Proteolysis 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 other renal disease models, including a mouse model of cisplatin-induced acute kidney injury.
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Recent publications from our collaboration with Nephrolab Cologne :
The proteome microenvironment determines the protective effect of preconditioning in cisplatin-induced acute kidney injury. Kidney Int, 95:333-49.
The Podocyte Protease Web: Uncovering the Gatekeepers of Glomerular Disease. Am J Physiol Renal Physiol, 315:F1812-16
N-Degradomic analysis reveals a proteolytic network processing the podocyte cytoskeleton. J Am Soc Nephrol, 28: 2867-2878.
The proteome microenvironment determines the protective effect of preconditioning in cisplatin-induced acute kidney injury. Kidney Int, 95:333-49.
The Podocyte Protease Web: Uncovering the Gatekeepers of Glomerular Disease. Am J Physiol Renal Physiol, 315:F1812-16
N-Degradomic analysis reveals a proteolytic network processing the podocyte cytoskeleton. J Am Soc Nephrol, 28: 2867-2878.
Proteolysis in cells exposed to mechanical stressAlmost every cell in our body is exposed to mechanical stress. In close collaboration with ICS-7 we are investigating the fate of mechanosensitive proteins. Together with other participants in the DFG-funded collaborative research unit 2743 "Mechanical Stress Protection" we aim to better understand the molecular mechanisms that maintain proteostasis in cells exposed to mechanical stress.
Check the webpage of FOR2743 for more detailed information. |
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