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Simmen, Rosalia
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I am Full Professor, Department of Physiology & Biophysics and Faculty Affiliate in the Winthrop P Rockefeller Cancer Institute Breast Cancer Program. I have been conducting basic and translational research in hormone-related aspects of women’s diseases for the last 30 years. I have a broad background in molecular, cellular and developmental biology, with specific training and expertise in steroid hormone receptors, signaling pathways, and tumor biology. As PI or Co-I on numerous university, Department of Defense, USDA and NIH-funded grants over the span of my independent academic career, I have collaborated with many groups of scientists to study the mechanistic underpinnings of steroid hormone receptors and associated co-regulators in the biology and pathobiology of the female reproductive tract. Our studies were the first to identify the Sp-related transcription factors Kruppel-like (KLF) family members KLF 9 and KLF13, as novel regulators of steroid receptor signaling in vivo and in vitro and to delineate their mechanisms of gene activation in concert with progesterone receptor and estrogen receptor, in endometrial and myometrial cells. These studies have provided strong support for the involvement of these and other KLFs in human uterine pathologies (endometriosis, endometrial cancer, and prolonged labor). In recent years, my research has established the infrastructure for elucidating the pathogenesis of endometriosis. In particular, we have developed an immunocompetent mouse model of endometriosis and have fortified our collaborations with clinicians within and outside of UAMS to provide medical translational relevance to our basic research on endometriosis.
My research program in mammary biology aims to understand how early exposure to a favorable ‘nutritional’ milieu influences neonatal/perinatal mammary development to promote molecular events favoring increased tissue differentiation and increase resistance to genetic and epigenetic changes that drive breast cancer. My group is one of the first to demonstrate that specific dietary factors regulate mammary tumor risk by targeting oncogenes and tumor suppressor genes in mammary epithelial populations with tumor initiating potential. We have found that a major target of dietary factors is the tumor suppressor PTEN via cross-talk with insulin and p53 signaling. My team also showed that very early developmental events in utero can alter mammary gland biology in female progeny to increase predisposition to tumor risk. Our research aims to mechanistically evaluate the epigenome and the metabolome as regulatory nexus by which the maternal environment controls breast cancer risk in progeny.
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Simmen, Rosalia