|Craig A. Elmets, M.D., Chairman|
Another major research interest is the immunogenicity of topically applied chemical carcinogens. Using polyaromatic hydrocarbons as prototypic carcinogenic chemicals, he has shown that topical application of these compounds results in the development of allergic contact hypersensitivity. Metabolism of the compounds is required for the development of this response which only occurs in mice with certain MHC haplotypes and in Ah receptor positive strains of mice. Bases on these results, he has developed the hypothesis that the presence of allergic contact hypersensitivity to polyaromatic hydrocarbons serves to protect mice from the carcinogenic effects of these agents. In support of this hypothesis, he has shown the MHC congenic strains of mice that do not develop polyaromatic hyrdrocarbon contact hypersensitivity are at increased risk for development of skin cancers by those agents.
A third area of research interest is in chemoprevention of skin cancer. In both animals and humans green tea polyphenols have a protective effect on UV-induced damage to the skin. He has shown in animals that this agent protects against UV induced immunosuppression and in humans it prevents the clinical and histological features of sunburn reaction and DNA damage. He is also investigating whether celecoxib exerts a chemopreventive effect against actinic keratoses in humans and whether topical application of DNA repair enzymes will prevent the development of non-melanoma skin cancers in renal transplant patients.
Elmets C.A., Athar M., Tubesing K.A., Rothaupt D., Xu H.: Susceptibility to the biological effects of polyaromatic hydrocarbons is influenced by genes of the major histocompatibility complex. Proc Natl Acad Sci USA 95: 14915-9, 1998.
Elmets CA, Singh D., Tubesing K., Matsui M., Katiyar S.K., Mukhtar H.: Prevention of cutaneous photodamage by polyphenols from green tea. J Amer Acad Dermatol. 44: 425-432, 2001
Gunn H., Marlon S., Elmets C.A., and Hui X.. Gamma delta T cells regulate the development of hapten specific CD8+ effector T-cells in contact hypersensitivity responses. J Invest Dermatology. 119: 137-42, 2002.
Huang C-M, Wang C-C, Kawai M., Barnes S., Elmets C.A.. Surfactant sodium lauryl sulfate enhances skin vaccination: Molecular characterization via a novel technique using ultrafiltration capillaries and mass spectrometric proteomics. Mol Cell Proteomics: M500259-MCP500200, 2005.
Huang C-C, Xu H, Wang C-C, Elmets C.A.. Proteomic characterization of skin and epidermis in response to environmental agents. Expert Review of Proteomics. 2: 809-820, 2005.
Meeran S.M., Manteena, S.K. Elmets C.A., and Katiyar, SK. (-)-Epigallocatechin-3-Gallate prevents photocarcinogenesis in mice through Interleukin-12-dependent DNA repair. Cancer Res. 66:5512-5520, 2006.
Elmets C.A. An animal model of psoriasis in mice deficient in epidermal Jun proteins. Arch Dermatol. 142:1499-500, 2006.
Yusuf N., Timares L., Seibert M.D., Xu H., and Elmets C.A. Acquired and innate immunity to polyaromatic hydrocarbons. Toxicol Appl Pharmacol. 224: 308-312, 2007.
Yusuf N., Irby C., Katiyar S.K., and Elmets C.A. Photoprotective effects of green tea polyphenols. Photodermatol Photoimmunol Photomed. 23: 48-56, 2007.
Yusuf N., Katiyar S.K., and Elmets C.A. The immunosuppressive effects of phthalocyanine photodynamic therapy in mice are mediated by CD4(+) and CD8(+) T cells and can be adoptively transferred to naive recipients. Photochem. Photobiol. Jan. 15, 2008 [epub ahead of print]
Yusuf N., Nasti T.H., Long J.A., Naseemuddin M., Lucas A.P., Xu H., and Elmets C.A. Protective role of Toll-like receptor 4 during the initiation stage of cutaneous chemical carcinogenesis. Cancer Res. 15: 615-22, 2008.
Timares L., Katiyar S.K. and Elmets C.A. DNA damage, apoptosis and Langerhans cells-activators of UV-induced immune tolerance.Photocehm. Photobiol. 84:422-36, 2008.
Menter A, Gottlieb A, Feldman SR, Van Voorhees AS, Leonardi CL, Gordon KB, Lebwohl M, Koo JY, Elmets CA, Korman NJ, Beutner KR, Bhushan R. Guidelines of care for the management of psoriasis and psoriatic arthritis: Section 1. Overview of psoriasis and guidelines of care for the treatment of psoriasis with biologics. J Am Acad Dermatol. 58(5): 826-850, 2008.
Gottlieb A, Korman NJ, Gordon KB, Feldman SR, Sebwohl M, Koo JU, Van Voorhees AS, Elmets, CA, Leonardi CL, Beutner KR, Bhushan R, Menter A. Guidelines of care for the management of psoriasis and psoriatic arthritis: Section 2. Psoriatic arthritis: Overview and guidelines of care for treatment with an emphasis on the biologics. J Am Acad Dermatol, 58(5): 851-864, 2008.
Varma R., Cafardi J.A., Cantrell W., and Elmets, C.A. Safety and efficacy of subcutaneously administered Efalizumab in adults with moderate-to-severe hand and foot psoriasis: An open-label study. Am J Clin Dermatol. 9: 105-9, 2008
Yusuf N, Katiyar SK, Elmets CE. The immunosuppressive effects of PC4 PDT are mediated by both CD4+ and CD8+ T-Cells. Photochem Photobiol, 84: 366-70, 2008.
Pradhan S, Kim HK, Thrash CJ, Cox MA, Mantena SK, Wu JH, Athar M, Katiyar SK, Elmets CA, Timares L. Critical role for the proapoptotic protein bid in ultraviolet-induced immune suppression and cutaneous apoptosis. J Immunol , 181: 3077-88, 2008.
Yusuf N, Huang C-M, Nasti TH, Huber BS, Tarannum J, Xu H, Elmets CA. Heat shock proteins HSP27 and HSP70 are present in the skin and are important mediators of allergic contact hypersensitivity. J Immunol, 182:675-83, 2009.
Active Grant Support
National Institutes of Health
VA Merit Review
National Institutes of Health