges facing cancer medicine. He has made fundamental discoveries in the molecular basis of childhood leukemia, and pioneered the use of genomic approaches, particularly DNA microarrays, to cancer biology. Todd is the Charles A. Dana Investigator in Human Cancer Genetics at the Dana-Farber Cancer Institute, associate professor of pediatrics at Harvard Medical School, and an investigator at Howard Hughes Medical Institute. Todd is the recipient of multiple awards, including Discover Magazine's Inventor of the Year (Health Category) in 2000, the Daland Prize of the American Philosophical Society in 2001, and the Outstanding Achievement Award (formerly Cornelius Rhoads Memorial Prize), American Association for Cancer Research in 2002.
Todd received his B.A. in 1985 from Carleton College and his M.D. in 1989 from the University of Chicago Pritzker School of Medicine.
Samir Hanash, M.D., Ph.D.
Fred Hutchinson Cancer Research Center
Dr. Samir Hanash's interests and expertise focus on the development and application of integrated approaches to the molecular profiling of cancer, with particular emphasis on proteomics. Dr. Hanash's Ph.D. training is in human genetics and his clinical training is in pediatric oncology. He has been a program principal investigator (PI) for multi-investigator projects funded by the National Cancer Institute (NCI) at the University of Michigan, including program projects and most recently, PI for an NCI-funded Director's Challenge program, which focuses on molecular profiling of lung, colon and ovarian cancer. He's also the PI of an NCI-funded Cancer Biomarker Development program, which focuses on the application of proteomics to the discovery of protein markers for the early diagnosis of lung and GI cancers. Dr. Hanash has organized and participated in several workshops sponsored by the NCI related to cancer diagnostics and molecular profiling. Dr. Hanash relocated from the University of Michigan to Fred Hutchinson Cancer Research Center in August 2004 to lead a newly developed program in molecular diagnostics.
Leroy E. Hood, M.D., Ph.D.
Institute for Systems Biology
Dr. Leroy Hood's research has focused on fundamental biology (immunity, evolution, genomics), systems medicine (prostate cancer and prion disease) and on bringing engineering to biology through the development of five instruments - the DNA and protein sequencers and synthesizers and the ink-jet oligonucleotide synthesizer - or deciphering the various types of biological information (DNA, RNA, proteins and systems). These instruments and their subsequent improvements constitute the technological foundation for modern molecular biology and genomics. Dr. Hood has applied these technologies to diverse fields including immunology, neurobiology, cancer biology, molecular evolution and systems biology, and medicine. Dr. Hood has been driven by the conviction that the needs of frontier biology should drive the choice of technologies to be developed. Once developed, these technologies can revolutionize biology and medicine. His professional career began at Caltech, where he was a pioneer in the field of molecular immunology and catalyzed the development of four instruments - the DNA gene sequencer and synthesizer, and the protein synthesizer and sequencer. He founded Applied Biosystems to commercialize these instruments. In particular, the DNA sequencer has revolutionized genomics by allowing the rapid automated sequencing of DNA, which played a crucial role in contributing to the successful mapping of the human genome during the 1990s. He applied all of these technologies to the study of molecular immunology (and discovered many of the fundamental mechanisms for antibody diversity) and neurobiology (he cured in mice the first neurological disease by gene transfer). In 1992, Dr. Hood moved to the University of Washington as founder and chairman of the cross-disciplinary Department of Molecular Biotechnology (MBT). There he developed the ink-jet oligonucleotide synthesizer to synthesize DNA chips and permit the simultaneous analyses of all 25,000 human genes. Agilent has commercialized this technology. At MBT he applied all of the technologies that he developed to the study of cancer biology and prion disease from a systems vantage point. In 2000, he co-founded the Institute for Systems Biology in Seattle, Wash. to more effectively continue pioneering systems approaches to biology and medicine. At ISB he has contributed seminal papers to delineating the systems approach to biology and disease and to pioneer developing new technologies (microfluidics/nanotechnology and molecular imaging). In collaboration with colleagues at Caltech and UCLA he is using these technologies to establish the framework for medicine evolving from its current reactive mode to predictive, preventive, personalized and participatory modes (P4 medicine) over the next five to 20 years. Dr. Hood was awarded the 1987 Lasker Prize for his studies on the mechanism of immune diversity. In 2002 he received the Kyoto Prize in Advanced Technology for the development of the five different instruments and in 2003 he received the Lemelson-MIT Prize for Innovation and Invention for the development of the DNA sequencer. Most recently, Dr. Hood's lifelong contributions to biotechnology have earned him the prestigious 2004 Biotechnology Heritage Award and his pioneering efforts in molecular diagnostics earned him the Association for Molecular Pathology (AMP) Award for Excellence in Molecular Diagnostics.
Peter W. Laird, Ph.D.
University of Southern California
Norris Comprehensive Cancer Center
Dr. Peter Laird earned his B.S. and his M.S., Cum Laude, from the University of Leiden, The Netherlands. He received his Ph.D. from the University of Amsterdam while working in the laboratory of Dr. Piet Borst. He received his postdoctoral training from Dr. Anton Berns at the Netherlands Cancer Institute and from Dr. Rudolf Jaenisch at the Whitehead Institute at MIT. He pioneered the use of mouse models to investigate the causal contribution of DNA methylation to cancer (Laird et al. 1995, Cell 81, 197), and invented two DNA methylation assays, COBRA (Xiong and Laird 1997, Nucleic Acids Res 25, 2532) and MethyLight (Eads et al. 2000, Nucleic Acids Res 28, E32), which has been issued a U.S. patent. Dr. Laird is currently associate professor of surgery and of biochemistry and molecular biology at the University of Southern California, Keck School of Medicine, and is principal investigator on three NCI R01 grants. He is director of basic research for surgery, and program leader at the USC/Norris Comprehensive Cancer Center. He serves on various editorial and scientific advisory boards and is co-founder of ORCA Biosciences, currently Epigenomics, AG.
Martin W. McIntosh, Ph. D.
Fred Hutchinson Cancer Research Center
Martin McIntosh, Ph.D., is an Associate Member at the Fred Hutchinson Cancer Research Center (FHCRC) and Principal Investigator of the Computational Proteomics Laboratory. Dr. McIntosh has a long history of research in biomarkers and early detection of disease, especially of ovarian cancer. He is the leader of an early detection project of the FHCRC's ovarian cancer SPORE award, one of three PIs of the NCI's proteomics initiative consortia, and co-chair of informatics for the HUPO biomarker initiative. Dr. McIntosh is PI of the Early Detection Research Network (EDRN) biomarker development laboratory (for breast and ovarian cancer), and his laboratory leads the data integration and mining for several consortia for cancer as well as neurodegenerative disease research. His primary research focus involves discovery and evaluation of biomarkers and biomarker panels for early disease detection. He serves in leadership positions both at the FHCRC and nationally for biomarker discovery research programs.
http://proteomics.fhcrc.org/CPL/members.html
Amanda G. Paulovich, M.D., Ph. D.
Fred Hutchinson Cancer Research Center
Dr. Amanda Paulovich, M.D. Ph.D. is a medical oncologist and Director of the Early Detection Initiative at the Fred Hutchinson Cancer Research Center. She earned M.D. and Ph.D degrees at the University of Washington. While a graduate student in Genetics, she trained in the laboratory of Nobel laureate Dr. Leland Hartwell studying checkpoint regulation of cell cycle progression in yeast in response to DNA damaging agents as well as genetic mechanisms used by yeast cells to tolerate irreparable DNA damage. She subsequently did a residency in Internal Medicine at Massachusetts General Hospital, a Fellowship in Medical Oncology at the Dana Farber Cancer Institute, and postdoctoral training with Dr. Eric Lander at the Broad Institute of Massachusetts Institute of Technology.
In September 2004, Dr. Paulovich joined the faculty of the Clinical Research Division at the Fred Hutchinson Cancer Research Center as Director of the Center's new Early Detection Initiative, and is continuing to pursue her interest in biomarkers of cancer risk and detection, using proteomic technologies such as mass spectrometry. She participates in several large, multi-institutional biomarker discovery initiatives and is a Steering Committee member for the International Cancer Biomarker Consortium (ICBC), a large-scale effort similar to the Human Genome Project aimed at making significant progress in the discovery of biomarkers by facilitating highly coordinated research and leveraging resources and expertise from around the world. She also serves on the advisory Boards of Bio-Rad Laboratories, the Canary Foundation, and the Women's Bioethics Project.
Nathalie B. Scholler, M.D., Ph. D.
Fred Hutchinson Cancer Research Center
Dr. Scholler is a Senior Staff Scientist in the Public Health Sciences Division of the FHCRC. Her primary research interests are investigating the immune response to cancer and developing diagnostic tests for cancer's early detection. Dr. Scholler received her MD from the Medical School of Marseille, France in 1988 and her Ph.D. in Immunology from the Center of Immunology of Marseille-Luminy (CIML) at the University of Aix-Marseille II, France, in 1995. Dr. Scholler is a member of the American Society of Gene Therapy, the American Association for the Advancement of Science, and the American Association of Immunologists.
Richard D. Smith, Ph.D.
Battelle/Pacific Northwest National Laboratory
Dr. Dick Smith's research has involved the development and application of advanced analytical methods and instrumentation, with particular emphasis on high-resolution separations and mass spectrometry and their applications in biological and biomedical research. Much of his research during the last 15 years has focused on the development and application of new ultra-sensitive and comprehensive methods for quantitatively probing the entire array of proteins expressed by a cell, tissue or organism, i.e., their "proteomes." Current interests also include greatly increasing the throughput and sensitivity of proteomics and metabolomics measurements to meet the needs systems biology research. Dr. Smith is an adjunct faculty member of the Department of Chemistry, Washington State University, and the Department of Chemistry, University of Utah, and an affiliate faculty member of the Department of Chemistry, University of Idaho. He has presented more than 350 invited or plenary lectures at national and international scientific meetings, and is the author or co-author of more than 575 publications. Dr. Smith holds 28 patents and has been the recipient of seven R&D 100 Awards. He is director of the NIH Research Resource for Integrative Proteomics located at PNNL.
Nicole Urban, Sc.D.
Fred Hutchinson Cancer Research Center
Dr. Nicole Urban leads the Translational and Outcomes Research Group at Fred Hutchinson Cancer Research Center. She is the principal investigator of two centers of excellence, including the NCI-funded Pacific Ovarian Cancer Research Consortium (POCRC)/SPORE in ovarian cancer and the Department of Defense-funded Center for the Evaluation of Biomarkers for Early Detection of Breast Cancer. She is also PI of an R01 to use a microsimulation model to study the cost-effectiveness of ovarian-cancer screening. Dr. Urban studies ways to improve the use, performance and efficacy of ovarian-cancer screening tools and is particularly interested in the evaluation of markers detectable in serum for use in cancer-risk assessment and early detection. Her population-based research emphasizes modeling and cost-effectiveness analysis, including mathematical modeling of disease progression, modeling of the behavior of biomarkers in the absence and presence of cancer, and measurement and analysis of costs and quality of life. Dr. Urban is trained in the areas of biostatistics and economics and has substantial knowledge about cancer-screening policy and biology.
EIF's Biomarker Discovery Project Clinical Advisors
Julie R. Gralow, M.D.
University of Washington
Seattle Cancer Care Alliance
Dr. Julie Gralow is an associate professor of Medical Oncology at the University of Washington School of Medicine and the Fred Hutchinson Cancer Research Center in Seattle.
As a breast cancer specialist and academician, Dr. Gralow's time is split between patient care, education, and clinical research. She is the principle investigator on several clinical trials related to breast cancer treatment, and is committed to patient education, outreach and wellness. She co-chairs the Southwest Oncology Group's Breast Cancer Committee, and is chair of the medical advisory committee of the Expedition Inspiration Breast Cancer Foundation. Dr. Gralow's primary research interests focus on the prevention and treatment of bone metastases in breast cancer. She has been published in Cancer Immunology, Immunotherapy and in the Journal of Clinical Oncology.
Aside from her academic duties, Dr. Gralow is the director of the American Cancer Society/University of Washington Medical Student Summer Research Fellowship Program. She participates in the Washington division of the American Cancer Society's Speakers Bureau and is a member of the American Association for Cancer Research, the American Society of Clinical Oncology, and the American Society for Breast Disease. In addition, Dr. Gralow is also Medical Director, Team Physician and co-founder of Team Survivor Northwest, an exercise and fitness program for women cancer survivors. She is co-author of Breast Fitness: An Optimal Exercise and Health Plan for Reducing Your Risk of Breast Cancer (St. Martin's Press, 2000).
Dr. Gralow earned her undergraduate degree in Biologic Sciences at Stanford University.
She attended medical school at the University of Southern California in Los Angeles, and trained as a resident in Internal Medicine at Harvard's Brigham and Women's Hospital in Boston. Dr. Gralow's Medical Oncology fellowship training was performed at the University of Washington School of Medicine and the Fred Hutchinson Cancer Research Center.
Eric P. Winer, M.D.
Breast Oncology Center
Dana-Farber Cancer Institute
Dr. Eric P. Winer is a medical oncologist who has specialized in the area of breast cancer for over 15 years. He graduated from Yale College in 1978, with a degree in History and Russian/East European Studies. He subsequently obtained his medical degree from Yale School of Medicine in 1983, followed by training in internal medicine at Yale. He moved to Duke University Medical Center in 1987 and completed a fellowship in medical oncology in 1989. He subsequently remained on the Duke faculty until 1997, where he specialized in breast cancer and became the Co-Director of the Multidisciplinary Breast Program.
In 1997, Dr. Winer moved to Dana-Farber Cancer Institute in Boston where he assumed the role of Director of the Breast Oncology Center and Associate Professor of Medicine at Harvard Medical. He oversees the clinical and clinical research components of the breast cancer program at Dana-Farber. In 2002, Dr. Winer became Chief of Adult Ambulatory Services at Dana-Farber.
In addition to his role at Dana-Farber, Dr. Winer is the co-chair of the Cancer and Leukemia Group B (CALGB) breast committee and is the chair of the American Society of Clinical Oncology (ASCO) Health Services Committee. Dr. Winer divides his time between patient care, clinical research, and administration. He is committed to caring for patients today and finding better treatments for patients in the future. Dr. Winer is widely published. His own research interests focus on the development of new treatments, reducing toxicity of existing treatments, and improving quality of life for breast cancer survivors.
EIF's Biomarker Discovery Project Regional Beneficiaries
Helena R. Chang, M.D., Ph.D.
UCLA School of Medicine
Revlon/UCLA Breast Cancer Center
Dr. Helena R. Chang, director of the Revlon/UCLA Breast Center and professor of surgery, is a world-renowned surgical oncologist, with a dedicated interest in breast cancer. She has held the Revlon Chair at UCLA since 1997 and has repeatedly been named as one of America's Top Doctors in her field. Dr. Chang received her Ph.D. in cancer immunology and M.D. from Temple University, and completed her general surgery training at Episcopal Hospital in Philadelphia and a surgical oncology fellowship at Memorial Sloan-Kettering Cancer Center. She also completed advanced research fellowship training in cell cycle regulation in cancer at Temple University.
As director of the Gonda/UCLA Breast Cancer Research Laboratory and the Clinical Trials Unit for Breast Cancer, Dr. Chang's research focuses on developing biomarker-based laboratory tests for breast cancer detection, tailored-treatment and cancer vaccine development. Her work has earned her numerous awards and honors.
Parkash S. Gill, M.D.
University of Southern California
Norris Comprehensive Cancer Center
Dr. Gill is a professor of Medicine and Pathology and head of the tumor and vascular biology laboratory at the University of Southern California Keck School of Medicine; his clinical affiliation is with the USC Ambulatory Health Center. Dr. Gill is a leading expert in angiogenesis and its role in the progression of a number of prevalent diseases including cancer, rheumatoid arthritis, diabetic retinopathy and macular degeneration. Dr. Gill played a pivotal role in the development of three marketed drugs including Taxol® and DaunoXome® and served on the FDA BRM Advisory Committee for five years.
Through the Entertainment Industry Foundatioin's National Women's Cancer Research Alliance, our goal is to accelerate promising treatment research to treat cancer patients more safely and increase patient access to some of the most significant clinical trials in the nation. Co-founded with Lilly Tartikoff, EIF grants have helped accelerate research that contributed to the development of the breakthrough treatment Herceptin®, the first successful drug that seeks out a particular gene found in one of three cases of the most aggressive form of breast cancer.
Dennis J. Slamon, M.D., Ph.D.
Jonsson Comprehensive Cancer Center
David Geffen School of Medicine at UCLA
In addition to his role as director of Clinical/Translational Research, Dr. Dennis J. Slamon serves as director of the Revlon/UCLA Women's Cancer Research Program at the Jonsson Comprehensive Cancer Center. He is a professor of Medicine, Chief of the Division of Hematology/Oncology and Executive Vice-Chair for Research for UCLA's Department of Medicine. Dr. Slamon also serves as Director of the Medical Advisory Board for the Entertainment Industry Foundation's National Colorectal Cancer Research Alliance (EIF's NCCRA). For 12 years, Dr. Slamon and his colleagues conducted the laboratory and clinical research that led to the development of the new breast cancer drug Herceptin, which targets a specific genetic alteration found in about 30 percent of breast cancer patients. In June 2000, President Bill Clinton appointed Dr. Slamon to the three-member President's Cancer Panel. He has won nearly a dozen national research awards honoring his scientific endeavors. In 2000, he was awarded the Translational Medicine Award by the USCD-Salk Institute as well as the Bristol-Myers Squibb Oncology Millennium Award for significant achievement and leadership in breast cancer research. In 2001, he was awarded the Wadsworth Center's Brown-Hazen Award for Excellence in the Basic Sciences, and in 2002, he received the Jeffrey A. Gottlieb Memorial Award from the MD Anderson Cancer Center in Texas. In 2003, he received the Dorothy P. Landon-AACR Prize for Translational Cancer Research, an international award given by the Kirk A. and Dorothy P. Landon Foundation and the American Association for Cancer Research. In 2004, the American Cancer Society presented Dr. Slamon with the Medal of Honor, the top award bestowed by the organization. A 1975 honors graduate of the University of Chicago, Pritzker School of Medicine, Dr. Slamon earned his Ph.D. in cell biology that same year. He completed his internship and residency at the University of Chicago Hospitals and Clinics, becoming Chief Resident in 1978. One year later, he became a fellow in the Division of Hematology/Oncology at UCLA.
Carlos L. Arteaga, M.D.
Vanderbilt-Ingram Breast Cancer Program
Vanderbilt University
Dr. Carlos L. Arteaga obtained his M.D. degree with honors in 1980 at the University of Guayaquil in Guayaquil, Ecuador. He trained in Internal Medicine and Medical Oncology at Emory University in Atlanta, Georgia, and The University of Texas Health Sciences Center in San Antonio, Texas. In 1988, he joined the faculty at Vanderbilt University where he is now Ingram Professor of Cancer Research, Professor of Medicine and Cancer Biology, and member of the Division of Hematology-Oncology. In addition, Dr. Arteaga is Director of the Breast Cancer Research Program and Breast Cancer SPORE of the NCI-designated Vanderbilt-Ingram Comprehensive Cancer Center. His funded research focuses on the role of growth factor receptors and oncogenes in the progression of breast tumor cells as well as the development of molecular therapeutics in breast cancer. Dr. Arteaga is certified by the American Board of Internal Medicine in Internal Medicine and in Medical Oncology and has over 120 peer-reviewed publications relevant to his research in the molecular and cell biology of mammary neoplasia.
In 1998, Dr. Arteaga was elected into the American Society of Clinical Investigation (ASCI) and serves as a member of the NIH Parent Committee for Review of Cancer Centers (2004-2008), the Board of Scientific Advisors of the National Cancer Institute (1999-2004), the Breast Cancer Core Committee of the Eastern Cooperative Oncology Group (ECOG), and the Board of Directors of the American Association for Cancer Research (AACR; 2004-2007). He co-chairs the Developmental Therapeutics Committee of ECOG and chairs the Special Conferences Committee of the AACR (2002-2005). Dr. Arteaga is the recipient of the 2003 AACR Richard and Hinda Rosenthal Foundation Award for innovative work leading to progress in clinical breast cancer. He chaired the 2001 AACR/NCI/EORTC Meeting in Molecular Targets and Cancer Therapeutics and the AACR Special Conference Advances in Breast Cancer Research in 2003. He is Associate Editor and member of the Editorial Board of the Journal of Mammary Gland Biology & Neoplasia, Clinical Cancer Research, Breast Cancer Research, Molecular Cancer Therapeutics, Journal of Clinical Oncology, Clinical Proteomics, and Cancer Biology & Therapy.
Joan S. Brugge, Ph.D.
Department of Cell Biology
Harvard Medical School
Dr. Joan S. Brugge is currently the Chair of the Department of Cell Biology at Harvard Medical School. She joined the faculty of the Harvard Medical School as a Professor in July 1997. A graduate of Northwestern University, Dr. Brugge did her graduate work at the Baylor College of Medicine, completing her Ph.D. in 1975. She then performed her postdoctoral training at the University of Colorado with Dr. Raymond Erikson. Dr. Brugge has held full professorships at the State University of New York, Stony Brook, and the University of Pennsylvania, where she was also named as an investigator at the Howard Hughes Medical Institute. From 1992-1997, Dr. Brugge was Scientific Director of the biotechnology company ARIAD. Dr. Brugge has received several awards recognizing her scientific accomplishments including an NIH Merit Award, an American Cancer Society Research Professorship and the Senior Career Recognition Award from the American Society of Cell Biology. In addition, she has been elected to the American Academy of Arts and Sciences, the National Academy of Sciences and the Institute of Medicine.
Nancy E. Davidson, M.D.
The Sidney Kimmel Comprehensive Cancer Center
Johns Hopkins Medicine
Dr. Nancy E. Davidson, a medical oncologist, is the Breast Cancer Research Professor of Oncology at the Johns Hopkins University School of Medicine and Director of the Breast Cancer Program at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins. She also holds a joint appointment in the Department of Biochemistry and Molecular Biology at the Johns Hopkins Bloomberg School of Public Health. At Johns Hopkins, she has integrated basic scientific investigation of the molecular and cellular biology of breast cancer with a nationally renowned clinical and translational program focused on new therapeutic approaches. Her most recent lab work examines the role of epigenetic regulation of the estrogen receptor gene in breast cancer. She has guided important national trials of new therapies for women with breast cancer including the use of chemoendocrine therapy for women with premenopausal breast cancer.
Funmi I. Olopade, M.D., FACP.
Pritzker School of Medicine
University of Chicago
Walter L. Palmer Distinguished Service Professor of Medicine and Human Genetics at the University of Chicago, Dr. Funmi I. Olopade epitomizes the "bench to bedside" philosophy in her application of scientific discoveries to clinical medicine and has seamlessly parlayed her findings into clinical applications. As a Hematologist/Oncologist, Dr. Olopade specializes in cancer risk assessment, prevention, early detection and treatment of aggressive breast cancer that disproportionately affects young women. A member of many professional societies including the Association of American Physicians, Dr. Olopade has national and international recognition as a physician scientist. A speaker in much demand, she effectively disseminates the benefits of her work, inspires students and colleagues, and is a role model for women scientists worldwide. Dr. Olopade received her medical degree with distinction from the University of Ibadan in Nigeria. She came to the United States as a resident in internal medicine at Cook County Hospital, Chicago, where she was named Chief Medical Resident. Dr. Olopade completed her postdoctoral fellowship training in the joint section of Hematology/Oncology at the University of Chicago and was appointed to the faculty in 1991. Dr. Olopade is now the Director of the Center for Clinical Cancer Genetics in the Department of Medicine and holds many other faculty, hospital, and administrative posts.
Dr. Olopade is the recipient of numerous honors and awards including the James S. McDonnell Foundation Scholar award, the Doris Duke Distinguished Clinical Scientist award and a 2005 MacArthur Fellowship "genius" grant.
C. Kent Osborne, M.D.
Breast Center Baylor College of Medicine
Dr. C. Kent Osborne was born in 1946 in St. Louis, Missouri. He received his A.B. and M.D. degrees from the University of Missouri, both with honors. He completed his internship and residency at Johns Hopkins Hospital in 1974, and then spent three years as a clinical associate at the Medicine Branch, Breast Cancer Section of the National Cancer Institute in Bethesda, Maryland. In 1977, Dr. Osborne took his first faculty position at The University of Texas Health Science Center at San Antonio, where he rose to the rank of Professor and became Director of the Division of Medical Oncology in 1992. In 1999, he and his team moved to the Baylor College of Medicine to develop a new multidisciplinary Breast Center.
Presently, Dr. Osborne is Professor of Medicine and Molecular and Cellular Biology, and Director of the Breast Center at the Baylor College of Medicine. He is also the Director of the Dan L. Duncan Cancer Center that is under development at the college. He currently holds the Tina and Dudley Sharp Chair in Oncology at Baylor College of Medicine. Dr. Osborne is a physician as well as a research investigator. He has focused on breast cancer his entire career. His research interests include understanding the biology of breast cancer and then developing new treatment approaches for the disease. He has published extensively on the mechanisms by which hormonal therapies such as Tamoxifen inhibit breast cancer growth and how breast cancers become resistant to these therapies. Dr. Osborne has also studied the role of various growth factors in breast cancer development and progression, and more recently how these other growth factors can interact with estrogen to stimulate tumor growth. For more than a decade, Dr. Osborne was Chairman of the Breast Cancer Committee for the Southwest Oncology Group, where he directed numerous nationwide clinical trials investigating new treatment strategies for breast cancer patients. He is currently the Principal Investigator of the Baylor Breast Cancer Specialized Program of Research Excellence grant, one of only nine such grants nationwide and the only one in Texas. He also directs a grant from the National Cancer Institute, the goal of which is to identify the gene pathways important in breast cancer growth and then to block these pathways for therapeutic purposes.
Among Dr. Osborne's previous awards are the Komen Foundation Award and the Brinker International Award for Breast Cancer Research. He received the European Institute of Oncology Annual Breast Cancer Award for 2004 and the Jacqueline Seroussi Award in Israel in 2005.
Frances M. Visco, Esq.
President
National Breast Cancer Coalition
Ms. Frances M. Visco, Esq., is the first president of the National Breast Cancer Coalition and Fund (NBCC/F), and is a member of its Board of Directors and Executive Committee. Ms. Visco was an honors graduate at St. Joseph's University and a graduate of Villanova University's School of Law, where she was an editor of the Law Review and chair of the Women's Law Caucus. Before leaving to focus on the work of NBCCF, she was a partner in a Philadelphia law firm. In 1993, President Bill Clinton appointed Ms. Visco as one of three members of the President's Cancer Panel. In addition, she was the first consumer to chair the Integration Panel of the Department of Defense's Peer-Review Breast Cancer Research Program. She co-chaired the National Action Plan on Breast Cancer and served on the National Cancer Policy Board. Ms. Visco has been a member of the Institute of Medicine panels and has served on other policy committees, including the steering committees of the Breast Cancer International Research Group and the Experts Advisory Panel for the Universal Health Insurance Program at the New America Foundation.
In addition, Ms. Visco has been at the forefront of women's health advocacy issues, testifying before congressional committees, lecturing on the politics of breast cancer throughout the United States and internationally, and discussing women's health on national television.
Ms. Visco is a 19-year breast cancer survivor. She resides in Philadelphia with her husband and 20-year-old son.
Beth Y. Karlan, M.D.
Board of Governors' Endowed Chair in Gynecologic Oncology and Director
Cedars-Sinai WCRI at the Samuel Oschin Comprehensive Cancer Institute (Lead Institution)
Expertise: Ovarian Cancer Early Detection and Biomarker Discovery
Early detection is a primary objective of ovarian cancer research because of its promise for improved survival and quality of life. The overall five year survival for women diagnosed with ovarian cancer is 50%, but when the cancer is detected early, while it is still confined to the ovaries, prolonged survival and even cure is possible for over 95% of these women. Unfortunately, at the current time the majority of cases are diagnosed at a late stage after the tumor has spread widely, in large part, due to a lack of effective screening and early detection techniques. Ovarian cancer mortality could be reduced dramatically, even without advances in therapy, if a majority of the women affected with ovarian cancer could be diagnosed at an early stage. We have had a long standing interest in discovering effective means of early detection since our initiation of the Gilda Radner Ovarian Cancer Detection Program in 1991. In addition to our ongoing studies of women at high risk for ovarian cancer due to their inherited genetic predisposition to the disease, we are working to discover serum biomarkers that can be used as a screening test for all women.
The focus of these efforts will be on the identification of genomic and proteomic profiles that comprise ovarian cancer-specific signatures. Profiles will be validated using our robust human tissue resources and matching serial serum samples in order to optimize and refine the ability of the biomarkers to predict disease status. It is generally agreed that a panel of tumor markers will be required to achieve adequate sensitivity and specificity for early stage disease. After more than 15 years of banking gynecologic tissue specimens, the Ovarian Tissue and Clinical Database Core Facility is a cornerstone of the WCRI research program. It provides a rich resource of clinical specimens from patients with ovarian carcinoma, from women at high risk of ovarian cancer due to an inherited predisposition, and from women with normal ovaries that have been removed for benign indications. Additionally, the core establishes, characterizes and maintains
in vitro and
in vivo models (primary monolayer cell cultures and murine xenografts, respectively) to facilitate research aimed at understanding genetic mechanisms involved in ovarian carcinogenesis and to support our preclinical investigations of molecular-targeted therapies. An additional strength of our core facility is its state-of-the-art relational database system that links all patient demographic, epidemiologic, and medical information with each banked specimen. This "linkage" facilitates translational research by allowing us to correlate laboratory research discoveries, clinical observations, and patient characteristics.
WCRI has begun to molecularly profile ovarian cancer's to identify novel molecular biomarkers for early detection and monitoring. Our preliminary data demonstrate that gene expression profiling can differentiate between the various ovarian cancer histologic subtypes. In addition, gene silencing by epigenetic mechanisms, such as DNA methylation, is now recognized as another critical trigger for neoplastic development and progression. Our preliminary data demonstrate that DNA methylation patterns in ovarian cancers characterize some highly aggressive tumors that do not respond to conventional therapies. Soluble tumor DNA shed into the surrounding fluid and/or serum when cancer cells die represents a stable analyze that can be amplified and then utilized for biomarker determination. Our goal will be to define the genetic and epigenetic fingerprints of ovarian cancer and to determine the molecular signatures most useful for diagnosis, early detection, and therapy design.
David M. Gershenson, M.D.
Chairman Gynecologic Oncology Department
University of Texas M. D. Anderson Cancer Center
Expertise: Tumor Angiogenesis and Molecular Targeting Strategies in Ovarian Cancer
Despite advances in surgery and chemotherapy, ovarian cancer remains the most common cause of mortality from a gynecologic malignancy. The majority of ovarian cancer patients respond to initial surgery and platinum-based chemotherapy, but of these about 70% will recur and succumb to disease. The poor outcome of ovarian cancer patients is due to widespread metastases and development of resistance to chemotherapy. Due to the poor survival of women with ovarian cancer, understanding the mechanisms contributing to ovarian cancer development and progression as well as novel therapeutic approaches are urgently needed.
Targeting the tumor vasculature (blood supply) is a particularly attractive therapeutic strategy because endothelial cells are thought to be inherently more genetically stable than tumor cells. One such strategy has included the use of a soluble VEGF decoy receptor, the VEGF Trap, comprised of fragments of VEGF receptor (VEGFR)-1 (flt1) and VEGFR2 (flk1, KDR). Our preclinical studies indicate that VEGF-Trap in combination with taxane chemotherapy is highly efficacious. Based on these findings we are initiating a clinical trial for treatment of patients with recurrent ovarian cancer using VEGF-Trap and docetaxel.
While VEGF-targeted strategies have shown promise in ovarian and other cancers, it is likely that additional targets will be required to further improve the therapeutic efficacy of anti-angiogenic approaches. To identify novel molecular targets in the ovarian cancer vasculature, we have performed recent studies to identify differentially overexpressed genes in the tumor endothelial cells as compared to normal ovarian endothelial cells. Using microarray profiling, we have identified a list of genes that are selectively overexpressed in the ovarian cancer vasculature. We are testing the functional significance of these targets using both
in vitro and
in vivo experimental models. Moreover, we have recently developed a highly efficient method of delivering short interfering RNA (siRNA)
in vivo using neutral nanoparticles for therapeutic applications. This strategy gives us opportunities to block abnormally expressed genes that are not "druggable" with other approaches. In proof-of-concept studies, we have demonstrated that targeting the EphA2 tyrosine kinase with siRNA incorporated in nanoparticles was highly efficacious in pre-clinical models. Based on discussions with the FDA, we are performing formal toxicology studies prior to bringing this approach to clinical trials. We are developing siRNA-based anti-angiogenic approaches for targeting the differentially expressed genes in the tumor vasculature. We are also developing additional nanoparticles to deliver siRNA selectively to cell types of interest (for example, tumor associated endothelial cells or tumor cells).
In summary, we have developed highly innovative strategies that hold promise for providing new targeted therapies for ovarian cancer patients. Our work is supported by extensive preliminary data and is being carried out by a highly qualified, multi-disciplinary research team.
Richard R. Barakat, M.D.
Chief, Gynecology Service Division of Gynecologic Oncology
Memorial Sloan-Kettering Cancer Center
Expertise: Molecular Profiling of Ovarian Cancers to Predict Prognosis
The Gynecology Research Laboratory at Memorial Sloan-Kettering Cancer Center is one of the world's leading research facilities in the study of ovarian cancer. One of the main long-term aims of the Gynecology Research Laboratory at MSKCC is to develop new models to predict outcome in advanced ovarian cancer. Though treatments are improving for patients with advanced ovarian cancer, those who succumb to disease ultimately develop platinum-resistant tumors. We are developing a new class of predictive models using microRNAs, which are recently discovered short RNAs that regulate the expression of many genes in our body. They are thought to be master regulators that control more function than classical messenger RNA. Approximately 20% of women with newly diagnosed advanced ovarian cancer will have tumors that are resistant to platinum chemotherapy, the mainstay of treatment for this malignancy. Currently we are unable to predict which patients are destined to have platinum resistant tumors. The broad goal of our work is to identify a microRNA gene expression profile that predicts which patients are more likely to recur as well as further expand our knowledge of the molecular basis of ovarian cancer. This will help us to tailor post-surgical treatments more effectively, such that we can offer additional therapy to those patients who are most likely to benefit. This project should help to bring us one step closer to the promise of personalized cancer care. Ovarian cancer is expected to strike 22,430 women in 2007 and lead to death in over 50% of those diagnosed.
Robert E. Bristow, M.D.
Director, The Kelly Gynecologic and Oncology Service
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Expertise: Ovarian Cancer Surgical Outcomes Analysis
Ovarian cancer is the leading cause of gynecologic cancer-related morbidity and mortality in the United States and many other developed countries worldwide. Improvements in clinical outcomes during the past 30 years have been incremental and have been the result of many different avenues of research including advances in surgical techniques, chemotherapeutic agents and delivery modalities, and supportive care. During this time period, standards of care for women with ovarian cancer have been firmly established. However, our research, as well as that of other investigators, indicates that a majority of women in the United States do not receive state-of-the-art care. The reasons for this are poorly understood. Consequently, outcomes analysis to elevate the standard of care for women with or at risk for ovarian cancer is an emerging and critically important field of investigation. A vital component of outcomes analysis for ovarian cancer is the identification of barriers to universal access to quality care. We have previously shown that these include patient demographic characteristics, qualifications (of lack thereof) of hospitals and individual providers, economic considerations, and the influence of third party payers to name just a few. Our current ovarian cancer research program is also focused on developing risk-adjusted measures of patient outcomes and healthcare provider performance and quantifying the short- and long-term impact of treatment on quality-adjusted patient survival. In addition to spotlighting the barriers to quality care, an equally important challenge is the development of model healthcare delivery platforms for women with ovarian cancer that are able to provide broadly accessible cutting-edge treatment at an economically affordable cost. Consequently, our multidisciplinary research team, comprised of experts in epidemiology, public health, health policy and management, and basic science research, is also focused on the cost-effectiveness and pharmaco-economic aspects of ovarian cancer outcomes analysis as well as the development of novel therapeutic agents.
