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Jerry Shapiro, MD., University of British Columbia, Vancouver, BC. Stem cells in the skin epidermis and hair follicles of adults are believed to serve as the ultimate source of cells for both healthy skin structures and skin cancers. The most common form of skin cancer for an individual to develop (with a 30% lifetime risk) is basal cell carcinoma (BCC). Hair follicles and BCCs can be regarded as ordered and disordered skin growths respectively, and they may both utilize similar molecular signaling mechanisms to grow. Cell growth mechanisms are similar to traffic lights. Cars (cells) are told when to "go" and when to "stop" by the traffic lights (molecular signals). We have already found that both BCCs and hair follicles exhibit activation of common "traffic light signals" involved in skin appendage formation (genes commonly involved in ordered skin appendage growth). We also found some specific signals that code for "hair follicleness" are either missing or over-represented in BCCs (these are genes important in ordered appendage growth that have failed to function correctly in BCC development). An important gene signaling pathway, the Notch signaling pathway, emerged as inappropriately active in BCC growth. It may be a key signaling system for BCC formation and growth. We plan to introduce "stop" and "go" controls of the Notch gene pathway to re-establish appropriate gene function and subsequently adjust the "traffic light signals" to stop BCC growth. We anticipate that these studies may lead to a revolutionary approach for BCC treatment based on modifying the expression of Notch signaling pathway genes. Peer-reviewed publications supported by the Canadian Dermatology Foundation M. Yu, D. Zloty, B. Cowan, J. Shapiro, A. Haegert, R. Bell, N. Carr, K.J. McElwee. Microarray analysis shows multiple signal transduction pathways are involved in basal cell carcinoma growth. J Invest Dermatol. In press. M. Yu, S. Kissling, R. Hoffmann, J. Shapiro, P. Freyschmidt-Paul, K.J. McElwee. IL-6 cytokine family member oncostatin M is a hair follicle expressed factor with hair growth inhibitory properties. Exp Dermatol. 2008; 17: 12-9. M. Yu, A. Finner, J. Shapiro, B. Lo, A. Barekatain, K.J. McElwee. Hair follicles and their role in skin health. Exp Rev Dermatol. 2006; 1: 855-871. W. Lu, J. Shapiro, M. Yu, A. Barekatain, B. Lo, A. Finner, K.J. McElwee. Alopecia areata: pathogenesis and potential for therapy. Exp Rev Mol Med. 2006;8:1-19. Tang L, Cao L, Sundberg JP, Lui H, Shapiro J. Restoration of hair growth in mice with an alopecia areata-like disease using topical anthralin. Exp Dermatol 2004;13:5-10. Tang L, Lui H, Sundberg JP, Bissonnette R, McLean DI, Shapiro J. Restoration of hair growth with topical diphencyprone in mouse and rat models of alopecia areata. J Am Acad Dermatol 2003;49(6):1013-9. Tang L, Bernardo O, Bolduc C, Lui H, Madani S, Shapiro J. The expression of insulin-like growth factor 1 in follicular dermal papillae correlates with therapeutic efficacy of finasteride in androgenetic alopecia. J Am Acad Dermatol 2003;49(2):229-33. Tang L, Cao L, Pelech S, Lui H, Shapiro J. Cytokines and signal transduction pathways mediated by anthralin in alopecia areata-affected Dundee experimental balding rats. J Investig Dermatol Symp Proc 2003;8(1):87-90. Tang L, Cao L, Bernardo O, Chen Y, Sundberg JP, Lui H, Shapiro J, et al. Topical mechlorethamine restores autoimmune-arrested follicular activity in mice with an alopecia areata-like disease by targeting infiltrated lymphocytes. J Invest Dermatol 2003;120(3):400-6. Tang L, Madani S, Lui H, Shapiro J. Regeneration of a new hair follicle from the upper half of a human hair follicle in a nude mouse. J Invest Dermatol 2002;119(4):983-4. ©2008 |
