)
Developing novel therapeutic treatment
Our research programme focuses on understanding the molecular pathogenesis of chronic degenerative diseases such as arthritis, with the goal of developing novel therapies to treat these conditions. We focus specifically on defining how the activity and availability of anabolic growth factors and metalloprotease inhibitors is regulated by their trafficking between pericellular heparan sulfate proteoglycans and the cell surface endocytic receptor LRP1.
)
)
Group Leader: Dr Linda Troeberg
View my research profileI lead a discovery research group focused on understanding molecular mechanisms that drive chronic diseases like chronic inflammation, age-related macular degeneration, and osteoarthritis. After a post-doctoral positions at the University of Cambridge and Imperial College London, I established my group at University of Oxford, before moving to UEA in 2019.
Please get in touch regarding PhD research opportunities
Heparan sulfate proteoglycans regulate cellular responses in health and disease
Heparan sulfate proteoglycans bind >500 proteins (including cytokines and growth factors), and regulate their localisation, stability, and signalling. We are interested in how dynamic changes in heparan sulfate structure alter cellular responses to external stimuli, both in health and in diseases like osteoarthritis, rheumatoid arthritis, and age-related macular degeneration.
e.g. We showed that specific heparan sulfate patterns promote type I interferon signalling in macrophages and exacerbate inflammatory arthritis.
)
Recycling of heparan sulfate ligands via the scavenger receptor LRP1
Many proteins that interact with heparan sulfate proteoglycans can be cleared from the extracellular environment by the scavenger receptor, LDL receptor-related protein 1 (LRP1). We are investigating molecular determinants that balance this equilibrium and how it becomes disrupted in chronic degenerative diseases.
e.g. Altered heparan sulfate structure in osteoarthritic cartilage correlates with loss of the protective metalloprotease inhibitor TIMP-3 via LRP1, accelerating joint damage.
)
Highlighted Publications
The extracellular heparan sulfatase SULF2 limits myeloid IFNβ signaling and Th17 responses in inflammatory arthritis
View a copy of the publicationSwart M, Redpath AN, Ogbechi J, Cardenas R, Topping L, Compeer EB, Goddard M, Chanalaris A, Williams R, Brewer DS, Smart N, Monaco C, Troeberg L. (2024). Cell Mol Life Sci. 81(1):350.
Mechanisms of TIMP-3 accumulation and pathogenesis in Sorsby fundus dystrophy
View a copy of the publicationBetts JHJ, Troeberg L. (2024). 30:74-91.
Suramin analogues protect cartilage against osteoarthritic breakdown by increasing levels of tissue inhibitor of metalloproteinases 3 (TIMP-3) in the tissue
View a copy of the publicationGreen, J., Tinson, R. A. J., Betts, J. H. J., Piras, M., Pelut, A., Steverding, D., Wren, S., Searcey, M. & Troeberg, L., 2023, In: Bioorganic & Medicinal Chemistry. 92, 14 p., 117424.
Interleukin 13 (IL-13)-regulated expression of the chondroprotective metalloproteinase ADAM15 is reduced in aging cartilage
View a copy of the publicationYang, C. Y., Chanalaris, A., Bonelli, S., McClurg, O., Hiles, G. L., Cates, A. L., Zarebska, J. M., Vincent, T. L., Day, M. L., Müller, S. A., Lichtenthaler, S. F., Nagase, H., Scilabra, S. D. & Troeberg, L., 2020, In: Osteoarthritis and Cartilage Open. 2, 4, 100128.
Heparan sulfate proteoglycan synthesis is dysregulated in human osteoarthritic cartilage
View a copy of the publicationChanalaris, A., Clarke, H., Guimond, S. E., Vincent, T. L., Turnbull, J. E. & Troeberg, L., 2019, In: American Journal of Pathology. 189, 3, p. 632-647 16 p.