Frank A Simmen, PhD
University of Arkansas for Medical Sciences
College of Medicine
Physiology & Cell Biology
Cancer Research Interest
- Disease Site Focus: Breast, GI, Gynecology
- Research Focus Area: Prevention, Treatment, Carcinogenesis
- Type of Research: Basic
- Research Interest Statement: Colorectal cancer risk increases with overweight and obesity. Understanding the molecular mechanism(s) that link obesity with colorectal cancer onset, progression and therapeutic response and which are amenable to intervention is paramount to reduce the current rates of both obesity and colorectal cancer. Malic Enzyme 1 (ME1) is a protein that participates in an important shuttle pathway by which excess acetyl-CoA moves from the mitochondria to the cytoplasm for incorporation into lipid. In addition, ME1 generates a significant portion of the cytoplasmic NADPH pool, the latter used in fatty acid and cholesterol biosynthesis. While the biological importance of ME1 to adipocyte biology and obesity is known, the underlying molecular mechanism(s) by which ME1 functions at the nexus of obesity and cancer remain speculative. Our laboratory is examining hypothesized molecular linkages between gastrointestinal tissues (and tumors) and adipocytes and involving ME1. Our long-term working model posits that ME1 is a nodal target for suppression of both obesity and colorectal cancer.
- Email Address: SIMMENFRANKA@UAMS.EDU
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- Simmen FA, Pabona JMP, Al-Dwairi A, [et al.]. Malic Enzyme 1 (ME1) Promotes Adiposity and Hepatic Steatosis and Induces Circulating Insulin and Leptin in Obese Female Mice. International journal of molecular sciences. 2023 24(7). PMID: 37047583. PMCID: PMC10095602.
- Brown AR, Alhallak I, Simmen RCM, [et al., including Simmen FA]. KrÃ¼ppel-like Factor 9 (KLF9) Suppresses Hepatocellular Carcinoma (HCC)-Promoting Oxidative Stress and Inflammation in Mice Fed High-Fat Diet. Cancers. 2022 14(7). PMID: 35406507. PMCID: PMC8996893.
- Alhallak I, Wolter KG, Castro Munoz A, [et al., including Simmen FA]. Breast adipose regulation of premenopausal breast epithelial phenotype involves interleukin 10. Journal of molecular endocrinology. 2021. PMID: 34382943. PMCID: PMC8489570.
- Heard-Lipsmeyer ME, Alhallak I, Simmen FA, [et al.]. Lesion Genotype Modifies High-Fat Diet Effects on Endometriosis Development in Mice. Frontiers in physiology. 2021 12:702674. PMID: 34712146. PMCID: PMC8547326.
- Simmen FA, Alhallak I, Simmen RCM. Malic enzyme 1 (ME1) in the biology of cancer: it is not just intermediary metabolism. Journal of molecular endocrinology. 2020 65(4):R77-R90. PMID: 33064660. PMCID: PMC7577320.
- Blossom SJ, Melnyk SB, Simmen FA. Complex epigenetic patterns in cerebellum generated after developmental exposure to trichloroethylene and/or high fat diet in autoimmune-prone mice. Environmental science. Processes & impacts. 2020 22(3):583-594. PMID: 31894794. PMCID: PMC7350281.
- Pabona JMP, Burnett AF, Brown DM, [et al., including Simmen FA]. Metformin Promotes Anti-tumor Biomarkers in Human Endometrial Cancer Cells. Reproductive sciences (Thousand Oaks, Calif.). 2020 27(1):267-277. PMID: 32046384. PMCID: PMC7077930.
- Fernandes LM, Al-Dwairi A, Simmen RCM, [et al., including Simmen FA]. Malic Enzyme 1 (ME1) is pro-oncogenic in ApcMin/+ mice. Scientific reports. 2018 8(1):14268. PMID: 30250042. PMCID: PMC6155149.
- Brown DM, Lee HC, Liu S, [et al., including Simmen FA]. Notch-1 Signaling Activation and Progesterone Receptor Expression in Ectopic Lesions of Women With Endometriosis. Journal of the Endocrine Society. 2018 2(7):765-778. PMID: 30151432. PMCID: PMC6106104.
- Blossom SJ, Fernandes L, Bai S, [et al., including Simmen FA]. Opposing Actions of Developmental Trichloroethylene and High-Fat Diet Coexposure on Markers of Lipogenesis and Inflammation in Autoimmune-Prone Mice. Toxicological sciences : an official journal of the Society of Toxicology. 2018 164(1):313-327. PMID: 29669109. PMCID: PMC6016708.
- Yu S, Wu X, Ferguson M, [et al., including Simmen FA]. Diets Containing Shiitake Mushroom Reduce Serum Lipids and Serum Lipophilic Antioxidant Capacity in Rats. The Journal of nutrition. 2016 146(12):2491-2496. PMID: 27798348. PMCID: PMC5118771.
- Simmen FA, Heard ME, Pabona JMP, [et al.]. Maternal Metabolic State and Cancer Risk: An Evolving Manifestation of Generational Impact, in Physiology in Health and Disease. Springer, 2016, pp 289-305.
- Montales MT, Melnyk SB, Liu SJ, [et al., including Simmen FA]. Metabolic history impacts mammary tumor epithelial hierarchy and early drug response in mice. Endocrine-related cancer. 2016 23(9):677-90. PMID: 27402613. PMCID: PMC4997088.
- Simmen RC, Simmen F, Kelley AS. Reversal of fortune: estrogen receptor-? in endometriosis. Journal of molecular endocrinology. 2016 57(2):F23-7. PMID: 27272520. PMCID: PMC4973618.
- Heard ME, Melnyk SB, Simmen FA, [et al.]. High-Fat Diet Promotion of Endometriosis in an Immunocompetent Mouse Model is Associated With Altered Peripheral and Ectopic Lesion Redox and Inflammatory Status. Endocrinology. 2016 157(7):2870-82. PMID: 27175969. PMCID: PMC4929556.