Dr. Kay Lee Fruman (Biological Sciences)
B.A. in Molecular Biology, University of California, Berkeley (1991)
Ph.D. in Immunology, Division of Medical Sciences, Harvard University (1997)
The goal of my laboratory is to study the function and regulation of an enzyme called S6K2 (S6 kinase 2). S6K2 was first identified as an enzyme kinase closely related to a well-known kinase, S6K1 (previously known as p70 S6K). S6K1 is involved in cell growth and size control. Since S6K2 was identified via DNA homology to S6K1, not much is known about S6K2's function in cells. Our laboratory’s long-term goal is to understand S6K2's regulation and function.
Why bother studying S6K2, among thousands of enzymes present in a cell? It's because it has potential therapeutic implications for both cancer research and immunological research. When people undergo organ transplantations they are given immunosuppressant drugs in order to suppress their immune system from fighting and rejecting the transplanted organ. S6K2 is one of the cellular proteins whose activity is inhibited by one of these immunosuppressant drugs, rapamycin. Rapamycin was isolated from Streptomyces hygroscopicus found in Rapa Nui (Easter Island), and when cells are exposed to rapamycin they stop or slow down cellular proliferation. Rapamycin's use is widening; it was recently approved for prevention of restenosis after cardiac treatments, and it is also being included in experimental treatment protocols for various forms of cancer. Use of such immunosuppressant drugs has resulted in marked improvement in transplantation and cancer outcomes. However, since rapamycin (as well as other anti-proliferative drugs for cancer and/or transplantation treatments) targets a broad range of cellular processes, it also has a broad range of side effects. Since most of the targeted cellular processes are not likely to be crucial in inhibiting cellular processes, the more we know about the mechanism of cell proliferation and these drugs' mechanism, the closer we are to designing better drugs that target only the necessary cellular processes, thereby limiting side effects. Much research has focused in the last decade on the molecular mechanism of cell growth and proliferation that are controlled by rapamycin. Preliminary data suggest that S6K2 may be involved in such cellular mechanisms. Supporting this hypothesis, many proto-oncogenes whose mutation contributes to cancer have been shown to also regulate S6K2, meaning S6K2 may be a player in oncogenesis. The goal of our laboratory is to study the regulation, cellular function, substrate, and localization behavior of S6K2 inside a cell using modern molecular and cell biological techniques.