Mitchell F. Denning, PhD

Associate Dean for Graduate Education;

Professor Cancer Biology;

Molecular Pharmacology & Neuroscience

Research Interests:

• Keratinocyte and melanocyte biology
• Ultraviolet radiation induced skin carcinogenesis
• Protein kinase C signaling

Bio

Our laboratory is interested in understanding the regulation of cell fate decisions (proliferation, differentiation, death) for keratinocytes and melanocytes within the normal epidermis, as well as how these processes become perturbed during ultraviolet radiation-induced skin carcinogenesis. We are focused on protein kinase C signaling pathways as key regulators of epidermal biology, and use a variety of molecular, biochemical and cell biological approaches to uncover novel signaling mechanisms. The cellular responses to ultraviolet radiation are complex, and we are interested in the multitude of biological effects elicited by UV radiation, including inflammation, cell cycle arrest, DNA damage repair and cell death. By understating both physiological and pathological regulatory mechanisms in the epidermis, we are able to test novel preventive and therapeutic approaches to combat the approximately 4.5 million new cases of skin cancers diagnosed annually in the USA.

Education

• BS in Biochemistry, University of Arizona
• PhD in Human Cancer Biology, University of Wisconsin-Madison
• Postdoctoral fellowship in Skin Carcinogenesis, National Cancer Institute, National Institutes of Health
• Postdoctoral fellowship in Cell-Cell Adhesion, Northwestern University

Publications/Research Listings

• Ripk3 signaling regulates HSCs during stress and represses radiation-induced leukemia in mice  Zhang, L; Luo, H; Ni, HM; Liu, S; Xing, H; Zhang, J; Sellin, M; Breslin, S J P; Wei, W; Denning, MF; Small, W Jr; Ding, WX; Huang, S; Zhang, J  Stem Cell Reports  2022 Jun 14;17(6):1428-1441. doi: 10.1016/j.stemcr.2022.04.009. Epub 2022 May 12. PMID: 35561683; PMCID: PMC9213819
• RIPK3 signaling and its role in the pathogenesis of cancers  Liu, S; Joshi, K; Denning, MF; Zhang, J  Cellular and Molecular Life Sciences  2021 Dec;78(23):7199-7217. doi: 10.1007/s00018-021-03947-y. Epub 2021 Oct 15. PMID: 34654937; PMCID: PMC9044760
• Targeting EphA2 suppresses hepatocellular carcinoma initiation and progression by dual inhibition of JAK1/STAT3 and AKT signaling  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 ,W  Cell Reports  2021 Feb 23;34(8):108765. doi: 10.1016/j.celrep.2021.108765. PMID: 33626345; PMCID: PMC7954228
• ABL1, overexpressed in hepatocellular carcinomas, regulates expression of NOTCH1 and promotes development of liver tumors in mice  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, W  Gastroenterology  2020 Jul;159(1):289-305.e16. doi: 10.1053/j.gastro.2020.03.013. Epub 2020 Jun 24. PMID: 32171747; PMCID: PMC7387191
• Inhibition of insulin-like growth factor 1 receptor enhances the efficacy of sorafenib in inhibiting hepatocellular carcinoma cell growth and survival  Wang, F; Bank, T; Malnassy, G; Arteaga, M; Shang, N; Dalheim, A; Ding, X; Cotler, SJ; Denning, MF; Nishimura, MI; Breslin, P; Qiu, W  Hepatology Communications  2018 Apr 17;2(6):732-746. doi: 10.1002/hep4.1181. PMID: 29881824; PMCID: PMC5983153
• The role of Rak in the regulation of stability and function of BRCA1  Kim, JL; Ha, GH; Campo, L; Denning, MF; Patel, TB; Osipo, C; Lin, SY; Breuer, EK  Oncotarget  2015 Oct 14;8(49):86799-86815. doi: 10.18632/oncotarget.5717. PMID: 29156836; PMCID: PMC5689726.
• PKC-dependent regulation of Kv7.5 channels by the bronchoconstrictor histamine in human airway smooth muscle cells  Haick, JM; Brueggemann, LI; Cribbs, LL; Denning, MF; Schwartz, J; Byron, KL  American Journal of  Physiology - Lung Cellular and Molecular Physiology  2017 Jun 1;312(6):L822-L834. doi: 10.1152/ajplung.00567.2016. Epub 2017 Mar 10. PMID: 28283479
• Inhibition of SIRT2 suppresses hepatic fibrosis  Arteaga, M; Shang, N; Ding, X; Yong, S; Cotler, SJ; Denning, MF; Shimamura, T; Breslin, P; Lüscher, B; Qiu, W  American Journal of Physiology – Gastrointestinal and Liver Physiology  2016 Jun 1;310(11):G1155-68. doi: 10.1152/ajpgi.00271.2015. Epub 2016 Apr 28. PMID: 27125275; PMCID: PMC4935480
• PKCα attenuates Jagged-1-mediated Notch signaling in ErbB-2-positive breast cancer to reverse trastuzumab resistance  Pandya, K; Wyatt, D; Gallagher, B; Shah, D; Baker, A; Bloodworth, J; Zlobin, A; Pannuti, A; Green, A; Ellis, IO; Filipovic, A; Sagert, J; Rana, A; Albain, KS; Miele, L; Denning, MF; Osipo, C  Clinical Cancer Research  2016 Jan 1;22(1):175-86. doi: 10.1158/1078-0432.CCR-15-0179. Epub 2015 Sep 8. PMID: 26350262; PMCID: PMC4703529
• Targeting Fyn in Ras-transformed cells induces F-actin to promote adherens junction-mediated cell-cell adhesion  Fenton, SE; Hutchens, KA; Denning, MF  Molecular Carcinogenesis  2015 Oct;54(10):1181-93. doi: 10.1002/mc.22190. Epub 2014 Jun 29. PMID: 24976598

Additional Publications List

Awards

• Keratinocyte and melanocyte biology
• Ultraviolet radiation induced skin carcinogenesis
• Protein kinase C signaling