This is a request for an ADAMHA RSDA (Level II). Alcohol dehydrogenase (ADH) is the rate-limiting step in the oxidation of alcohol by mammals. ADH gene expression occurs primarily in the liver where it serves a major detoxification function. Since human ADH shows a strong preference for expression in the liver, it is of great interest to my laboratory to study the mechanism of this tissue-specificity. In addition, glucocorticoids have been reported to regulate liver ADH gene expression, and preliminary studies in this lab indicate a direct effect of glucocorticoids on transcription. Regulation at the level of transcription initiation will be analyzed in detail to ascertain the cis- acting DNA elements and ultimately the trans-acting protein factors necessary to produce the high level of ADH gene expression seen in liver. The involvement of glucocorticoids in regulating ADH transcription will be analyzed in further detail. This knowledge will be important for understanding the overall effects of alcohol abuse and alcoholism upon humans since the ability of individuals to induce liver ADH levels during times of ethanol-induced stress may play a role in determining the extent to which they suffer from this disease. The broader benefit of these biochemical studies is that it will provide information which will further our general understanding of mammalian transcriptional regulation, a process which is ill understood. The ADH project is just coming to fruit right now and promises to provide a wealth of information on liver-specific transcriptional regulation and alcohol metabolism in the liver. A five-year RSDA (Level II) fits perfectly into my scientific career development. Since taking the position at colorado state University I have encountered other responsibilities, primarily teaching, which divert my attention from research. An RSDA would help reduce the teaching burden and allow me to more fully focus my energy to the ADH research project which is becoming increasingly more complex. Such an award would allow me to spend more time in the lab myself, a task which I have been trained to perform very efficiently and which is very rewarding personally. It would also increase the amount of time I can spend developing collaborative relationships with other laboratories in order to learn new techniques and develop new ideas.
