Bio/Research
The overall goal of my research is to determine the molecular mechanisms by which female steroid hormones regulate development, differentiation and/or cellular proliferation and survival in hormone responsive tissues and cancers via their cognate receptors, including the estrogen, androgen and pr...
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Bio/Research
The overall goal of my research is to determine the molecular mechanisms by which female steroid hormones regulate development, differentiation and/or cellular proliferation and survival in hormone responsive tissues and cancers via their cognate receptors, including the estrogen, androgen and progesterone receptors. Estrogens regulate the expression of diverse regulatory proteins and growth factors via one or both of two estrogen receptor subtypes (ERα & ERβ). My lab is actively studying several aspects of ER, PR and AR action, including the role of post translational modifications in the transcriptional activation of these receptors, the roles of co-regulatory proteins in receptor-mediated responses, the molecular nature of transcriptional activation and/or repression in the regulation of target gene expression, nongenomic actions of estrogens, and the detailed structural requirements for ligand binding to each receptor, especially in regard to discrimination between agonists and selective receptor modulators (SRMs). I am also interested in using high throughput sequencing to identify and characterize ER/PR and AR genomic targets and their regulated transcripts in breast and prostate cancer cells, as well as the transcription factors that co-associate at these targets and the mechanisms by which distal DNA response elements elements are able to organize and coordinate transcription initiation and repression. I am also interested in the role of tumor initiating cells in breast tumor invasion and metastasis. More recently, we have begun to use cryo-EM to determine the structures of larger steroid receptor complexes bound to DNA. We are also beginning to use patient-derived xenograft (PDX) models as potential avatars for breast cancer patients.
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