My research is focused on identifying the genetic contributions and functional pathways associated with risk of developing melanoma and other cancers. While early-stage melanoma is largely curable via surgical resection, late-stage melanoma remains nearly incurable despite decades of research. Much of the effort in my laboratory is directed towards better understanding genetic factors contributing to melanoma risk, with a goal of ultimately facilitating prevention and early-detection efforts in at-risk individuals. Our group is utilizing a combination of linkage, positional cloning, candidate gene sequencing, and whole-genome and -exome sequencing methodologies to identify novel cancer risk variants in multiplex cancer families. As well as evaluating such variants as potential high-penetrance alleles, we are assessing them as potential medium-to-low penetrance rare cancer risk alleles in the general population. We are also participating in several ongoing genome-wide association studies (GWAS) and GWAS meta-analyses to identify novel common risk variants influencing risk in the population and undertaking functional studies to characterize the mechanism by which these variants mediate cancer risk. We are also participating in an ongoing large-scale RNAi drug sensitization screening effort with the aim of identifying molecularly-informed combination therapies to move into preclinical and clinical testing. We are actively validating and replicating a number of candidate sensitizing genes, evaluating therapeutic combinations selected based on these data in vitro, and functionally characterizing the mechanism by which inhibiting gene function sensitizes cancer cells. Finally, we are participating in cancer genome and exome sequencing studies to identify novel cancer oncogenes and tumor suppressors, performing functional studies characterizing the mechanism by which mutations of these genes contribute to tumorigenesis or progression.