Melanoma chromatin dynamics

Cutaneous melanoma is a highly aggressive skin cancer and one of the most challenging cancers in its therapeutic management. Emerging studies clearly demonstrate that cancer is a result of the concerted action of genetic and epigenetic alterations. Surprisingly, our understanding of the ‘epigenetic landscape’ of melanoma remains poorly understood. Our recent work has shed light on the underlying mechanisms of chromatin dynamics in cancer. We have identified a critical role for histone variants of the H2A family in melanoma progression. We identified that the histone variant macroH2A acts as a barrier to melanoma growth and metastasis by suppressing key oncogenic factors, i.e. CDK8. We have also identified a key role for the histone variant H2A.Z.2 in promoting melanoma cell proliferation and sensitivity to targeted therapies. Our current efforts include studies to i) further understand the role of histone variants in melanoma pathogenesis, ii) generate insight into the epigenetic landscape of malignant melanoma through ChIP-seq and genomic approaches, iii) perform loss-of-function screens targeting chromatin factors in order to identify key players in melanoma pathogenesis and acquired drug resistance to targeted therapies.