Projects per year
Personal profile
Academic Background
Our research programme focuses on understanding the molecular pathogenesis of chronic degenerative diseases such as osteoarthritis, 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.
(i) Defining molecular pathways that drive cartilage loss 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 is caused by increased expression of these metalloproteases and decreased levels of their endogenous inhibitor, tissue inhibitor 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) proteoglycans 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 tissue repair in OA, and designing small molecule inhibitors to target TIMP-3 loss as a therapy for osteoarthritis.
(ii) LRP1/HS axis also regulates macrophage behaviour. We found that LRP1 also dynamically regulates TIMP-3 levels in macrophages, where TIMP-3 is the primary inhibitor of TNF release by the metalloproteinase ADAM17. This enables LRP1 to control termination of TNF release during the inflammatory response. As in chondrocytes, macrophage HS protects TIMP-3 and other ligands from uptake by LRP1. We are examining changes in expression of HS biosynthesis enzymes and core proteins upon macrophage phenotype and activation, and looking at how this alters retention and biological activity of HS-binding cytokines, chemokines and growth factors during inflammation.
(iii) LRP1/HS in age-related macular degeneration (AMD). The LRP1/HS axis also regulates extracellular matrix turnover in the retina. Mutations in TIMP-3 cause Sorsby Fundus Dystrophy (SFD), a rare inherited form of macular degeneration that can serve as a model for the more common age-related macular degeneration (AMD). To better understand the molecular pathogenesis of AMD, we are investigating how retinal levels of wild-type and SFD mutants of TIMP-3 are regulated by LRP1 and HS.
External positions
University Research Lecturer, University of Oxford
2012 → 2018
Career Development Fellow - Versus Arthritis, University of Oxford
2011 → 2016
Post-doctoral researcher, Imperial College London
Network
-
Investigation of tissue inhibitors of metalloproteinases (TIMPs) from marine organisms
11/03/22 → 10/03/24
Project: Research
-
Does aberrant extracellular trafficking cause both age-related and genetic forms of macular degeneration?
1/10/21 → 30/09/24
Project: Training
-
Treatment of osteoarthritis by inhibition of aggrecanases using targeted delivery of engineered TIMP-3
1/01/21 → 31/12/23
Project: Research
-
Targeting heparan 6-O-sulfation to promote repair of oesteoarthritic cartilage
1/10/19 → 31/12/23
Project: Research
-
-
ADAM17 mediates proteolytic maturation of voltage-gated calcium channel auxiliary α2δ subunits, and enables calcium current enhancement
Kadurin, I., Dahimene, S., Page, K. M., Ellaway, J. I. J., Chaggar, K., Troeberg, L., Nagase, H. & Dolphin, A. C., 17 Mar 2022, In: Function. 3, 3, zqac013.Research output: Contribution to journal › Article › peer-review
Open AccessFile1 Citation (Scopus)4 Downloads (Pure) -
Osteoarthritis pathophysiology: Therapeutic target discovery may require a multifaceted approach
Vincent, T. L., Alliston, T., Kapoor, M., Loeser, R. F., Troeberg, L. & Little, C. B., May 2022, In: Clinics in Geriatric Medicine. 38, 2, p. 193-219 27 p.Research output: Contribution to journal › Review article › peer-review
Open AccessFile3 Citations (Scopus) -
Quantitative proteomics reveals that ADAM15 can have proteolytic-independent functions in the steady state
Yang, C. Y., Bonelli, S., Calligaris, M., Carreca, A. P., Müller, S. A., Lichtenthaler, S. F., Troeberg, L. & Scilabra, S. D., Jun 2022, In: Membranes. 12, 6, 578.Research output: Contribution to journal › Article › peer-review
Open AccessFile1 Citation (Scopus)2 Downloads (Pure) -
Research priorities to reduce the impact of musculoskeletal disorders: A priority setting exercise with the child health and nutrition research initiative method
Paskins, Z., Farmer, C. E., Manning, F., Andersson, D. A., Barlow, T., Bishop, F. L., Brown, C. A., Clark, A., Clark, E. M., Dulake, D., Gulati, M., Le Maitre, C. L., Jones, R. K., Loughlin, J., Mason, D. J., McCarron, M., Millar, N. L., Pandit, H., Peat, G., Richardson, S. M. & 8 others, , Sep 2022, In: The Lancet Rheumatology. 4, 9, p. e635-e645 11 p.Research output: Contribution to journal › Review article › peer-review
Open AccessFile1 Citation (Scopus)3 Downloads (Pure) -
The Extracellular Matrix of Articular Cartilage Controls the Bioavailability of Pericellular Matrix-Bound Growth Factors to Drive Tissue Homeostasis and Repair
Vincent, T. L., McClurg, O. & Troeberg, L., 26 May 2022, In: International Journal of Molecular Sciences. 23, 11, 6003.Research output: Contribution to journal › Review article › peer-review
Open AccessFile1 Citation (Scopus)5 Downloads (Pure)
Prizes
-
Arthritis Research UK Career Development Fellowship
Troeberg, Linda (Recipient), 2011
Prize: Fellowship awarded competitively
-
St Hilda’s College Associate Research Fellowship
Troeberg, Linda (Recipient), 2016
Prize: Fellowship awarded competitively
Activities
-
Versus Arthritis Musculoskeletal Disorders Research Advisory Group (External organisation)
Linda Troeberg (Member)
2019 → 2024Activity: Membership › Network, Working Group or Professional Association
-
Advance HE (External organisation)
Linda Troeberg (Senior Fellow)
2019 → …Activity: Membership › Network, Working Group or Professional Association
-
Journal of Biological Chemistry (Journal)
Linda Troeberg (Peer reviewer)
2016Activity: Editorial work › Publication editorial role
-
Journal of Biological Chemistry (Journal)
Linda Troeberg (Editorial board member)
2016 → …Activity: Editorial work › Publication editorial role
-
British Society for Matrix Biology (External organisation)
Linda Troeberg (Member)
2014 → 2017Activity: Membership › Committee