Adipocyte Biology and Gene Regulation Section
The Adipocyte Biology and Gene Regulation Section studies epigenetic regulation of PPARg and adipogenesis (generation of fat), with a focus on histone-modifying enzymes. PPARg is the master regulator of adipogenesis, and it cooperates with other adipogenic transcription factors to promote adipogenesis. Understanding how epigenetic mechanisms regulate PPARg and adipogenesis may provide new ways to treat obesity and lipodystrophy, the two diseases that are tightly associated with type 2 diabetes.
Nuclear Receptor Biology Section
Our section investigates the functions of thyroid hormone (T3) receptors and other nuclear receptors in mammalian development. The diverse actions of T3 in different tissues are determined in part by T3 receptor α 1 and β isoforms, which act as ligand-regulated transcription factors. T3 action is also regulated by deiodinase enzymes that activate and inactivate the hormone in different tissues. In addition, we investigate retinoid-related orphan receptors, which also belong to the nuclear receptor family, but lack known physiological ligands. Our studies should elucidate hormonal and transcriptional mechanisms that underlie developmental, homeostatic, and disease processes.
Receptor and Hormone Action Section
Marvin C. Gershengorn, M.D.
The Receptor and Hormone Action Section studies the molecular details of signaling and the regulation of G protein-coupled, seven transmembrane-spanning receptors. The receptors for thyrotropin (also called thyroid-stimulating hormone, TSH) and thyrotropin-releasing hormone (TRH) are of particular interest. Researchers focus on the signaling mechanisms of these receptors and the physiological responses to activation in the central nervous system for TRH and in preadipocytes/adipocytes and bone for TSH. Researchers are developing small molecule "drug-like" ligands for these receptors as probes of these actions and as potential lead drugs to treat human disease.
Steroid Hormones Section
The Steroid Hormones Section aims to understand the three characteristic parameters of steroid-regulated gene expression at the molecular level. These parameters include: (1) total activity, (2) the steroid concentration at which half-maximal response is seen (EC50), and (3) the partial agonist activity of anti-steroids. The parameters are not invariant, as was believed for many years, but can be modulated by numerous factors. Increased mechanistic insight into modulatory factor actions will permit greater control of differential gene expression by steroid hormones during development, differentiation, homeostasis, and endocrine therapies.