Summer Research Description: Metastatic melanoma is considered incurable, killing nearly 10,000 people per year. Nearly 40% of metastatic melanomas express mutant BRAF (V600E), and are thus initially responsive to the targeted BRAF inhibitor vemurafinib. However, BRAF-mutant melanomas rapidly acquire vemurafinib resistance, demonstrating the need for more effective therapies to induce melanoma cell killing. Up to 50% of BRAF-mutant melanomas overexpress MerTK, a receptor tyrosine kinase that increases cell survival signaling through multiple signaling pathways, including Rac1, JAK-STAT, NF-kB, and PI3K-Akt pathways. Our preliminary studies show that MerTK inhibition in combination with vemurafinib improved vemurafinib-mediated growth inhibition in BRAF-mutant melanomas by increasing the number of dying tumor cells. However, the signaling pathways affected in BRAF-mutant melanomas remains unknown. The overall goal of our future studies is to examine the signaling pathways that are operable in MerTK-expressing, BRAF-mutant melanomas, to determine how these pathways are affected by MerTK inhibition, and how blockade of these pathways results in cell death.