University of Arkansas for Medical Sciences Logo University of Arkansas for Medical Sciences
College of Medicine: Department of Physiology and Cell Biology

Rosalia C.M. Simmen, Ph.D.

Rosalia Simmens portrait

Professor Emeritus, Department of Physiology & Cell Biology
Faculty, The Winthrop P. Rockefeller Cancer Institute (Cancer Biology/Breast Cancer Program)

Ph.D., University of Hawaii (Biochemistry)
Postdoctoral Fellow, Baylor College of Medicine (Cell Biology)

Office: 501-526-7575
E-mail: simmenrosalia@uams.edu

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. In this regard, I am very honored to receive the UAMS COM 2023 Master Teacher Award.

Track Director, Cell Biology and Physiology Track of the Graduate Programs in Interdisciplinary Biomedical Sciences (GPIBS, UAMS)

Deputy Editor-in-Chief, Endocrine Connections (UK) (https://ec.bioscientifica.com/page/edboard/editorial-board)

Editorial Board Member

Philippine Science Letters ( https://philsciletters.net/ )

International Journal of Molecular Sciences (http://www.mdpi.com/journal/ijms/ )

Chinese Journal of Physiology (Taiwan; https://www.cjphysiology.org/)

Senior Editor, Journal of Endocrinology (http://joe.endocrinology-journals.org/ ) to 2021

Senior Editor, Journal of Molecular Endocrinology ( http://jme.endocrinology-journals.org/ ) to 2021

Graduate Course Coordinator: PHYS 5103 (General Physiology)

Representative Publications

  1. Alhallak I, Quick CM, Graham GL, Simmen RCM. 2023. A pilot study on the co-existence of diabetes and endometriosis in reproductive-age women: potential for endometriosis progression. Reprod Sci. 2023 Feb 14. doi: 10.1007/s43032-023-01190-3. PMID: 36788175.
  2. Alhallak I, Wolter KG, Castro Munoz A, Simmen FA, Ward RJ, Petty SA, Li LX, Simmen RCM. 2021. Breast adipose regulation of premenopausal breast epithelial phenotype involves interleukin 10. J Mol Endocrinol. 9;67(4):173-188. doi: 10.1530/JME-21-0100. PMID: 34382943; PMCID: PMC8489570.
  3. Heard-Lipsmeyer ME, Alhallak I, Simmen FA, Melnyk SB, Simmen RCM. 2021. Lesion Genotype Modifies High-Fat Diet Effects on Endometriosis Development in Mice. Front Physiol. 14;12:702674. doi: 10.3389/fphys.2021.702674. PMID: 34712146; PMCID: PMC8547326.
  4. Simmen, RC, Quick, CM, Kelly AS, Zheng W. 2019. Endometriosis and endometriosis-associated tumors. Chapter 12. In: W. Zheng et al (eds), Gynecologic and Obstetric Pathology, Vol 2.
  5. Brown DM, Lee H-C, Liu S, Quick CM, Fernandes LM, Simmen FA, Tsai S-J, Simmen RC. 2018. Notch-1 signaling activation and progesterone receptor expression in ectopic lesions of women with endometriosis. J Endocrine Society 2 (7): doi.10.1210/js.2018-00007.
  6. Saguyod SJU, Kelley AS, Velarde MC, Simmen RC. 2018.  Diet and endometriosis-revisiting the linkages to inflammation. J Endometriosis Pelvic Pain Disorders. 10: 51-58 DOI_10.1177/2284026518769022.
  7. 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. 2016. Endocrine-Related Cancer 23 (9):677-90. PMID:27402613; PMCID:PMC4997088; DOI:10.1530/ERC-16-0136
  8. Simmen RC, Kelley AS. Reversal of fortune: estrogen receptor-β in endometriosis. 2016. J Mol Endocrinol. 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
  9. Pabona JM, Zhang D, Ginsburg DS, Simmen FA, Simmen RC. 2015. Prolonged pregnancy in women is associated with attenuated myometrial expression of progesterone receptor co-regulator Krüppel-like Factor 9. J Clin Endocrinol Metab. 100(1):166-74. PubMed PMID: 25313913; PubMed Central PMCID: PMC4283014.
  10. Heard ME, Simmons CD, Simmen FA, Simmen RC. 2014. 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. 155(4):1532-46. PubMed PMID: 24476135; PubMed Central PMCID: PMC3959595
  11. Montales MT, Melnyk SB, Simmen FA, Simmen RC. 2014. 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. 35(9):2102-12. PubMed PMID: 24832086; PubMed Central PMCID: PMC4146417.
  12. Rahal OM, Machado HL, Montales MT, Pabona JM, Heard ME,  Nagarajan S, Simmen RC. 2013. 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. 11(3):1149-62. PubMed PMID: 24012543; PubMed Central PMCID: PMC4034693.
  13. Montales MT, Rahal OM, Kang J, Rogers TJ, Prior RL, Wu X, Simmen RC. 2012. 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. 33(3):652-60. PubMed PMID: 22219179.
  14. Pabona JM, Simmen FA, Nikiforov MA, Zhuang D, Shankar K, Velarde MC, Zelenko Z, Giudice LC, Simmen RC. 2012. Krüppel-like factor 9 and progesterone receptor coregulation of decidualizing endometrial stromal cells: implications for the pathogenesis of endometriosis. J Clin Endocrinol Metab. 97(3):E376-92. PubMed PMID: 22259059; PubMed Central PMCID: PMC3319212.

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