This laboratory is involved in studies of the molecular mechanisms by which steroid receptors regulate gene transcription.
Current projects address four main research problems.
The functional role and mechanism of action of coregulatory proteins that are essential for receptor-mediated gene activation. Coactivators have been implicated to function as bridging proteins between the receptor and the basal transcriptional apparatus and to be involved in targeted remodeling of chromatin structure as a result of their intrinsic histone acetyltransferase enzyme activity. Steroid receptors are phosphoproteins and they undergo increased phosphorylation as an early response to hormone binding. To define a functional role for phosphorylation we have identified multiple serine phosphorylation sites in the progesterone receptor, have constructed site-directed mutants and are currently analyzing the mutants for altered receptor function in vivo in gene transfection studies. Synthetic steroid antagonists are important compounds both clinically for treatment of breast cancer and other human diseases, and as probes to study receptor mechanisms.