Rosalia C.M. Simmen, Ph.D.
Professor, Department of Physiology & Biophysics Faculty, The Winthrop P. Rockefeller Cancer
My laboratory conducts basic and translational research in hormone-related aspects of women’s diseases, with a focus on steroid hormone receptors, signaling pathways, and tumor biology. We employ diverse cellular and molecular techniques and experimental models including gene arrays and single nuclear RNA sequencing for gene discovery, cell lines for analyses of signaling pathways, and human tissues and mouse models of diseases to address basic goals with translational potential. Studies conducted by my group were the first to identify the Sp-related transcription factors Kruppel-like (KLF) family members KLF9 and KLF13 as novel regulators of steroid receptor signaling and to elucidate their mechanisms of gene activation in concert with progesterone receptor and estrogen receptor, in uterine endometrial and myometrial cells. Our studies have provided strong support for the involvement of these and other KLFs in human uterine pathologies. Another area of investigation focuses on metabolic networks and pathways that are regulated/dysregulated by diet, dietary components, and adiposity to understand the metabolic basis of breast cancer and for developing interventions for breast cancer prevention and therapy. We have found that maternal metabolic perturbations (pre-pregnancy through lactation) in mouse models profoundly influence mammary tumor risk in progeny, that mammary adiposity significantly affects underlying mammary epithelial subpopulations with tumor-initiating potential, and that high-fat diet induced oxidative stress is associated with deregulated transcriptional profiles of oncogenes, tumor suppressors and inflammatory cytokines, leading to abnormal expansion of mammary epithelial basal stem-cell like populations. In more recent studies, we have evaluated the potential link of diabetes status to endometriosis progression using archived human endometriotic lesions. These lines of research have benefited from funding support from the National Institutes of Health, USDA Department of Agriculture, US Department of Defense, and many institutional and foundation grants.
I have a strong interest and commitment to guiding the next generation of scientists and in that capacity, I am an active contributor to graduate and medical education.