Melanoma is a highly metastatic tumor arising from melanocytes or nevi. It is the most lethal form of skin cancer and both the incidence and consequent mortality rates have increased globally in recent decades. Epithelial-to-mesenchymal transition (EMT) is the process in which epithelial cells lose their epithelial characteristics and become motile. Although melanocytes are not epithelial cells, EMT inducing transcription factors such as ZEB1 and ZEB2 play pivotal roles in the cellular plasticity of melanocytes and melanoma. We are particularly interested in ZEB switching, a process that drives ZEB2high ZEB1low differentiated proliferating melanoma cells to become ZEB2low ZEB1high dedifferentiated invasive melanoma cells. We aim at studying the transcriptional/epigenetic regulation of ZEB switching and unravel the molecular regulators that orchestrate this important transcription factor switch which results in the acquisition of high-grade malignancy in melanoma. This work will result in the identification of drug targets which allows inhibition of this malignant process during melanoma progression and could result in improvement of targeted therapy and immunotherapy by reducing melanoma dedifferentiation and therapy resistance.