Dr Linda Troeberg
Regulating pericellular proteolysis in osteoarthritis and chronic inflammation
"My primary research interest is how tissue homeostasis is regulated by the crosstalk between cells and their immediate pericellular environment, and how this regulatory unit is disturbed in pathological conditions such as osteoarthritis and chronic inflammation. In particular, my research focuses on defining how tissue-remodelling metalloproteinases and their endogenous inhibitors are regulated by trafficking between pericellular heparan sulfate proteoglycans and receptor-mediated endocytosis."
Targeting excess metalloprotease activity in osteoarthritis
"Osteoarthritis is characterised by an increase in the activity of metalloproteases that degrade cartilage extracellular matrix components, and so impair the structural integrity of the tissue. This increase in metalloprotease activity is caused both by an increase in expression of the metalloproteinases and by a decreased level of their endogenous inhibitor, tissue inhibitors of metalloproteinases 3 (TIMP-3). Our group established that levels of TIMP-3 in cartilage are regulated by the equilibrium between its binding to heparan sulfate (HS) glycans in the extracellular matrix and its cellular endocytosis by the scavenger receptor, LDL receptor-related protein 1 (LRP1). Current projects focus on defining how HS sulfation patterns change in OA, and designing small molecule inhibitors to target TIMP-3 loss as a therapy for osteoarthritis."
Targeting metalloprotease-dependent TNF release in macrophages.
"We discovered that the HS/LRP pathway regulates TIMP-3 in macrophages, where TIMP-3 is the primary inhibitor of TNF release by the metalloproteinase ADAM17. We are currently investigating how this pathway regulates the acute inflammatory response, and whether it is disrupted in chronic inflammatory conditions."
Dr Linda Troeberg and Dr Stephen Wren have been awarded funding by St Hilda's College Research Committee to support cross-disciplinary research between their groups at the Target Discovery Institute and the Kennedy Institute of Rheumatology respectively. This will take the form of a laboratory-based study to investigate potential novel agents to treat osteoarthritis. Lucy Britton, a second year St Hilda’s Biochemistry student, was selected for the internship, and joined their groups for eight weeks in the summer of 2017.