Dominant-Negative Fas Mutation Is Reversed by Down-expression of c-FLIP

My PhD research was conducted under the supervision of Jean‑Luc Taupin in Bordeaux, France, where I investigated the role of the CD95/CD95L system in immune homeostasis. CD95, also known as Fas, is a death receptor belonging to the tumor necrosis factor (TNF) receptor superfamily. Upon binding to its ligand, CD95L (FasL), CD95 activates an apoptotic signaling pathway that contributes to immune surveillance and the maintenance of immune tolerance. I subsequently joined the laboratory of Marcus Peter at the University of Chicago (2002–2005, USA). During this period, we demonstrated that stimulation of CD95 in cancer cells resistant to CD95-mediated apoptosis promotes carcinogenesis through the activation of non-apoptotic signaling pathways. In 2006, I was appointed Assistant Professor at INSERM, the French National Institute of Health and Medical Research. In Bordeaux, I established my own research group and showed that certain anti-tumor agents induce the rapid redistribution of CD95 into lipid rafts, thereby facilitating apoptotic signaling and promoting the elimination of malignant cells. In 2010, I moved to the University of Rennes (France), where I was appointed Director of Research at INSERM (Full Professor level). There, I founded and led an INSERM research unit at the Centre Eugène Marquis, focusing on death receptors, inflammation, and tumor adaptation. Our work has shown that CD95L, a member of the TNF superfamily, exists both as a membrane-bound cytokine (m-CD95L) and as a soluble form (s-CD95L) generated by metalloprotease-mediated shedding. We demonstrated that s-CD95L levels are elevated in patients with Systemic lupus erythematosus and Triple-negative breast cancer, and that it contributes to disease severity by promoting Th17 cell trafficking to inflamed tissues and enhancing metastatic dissemination of tumor cells. In addition, my team identified a novel molecular complex induced by s-CD95L, termed the Motility-Inducing Signalling Complex (MISC), which activates a non-apoptotic c-Yes/Orai1/Ca²⁺/PI3K signaling pathway. Current research in my laboratory focuses on elucidating the role of CD95 in the progression of chronic inflammatory diseases and breast cancer. In collaboration with chemists and computational modelers, we have developed innovative peptidomimetics that selectively inhibit the pro-inflammatory signaling of CD95 without affecting its apoptotic function. These compounds have demonstrated therapeutic potential by alleviating clinical symptoms in lupus-prone mouse models.