Inflammation plays a major role in onset and progression of many inflammation-associated diseases diseases, including colon cancer, inflammatory bowel disease and rheumatoid arthritis. Several proteases are crucial for the onset and propagation of the pathology. Among these are cysteine cathepsins and caspases that are often found at the sites of inflammation. There is increasing evidence that inflammation is tightly linked with cell death processes such as necroptosis. Although the involvement of these proteases in the disease is well documented, little is known about the molecular mechanisms of protease involvement in disease progression. Understanding the protease signaling pathways in pathogenesis may have a major impact on diagnosis and therapy of inflammation-associated diseases, including cancer, inflammatory bowel disease and rheumatoid arthritis. This project aims at detecting cathepsins and caspases in inflammatory disease models and cancer, and identifying and validating a limited set of promising substrates. We focus on cathepsins, as major proteases in inflammation and necrotic cell death, and caspase-7 and its substrates, as a possible anti-inflammatory mechanisms associated with apoptotic cell death and in activated macrophages. Finally, we will explore the role of cathepsins in a model of immunogenic cell death, a type of cell death that increases the immunogenicity of cancer cells. The overall objective of the project is thus to unravel protease signaling pathways in models of inflammation-associated diseases that would lead to a better understanding of underlaying mechanisms, with diagnostic, prognostic and therapeutic potential.