Mitchell Denning, PhD

Pathology

Molecular Pharmacology and Therapeutics
Professor

Languages Spoken

English

Biography

Interests
Skiing, Bicycling

Research

  • Alcohol inhibits osteopontin-dependent transforming growth factor-beta1 expression in human mesenchymal stem cells Driver, J.; Weber, C. E.; Callaci, J. J.; Kothari, A. N.; Zapf, M. A.; Roper, P. M.; Borys, D.; Franzen, C. A.; Gupta, G. N.; Wai, P. Y.; Zhang, J.; Denning, M. F.; Kuo, P. C.; Mi, Z., The Journal of biological chemistry
  • FYNagling divergent adhesive functions for Fyn in keratinocytes Fenton, S. E.; Denning, M. F., Experimental dermatology
  • PKCalpha 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, I. O.; Filipovic, A.; Sagert, J.; Rana, A.; Albain, K. S.; Miele, L.; Denning, M. F.; Osipo, C., Clinical cancer research : an official journal of the American Association for Cancer Research
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  • TACC3 deregulates the DNA damage response and confers sensitivity to radiation and PARP inhibition Ha, G. H.; Kim, J. L.; Petersson, A.; Oh, S.; Denning, M. F.; Patel, T.; Breuer, E. K., Oncogene
  • Targeting Fyn in Ras-transformed cells induces F-actin to promote adherens junction-mediated cell-cell adhesion Fenton, S. E.; Hutchens, K. A.; Denning, M. F., Molecular carcinogenesis
  • The role of Rak in the regulation of stability and function of BRCA1 Kim, J. L.; Ha, G. H.; Campo, L.; Denning, M. F.; Patel, T. B.; Osipo, C.; Lin, S. Y.; Breuer, E. K., Oncotarget
  • BaxDelta2 promotes apoptosis through caspase-8 activation in microsatellite-unstable colon cancer Zhang, H.; Lin, Y.; Manas, A.; Zhao, Y.; Denning, M. F.; Ma, L.; Xiang, J., Molecular cancer research : MCR
  • Crosstalk between PKCalpha and Notch-4 in endocrine-resistant breast cancer cells Yun, J.; Pannuti, A.; Espinoza, I.; Zhu, H.; Hicks, C.; Zhu, X.; Caskey, M.; Rizzo, P.; D'Souza, G.; Backus, K.; Denning, M. F.; Coon, J.; Sun, M.; Bresnick, E. H.; Osipo, C.; Wu, J.; Strack, P. R.; Tonetti, D. A.; Miele, L., Oncogenesis
  • Mouse models of the skin: models to define mechanisms of skin carcinogenesis Wheeler, D. L.; Verma, A. K.; Denning, M. F., Journal of skin cancer
  • Long QT2 mutation on the Kv11.1 ion channel inhibits current activity by ablating a protein kinase Calpha consensus site Donovan, A. J.; Lansu, K.; Williams, J. G.; Denning, M. F.; Gentile, S., Molecular pharmacology
  • Specifying protein kinase C functions in melanoma Denning, M. F., Pigment Cell & Melanoma Research
  • The black box illuminated: signals and signaling Mascia, F.; Denning, M.; Kopan, R.; Yuspa, S. H., The Journal of investigative dermatology
  • Fyn is induced by Ras/PI3K/Akt signaling and is required for enhanced invasion/migration. Yadav, V.; Denning, M. F., Molecular carcinogenesis
  • The calcium ATPase SERCA2 regulates desmoplakin dynamics and intercellular adhesive strength through modulation of PKCα signaling Hobbs, R. P.; Amargo, E. V.; Somasundaram, A.; Simpson, C. L.; Prakriya, M.; Denning, M. F.; Green, K. J., The FASEB journal : official publication of the Federation of American Societies for Experimental Biology
  • Functional alterations in protein kinase C beta II expression in melanoma. Voris, J. P.; Sitailo, L. A.; Rahn, H. R.; Defnet, A.; Gerds, A. T.; Sprague, R.; Yadav, V.; Le Poole, I. C.; Denning, M. F., Pigment Cell & Melanoma Research
  • Loss of protein kinase C delta gene expression in human squamous cell carcinomas: a laser capture microdissection study. Yadav, V.; Yanez, N. C.; Fenton, S. E.; Denning, M. F., American Journal of Pathology
  • Protein kinase C/mitogen-activated protein kinase signaling in keratinocyte differentiation control. Denning, M. F., Journal of Investigative Dermatology
  • Sun-sensitizing effects of PKCepsilon shine on multiple mouse strains. Denning, M. F., Journal of Investigative Dermatology
  • The protein kinase Cdelta catalytic fragment is critical for maintenance of the G2/M DNA damage checkpoint. LaGory, E. L.; Sitailo, L. A.; Denning, M. F., Journal of Biological Chemistry
  • Mcl-1 functions as major epidermal survival protein required for proper keratinocyte differentiation. Sitailo, L. A.; Jerome-Morais, A.; Denning, M. F., Journal of Investigative Dermatology
  • PDGF receptor activation induces p120-catenin phosphorylation at serine 879 via a PKCalpha-dependent pathway Brown, M. V.; Burnett, P. E.; Denning, M. F.; Reynolds, A. B., Experimental cell research
  • Role for protein kinase C-alpha in keratinocyte growth arrest Jerome-Morais, A.; Rahn, H. R.; Tibudan, S. S.; Denning, M. F., Journal of Investigative Dermatology
  • Inhibition of PAX3 by TGF-beta modulates melanocyte viability. Yang, G.; Li, Y.; Nishimura, E. K.; Xin, H.; Zhou, A.; Guo, Y.; Dong, L.; Denning, M. F.; Nickoloff, B. J.; Cui, R., Molecular cell
  • Plakophilin 2: a critical scaffold for PKC alpha that regulates intercellular junction assembly. Bass-Zubek, A. E.; Hobbs, R. P.; Amargo, E. V.; Garcia, N. J.; Hsieh, S. N.; Chen, X.; Wahl, J. K., 3rd; Denning, M. F.; Green, K. J., Journal of Cell Biology
  • Protein kinase C family: on the crossroads of cell signaling in skin and tumor epithelium Breitkreutz, D.; Braiman-Wiksman, L.; Daum, N.; Denning, M. F.; Tennenbaum, T., Journal of Cancer Research & Clinical Oncology
  • Tightening the epidermal barrier with atypical PKCs Denning, M. F., Journal of Investigative Dermatology
  • Defining the caspase-containing apoptotic machinery contributing to cornification in human epidermal equivalents. Chaturvedi, V.; Sitailo, L. A.; Bodner, B.; Denning, M. F.; Nickoloff, B. J., Experimental dermatology
  • Disruption of EphA2 receptor tyrosine kinase leads to increased susceptibility to carcinogenesis in mouse skin. Guo, H.; Miao, H.; Gerber, L.; Singh, J.; Denning, M. F.; Gilliam, A. C.; Wang, B., Cancer research
  • Enhanced killing of melanoma cells by simultaneously targeting Mcl-1 and NOXA. Qin, J. Z.; Xin, H.; Sitailo, L. A.; Denning, M. F.; Nickoloff, B. J., Cancer research
  • PKCdelta clustering at the leading edge and mediating growth factor-enhanced but not ecm-initiated, dermal fibroblast migration., Fan, J.; Guan, S.; Cheng, C. F.; Cho, M.; Fields, J. W.; Chen, M.; Denning, M. F.; Woodley, D. T.; Li, W., Journal of Investigative Dermatology
  • The proapoptotic tumor suppressor protein kinase C-delta is lost in human squamous cell carcinomas. D'Costa, A. M.; Robinson, J. K.; Maududi, T.; Chaturvedi, V.; Nickoloff, B. J.; Denning, M. F., Oncogene
  • The protein kinase C delta catalytic fragment targets Mcl-1 for degradation to trigger apoptosis. Sitailo, L. A.; Tibudan, S. S.; Denning, M. F., Journal of Biological Chemistry
  • A caspase-resistant mutant of PKC-delta protects keratinocytes from UV-induced apoptosis. D'Costa, A. M.; Denning, M. F., Cell Death & Differentiation
  • Knockdown of p53 levels in human keratinocytes accelerates Mcl-1 and Bcl-x(L) reduction thereby enhancing UV-light induced apoptosis. Chaturvedi, V.; Sitailo, L. A.; Qin, J. Z.; Bodner, B.; Denning, M. F.; Curry, J.; Zhang, W.; Brash, D.; Nickoloff, B. J., Oncogene
  • Survival role of protein kinase C (PKC) in chronic lymphocytic leukemia and determination of isoform expression pattern and genes altered by PKC inhibition. Alkan, S.; Huang, Q.; Ergin, M.; Denning, M. F.; Nand, S.; Maududi, T.; Paner, G. P.; Ozpuyan, F.; Izban, K. F., American Journal of Hematology
  • Bax activation and induction of apoptosis in human keratinocytes by the protein kinase C delta catalytic domain. Sitailo, L. A.; Tibudan, S. S.; Denning, M. F., Journal of Investigative Dermatology
  • Epidermal keratinocytes: regulation of multiple cell phenotypes by multiple protein kinase C isoforms Denning, M. F., International Journal of Biochemistry & Cell Biology
  • Low-dose UV-radiation sensitizes keratinocytes to TRAIL-induced apoptosis. Qin, J. Z.; Bacon, P.; Panella, J.; Sitailo, L. A.; Denning, M. F.; Nickoloff, B. J., Journal of cellular physiology
  • Protein kinase C-delta is commonly expressed in multiple myeloma cells and its downregulation by rottlerin causes apoptosis. Ni, H.; Ergin, M.; Tibudan, S. S.; Denning, M. F.; Izban, K. F.; Alkan, S., British journal of haematology
  • Role for Id-1 in immunobiology of normal keratinocytes and in basal cell carcinoma. Chaturvedi, V.; Bonish, B.; Bacon, P.; Qin, J. Z.; Denning, M. F.; Foreman, K. E.; Diaz, M. O.; Robinson, J.; Nickoloff, B. J., Experimental dermatology
  • Activation of caspase-9 is required for UV-induced apoptosis of human keratinocytes Sitailo, L. A.; Tibudan, S. S.; Denning, M. F., The Journal of biological chemistry
  • Activation of protein kinase C triggers irreversible cell cycle withdrawal in human keratinocytes Tibudan, S. S.; Wang, Y.; Denning, M. F., The Journal of investigative dermatology
  • Caspase activation and disruption of mitochondrial membrane potential during UV radiation-induced apoptosis of human keratinocytes requires activation of protein kinase C Denning, M. F.; Wang, Y.; Tibudan, S.; Alkan, S.; Nickoloff, B. J.; Qin, J. Z., Cell death and differentiation
  • Jagged-1 mediated activation of notch signaling induces complete maturation of human keratinocytes through NF-kappaB and PPARgamma Nickoloff, B. J.; Qin, J. Z.; Chaturvedi, V.; Denning, M. F.; Bonish, B.; Miele, L., Cell death and differentiation
  • Life and death signaling pathways contributing to skin cancer Nickoloff, B. J.; Qin, J. Z.; Chaturvedi, V.; Bacon, P.; Panella, J.; Denning, M. F., The journal of investigative dermatology.Symposium proceedings / the Society for Investigative Dermatology, Inc.[and] European Society for Dermatological Research
  • P21Waf1 control of epithelial cell cycle and cell fate Weinberg, W. C.; Denning, M. F., Critical reviews in oral biology and medicine : an official publication of the American Association of Oral Biologists
  • Regulation of apoptosis by p53 in UV-irradiated human epidermis psoriatic plaques and senescent keratinocytes, Qin, J. Z.; Chaturvedi, V.; Denning, M. F.; Bacon, P.; Panella, J.; Choubey, D.; Nickoloff, B. J., Oncogene
  • Abnormal NF-kappaB signaling pathway with enhanced susceptibility to apoptosis in immortalized keratinocytes Chaturvedi, V.; Qin, J. Z.; Denning, M. F.; Choubey, D.; Diaz, M. O.; Nickoloff, B. J., Journal of dermatological science
  • Inhibition of tyrosine kinase activity induces caspase-dependent apoptosis in anaplastic large cell lymphoma with NPM-ALK (p80) fusion protein Ergin, M.; Denning, M. F.; Izban, K. F.; Amin, H. M.; Martinez, R. L.; Saeed, S.; Alkan, S., Experimental hematology
  • Phosphorylation of murine homeodomain protein Dlx3 by protein kinase C Park, G. T.; Denning, M. F.; Morasso, M. I., FEBS letters
  • Protein kinase Cdelta-mediated phosphorylation of alpha6beta4 is associated with reduced integrin localization to the hemidesmosome and decreased keratinocyte attachment Alt, A.; Ohba, M.; Li, L.; Gartsbein, M.; Belanger, A.; Denning, M. F.; Kuroki, T.; Yuspa, S. H.; Tennenbaum, T., Cancer research
  • Characterization of apoptosis induced by protein kinase C inhibitors and its modulation by the caspase pathway in acute promyelocytic leukaemia Amin, H. M.; Ergin, M.; Denning, M. F.; Quevedo, M. E.; Alkan, S., British journal of haematology
  • Cross-talk between epidermal growth factor receptor and protein kinase C during calcium-induced differentiation of keratinocytes Denning, M. F.; Dlugosz, A. A.; Cheng, C.; Dempsey, P. J.; Coffey, R. J., Jr; Threadgill, D. W.; Magnuson, T.; Yuspa, S. H., Experimental dermatology
  • Id-1 delays senescence but does not immortalize keratinocytes Nickoloff, B. J.; Chaturvedi, V.; Bacon, P.; Qin, J. Z.; Denning, M. F.; Diaz, M. O., The Journal of biological chemistry

Role of protein kinase C isoforms in normal skin biology, the response of skin to ultraviolet radiation, and skin carcinogenesis

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. They recently demonstrated 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. They are also examining the involvement of PKC activation in cell cycle withdrawal (G0) during normal keratinocyte differentiation. Their long-term goals are to target these signaling pathways for therapeutic or preventive interventions in skin cancer. viruses, interaction of the major Simian Virus 40 (SV40) oncogenes with cellular proteins, pathogenesis of mesothelioma.