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 my laboratory centers on the regulators of gene expression in the mammary gland and uterus that are essential for these tissues' proper function and development. We seek to understand how systemic hormones and extra-cellular factors regulate the normal (and abnormal as in tumorigenesis) development of these tissues and to characterize the key gene products and signaling molecules that mediate these events. We use a variety of in vivo and in vitro models in our studies. We also use diverse cellular and molecular techniques including gene arrays for gene discovery, cell lines for analyzing signaling pathways, and rats and mouse mutants for studying in vivo gene regulation. The aim of all these studies is to provide important insights into regulatory mechanisms that control tissue growth and development in the whole animal.

A recent major focus is how maternal obesity alters the health status of female offspring. Recent studies have indicated that exposure to an obesogenic maternal (intra-uterine) environment predicts a vicious cycle of obesity in the population. Stemming the tide of obesity in pregnant women and understanding how maternal obesity is linked to increased risks for multiple morbidities such as metabolic dysfunctions, cardiovascular complications and cancer are paramount to improving public health and in limiting the rising health costs in the US and globally. Using the uterus and mammary gland of progeny as targets of maternal obesogenic effects during pre-pregnancy, gestation and lactation, we seek to understand the mechanistic underpinnings of how maternal obesity may promote fetal programming of breast and uterine cancer. In this regard, a major goal is to determine the developmental window, dose, and duration of sensitivity to nutritional components and environmental agents that will predispose neonates and young adults to a healthy life at adulthood.

Pabona JMP, Simmen FA, Nikiforov MA, Zhuang D, Shankar K, Velarde MC, Zelenco Z, Guidice LC, Simmen RCM. 2012. Krüppel-like factor 9 and progesterone receptor co-regulation of decidualizing stromal cells: implications for the pathogenesis of endometriosis. J Clin Endocrinol Metab 97: 376-392.

Montales MT, Rahal O, Kang J, Rogers T, Prior RL, Wu X, Simmen RCM.  2012. Repression of mammosphere formation of human breast cancer cells by soy isoflavone genistein and blueberry polyphenolic acids suggest diet-mediated targeting of cancer stem-cell like/progenitor cells. Carcinogenesis 33: 652-660.

Rahal O, Simmen RCM.  2011. Paracrine-acting adiponectin promotes mammary epithelial differentiation and synergizes with genistein to enhance transcriptional response to estrogen receptor β signaling.  Endocrinology 152: 3409-3421.

Simmen FA, Simmen RCM.  2011. The maternal womb: a novel target for cancer prevention in the era of the obesity pandemic?  European J Cancer Prev. 20: 539-548.

Su Y, Shankar K, Rahal O, Simmen RCM.  2011. Bidirectional signaling of mammary epithelium and stroma: implications for breast cancer-preventive actions of dietary factors. J Nutr Biochem 22: 60-611.

Simmons CD, Pabona JM, Heard ME, Friedman TM, Spataro MT, Godley AL, Simmen FA, Burnett AF, Simmen RCM. 2011.  Krüppel-like factor 9 loss-of-expression in human endometrial carcinoma links altered expression of growth-regulatory genes with aberrant proliferative response to estrogen.  Biol Reprod 85: 378-385.

Rahal O, Simmen, RCM. 2010.  PTEN and p53 cross-regulation induced by soy isoflavone genistein promotes mammary epithelial cell cycle arrest and lobuloalveolar differentiation.  Carcinogenesis 31(8): 1491-1500.

Pabona JMP, Zeng Z, Simmen FA, Simmen RCM.  2010.  Functional differentiation of uterine stromal cells involves cross-regulation between bone morphogenetic protein 2 and Krüppel-like factor (KLF) family members KLF9 and KLF13.  Endocrinology 151(7): 3396-3406.

Simmen RCM, Pabona, J.M.P., Velarde, M.C., Simmons, C., Rahal, O. and Simmen, F.A.  2010.  The emerging role of Krüppel-like factors in endocrine-responsive cancers of the female reproductive tissues.  J Endocrinology 204: 223-231.

Simmons, CD, Pabona JMP, Zeng Z, Velarde MC, Gaddy D, Simmen FA, Simmen RCM.  2010.  Response of adult mouse uterus to early disruption of estrogen receptor-α signaling is influenced by Krüppel-like factor 9. J Endocrinology 205: 147-157.

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: 801-811.

Su Y, Shankar K, Simmen RCM.  2009.  Early soy exposure via maternal diet regulates rat mammary epithelial differentiation by paracrine signaling from stromal adipocytes. J Nutr 139: 945-951.

Su Y, Simmen RCM.  2009.  Soy isoflavone genistein upregulates epithelial adhesion molecule E-cadherin expression and attenuates β-catenin signaling in mammary epithelial cells. Carcinogenesis 30: 331-339.

*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.

USDA/ARS: The Effects of Dietary Factors during Development on Long-Term Health Consequences (Lead Scientist on Project I: ‘Early Exposure to Dietary Factors and Disease Prevention)

National Institutes of Health/National Cancer Institute: Dietary Factors in Colon Cancer Prevention (Co-I)

Department of Defense Breast Cancer Research Program: Dietary Regulation of the Tumor Suppressor PTEN Network and Tumor Initiating Population in the Mammary Gland (Mentor to Omar Rahal, PhD student)

Arkansas Breast Cancer Research Program/UAMS Translational Research Institute: Maternal Obesity and Fetal Origin of Adult Breast Cancer (PI)