ETHANOL EFFECTS ON VITAMIN TRANSPORT/MITOGENIC SIGNALING

候选人的近期和长期目标反映了一个长期的

The Candidate's immediate and long-term goals reflect a longstanding interest in the effects of ethanol on fetal growth and development. The "immediate" goal is to continue the ethanol related research which is presently funded and ongoing. The latter has evolved from previous work defining the impact of ethanol of fetal development. These essentially completed, more mechanistically oriented studies are now in progress. As should be the case, they have supplied, along with some answers, many question, especially regarding basic mechanisms of fetal cell mitogenic response. "Long-term" goals will b e to focus research on these ,but this will require a relatively stable faculty getting- tenure will be needed and a small (not absent) teaching load. The impacts of this award will be three-fold. First will be to replace the major "soft" money component of my salary, thereby allowing me to 1) continue working on the above projects for their duration and 2) obtain future grants related to these, as the Principal investigator, without salary constraints. Second, I am at a juncture in my career at which I must obtain tenure in order to continue at this institution. A five year salary commitment would greatly enhance the chances of this, allowing continuity of ongoing research. Third, the above salary commitment would release me from the additional teaching load required should further departmental monies be need for my support. Two related research approaches will utilized for the following studies. For the first, the overall goal is an improved understanding of the effects of ethanol on fetal nutrition by determining its effects on placental and fetal cell vitamin transport. Specific aims are 1) to establish the mechanisms of thiamine (B1) and vitamin B6 transport by the term human placenta, 2) to determine the effect of ethanol on these and 30 to undertake concomitant studies with fetal rat hepatocytes in culture. The second is to determine the mechanism(s) by which ethanol impairs fetal cell proliferation. More specifically, the means by which ethanol blocks the epidermal growth factor (EGF) mediated mitogenic responses in rat fetal hepatocytes will be probed. This will focus on the effect of ethanol on EGF receptor tyrosine kinase activity s the site of purturbation of replicative capacity. Inhibition of this process by ethanol may explain, at least in part, the adverse effects of in utero ethanol exposure on the fetus.