Research Interests My research has been in the fields of hormone action and signal transduction pathways regulating cell growth, differentiation, metabolism, and tissue-specific gene expression. Recent activities have focused primarily on uterine tumors and reproductive endocrinology. My laboratory was the first to define the expression and functional role of PKCs in endometrial cancer. PKC delta modulates apoptosis and response to chemotherapy and its expression is lost in higher-grade tumors suggesting it acts as a tumor suppressor. Conversely, PKC alpha is critical for the survival, growth, and invasion of endometrial cancer cells and modulates estrogen and other signaling pathways implicated in the development and progression of endometrial malignancies. We have also used gene expression and protein analyses to identify drivers of the growth of uterine fibroids (leiomyomas)and identified a panel of genes that distinguish them from malignant leiomyosarcomas.
In collaboration with Drs Santoro and Polotsky, we have performed translational research and clinical trials, developing models to investigate mechanisms underlying the relative hypogonadotropic hypogonadism of obesity, characterized by decreased LH, FSH, attenuated response to hypothalamic GnRH, and impaired ovarian hormone secretion. Obesity is implicated in reproductive dysfunction, infertility, miscarriage, and adverse pregnancy outcomes but the etiology remains largely unknown. We have used pharmacologic and dietary interventions combined with blood and urine hormone and biomarker measurements to provide critical insights into the deficits in the hypothalamic-pituitary-ovarian axis, in human subjects, which underlie this phenotype we identified as “Reprometabolic syndrome’. I have worked with Dr. Eva Burger in Orthopedics in clinical trials to identify molecular markers of calmodulin and melatonin signaling, in order to predict curve progression in adolescent idiopathic scoliosis and thereby guide appropriate treatment and surgical intervention. Lastly, I have collaborated with Dr. Kiyoshi Ohtani (Kwansei Gakuin University) investigating the role of E2F family members in the regulation of in cancer cell growth and survival and the potential use of E2F1 response elements to drive cancer cell specific gene expression and potential therapeutic strategies.
Full List of Publications
Recent Publications
A randomized clinical trial demonstrating cell type specific effects of hyperlipidemia and hyperinsulinemia on pituitary function. McDonald R, Kuhn K, Nguyen TB, Tannous A, Schauer I, Santoro N, Bradford AP.PLoS One. 2022 May 11;17(5):e0268323. doi: 10.1371/journal.pone.0268323. eCollection 2022. PMID: 35544473. Clinical Trial.
Effects of pulsatile intravenous follicle-stimulating hormone treatment on ovarian function in women with obesity. Luu TH, Kuhn K, Bradford AP, Wempe MF, Wittenburg L, Johnson RL, Carlson NE, Kumar TR, Polotsky AJ Fertil Steril. 2023 Oct;120(4):890-898. doi: 10.1016/j.fertnstert.2023.05.170. Epub 2023 Jun 3.PMID: 37276947.
A high-fat eucaloric diet induces reprometabolic syndrome of obesity in normal weight women. Santoro N, Kuhn K, Pretzel S, Schauer IE, Fought A, D'Alessandro A, Stephenson D, Bradford AP. PNAS Nexus. 2023 Dec 18;3(1):pgad440. doi: 10.1093/pnasnexus/pgad440. eCollection 2024 Jan.PMID: 38178979 Free PMC article.
Analysis of Inflammatory Markers in Response to Induction of Reprometabolic Syndrome by a Eucaloric High Fat Diet in Normal Weight Women. Nguyen T, Kuhn K, Bolt M, Duffy K, Bradford AP, Santoro N.Reprod Sci. 2024 Sep;31(9):2820-2828. doi: 10.1007/s43032-024-01586-9. Epub 2024 May 6.PMID: 38710978
Effects of a eucaloric high-fat diet on anterior pituitary hormones and adipocytokines in women with normal weight. Nguyen T, Kuhn K, Fought A, Bolt M, Bradford AP, Santoro N.Fertil Steril. 2024 Aug;122(2):379-381. doi: 10.1016/j.fertnstert.2024.05.160. Epub 2024 Jun 3.PMID: 38838803 Free PMC article.
Effects of a Reprometabolic Syndrome-Inducing Eucaloric High-Fat Diet on Insulin Sensitivity, Body Composition, the Lipidome, and the Microbiome. Schauer IE, Kuhn K, Bradford AP, Fought AJ, Frank DN, Kotter CV, Robertson CE, Duffy K, Santoro N.Metabolites. 2026 Apr 22;16(5):286. doi: 10.3390/metabo16050286.PMID: 42187995
Utility of Tumor Suppressor E2F Target Gene Promoter Elements to Drive Gene Expression Specifically in Cancer Cells. Kurayoshi K, Tanaka M, Nakajima R, Zhou Y, Shirasawa M, Fikriyanti M, Fujisawa JI, Iwanaga R, Bradford AP, Araki K, Ohtani K.Cells. 2025 Dec 9;14(24):1953. doi: 10.3390/cells14241953. PMID: 41439972 Free PMC article.
Eucaloric High-fat Diet Effects on Reproductive Hormone Profiles: Mimicking Reprometabolic Syndrome in Normal Weight Women. Kuhn K, Bradford AP, Schauer IE, Duffy K, Bolt M, Santoro N.J Clin Endocrinol Metab. 2026 Apr 22;111(5):1356-1364. doi: 10.1210/clinem/dgaf590. PMID: 41206369
Murine Embryonic Stem Cells Possess Distinct E2F Activity That Activates Tumor Suppressor Promoter Elements. Zhou Y, Nakajima R, Shirasawa M, Fikriyanti M, Kitagawa M, San TY, Iwanaga R, Bradford AP, Kurayoshi K, Araki K, Ohtani K.Genes Cells. 2026 May;31(3):e70121. doi: 10.1111/gtc.70121.PMID: 42118501
Effectiveness of preconception weight loss interventions on fertility in women: a systematic review and meta-analysis. Caldwell AE, Gorczyca AM, Bradford AP, Nicklas JM, Montgomery RN, Smyth H, Pretzel S, Nguyen T, DeSanto K, Ernstrom C, Santoro N.Fertil Steril. 2024 Aug;122(2):326-340. doi: 10.1016/j.fertnstert.2024.02.038. Epub 2024 Feb 24. PMID: 38408693