|Nabiha Yusuf, Ph.D.|
University of Alabama at Birmingham
Education and Academic Affiliation
Our laboratory is involved in evaluating the effect of environmental influences such as chemical carcinogens and ultraviolet radiation on the skin immune system. The focus of our research is on the role of innate immunity in the development of skin carcinogenesis. Toll-like receptors (TLRs), one component of innate immunity, are intricately associated with a number of dermatologic conditions. We have found that the innate immune system mediates through Toll like receptor-4 (TLR4) signaling to activate the cell mediated adaptive immune response against chemically induced tumors. TLR4 signaling had a protective effect against 7,12-dimethylbenz(a)anthracene (DMBA) induced skin cancer in certain strains of mich which develop cell mediated immune response to this chemical carcinogen. We are currently in the process of evaluating the role of the innate immune system in ultraviolet B (UVB) radiation induced skin cancer. The mechanisms by which UVB radiation influences cell mediated immune responses have been the subject of extensive investigation. However, there is little information on the role of innate immunity in this process. Our recent experiments suggest that certain components of innate immunity, especially TLR4, may play an important role in photoimmunosuppression. Currently, we are investigating whether the resistance of TLR4 gene knockout mice to UVB-induced immunosuppression has implications for photocarcinogenesis. The ultimate goal of these studies will be to define the role of TLR4 in the development of immune suppression and tumor development that occurs following UV radiation. This may allow us to identify genetic loci that are involved in these processes and to develop immunopreventive and immunotherapeutic approaches toward them.
Elmets C.A., Yusuf N., Hamza S., Iranikhah N., Smith J., Volk A.L., Skelton H., Smith K.. Topical application of Dimethylbenz(a)anthracene results in the generation of multiple melanocytic nevi in C3H/HeN mice. Toxicol Appl Pharmacol. 195(3):355-60, 2004.
Hasan N., Yusuf N., Toossi Z., Islam N. Suppression of Mycobacterium tuberculosis induced reactive oxygen species (ROS) and TNF-alpha mRNA expression in human monocytes by allicin. FEBS Lett. 580(10): 2517-22, 2006.
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., Timares L., Seibert M.D., Xu H., and Elmets C.A. Acquired and innate immunity to polyaromatic hydrocarbons. Toxicol Appl Pharmacol. 224: 308-12, 2007.
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. 68(2): 615-22, 2008.
Yusuf N., Katiyar S.K., and Elmets, C.A. 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. 84(2):366-70, 2008.
Yusuf N., Nasti T.H., Katiyar S.K., Jacobs M.K., Seibert M.D., Ginsburg A.C., Timares L., Xu H. and Elmets C.A. Antagonistic roles of CD4+ and CD8+ T-cells in 7,12-dimethylbenz(a)anthracene cutaneous carcinogenesis. Cancer Res. 68(10): 3924-30, 2008.
Active Grant Support
VA Merit Review
UAB SDRC Pilot and Feasibility Study #14
UAB Faculty Development Grant Program