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Rosalia C M Simmen, PhD
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Professor of Physiology and Biophysics, University of Arkansas for Medical Sciences/College of Medicine/Department of Physiology & Biophysics |
Senior Investigator, Developmental Biology, Arkansas Children’s Nutrition Center |
Phone: (501) 364-2849 |
Research Overview
Research in Dr. Simmen’s laboratory focuses on the areas of molecular endocrinology and tumor biology to evaluate key regulators in the development and function of female reproductive tissues, namely uterus and mammary gland. The overall goal is to further understand the signal transduction pathways that affect these tissues’ response to steroid hormones and growth factors during normal development and which may be compromised leading to abnormal development and carcinoma. Dr. Simmen has investigated components of estrogen and progesterone receptor signaling in uterine endometrial cells in vivo using various mammalian models including pigs, rats, and mice, and in vitro using human endometrial carcinoma cell lines, and has recently identified a novel steroid receptor co-activator Basic Transcription Element Binding Protein-1 (BTEB1) whose gene ablation in mice results in sub-fertility and delayed parturition. Dr. Simmen’s laboratory has also elucidated several molecular mechanisms that may underlie the protective effects of dietary components present in infant formulas (whey and soy proteins) on adult onset of mammary carcinoma, using rat models of carcinogenesis. Normal cells differ from cancer cells in their ability to undergo apoptosis, a genetically regulated suicide mechanism involved in cellular homeostasis and development. Dr. Simmen’s laboratory has shown the induction of this pathway through dietary regulation of tumor suppressor (PTEN, p53) and oncogene (wnt) expression. A major goal is to determine the developmental window, dose, and duration of sensitivity to nutritional components that will predispose neonates and young adults to a healthy life at adulthood. Dr. Simmen’s laboratory uses interdisciplinary approaches involving molecular, cellular, genetic, and biochemical methodologies to pursue these research objectives. Dr. Simmen also directs the Histology Core Laboratory of the Arkansas Children’s Nutrition Center.
Key Publications
Zhang D, Zhang X-L, Michel FJ, Blum JL, Simmen FA, Simmen R.C.M. 2002. Direct interaction of the Krüppel-like Family (KLF) member, BTEB1 and Progesterone receptor mediates progesterone-responsive gene expression in endometrial epithelial cells. Endocrinology 141:62-73.
Simmen RCM , Eason RR, McQuown JR, Linz AL, Kang TJ, Chatman L Jr, Till SR, Fujii-Kuriyama Y, Simmen FA, Oh SP. 2004. Subfertility, uterine hypoplasia, and partial progesterone resistance in mice lacking the Krüppel-like factor9/basic transcription element-binding protein 1 (Bteb1) gene. J. Biol. Chem. 279:29286-29294.
Eason RR, Velarde MC, Chatman L Jr, Till SR, Geng Y, Ferguson M, Badger TM, Simmen RCM. 2004. Dietary exposure to whey proteins alters rat mammary gland proliferation, apoptosis, and gene expression during postnatal development: implications for cancer protective mechanisms. J. Nutr. 134: 3370-3377.
Velarde MC, Parisek SI, Eason RR, Simmen FA, Simmen RCM. 2005. The secretory leukocyte protease inhibitor (SLPI) gene is a target of epidermal growth factor receptor action in endometrial epithelial cells. J. Endocrinol. 184: 141-151.
Dave B, Eason RR, Till SR, Geng Y, Velarde MC, Badger TM, Simmen RCM. 2005. The soy isoflavone genistein promotes apoptosis in mammary epithelial cells by inducing the tumor suppressor PTEN. Carcinogenesis 26:1793-1803.
Velarde MC, Geng Y, Eason RR, Simmen FA, Simmen RCM. 2005. Null mutation of Krüppel-like factor 9/basic transcription element binding protein-1 alters peri-implantation uterine development in mice. Biol. Reprod. 73: 472-481.
Velarde MC, Iruthayanathan M, Eason RR, Zhang D, Simmen FA, Simmen RCM. 2006. Progesterone receptor transactivation of the secretory leukocyte protease inhibitor gene in Ishikawa endometrial epithelial cells involves recruitment of Krüppel-like factor 9/basic transcription element binding protein-1. Endocrinology 147:1969-1978.
Dave B, Eason RR, Geng Y, Su Y, Badger TM, Simmen RCM. 2006. Tp53-associated growth arrest and DNA damage repair gene xpression is attenuated in mammary epithelial cells of rats fed whey proteins.J. Nutr.(in press).
*To find additional publications by this author, please visit Pubmed Central, a National Institutes of Health-operated site for electronic distribution of life sciences research reports.
Research Support
National Institutes of Health/National Institutes of Child Health and Human Development: Uteroferrin gene expression during development - PI
USDA/ARS: The Effects of Dietary Factors during Development on Long-Term Health Consequences: Effects of Dietary Factors on Cancer Prevention-PI on Sub-Project “Diet and Mammary Cancer Risk