LIONEL LARUE

The laboratory focuses on discovering the major players in molecular melanoma and establishing genetically rational, immunologically coherent, and relevant in vivo and in vitro melanoma models suitable for use in a pharmaceutical preclinical pipeline. The incidence of cutaneous melanoma is increasing regularly in France and western countries. The rate of mortality remains high despite the availability of innovative therapies on the market. The failure of these new therapies is due in part to insufficient basic knowledge, inappropriate cell systems, and in vivo melanoma models. Malignant melanoma is an aggressive human tumor and both genetics and epigenetics events contribute to regulating its initiation and progression. The laboratory aims to improve understanding, in an integrative manner, of the molecular and cellular mechanisms associated with the normal and pathological development of melanocytes and melanoma. Consequently, we generate crucial information for the understanding of the establishment of melanocytes from melanoblasts during development and the renewal of melanocytes from melanocyte stem cells. This last event is, of course, important during aging. We decipher, in vitro and in vivo, various signaling pathways, including MAPK, PI3K, and WNT. In particular, we study proteins engaged in melanoma initiation: BRAF/NRAS, involved in proliferation, and CDKN2A/PTEN/CTNNB1 involved in immortalization. Generating appropriate models and approaches are essential for advances in understanding melanoma initiation and progression. We are also developing a coherent preclinical in vitro and in vivo pipeline using human and mouse cell lines (2D and 3D) and associated murine models to allow the prioritization of new therapies.