Mehdi KhaledLaboratoire d'immunologie intégrative des tumeurs et génétique oncologique - Gustave Roussy / Inserm
Mes recherches
After completing my PhD in 2005, on the mechanisms driving melanocyte differentiation, I decided to broaden my interest and joined the laboratory of David Fisher in Boston. There, I developed in parallel projects aiming at inducing melanocytes differentiation with small molecules and projects on the molecular regulation of melanoma invasion. My postdoctoral work helped to reveal that melanoma metastasis is induced by loss of MITF, the master gene of melanocyte’s differentiation. Based on those observations and with the support of an ATIP-Avenir grant, I setup my own research group at Gustave Roussy in 2013. My main interest is to understand how melanomas are taking profit of their lineage-specific transcriptional program to metastasize.
Mon projet ATIP-Avenir
Since its creation, our laboratory aims to gain fundamental knowledge on the molecular mechanisms driving normal and pathological function of the melanocytic lineage. Interestingly, melanocyte function and melanoma tumor progression rely both on the expression of the transcription factor MITF. This gene, mutated in a subset of melanoma, has been shown to play a pivotal role in melanomagenesis by stimulating cell proliferation when its expression is high, and to promote metastasis when its expression is low. Since interfering with MITF expression level in any direction will contribute to melanoma progression, it cannot serve as therapeutic targets. Therefore, to better understand melanoma etiology, it is crucial to precisely know its regulation and what are its downstream target in in order to identify vulnerability that could be targeted by treatment aiming at preventing cancer spreading.
The originality of our approach was to study in parallel normal and pathological MITF network, in order to comprehensively evaluate the consequence of such regulation