Alice Pauline Pentland, M.D.

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Research in the Pentland Lab addresses the role of cyclooxygenases and phospholipases in epidermal function. There are two major areas these studies address: their role in carcinogenesis and in cell differentiation. The role of these lipid mediators in the induction of squamous cell carcinoma of the skin is being studied in the context of ultraviolet light injury. Ultraviolet light exposure is known to be a complete carcinogen, inducing both squamous and basal cell carcinomas in skin. Recent work has shown that significant contributions to tumor initiation and promotion may be made by eicosanoids (arachidonic acid and its metabolites). Most importantly, available inhibitors of prostaglandin synthesis have been shown to have anti-tumor properties in colon cancer in humans. UV exposure results in substantial increases in eicosanoid formation; work in the lab is therefore designed to directly link UV-induced eicosanoid synthesis to tumor initiation and promotion in humans.

The validity of this hypothesis will be tested by showing 1) eicosanoid metabolite formation is induced by chronic irradiation and in squamous cell carcinoma; 2) the increased quantities of these metabolites formed in epidermis produce in vitro changes supportive of tumor formation; and 3) UV carcinogenesis is decreased in knockout animals lacking prostaglandin forming enzymes COX-1, COX-2, and the PGE receptor EP2. In vitro overexpression of cyclooxygenase and phospholipase enzymes on the response of cell cultures to UV irradiation is currently being examined. The impact of product synthesis on UV-induced changes in cell cycle progression and apoptosis are a central focus. Emphasis is placed on the signaling mechanisms triggered by UV irradiation and the impact of prostaglandins or free fatty acids on keratinocyte function. In addition to these approaches in tissue culture, acute and chronic in vivo experiments are also underway with COX-1 and COX-2 knockout mice. Prostaglandin receptor regulation in vivo and in vitro by irradiation, which contributes to cAMP and Ca++ second messenger pathways are also under study. New in vivo confocal microscopy techniques to characterize the burden of mutation and repair in skin are also being employed. The trainees will also become expert in the fields of photobiology and eicosanoid biology. These two areas are underrepresented in Dermatology training programs, and are therefore important additions to the training program at Rochester.

Current Appointments

• Chair - Department of Dermatology (SMD)
• James H. Sterner Professorship in Dermatology - Department of Dermatology (SMD)
• Professor - Department of Dermatology (SMD)