Dr. Capparelli’s research focuses on resistance to MAPK targeting agents and Immunotherapy in cutaneous melanoma. The incidence rate of melanoma is rising despite recent therapeutic advances. Intra-tumoral heterogeneity and cellular plasticity allow tumors to adapt to foreign microenvironments and tolerate therapeutic insults. It is critical to characterize the mechanisms that underlie plasticity of melanoma in order to overcome the onset of metastasis and drug tolerance following treatments. Since 2012, we have demonstrated that fibroblast-derived NRG1 promotes resistance to MAPK inhibitor therapy, and targeting adaptive ErbB3/ErbB2 signaling with neutralizing antibodies to either ErbB2 or ErbB3 enhances the effects of MAPK targeting agents in melanoma in vitro and in vivo. Our studies have formed the basis for a clinical trial, NCT03580382, designed to evaluate CDX-3379, a human monoclonal antibody targeting ErbB3, in combination with the MEK inhibitor, trametinib, in patients with advanced stage NRAS mutant and BRAF/NRAS wild-type (WT) melanoma. Our current research focuses on the role of SOX10 in cutaneous melanoma with regard to tumor cell heterogeneity and plasticity across genotypes. We aim to determine mechanisms underlying tolerant states and identify vulnerabilities that will eliminate this population of cells to likely prevent or delay resistance.