Tumor necrosis factor (TNF) is a master pro-inflammatory cytokine whose pathogenic role in
inflammatory disorders has long been attributed to the induction of pro-inflammatory mediators.
Very recent in vivo studies demonstrated that TNF also causes inflammation by inducing RIPK1
kinase-dependent cell death. Consequently, RIPK1 is emerging as an attractive therapeutic target
in the treatment of TNF-driven inflammatory pathologies. RIPK1 has a dual role in the TNFR1
pathway. It functions as a platform for gene activation and as a kinase for cell death induction, but
our understanding of RIPK1 activity and regulation is still very limited. This PhD project aims at
revealing and characterizing, using biochemical, cellular and in vivo approaches, the crucial role of
phosphorylation in the regulation of RIPK1-mediated functions. The project also includes the
development of phospho-specific RIPK1 antibodies and of a transgenic phospho-mimetic RIPK1
mouse line, which can all serve as diagnostic/predictive tools for the potential beneficial use of
RIPK1 inhibitors in specific inflammatory conditions.