Dissecting lysine methylation signaling in melanoma pathobiology

Melanoma is the most lethal fonn of skin cancer with rising incidence and once it spreads through the body (metastatic melanoma), it is challenging to treat with standard cancer therapies. Recent advances in targeted or immune therapies have raised hope for a ‘melanoma cure’, however they are only effective in small subsets of patients, cause toxicity to the body, and/or have been plagued resistance to the dmg where the tumor no longer responds to the drug. Therefore, new approaches are urgently needed. This research proposal focuses on the protein lysine methyltransferase SETD6. During the last few years we have identified and characterized the cellular and physiological functions of SETD6. We have obtained strong preliminary data suggesting that SETD6 is involved in driving melanoma. Therefore, in the current research proposal, we aim to test the specific hypothesis that SETD6 plays an important role in melanoma biology. Cancer treatment is currently shifting toward more personalized approaches whose successful application requires knowledge of the global differences in patterns of specific markers of cancer. Accordingly, there is a critical need for technologies capable of proteome-wide analyses to identify such biomarkers. In the proposed research, we will also employ such cutting-edge experimental approaches to identify novel biomarkers and therapeutic targets for melanoma. The proposed research by this collaborative team will have broad implications for basic science and translational research for melanoma, and beyond.