Distinguished Scientific Fellow
Van Andel Research Institute
Grand Rapids, Michigan
The goal of Drs. Tsarfaty and Vande Woude’s research is to understand the role of the Met oncogene in breast cancer progression, metastasis, and therapeutic resistance. Met is over-expressed in 20%-30% of breast cancer tumors and is a strong, independent predictor of decreased survival. Met expression is highest in tumors that lack expression of estrogen and HER2 receptors, commonly called triple negative breast cancer. The team’s recent studies have demonstrated that Met is involved in resistance to trastuzumab (Herceptin®), a targeted therapy developed for HER2+ breast cancer. These findings and many others underscore the strong relationship of Met with tumor progression and resistance to anti-HER2 therapy.
Drs. Tsarfaty's and Vande Woude's laboratories have combined several unique models to evaluate the influence of the Met oncogene, and in 2013-2014, they will continue to determine the mechanisms of Met that contribute to breast cancer metastasis and therapy resistance.
These two laboratories have combined several unique models to evaluate how the Met oncogene influences tumor cell invasion, metabolism, and therapeutic resistance in breast cancer. In this grant period, they examined the role of Met signaling on collective cell migration and developed a computational resource for quantifying cell motility. We continued their examination of cancer metabolism and demonstrated that simultaneous inhibition of both glycolysis and Met signaling reduces tumor growth and tumor blood volume. In addition, the researchers examined efficacy of combination therapy of tyrosine kinase inhibitors on triple-negative breast cancer (TNBC) progression using patient-derived tumorgraft models of TNBC. Overall, these studies will have a significant impact on our understanding of how receptor tyrosine kinase signaling influences cell invasion, metabolism, and therapeutic resistance in breast cancer.
Dr. George F. Vande Woude received his M.S. (1962) and Ph.D. (1964) from Rutgers University. From 1964-1972, he served first as a postdoctoral research associate, then as a research virologist for the US Department of Agriculture at Plum Island Animal Disease Center. In 1972, he joined the National Cancer Institute as Head of the Human Tumor Studies and Virus Tumor Biochemistry Sections. In 1980, he was appointed Chief of the Laboratory of Molecular Oncology and, in 1983, he was selected to be Director of the Advanced Bioscience Laboratories-Basic Research Program at the National Cancer Institute, Frederick, MD, a position he held until 1998. From 1995-1998, Dr. Vande Woude was Special Advisor to the Director of the National Cancer Institute and served to reorganize the intramural basic science at NCI. In 1999, he was selected to be the first Director of the newly created Van Andel Research Institute in Grand Rapids, Michigan, a position he held until February 2009. He is currently a Distinguished Scientific Fellow.
Dr. Vande Woude used recombinant DNA technology to isolate integrated forms of acute transforming retroviruses and compare their oncogenes to cellular protooncogenes. His laboratory was first to determine the structure and sequence of proviral long terminal repeats (LTR), to demonstrate their enhancer function of the LTR promoter, and to show the utility of LTR expression vectors in eukaryotic cells. His laboratory was first to demonstrate that a normal cellular protooncogene could be activated as an oncogene. These findings provided a foundation for the search for active oncogenes in tumors. His studies of the mos oncogene have continued for almost two decades and led to the discovery that the normal mos product regulates vertebrate meiotic maturation and is responsible for the production of an unfertilized egg. The MPF results provided the first direct connection between oncogene function and the cyclin dependent kinases that regulate cell cycle.
Still another important contribution was Dr. Vande Woude's discovery of the human met oncogene, a member of the tyrosine kinase growth factor receptor family that is ubiquitously expressed in mammalian tissues. The Vande Woude lab, together with the laboratory of Dr. Stuart Aaronson, discovered that the Met ligand is a hepatocyte growth factor (HGF). This connection significantly expanded the importance of this ligand-receptor pair in the mitogenic, motogenic, and morphogenic behavior of epithelial cells. His laboratory was first to show that inappropriate Met expression renders cells tumorigenic and occurs in human tumors. His laboratory demonstrated that cells inappropriately expressing HGF/Met autocrine signaling display potent metastatic activity in vivo. This tyrosine kinase growth factor receptor pathway displays all of the phenotypes essential for malignant growth.
Dr. Vande Woude is the recipient of the National Institutes of Health Merit Award, the Robert J. and Claire Pasarow Foundation Award for Cancer Research, and a Lifetime Achievement Award in Technology Transfer from the National Aeronautics and Space Administration. In 1993, he was elected to the National Academy of Sciences and has served as Chair of the Section for Medical Genetics, Hematology & Oncology (2004-2007). He served on the Award Assembly of the General Motors Cancer Research Foundation (1990-1994) and on the scientific advisory boards of Jefferson Medical College, Thomas Jefferson University (1995- ); Karmanos Cancer Institute & Prentis Comprehensive Cancer Center at Wayne State University (2001- ); US Military Cancer Institute (2001- 2004); Member, External Advisory Board, Simmons Cancer Center, University of Texas, Southwestern (2007- ) and served as Chair of the External Advisory Board, Children's Cancer Research Institute, University of Texas Health Science Center (2003-2009). Dr. Vande Woude is a member of the National Dialogue for Cancer (now C-Change) (2001- ), served as a member of the Board of Directors for the American Association of Cancer Research (2001-2004), and as Chair of the Council of Scientific Advisors (2006- ) and served on the National Cancer Legislation Advisory Committee (2000-2001). From 2002-2004, Dr. Vande Woude was awarded the Alice Hogge and Arthur A. Baer Professorship and served as Visiting Professor, Department of Radiation and Cellular Oncology, University of Chicago.
Dr. Vande Woude is a member of the American Chemical Society, the American Association for the Advancement of Science, the American Academy of Microbiology, and the American Association for Cancer Research. He is the founder and President of the Foundation for Advanced Cancer Studies (1985-), which sponsors annual meetings on Oncogenes and Cancer Genetics and Tumor Suppressor Genes that are designed to accommodate and encourage participation by young cancer research investigators.
Dr. Vande Woude is the author of over 240 scientific research articles and over 60 articles in books or monographs. He has served as Editor of Journal of Virology and as an Editorial Board Member of Cell, Cancer Research, and Journal of Virology and is currently an Editorial Board Member of Oncogene, Molecular Imaging, Cell Cycle and Molecular Cancer Research. Dr. Vande Woude was Founding Editor of Cell Growth and Differentiation and, since 1989, has been co-Editor (with George Klein) of Advances in Cancer Research.