The unifying theme of my research is to understand the genetic mechanisms involved in the development and progression of melanocytic skin tumors and harness our understanding to improve melanoma treatment. I am well positioned to accomplish this goal since I am an expert dermatopathologist and a scientist with expertise in cancer genetics and bioinformatics. My efforts have been focused on identifying oncogenic drivers in melanocytic tumors, with the goal to identify and move new knowledge from the laboratory directly to patient care. By combining the histopathologic classification with a better understanding of the biology of melanocytic tumors gained in the laboratory I seek to make a significant impact on patient care.

My work has contributed to our understanding of the initiating oncogenic events in melanocytic tumors. In 2013 I was the lead author of an article in the Journal of the National Cancer Institute definitively showing that BRAF mutations are both clonal and heterozygous in melanocytic nevi, thereby establishing that they are initiating events. Subsequently, I worked to identify an array of kinase gene fusions in Spitz tumors, with lead author publications in Nature Communications and the Journal of Pathology describing the discovery of MET and NTRK3 gene fusions as initiating events in Spitz tumors.

In a 2015 New England Journal of Medicine paper, I was a member of the team that identified multiple pathways of genetic progression in melanocytic tumors and showed that the diagnostically controversial entity "dysplastic nevus" has more oncogenic drivers than benign nevi and fewer than melanoma. This work demonstrated for the very first time that the step-wise progression model of cancer also applies to melanocytic tumors and forms the groundwork for future studies further delineating the diverse pathways of melanoma progression and potential targets for therapeutic intervention. In 2017 I was the lead author of an article in Nature Communications demonstrating that activating mutations of beta-catenin lead to progression of conventional nevus to deep penetrating nevus.

A particular area of interest is the genetics of acral and mucosal melanomas. These melanomas arise in sun-protected sites and typically do not harbor a large number of ultraviolet light induced mutations but instead have highly rearranged genomes with many amplifications and deletions. Our group has developed new methodologies for genomically profiling small archival tissue samples and used this technique to identify SPRED1 as a tumor suppressor in mucosal melanoma. In a publication in Science, we demonstrated that loss of SPRED1 cooperates with KIT mutation and that dual inhibition of KIT and MEK is synergistic against KIT mutant melanomas with SPRED1 loss. These findings are currently being translated to the clinic through an investigator-initated clinical trial in collaboration with UCSF melanoma oncology.