Professor, Department of Physiology & Biophysics

Faculty, The Winthrop P. Rockefeller Cancer Institute (Breast Cancer Program) 

Ph.D., University of Hawaii (Biochemistry)

Postdoctoral Fellow, Baylor College of Medicine (Cell Biology)

Office: (501) 526-7575

E-mail address: simmenrosalia@uams.edu

My laboratory conducts basic and translational research in hormone-related aspects of women’s diseases, with focus on steroid hormone receptors, signaling pathways, and tumor biology. We employ diverse cellular and molecular techniques and experimental models including gene arrays for gene discovery, cell lines for analyses of signaling pathways, and human 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/dys-regulated by diet and dietary components to understand the metabolic basis of breast cancer and for developing nutritional interventions for breast cancer prevention and therapy. We have found that maternal metabolic perturbations (pre-pregnancy through lactation) 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.

I have a strong interest and commitment in guiding the next generation of scientists and in that capacity, am an active contributor to graduate and medical education.

Senior Editor, Journal of Endocrinology ( http://joe.endocrinology-journals.org/ )

Senior Editor, Journal of Molecular Endocrinology ( http://jme.endocrinology-journals.org/ )

Editorial Board Member, Philippine Science Letters ( http://www.philsciletters.org/ )

Graduate Courses (Course Coordinator): PHYS 5013 (Graduate Physiology); PHYS 5014 (Cellular and Molecular Endocrinology)

Representative Publications:

  1. Pabona JM, Simmen FA, Nikiforov MA, Zhuang D, Shankar K, Velarde MC, Zelenko Z, Giudice LC, Simmen RC. Krüppel-like factor 9 and progesterone receptor coregulation of decidualizing endometrial stromal cells: implications for the pathogenesis of endometriosis. J Clin Endocrinol Metab. 2012 Mar;97(3):E376-92. PubMed PMID: 22259059; PubMed Central PMCID: PMC3319212.
  2. Montales MT, Rahal OM, Kang J, Rogers TJ, Prior RL, Wu X, Simmen RC. Repression of mammosphere formation of human breast cancer cells by soy isoflavone genistein and blueberry polyphenolic acids suggests diet-mediated targeting of cancer stem-like/progenitor cells. Carcinogenesis. 2012 Mar;33(3):652-60. PubMed PMID: 22219179.
  3. Rahal OM, Machado HL, Montales MT, Pabona JM, Heard ME, Nagarajan S, Simmen RC. Dietary suppression of the mammary CD29(hi)CD24(+) epithelial subpopulation and its cytokine/chemokine transcriptional signatures modifies mammary tumor risk in MMTV-Wnt1 transgenic mice. Stem Cell Res. 2013 Nov;11(3):1149-62. PubMed PMID: 24012543; PubMed Central PMCID: PMC4034693.
  4. Heard ME, Simmons CD, Simmen FA, Simmen RC. Krüppel-like factor 9 deficiency in uterine endometrial cells promotes ectopic lesion establishment associated with activated notch and hedgehog signaling in a mouse model of endometriosis. Endocrinology. 2014 Apr;155(4):1532-46. PubMed PMID: 24476135; PubMed Central PMCID: PMC3959595.
  5. Montales MT, Melnyk SB, Simmen FA, Simmen RC. Maternal metabolic perturbations elicited by high-fat diet promote Wnt-1-induced mammary tumor risk in adult female offspring via long-term effects on mammary and systemic phenotypes. Carcinogenesis. 2014 Sep;35(9):2102-12. PubMed PMID: 24832086; PubMed Central PMCID: PMC4146417.
  6. Pabona JM, Zhang D, Ginsburg DS, Simmen FA, Simmen RC. Prolonged pregnancy in women is associated with attenuated myometrial expression of progesterone receptor co-regulator Krüppel-like Factor 9. J Clin Endocrinol Metab. 2015 Jan;100(1):166-74. PubMed PMID: 25313913; PubMed Central PMCID: PMC4283014.
  7. Simmen RC, Kelley AS. Reversal of fortune: estrogen receptor-β in endometriosis. J Mol Endocrinol. 2016 Aug; 57(2):F23-7. doi: 10.1530/JME-16-0080. (Recommended by F1000; http://f1000.com/prime/726407531). PMID: 27272520; PMCID:PMC4973618 DOI:10.1530/JME-16-0080
  8. Montales MTE, Melnyk SB, Liu SJ, Simmen FA, Liu YL, Simmen RC. Metabolic history impacts mammary tumor epithelial hierarchy and early drug response in mice. Endocrine-Related Cancer 2016 Sep; 23 (9):677-90. PMID:27402613; PMCID:PMC4997088; DOI:10.1530/ERC-16-0136

 

Link to Dr. Rosalia C.M. Simmen at Pub-Med:

http://www.ncbi.nlm.nih.gov/myncbi/rosalia.simmen.1/bibliography/40441863/public/?sort=date&direction=descending

Link to Dr. Rosalia C.M. Simmen at Research Gate:

https://www.researchgate.net/profile/Rosalia_Simmen