Many antigenic peptides presented by MHC class I molecules are initially created through proteolysis by the proteasome as precursors. The trimming of these precursors to the final epitope is performed in the ER by ERAP-1 and ERAP-2. Genome wide Association Studies have linked ERAP1 and ERAP2 with predisposition to human diseases with autoimmune aetiology such as rheumatic diseases (most notably Ankylosing Spondylitis) and also with cancers and response to cancer immunotherapy. Also, the function of these proteases and their 3D-structure are well documented. While the short term goal of the proposal is the identification of promising leads, the long term goal is the generation of novel pharmacological approaches towards the treatment of ERAP-associated human diseases based on the modulation of antigen processing and adaptive immune response with applications in autoinflammatory diseases and in cancer immunotherapy.
former members :Ronan Gealageas - PostDoc; Paul Hermant -PhD student; Keguang Cheng - PostDoc; Omar Castillo - PostDoc
The project CAPSTONE has been granted by EU MSCA for 4 years (Jan 2021-Dec 2024).
The project “ERAPIMM” has been granted by ANR for 3 years (Nov 2020- Nov 2023). The below teams collaborate in a project aiming at discovering and developing of ERAP inhibitors as a new approach to treat autoimmune & auto-inflammatory diseases. In particular, the teams will specifically study applications in Type 1 diabetes, Behcet’s disease and Spondyloarthritis.
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