Arthritis Research Group

Research Overview

Under the campus partnership, our research is embedded in MCRI.  Full research profile may be found at https://www.mcri.edu.au/research/themes/cell-biology/arthritis-rheumatology.

The goal of the Arthritis Research Group  is to understand the complex interactions between cartilage cells and their matrix in both healthy cartilage and arthritic diseases. The Group focuses on the structure and function of the major cartilage molecules and the enzymes that destroy them in arthritic disease.

Some studies are done in explant and cell culture systems, or with highly-purified enzymes and substrates in vitro. Other studies use unique, genetically-modified mice deficient in specific cartilage molecules. Studies with these mice can provide valuable insights into the mechanisms of joint destruction in arthritis, with the potential to identify new target molecules and/or activities, for the development of disease-modifying arthritis therapies.

Projects :

  • Mice resistant to collagen II degradation have a unique skeletal phenotype
  • The role of an aggrecan 32mer fragment in osteoarthritis
  • An ultrasensitive assay to detect cartilage degradation products in patient fluids
  • Identifying novel cartilage proteins with new functions

Staff

  • Ms Suzanne Golub, Research Assistant
  • Ms Karena Last, Research Assistant
  • Ms Jia-Xi Han, Research Assistant
  • Ms Lynette Ong, PhD Student
  • Dr Heather Stanton, Research Officer/Administrator

Collaborators

  • Professor Hideaki Nagase, Kazuhiro Yamamoto & Dr Linda Troeberg, Kennedy Institute of Rheumatology, Oxford, UK
  • Dr Anne-Marie Malfait & Dr Rachel Miller, Rush University, Chicago, USA
  • Prof Alan Grodzinsky, Massachusetts Institute of Technology, Boston, USA
  • Prof Virginia Kraus, Duke University, USA
  • Prof Anders Aspberg, University of Copenhagen, Denmark
  • Prof Frank Beier, University of Western Ontario, Canada
  • Dr Paul Holden, Oregon Health & Science University, Oregon, USA
  • Prof Danny Chan, University of Hong Kong, China
  • A/Prof Philip Sutton, MCRI
  • Prof John Bateman, MCRI
  • A/Prof Shireen Lamande, MCRI
  • Dr Marc Seal, Royal Children’s Hospital
  • Prof David Jackson, University of Melbourne
  • Prof Eleanor Mackie, University of Melbourne
  • A/Prof Natalie Sims, St Vincent’s Institute, Melbourne
  • Prof Chris Little, University of Sydney, NSW

Funding

  • USA Department of Defense
  • National Health & Medical Research Council  
  • Australian Research Council

Research Opportunities

This research project is available to PhD, Masters, Honours students to join as part of their thesis.
Please contact the Research Group Leader to discuss your options.

Research Publications

  • Kosasih, HJ., Last, K., Rogerson, FM., Golub, SB., Gauci, SJ., Russo, VC., Stanton, H., Wilson, R., Lamande, S., Holden, P., Fosang, AJ. (2016) A disintegrin and metalloproteinase with thrombospondin motifs-5 (ADAMTS-5) forms catalytically active oligomers. J. Biol. Chem. 291, 3197-3208
  • Ismail HM, Miotla-Zarebska J, Troeberg L, Tang X, Stott B, Yamamoto K, Nagase H, Fosang AJ, Vincent TL. & Saklatvala J. (2016) JNK2 controls aggrecan degradation in murine articular cartilage and the development of experimental osteoarthritis. Arthritis Rheumatol. 68, 1165-1171
  • Lees, S. Golub, SB., Last, K., Zeng, W., Jackson, DJ. &, Sutton, P. & Fosang, AJ. (2015) Bioactivity in an aggrecan 32-mer fragment is mediated via Toll-like receptor 2 Arthritis  Rheumatol. 67, 1240-1249
  • Fosang, AJ. & Colbran, RJ. (2015) Transparency is the key to quality. J. Biol. Chem. 290: 29692-29694
  • Fosang AJ., Golub, SB., East CJ., Rogerson, FM. (2013) Abundant LacZ activity in the absence of Cre expression in the normal and inflamed synovium of adult Col2a1-Cre; ROSA26R(LacZ) reporter mice. Osteoarthritis Cart 21, 401-404
  • Struglics, A., Lohmander, S., Last K., Akikusa J., Allen R. & Fosang, AJ. (2012) Aggrecanase cleavage in juvenile idiopathic arthritis patients is minimally detected in the aggrecan interglobular domain but robust at the aggrecan C-terminus. Arthritis Rheum 64, 4151-4161
  • Bastow ER., Last K., Golub, S., Stow J., Stanley A. & Fosang AJ. (2012) Evidence for lysosomal exocytosis and release of aggrecan-degrading hydrolases from hypertrophic chondrocytes, in vitro and in vivo. Biology Open 1, 318-328
    Fosang AJ. & Beier F (2011) Emerging frontiers in cartilage and chondrocyte biology. Best Practice & Research Clinical Rheumatology 25, 751-766
  • Stanton, H., Golub, SB., Rogerson, FM., Last, K., Little, CB., Fosang, AJ. (2011) Investigating ADAMTS-mediated aggrecanolysis in mouse cartilage. Nature Protocols 6, 388-404
  • Stanton, H., Rogerson, FM., East, CJ., Golub, SB., Lawlor, KE., Meeker, CT, Little, CB., Last, K., Farmer, PJ., Campbell, IK., Fourie, AM., & Fosang, AJ. (2005) ADAMTS-5 is the major aggrecanase in mouse cartilage, in vivo and in vitro. Nature 434, 648-652