RESEARCH DAY 2008: “Complex Determinants in Health: Interactions of Genetic Factors and Environmental Influences,” will take place, Friday, Nov. 21, at the Fayez S. Sarofim Research Building of The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases. [more]
GRANTS 102: These intensive workshops help junior faculty members refine their skills for developing competitive grant applications. [more]
CLINICAL RESEARCH BUDGETING / BILLING training clarifies the clinical research billing processes, ensures full cost recovery of clinical research studies and reduces billing errors. [more]
MANDATORY EFFORT REPORTING TRAINING. All faculty with effort on sponsored projects and other employees involved in the effort certification process must complete approved training [more]
Research in my laboratory encompasses two distinct but linked areas of investigation. The first pertains to the biology and pharmacology of the Retinoid X Receptor (RXR). Drugs that activate this receptor (rexinoids) have been shown to reverse insulin resistance in animal models of diabetes, to suppress the development of breast cancer in an animal model of carcinogen - induced breast cancer and to induce apoptosis in human myeloid leukemia cells.
We are using a variety of molecular techniques to investigate the molecular basis for the effects of rexinoids on gene expression in cultured adipocytes and diabetic rodents. A second area of particular interest to the laboratory is the investigation of the factors controlling the expression of the enzyme tissue transglutaminase. Expression of tissue transglutaminase is selectively activated in cells undergoing physiological apoptosis.
We have isolated the promoter for this enzyme and have used transgenic mouse models to demonstrate the specific localization of transglutaminase expression to sites of in vivo apoptosis. We are currently dissecting the detailed structure of the transglutaminase promoter to identify the cis- and trans acting factors that regulate transglutaminase expression in vivo.
Research in my laboratory introduces students to the use of animal models of human diseases such as diabetes and breast cancer, as well as various transgenic mouse models, to delineate the molecular mechanisms of hormone action in vivo. Students will acquire expertise in the technologies of DNA cloning, quantitative PCR analysis, DNA transfection and transgenic mouse biology.
Depre, C., Shipley, G. L., Chen, W., Han, Q., Ahuja, H. S., Stepkowski, S., Davies, P. J. A. and Taegtmeyer, H. Isoform-specific regulation of metabolic gene expression in unloaded rat heart. Nature Medicine 4 (11):1269-75, 1998.
Ritter, S. J. and Davies, P. J. A. Identification of a transforming growth factor- 1/bone morphogenetic protein 4 (TGF 1/BMP4) response element within the mouse tissue transglutaminase gene promoter. J. Biol. Chem. 273:12798-12806, 1998.
Mukherjee, R., Davies, P. J. A., Cesario, R., Jow, L., Crombie, D., Hamann, L. G., Boehm, M. F., Mondon, C., Nadzan, A. M., Paterniti, Jr., J. R., and Heyman, R. A. RXR agonists activate RXR:PPAR heterodimers and sensitive diabetic and obese mice to insulin. Nature 386:407-410, 1997.
Nagy, L., Thomazy, V. A., Saydak, M. M., Stein, J. P., and Davies, P. J. A. The promoter of the mouse tissue transglutaminase gene directs tissue-specific, retinoid-regulated and apoptosis-linked expression. Cell Death and Differentiation. 4:534-547, 1997.
