Melanoma is the most deadly of the skin cancers. My research is focused on melanoma chemoprevention. All of my current projects use agents that are designed to alleviate the mutagenic effects of UV-induced oxidative stress in order to prevent melanoma. The most mature of these projects is centered on an NCI-funded Phase II clinical trial of N-acetylcysteine for relief of UV-induced oxidative stress in human nevi (moles). In addition to testing this promising new agent in patients, we are working towards an understanding of the genetic basis of susceptibility to melanoma and response to chemopreventive agents. This effort is the foundation of our ultimate goal of offering patients a personalized program for melanoma prevention.

Another chemoprevention project arose from collaborative work with Drs. Sancy Leachman (Chair of Dermatology at OHSU) and Zalfa Abdel-Malek (world expert on melanocyte biology at the University of Cincinnati). Our group studies the melanocytes (pigment producing cells from which melanoma arises) and the effects on these cells of mutations in the melanocortin-1 receptor gene (MC1R, a.k.a the red hair gene). Our group conducted microarray expression studies of MC1R mutant melanocytes. The results suggested that a particular class of antioxidant represented by the natural product sulforaphane might compensate for loss of function of the mutant receptor, and thereby lower the risk for melanoma in patients with inherited mutations in MC1R. Preliminary in vitro and clinical studies are supportive of this model and Dr. Leachman and Dr. Cassidy are working to secure funding for testing sulforaphane for efficacy in a mouse model of UV-induced melanoma as one of the final steps in our efforts to advance the agent into a clinical trial in humans.