iRhom2a new therapeutic target in osteoarthritis

Project title: iRhom2a new therapeutic target in osteoarthritis

Start/end date: January 2021 – March 2023

Funding Agency/Programme: Fondazione con il Sud – Bando Capitale Umano ad Alta Qualificazione 2018

Partnership: Fondazione Ri.MED (Coordinator); Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione S.r.l. – IRCCS ISMETT.

Abstract: Osteoarthritis (OA) is a disabilitating disease with no cure available. iRhom2 is an essential regulator of ADAM17, a protease playing a crucial role in the progression of the disease. Based on solid preliminary data, we hypothesized that inactivation of iRhom2 could be beneficial in OA and represents a new therapeutical target for the disease. Proving this hypothesis using in vivo models and developing a molecule for the therapeutical inactivation of iRhom2 is the central aim of the project.

• Quantitative Proteomics Reveals Changes Induced by TIMP-3 on Cell Membrane Composition and Novel Metalloprotease Substrates
• Strategies to Target ADAM17 in Disease: From Its Discovery to the IRhom Revolution
• A Top-down Approach to Uncover the Hidden Ligandome of Low-Density Lipoprotein Receptor-Related Protein 1 in Cartilage
• The Repertoire of Tissue Inhibitors of Metalloproteases: Evolution, Regulation of Extracellular Matrix Proteolysis, Engineering and Therapeutic Challenges
• High-Resolution Secretome Analysis of Chemical Hypoxia Treated Cells Identifies Putative Biomarkers of Chondrosarcoma
• Quantitative Proteomics Reveals That ADAM15 Can Have Proteolytic-Independent Functions in the Steady State
• Tissue Inhibitor of Metalloproteases 3 (TIMP-3): In Vivo Analysis Underpins Its Role as a Master Regulator of Ectodomain Shedding