Overview
The main focus of my research has been to define the roles of nuclear hormone receptors (NHRs) in the pathogenesis of disease, with a focus on hormone-related cancers.
During earlier stages of my research career, definition of the structural and molecular determinants of NHR receptor biology and pharmacology was the main focus. Information obtained from these studies was used to guide the development of receptor modulators for therapeutic interventions and to gain insights into the pharmacology of estrogen and androgen receptor ligands. More recently, my research has shifted to define receptor-mediated signaling pathways relevant to the pathogenesis of breast and prostate cancers. One example of this is the definition of signaling pathways downstream of the orphan nuclear receptor, estrogen-related receptor alpha (ERRα) in breast cancer. Using gene expression signature defined in breast cancer cells we demonstrated that the activity of ERRα tracks with poor prognosis in all breast cancer subtypes. We confirmed a causal role for ERRα in breast cancer growth in both cellular and xenograft models of breast cancer. More recently, we further defined the role(s) of this receptor in tumor metabolism and validated its utility as a therapeutic target in triple negative breast cancer (TNBC). In addition to the cancer cell intrinsic effects of ERRα, this receptor is also expressed in T cells and in macrophages. We are currently evaluating the impact of modulating ERRα activity in these immune cells and how that influences tumor biology.