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Professor Amanda Fosang
Professor Amanda Fosang has an established career researching cartilage biology in health and disease. After completing her postdoctoral studies at the Kennedy Institute of Rheumatology in London, she returned to Australia and was awarded an RD Wright Fellowship by the NHMRC in 1994. Since then she has received continuous competitive grant and fellowship funding from the NHMRC. She joined the University of Melbourne, Department of Paediatrics in 1994 and became a group leader of Murdoch Childrens Research Institute at its inception in 2000.
Professor Fosang has generated unique genetically-modified mice for evaluating cartilage damage in arthritic disease. Her work showing that the ADAMTS-5 protein is the major proteinase in mouse cartilage was published in Nature in 2005. She joined the Board of Directors for the Osteoarthritis Research Society International (OARSI) in 2012 and is the first Australian appointed as an Associate Editor to the Journal of Biological Chemistry. She has supervised numerous students to course completion.
- University of Melbourne Department of Paediatrics
- Associate Editor, Journal of Biological Chemistry
- NHMRC Principal Research Fellow 2010
- Basic Science Award, Osteoarthritis Research Society International, 2009
- Selwyn-Smith Medical Research Prize, University of Melbourne, 2007
- Barry Preston Award, Matrix Biology Society of Australia & New Zealand, 2007
- Discovery Award for Excellence in Research Achievement, Murdoch Childrens Research Institute, 2006
- NHMRC Principal Research Fellow, 2006
Professor Fosang's goal is to understand the complex interactions between cartilage cells and their matrix in both healthy cartilage and arthritic diseases. Her work focuses on the structure and function of the key cartilage structural molecules and the enzymes that destroy them in arthritis.
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. These studies 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.
- Skeletal development and arthritis severity in mice resistant to collagen destruction
- Signalling through a bioactive fragment of aggrecan
- An ultrasensitive assay to detect cartilage degradation products in patient fluids
- Identifying novel cartilage proteins with new functions
- Assessing the efficacy of monoclonal neo-epitope antibodies as therapeutics for cartilage damage
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
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
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