The Bar-Eli Laboratory focuses on studying the molecular events associated with the acquisition of the melanoma malignant phenotype.We demonstrated that the progression of human melanoma isassociated withnuclearlossof AP-2α transcription factor which serves as an excellent survival marker. AP-2α loss deregulates genes such as c-kit, the adhesion molecule MCAM/MUC18 and the thrombin receptor, PAR-1. In turn, PAR-1 contributes to melanoma metastasis by regulating connexin-43, the tumor suppressor gene, maspin and the angiogenic factor, IL-8.We have generated two fully human antibodies to IL-8 and MCAM/MUC18 and demonstrated their efficacy in inhibiting melanoma growth and metastasis in vivo. Our lab is utilizing nano-particles encapsulated with siRNA for PAR-1 and IL-8 to inhibit angiogenesis and metastasis in vivo. We also demonstrated overexpression and activity of CREB in metastatic melanoma cells.CREB regulates CYR-61 and ADAR1 (involved in RNA editing), thus, contributing to melanoma metastasis. We have recently reported that metastaticmelanoma cell lines and tumor specimens do not express the ADAR1 enzyme. ADAR1 is involved in A-to-I RNA editing of mRNAs and miRs (Nemlich et. al., J. Clin. Invest., 2013). In our recent observations published in Nat. Cell Biology (2015) , we identified3 miRs undergoing A-to-I editing in the non-metastatic melanoma cells, but not in the metastatic cells that do not express ADAR1. (Nat. Comm., 2018) The functions of the edited miRs are different from the WT forms as they recognize and regulate differentset of genes. The proposed studies are aimed to fulfill this gap in our understanding of how certain miRNAs undergoing A-to-I editing contribute to melanoma growth and metastasis.