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(2) Skin cancer research focuses largely on the biology of cutaneous carcinoma and melanoma cells. Specifically, the effects of gangliosides on the biological properties of squamous cell carcinomas and melanoma cells are being investigated by members of Dr. Paller's lab. The role of the glucocorticoid receptor as a potential tumor suppressor is being investigated in squamous cell carcinomas of the skin and in prostate gland cancer by members of Dr. Budunova's laboratory. Since epithelial stem cells are the ultimate targets of neoplastic transformation, a collaborative investigation is ongoing between Dr. Lavker and Dr. Budunova's laboratories to specifically study the effects of ectopic expression of the glucocorticoid receptor on the hair follicle stem cells. Evidence has been presented that transgenic mice that ectopically express the glucocorticoid receptor in basal cells have diminished number of putative hair follicle stem cells. This finding might help to explain why these mice elaborate fewer papillomas than wild type mice following 2-stage chemical carcinogenesis protocols. (3) In cutaneous inflammation and immunology, a major focus centers on the role that the neurologic system plays in modulating the inflammatory response and wound healing in the skin and eye. Specific research programs are directed towards understanding: (i) the interrelationship between the toll-like receptors, localized on epidermal and ocular keratinocytes, and keratinocyte activation via bacterial-derived products; (ii) the action of neuropeptides in the generation and maintenance of the inflammatory response; and (iii) the mediation of cutaneous and ocular inflammation by neurotrophins such as nerve growth factor and the vanilloid receptors. (4) In cutaneous aging, research is centered on understanding the intrinsic and extrinsic effects of age on the structure of the epidermis and dermis. Emphasis is placed on characterizing the contributions that ultraviolet B and ultraviolet A play in the pathogenesis of photodamaged skin. The role of ultraviolet light in the pathogenesis of corneal injury and ptyergium development is also being studied. (5) Several studies focus on wound healing. Dr. Paller's lab studies the affect of ganglioside depletion on wound healing using a mouse transgenic model. Dr. Robert Lavker (Derm) and Thomas Mustoe (Chair, Plastic Surgery) are collaborating to understand the role of epidermis in "scarless wound healing". Another area under investigation is the role of follicular epithelium in epidermal wound healing, baed on the known migration of progeny of the bulge-derived follicular epithelial stem cells into the epidermis. Studies also focus on the effects of the glucocorticoid receptor on follicular-derived epidermal wound healing. Finally, the limbal/corneal epithelium is being explored as a general model for epithelial wound repair as a collaborative effort of members of the Departments of Dermatology and Cell and Molecular Biology. (6) In the area of novel therapies for cutaneous diseases, metastatic melanoma, psoriasis and CTCL are currently under investigation. Specific programs are: (i) understanding the specificity and efficacy of Newcastle Disease Virus oncolysate as an immunotherapeutic agent against melanoma; (ii) using novel biological molecules for the treatment of psoriasis with emphasis on the inhibition of T-cell activation, proliferation and migration to the skin; and (iii) evaluating biological response modifiers in CTCL patients at various stages of the disease.
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