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 at 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 regulatory factors of rat class I alcohol dehydrogenase (ADH) and the cis-and trans-acting elements that mediate the effect of hormones and other factors on the ADH gene. 2. Mechanisms of liver fibrogenesis. Investigation of factors that activate stellate cells to collagen producing myofibroblast-like cells and mechanisms whereby acetaldehyde stimulates fibrogenesis. Studies of compounds such as retinoids which suppress fibrogenesis 3. Studies of genetic susceptibility and mechanisms for intraepithelial neoplasia and for chronic pancreatitis. 4. Ethanol cytokine interaction in the regulation of liver regeneration. 5. Pathogenesis of steatohepatitis. This work includes investigation of epidemiological factors, toxic factors, mitochondrial abnormalities and immunologic mechanisms. 6. Molecular and biochemical analysis of adenylyl cyclase in alcoholism. 7. Hypothalamic-pituitary-adrenal axis (HPA) and alcoholism. 8. Studies of endogenous hypothalamic opioid activity in patients with positive or negative family history of alcoholism. 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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