The continuation of the Mentored Clinical Scientist Development Award has been designed to allow Dr. Ellen Behrend to progress further toward becoming an independent researcher. An opportunity has arisen for Dr. Behrend to establish her own laboratory at Auburn University. Continuation of her Award will allow Dr. Behrend to finish her degree, to set up a laboratory and establish an independent research program while still receiving guidance from her sponsor, and to dedicate 75 percent of her effort to research. Completion of her coursework at Auburn with a 4.0 average speaks to her intellectual capabilities, and her publication record over the past 3 years speaks to her dedication to academics. The sponsor, Dr. Robert Kemppainen, serves as a strong role model, having performed research in the basic and veterinary clinical sciences. Participation in the activities and interaction with the faculty of the sponsor's department will allow continued exposure to basic science research and endeavors. Serving on the clinical faculty with a 25 percent time commitment to clinics and teaching will provide Dr. Behrend the opportunity to improve her skills in those areas. The goal of the proposed research is to determine the role of Dexras1, a unique glucocorticoid-induced protein identified by the sponsor, in corticotroph function and glucocorticoid feedback. This is a continuation of the goal of the original award to determine the mechanism of negative feedback in corticotrophs. Ongoing research supports the idea that glucocorticoids cause the rapid induction of new mRNA(s) and protein(s) in corticotrophs which then act to suppress ACTH release. The protein(s) mediating these effects needs to be identified and characterized to ultimately understand how and where negative feedback works in corticotrophs. Dexras1 appears to be a member of the Ras family of small GTPases, a family of proteins known to be involved in cellular transport and secretion. Thus, since Dexras1 is glucocorticoid-induced and Ras proteins are involved in secretion, we hypothesize that Dexras1 is likely to be involved in feedback. Dr. Behrend's research will focus on determining how Dexras1 works within corticotrophs. For the project, possible Dexras1 interactors will be identified with the yeast two-hybrid system and the appropriate plasmids will be isolated and categorized by PCR amplification and restriction digest analysis. Unique clones will be sequenced and identified by comparison with GenBank. Those clones whose identity suggest a role in the secretory pathway will be studied further; their interaction will be verified by in vitro and in vivo transcription and translation with co-immunoprecipitation of the products.
| Kemppainen, Robert J; Cox, Elaine; Behrend, Ellen N et al. (2003) Identification of a glucocorticoid response element in the 3'-flanking region of the human Dexras1 gene. Biochim Biophys Acta 1627:85-9 |
| Kemppainen, R J; Behrend, E N (1998) Dexamethasone rapidly induces a novel ras superfamily member-related gene in AtT-20 cells. J Biol Chem 273:3129-31 |
