The goal of our laboratory is to understand the molecular basis of melanoma susceptibility, progression and chemosensitivity. Our research is translationally-based and framed around 3 core questions: (1). What genetic risk factors contribute to melanoma development and how can the medical community leverage this information to manage patients? With banked biospecimens from over 200 melanoma-prone kindreds worldwide, we routinely screen our families for mutations in common melanoma-predisposing loci in order to better correlate genotype and phenotype. Moreover, we also participate with GenoMEL in an international effort to define new risk alleles for melanoma. Lastly, in conjunction with the MGH Melanoma/Pigmented Lesion Center, our research is also aimed at understanding the clinical utility of "personalized" molecular medicine in the management of melanoma patients. (2). What are the mutational targets that drive the formation of melanomas? Beyond heritable alterations, we are also interested in patterns of acquired mutagenesis that define the genetic circuitry responsible for melanoma progression. (3). What is the role of ultraviolet radiation in the induction of cutaneous melanoma? Decades of epidemiological data support a role for ultraviolet radiation (UVR), in the form of excessive solar exposure, as a behavioral risk factor for cutaneous melanoma. Despite these observations, the exact mechanisms by which UVR induces melanoma, among other skin malignancies, is not known. We employ both cellular and animal studies to unravel the downstream molecular events that lead to melanoma initiation.