Profile Image
Mitchell Denning Photo
Mitchell Denning
Primary Department
Cancer Biology
Joint Department
Department of Pathology and Laboratory Medicine
Advanced Degrees
University of Wisconsin, Madison , Madison , WI , United States
Non-melanoma skin cancers (basal and squamous cell carcinomas) are the most common type of human cancer. Dr. Denning's laboratory studies signaling pathways which regulate normal skin homeostasis to better understand how alterations in these signaling pathways contribute to malignancy. They are focusing on the involvement of the protein kinase C (PKC) family of enzymes in the multi-step transformation of human keratinocytes. PKC is a central regulator of the normal keratinocyte differentiation program, and alterations in epidermal differentiation and PKC signaling are evident in malignant keratinocytes as well as a large number of benign skin diseases. PKC is directly activated by phorbol ester tumor promoters commonly used in mouse skin chemical carcinogenesis studies. Dr. Denning's lab discovered that PKC is also activated by ultraviolet radiation, the main environmental carcinogen for human skin cancer formation. They are using a variety of cell biological, biochemical, pharmacological, and molecular genetic approaches to characterize the functional significance of PKC activation in normal and neoplastic keratinocytes. Their long-term goals are to target these signaling pathways for therapeutic or preventive interventions in skin cancer.
Cell cycles
Growth Factors
Signal Transduction
Skin Diseases
Tissue Engineering
Transgenic Animals
UV Radiation
Reactive Oxygen Species
Recombinant DNA
Zhang, L; Luo, H; Ni, HM; Liu, S; Xing, H; Zhang, J; Sellin, M; Breslin S J, P; Wei, W; Denning, MF; Small, W; Ding, WX; Huang, S; Zhang, JRipk3 signaling regulates HSCs during stress and represses radiation-induced leukemia in mice. Stem cell reports 2022 ;
Liu, S; Joshi, K; Denning, MF; Zhang, JRIPK3 signaling and its role in the pathogenesis of cancers. Cellular and molecular life sciences : CMLS 2021 ;
Wang, H; Hou, W; Perera, A; Bettler, C; Beach, JR; Ding, X; Li, J; Denning, MF; Dhanarajan, A; Cotler, SJ; Joyce, C; Yin, J; Ahmed, F; Roberts, LR; Qiu, WTargeting EphA2 suppresses hepatocellular carcinoma initiation and progression by dual inhibition of JAK1/STAT3 and AKT signaling. Cell reports 2021 ;34(8)
Wang, F; Hou, W; Chitsike, L; Xu, Y; Bettler, C; Perera, A; Bank, T; Cotler, SJ; Dhanarajan, A; Denning, MF; Ding, X; Breslin, P; Qiang, W; Li, J; Koleske, AJ; Qiu, WABL1, Overexpressed in Hepatocellular Carcinomas, Regulates Expression of NOTCH1 and Promotes Development of Liver Tumors in Mice. Gastroenterology 2020 ;159(1)
Wang, F; Bank, T; Malnassy, G; Arteaga, M; Shang, N; Dalheim, A; Ding, X; Cotler, SJ; Denning, MF; Nishimura, MI; Breslin, P; Qiu, WInhibition of insulin-like growth factor 1 receptor enhances the efficacy of sorafenib in inhibiting hepatocellular carcinoma cell growth and survival. Hepatology communications 2018 ;2(6)
Kim, JL; Ha, GH; Campo, L; Denning, MF; Patel, TB; Osipo, C; Lin, SY; Breuer, EKThe role of Rak in the regulation of stability and function of BRCA1. Oncotarget 2017 ;8(49)