Steroid hormone receptors are ligand-regulated transcription factors that control diverse physiological and developmental processes. In addition, estrogen and androgen receptors (ER and AR) are implicated in the etiology of breast and prostate cancer, respectively, whereas the glucocorticoid receptor (GR) is an important therapeutic target for cancer and inflammatory diseases. The goal of my laboratory is to elucidate the mechanism of signal transduction and transcriptional regulation by these receptors. Specifically, the lab is interested: 1) How molecular chaperones regulate steroid receptor action; 2) how transcriptional regulatory molecules (coactivators and corepressors) modulate ER, GR and AR transcriptional activity and the role of steroid receptor phosphorylation in the recruitment of coactivators and corepressors, 3) how Rho GTPases and the actin cytoskeleton regulate steroid receptor transcriptional response, and 4) the mechanism of GR-induced cell growth arrest and apoptosis. We are using genetic (mouse knock-outs and knock-ins), biochemical (microarrays and high-throughput screening of small molecules that disrupt receptor:coactivator interaction) as well as cell biological strategies (studying macromolecular complexes using color variants of GFP) to elucidate the mechanism of ER, AR and GR function in vivo. Understanding the mechanism of steroid receptor-regulated gene expression may reveal novel points of intervention to be exploited in the development of new therapies for steroid-dependent malignancies, such as breast and prostate cancer.