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Proteolysis is an irreversible post-translational modification that is involved in almost every aspect of cellular fate and behavior. In addition, extracellular proteases provide cellular control of the extracellular environment. This prominent biological relevance of this enzyme class is reflected by its high representation (~ 2 % of genes, coding for at least 560 proteases and 160 endogenous protease inhibitors) in the human genome.
In normal tissue homeostasis, the interacting network of proteases and their natural inhibitors maintain a proteolytic balance. During any pathological tissue remodelling process, this balance is disturbed affecting proteases of (at least) three major families, metalloproteases (MMPs, ADAM and ADAM-TS), serine proteases, and cysteine proteases (cathepsins). In tissue remodelling proteases may degrade or fail to degrade extracellular matrix proteins. However, proteases are also essential for immune cell function in inflammation. For instance, the cathepsins are involved in tumor- and lung metastasis-associated stromal activation and inflammation.
In this lab we aim to understand protease regulation and function in physiological processes but also in a variety of diseases. In this regard protease-driven carcinoma progression and metastasis are in the focus of our research. To this end we develop models for selective inhibition of protease activities thereby interfering with disease progression.
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