The research training objective is to provide a proper environment for the development of independent investigators in the field of alcoholism as it relates to molecular and cellular pathology. Post-doctoral fellows will work closely with a preceptor on a project related to the research of the preceptor. The trainees will interact among themselves, with other preceptors in the program, and with the research community as a whole of the Institution. Also, they can obtain formal instruction in biochemistry, biostatistics, and research methodology, and will be exposed to lectures and interaction with established investigators in the field of alcoholism. The principal areas and significance of the research training offered are: 1. Hormonal regulation of the rat class I alcohol dehydrogenase (ADH). This study identifies the cis- and trans- acting elements that mediate the effect of hormones on the ADH gene. 2. Mechanisms of liver fibrogenesis. Investigation of factors that activate stellate cells to collagen producing myofibroblast-like cell and mechanisms whereby acetaldehyde stimulates fibrogenesis. 3. Alterations in water transport across membranes. Study of effects of ethanol on aquaporin water transport proteins and water permeability across cells. 4. Effects of ethanol on hepatic regenerative growth. Studies of possible factors that may accelerate recovery from ethanol-induced liver injury. 5. Differences in dynamics of the hypothalamic-pituitary-adrenal axis as a risk factor for alcoholism. 6. Molecular and biological analysis of adenyl cyclase in alcoholism. These studies include a search for markers of predisposition towards alcoholism. 7. Regulation of growth and differentiation of intestinal epithelial cells. Study of effects of ethanol in intestinal cell differentiation and function. These areas of research will provide extensive training in different methods of biochemistry, molecular biology and cell culture. Trainees will be exposed to the application of basic research to studies of patients with alcoholism. The final objective is to instill in the trainee the ability to approach original questions of research relating to the pathogenesis of damaging effects of alcoholism on the body.
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