Proteolytic processing in health and disease
Proteolysis fulfills essential functions in biological signal transduction and maintenance of proteostasis. Not surprisingly, deregulated proteolysis is a major cause and driver of disease and proteases are popular drug targets. However, incomplete knowledge on their physiological substrates in different tissues and organs often leads to undesired side effects. We apply our degradomics approaches in collaborative work to contribute to a better, systems-level understanding of physiological and pathological functions of proteases and proteolytic processing.
Proteolysis in renal signaling and disease
Our first N-terminome study of glomeruli revealed the existence of many proteolytically modified proteoforms. Treatment with puromycin aminonucleosid (PAN), a nephrotoxic agent that induces podocyte damage, activated caspases and induced altered processing of cytoskeletal proteins both in human podocyte cultures and in rats in vivo. We are now extending this work to investigate altered proteolytic processing in other renal disease models.
Collaboration with Dr. Markus Rinschen and Prof. Thomas Benzing (Nephrolab Cologne, CECAD, CMMC, University of Cologne)