E-mail: drl@helix.nih.gov
Dr. Lowy received his M.D. from New York University Schol of Medicine in 1968. Between 1970 and 1973, he was a Research Associate in the Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health. He trained in Internal Medicine at Stanford University and Dermatology at Yale University, and started his laboratory at the National Cancer Institute in 1975. He has been Chief of the Laboratory of Cellular Oncology since 1983, has received the Wallace Rowe Award for Virus Research, and has been a member of many scientific advisory boards, grants committees, and editorial boards. Since 1996, he has also been the Deputy Director of the Division of Basic Sciences, NCI.
My laboratory has had a long-term interest in the molecular biology of tumor viruses, oncogenes, and tumor suppressor genes. Much of the work is concerned with fundamental aspects of normal and abnormal cell growth, but some of the research has direct clinical application. The systems studied include papillomaviruses and signaling through the Ras oncoproteins. Papillomaviruses. Papillomaviruses are associated with benign and malignant tumors in humans and animals. A sub-set of HPV types infect the genitalia, and some of these types have been etiologically linked to cervical cancer, which is the second most common cancer among women worldwide. The papillomavirus research is carried out in collaboration with John Schiller's laboratory, which is also in the LCO.
We have examined biochemical and genetic aspects of the papillomavirus oncogenes and their protein products. In addition, we have developed techniques for large scale production of virus-like particles (VLPs) composed of papillomavirus structural proteins. The VLPs are providing insight into basic aspects of papillomavirus biology as well as serving as the basis for a candidate subunit vaccine against papillomaviruses. Our vaccine studies in animals have shown that immunization with VLPs can induce substantial protection against experimental challenge with papillomaviruses that induce cutaneous or mucosal lesions, and human vaccine trials are planned. Regulation of Ras oncoproteins. Most of the oncogene/tumor suppressor gene research has been concerned with the ras oncogene and NF1 tumor suppressor gene, which is mutated in type I neurofibromatosis. The ras gene product, Ras, plays a key role in signal transduction and is mutationally activated in many human and animal tumors. Much of our recent work on Ras has emphasized elucidation of the mechanisms underlying the regulation of its activity. The analysis of two closely related, widely expressed such genes, sos-1 and sos-2, has identified important ubiquitin-dependent differences in the stability of their encoded proteins and in the relative efficiency with which they activate Ras. Efforts to understand the molecular mechanisms underlying this difference and others between Sos1 and Sos2 are in progress, as are studies on signaling through Sos and other regulators of Ras activity.
Representative Publications
Last revised on April 14, 1997.
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