Professor Amanda Fosang
Professor Amanda Fosang is a National Health and Medical Research Council (NHMRC) Principal Research Fellow with 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 molecule 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 was appointed Chair of the OARSI Asian Task Force in 2013. She was the first Australian appointed to the Journal of Biological Chemistry as an Associate Editor. Professor Fosang coordinates the BSc and BBMed Honours Program for the University of Melbourne Department of Paediatrics and Murdoch Childrens. She has supervised five PhD students and 11 BSc Honours students to course completion.
- NHMRC Principal Research Fellow, University of Melbourne
- Department of Paediatrics BSc BBMed Honours course coordinator
- Associate Editor, Journal of Biological Chemistry
- NHMRC Principal Research Fellow, 2006, 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
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 cartilage molecules, aggrecan and type II collagen, and the enzymes that destroy them in arthritic disease.
Recently her group has been studying the degradation products generated by these enzymes, and how these products might regulate cellular function. 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 engineered to resist cartilage destruction.
Studies with these mice can provide valuable insights into the mechanisms of joint destruction in arthritis. Her studies on cartilage biology and arthritic diseases will identify new target molecules and/or activities, for the development of disease-modifying arthritis therapies.
- How aggrecanases contribute to cartilage destruction
- Mice resistant to collagen destruction teach us about skeletal development
- Signalling through a bioactive fragment of aggrecan
- An ultrasensitive assay to detect aggrecan degradation products in patient fluids
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
Magarinos, N., Bryant, K., Fosang, AJ., Adachi, R., Stevens, R., McNeil. HP. (2013) MMP zymogens are targets of mast cell tryptase. J. Immunol .191, 1404-1412
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., Melrose, J., Little, CB. & Fosang AJ. (2011) Proteoglycan degradation by the ADAMTS family of proteinases. Biochim. Biophys. Acta 1812, 1616-1629
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
Rogerson, FM., Chung, YM., Deutscher, ME., Last, K. & Fosang AJ. (2010) Cytokine-induced increases in ADAMTS-4 mRNA expression do not lead to increased aggrecanase activity in ADAMTS-5-deficient mice. Arthritis Rheum. 62, 3365-3373
Fosang, AJ., Last, K., Poon, CJ., & Plaas, AH. (2009) Keratan sulphate in the interglobular domain has a microstructure that is distinct from keratan sulphate elsewhere on pig aggrecan. Matrix Biol. 28, 53-61