Project 1 aims to investigate the heterogeneity of melanoma cells and their role in metastatic dissemination during the early stages of melanomagenesis. Using genetically engineered mouse and patient-derived xenograft models, along with advanced techniques such as single-cell and spatial transcriptomics, barcoded lineage tracing, and functional genetic approaches, we seek to understand how transcriptionally heterogeneous melanoma cell states develop and whether and how these cells interconvert between phenotypically distinctive states. Our goal is to identify markers that can identify early-stage melanoma patients who are at high risk for metastatic dissemination. This will enable us to provide adjuvant therapy to patients who will benefit from adjuvant treatment while sparing those with minimal risk from the toxicity and high cost of treatment.