Since 1981 have been involved in the study of hepatobiliary disease as a research technician and post-doctoral fellow. In addition, I obtained advanced clinical training in veterinary internal medicine with an emphasis on hepatobiliary disorders in companion animals. I am firmly committed to becoming an independent investigator in hepatobiliary research. Presently I am an assistant professor at Tufts Veterinary School. At this point in my career, I have developed proficiency in the clinical and teaching aspects of my job while generating the preliminary data which is the foundation of this grant proposal. I am ready to awareness and exposure to other scientists working in my field. Presently I work with Dr. Anwer, a noted research in bile salt transport, investigating bile acid induced apoptosis in rat hepatocytes. Since hepatic retention of bile acid accompanies cholestatic liver disease, it is likely that bile acids contribute to ongoing hepatic pathology in these disorders. The objective of my proposal is to understand the cellular signaling mechanisms that regulate bile acid induced apoptosis. We have shown that agents which increase induced apoptosis. We propose to investigate the downstream phosphorylation events controlled by these agents which are necessary for the observed cytoprotection. Since the cytoprotective agents cause marked morphologic changes in our hepatocytes, we propose to investigate the role of the hepatocyte cytoskeleton and the extracellular matrix in the cytoprotective response. During th3e course of the award, I will use the expertise of scientists at our Boston campus, particularly my postdoctoral advisor, Dr. Win Arias, a respected hepatologist, and the GRASP Digestive Disease Center's training programs in molecular biology and cell aspect of my proposal. I will also attend seminars and course work offered by the medical school's Physiology Department.
