I have dedicated the last 25 years of my research to understanding the molecular mechanisms of nuclear hormone receptor action in human breast carcinoma cells and tumor systems and testing of novel therapeutics for breast cancer. My ongoing work focuses on post-translational modifications of nuclear receptors and coactivators, particularly phosphorylation, with my earliest publications demonstrating that the NCOA family of coactivators were targets for kinase mediated phosphorylation. Building upon this I demonstrated expertise in identifying novel sites of nuclear receptor phosphorylation and the role in the regulation of estrogen receptor (ER) function. Our most recent work on ERα phosphorylation has used CRISPR/Cas9 to create breast cancer cell lines with mutations in ERα phosphorylation sites, and ‘knock-in’ serine to alanine mutations of ERα phosphorylation sites Serine 171 and Serine 216 in mice to understand how ERα phosphorylation impacts physiological processes. We collaborate with Franck Marvis-Jarvis in a grant to evaluate ER function in male and female pancreatic beta cells. The other major area of research in my laboratory is development and testing novel therapeutics directed against specific signaling pathways in breast cancer. In collaboration with Robert Gensure at Tufts University, we are currently testing novel PTHrP antagonists for bone metastatic breast cancer.
