The research group ProTarg studies enzymes that cleave proteins. Such degradation is irreversible and these enzymes are therefore potential targets for drugs. Hence the name: "PROteases as pharmacological TARGets"!
The research group
Our main focus is proteolytic enzymes and in particular the cysteine proteases (including legumain, cathepsins and caspases). When these enzymes cleave other proteins (substrates) several things can happen. The cleavage of the protein may cause activation, mediators can be released or the protein can be degraded to peptides and amino acids. This is always irreversible reactions: Cells must synthesize new proteins to replace those which have been cleaved. It has been shown that proteolytic enzymes are involved in inflammatory reactions and diseases like cancer and atherosclerosis. Thus, the inhibition of these enzymes with drugs is considered to be an interesting strategy in treatment. Proteolytic enzymes are responsible for controlled cell death. To let cells die in a controlled manner is very important and if these mechanisms fail unrestricted growth can result and lead to cancer. Also, cells can die when they should continue to live. If this happens in the brain it may result in neurodegenerative diseases like Parkinson’s disease and Alzheimer’s disease. If we can understand the roles that proteases play in these diseases we hope to be able to establish a more rational treatment with drugs. This is what we aim to study in ProTarg (= «Proteolytic Enzymes as Drug Targets»)!
Some topics of interest in our projects:
- Is high expression of cysteine proteases connected to the development of cancer and atherosclerosis?
- How is the interplay between proteases and endogenous inhibitors (cystatins) in normal cells and cancer cells?
- Is legumain (or cystatin E/M) of prognostic value in cancer or atherosclerosis?
- Which are the substrates for the cysteine protease legumain? – and what are the cellular consequences of legumain activity?
- Is legumain involved in controlled cell death by apoptosis?
- Can legumain serve as a pharmacological target to stop the progression of cancer?
We have collaborations with other research groups at the School of Pharmacy, Oslo University Hospital and international institutions.