Margaret A. Shupnik, Ph.D.
- Professor of Medicine and Physiology, Division of Endocrinology and Metabolism
- Senior Associate Dean for Research, University of Virginia
- Past President, Endocrine Society (2007-2008)
- Chair of Executive Committee (President), International Society of Endocrinology (2012-2016)
- Undergraduate: B.S., Pennsylvania State University, University Park, PA (Chemistry)
- Graduate: Ph.D., University of Wisconsin, Madison, WI (Biochemistry)
- Postdoctoral: NIH Research Fellow (Physiology, Laboratory of Toxicology), Harvard School of Public Health, Boston, MA
Our laboratory studies how steroids and peptide hormones regulate gene expression and how these interactions influence physiological and pathophysiological processes. We work on pathways by which steroids such as estrogen control cell function in a tissue-specific manner to influence differentiation, proliferation, and secretion. We found tissue-specific receptor isoforms and specific pathways for receptor regulation that influence steroid mechanisms of action in cell and tissue-specific ways. These studies included the first demonstration of a unique steroid-regulated, tissue-specific promoter and isoform for estrogen receptor-alpha, which regulates neuroendocrine tissue sensitivity to estradiol, and tissue-specific regulation of steroid receptors in normal versus tumor tissues. Our collaborative translational work has defined both transcriptional and cytoplasmic signaling pathways underlying estradiol actions and anti-estrogen resistance in breast cancer, and defined new tissue-specific non-genomic pathways of estradiol and androgen action that are active in many tissues. These pathways, including intracellular and paracrine cross-talk between growth factor and steroid pathways, have important implications for the function of reproductive tissues, and estrogen-sensitive tissues such as adipocytes, brain, and bone. Currently, we are also working on models of breast cancer progression and metastasis to distant sites such as liver and bone. A second area of interest is hypothalamic hormone regulation of pituitary gene function, including mechanisms by which GnRH pulse frequency differentially controls gonadotropin gene transcription. We are examining an animal model of polycystic ovarian disease (PCOS), the prenatal androgenized mouse, to understand how hyperandrogenism and insulin resistance influence fertility. We are systematically investigating how hyperandrogenism may reprogram hypothalamic, pituitary, and other tissue responses in vivo, and may influence responses to other peptide and steroid hormones. We hope to understand how current and potential new therapies may restore appropriate GnRH pulse patterns and pituitary responses, and thus fertility.
Our work is currently funded by:
- NIH P30 CA44579 (National Cancer Institute, Shupnik - Endocrine Program Leader)
- NIH U54 HD28934 (Eunice Kennedy Shriver NICHD Specialized Cooperative Centers Program in Reproduction and Infertility Research, Marshall PI Master / Shupnik PI Project 2, “Steroid and insulin modulation of GnRH stimulation of gonadotropes,” 04/01/09–03/31/14)