The laboratory has two major research interests. The first is the regulation of progesterone receptor (PR), a ligand-activated transcription factor, by phosphorylation. Using chicken PR as a model system, we have found that this protein can be activated in a ligand- independent manner by activators of kinases. While human PR does not appear to exhibit ligand-independent activation, treatment with 8-Br cAMP, an activator of protein kinase A, causes some steroid antagonists to act as agonists. We have identified many of the phosphorylation sites in human and chicken PR and the role of these sites as well as the pathways by which kinases activate the receptors in the absence of ligand or in the presence of antagonists is a major focus of the laboratory. The second interest is the role of steroid receptor family members in prostate cancer. Projects include: 1) analysis of androgen receptor for ligand-independent activation or antagonist/agonist switch; 2) Analysis of the mechanism by which vitamin D inhibits the growth of prostate cancer cells and studies to determine whether vitamin D can be used as a chemotherapeutic or chemopreventive agent in prostate cancer.