My lab is interested in how the ovarian steroid hormones, estradiol and progesterone, act in the brain to regulate gene expression and female reproductive behavior in rodents. These hormones elicit many of their biological effects by binding to their respective intracellular steroid receptors located in specific brain regions. Nuclear receptor coactivators have been found to dramatically enhance the transcriptional activity of steroid receptors (see the Nuclear Receptor Signaling Atlas). We have found that neurons, located in brain regions that regulate reproduction, coexpress steroid receptors and nuclear receptor coactivators (Figure 1).
We are exploring how these coactivators function with steroid receptors in brain to activate behaviorally-relevant genes (Figure 2). More recently, we have been using protein-protein interaction assays (Figure 3) to explore which coactivators from brain interact with estrogen and progestin receptors (Figure 4). We are collaborating with the labs of Shaila Mani and Larry Denner to investigate the role of coactivators in PR action in brain. We hope to determine the mechanisms by which PR, in the absence of progesterone, can be activated by dopamine in brain. One goal of our research is to identify novel coactivators and other proteins that function in hormone action in the brain. By enhancing our knowledge of hormone action, we may better understand mechanisms involved in a variety of hormone-dependent diseases, including breast cancer.
In addition, our lab is collaborating with Adele Wolfson's lab in the Chemistry Department to investigate the expression and regulation of the enzyme thimet oligopeptidase (TOP) in rodent brain and with the labs of Drew Webb in the Biology Department at Wellesley and Angelo Poletti at the University of Milano to investigate the role of estrogens in prostate cancer.
See the Team page for a more detailed description of each student's ongoing project in our lab