Rosalia C M Simmen, PhD
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 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 and mouse 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, E-cadherin) 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.

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. Nutr. 2006 May;136(5):1156-60.

Su Y, Eason RR, Geng Y, Till SR, Badger TM, Simmen RCM. In utero exposure to maternal diets containing soy protein isolate, but not genistein alone, protects young adult rat offspring from NMU-induced mammary tumorigenesis. Carcinogenesis 2007; 28:1046-1051.

Su Y, Simmen FA, Xiao R, Simmen RCM. Expression profiling of rat mammary epithelial cells reveals candidate signaling pathways in dietary protection from mammary tumors. Physiol Genomics 2007; 30: 8-16.

Xiao R, Su Y, Simmen RC, Simmen FA. Dietary soy protein inhibits DNA damage and cell survival of colon epithelial cells through attenuated expression of fatty acid synthase. Am J Physiol Gastrointest Liver Physiol. 2008 Apr;294(4):G868-76.

Zeng Z, Velarde MC, Simmen FA, Simmen RC. Delayed parturition and altered myometrial progesterone receptor isoform a expression in mice null for kruppel-like factor 9. Biol Reprod. 2008 Jun;78(6):1029-37.

Simmen FA, Su Y, Xiao R, Zeng Z, Simmen RC.  The Krüppel-like factor 9 (KLF9) network in HEC-1-A endometrial carcinoma cells suggests the carcinogenic potential of dys-regulated KLF9 expression.  Reprod Biol Endocrinol. 2008 Sep 10;6:41.

Pabona JM, Velarde MC, Zeng Z, Simmen FA, Simmen RC.  Nuclear receptor co-regulator Kruppel-like factor 9 and prohibitin 2 expression in estrogen-induced epithelial cell proliferation in the mouse uterusJ Endocrinol. 2009 Jan;200(1):63-73.

Su Y, Simmen RCM. Soy isoflavone genistein upregulates epithelial adhesion molecule E-cadherin expression and attenuates β-catenin signaling in mammary epithelial cells. Carcinogenesis. 2009 Feb;30(2):331-9. .

Su Y, Shankar K, Simmen RC. Early soy exposure via maternal diet regulates rat mammary epithelial differentiation by paracrine signaling from stromal adipocytes. J Nutr. 2009 May;139(5):945-51.

Wu X, Rahal O, Kang J, Till SR, Prior RL, Simmen RCM. 2009. In utero and lactational exposure to blueberry via maternal diet promotes mammary epithelial differentiation in prepubescent female rats. Nutr Res 29: 802-811.

Simmen RC, Pabona JM, Velarde MC, Simmons C, Rahal O, Simmen FA. The emerging role of Krüppel-like factors in endocrine-responsive cancers of female reproductive tissues. J Endocrinol. 2010 Mar;204(3):223-31. Epub 2009 Oct 15.

*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.

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

Department of Defense Breast Cancer Research Program (Concept Award): Diet, Stem Cells, and Breast Cancer Prevention - PI