research

A/Professor Amanda Fosang

contact details

Amanda Fosang  A/Professor Amanda Fosang
  Arthritis & Rheumatology
  Murdoch Childrens Research Institute
  Royal Children's Hospital
  Flemington Road
  Parkville
  Victoria 3052

   T   +61 3 8341 6466
   F   +61 3 8341 6429
    E   amanda.fosang@mcri.edu.au

biography

Amanda Fosang is an NHMRC Principal Research Fellow with an established career researching cartilage biology in health and disease. After completing her post-doctoral studies at the Kennedy Institute of Rheumatology, London, Amanda returned to Australia and was awarded an RD Wright Fellowship by the NHMRC (1994). She joined the Department of Paediatrics and has since received continuous competitive grant and fellowship funding from the NHMRC.

Amanda has generated unique mice for evaluating cartilage damage in arthritic disease. Her work showing that ADAMTS-5 is the major aggrecanase in mouse cartilage was published in Nature in 2005. Amanda is an Associate Editor for the journals Arthritis & Rheumatism and Osteoarthritis and Cartilage. She coordinates the BSc Honours Program for the University of Melbourne Department of Paediatrics and MCRI. She has supervised 5 PhD students and 11 BSc Honours students to course completion.

achievements

Amanda received the Murdoch Childrens Discovery Award for Excellence in Research Achievement in 2006, the Selwyn-Smith Medical Research Prize from the University of Melbourne in 2007, the Barry Preston Award from the Pan Pacific Connective Tissues Society in 2007, and the Basic Science Award from Osteoarthritis Research Society International in 2009.

research focus & interest

My goal is to understand the complex interactions between cartilage cells and their matrix, in both healthy situations and in arthritic diseases. The emphasis of our work are the enzymes that destroy cartilage, including families of enzymes called "aggrecanases", "collagenases" and "hyaluronidases". We study the breakdown products created, and how the breakdown products regulate cellular function. Some of our work is done in explant and cell culture systems, or involves studies with highly purified enzymes and substrates in vitro.Other work involves studies with genetically-modified mice.  We have eight unique lines of mice which have been engineered to resist cartilage destruction. The mice provide valuable insights into the mechanisms of joint destruction in arthritis. Our studies on cartilage biology and arthritic disease will identify new target molecules and/or activities, for the development of disease-modifying arthritis therapies.

publications

Sumer, EU., Sondergaard, BC., Rousseau, JC., Delmas PD., Fosang, AJ., Karsdal, MA., Christiansen, C. & Qvist, P. (2007) MMP and non-MMP-mediated release of aggrecan and its fragments from articular cartilage: a comparative study of three different aggrecan and glycosaminoglycan assays.
Osteoarthritis Cartilage 15, 212-221                    [IF = 3.8]


Little, CB., Meeker, CT., Golub, SB., Lawlor, KE., Farmer, P., Smith, SM. & Fosang, AJ. (2007) Blocking aggrecanase cleavage in the aggrecan interglobular domain abrogates cartilage erosion and promotes cartilage repair
J. Clin Invest 117, 1627-1636                        [IF = 16.9]


Karsdal, MA., Sumer, EF., Wulf, H., Madsen, SH., Christiansen, C., Fosang, AJ., & Sondergaard, BC. (2007) Induction of increased cAMP levels in articular chondrocytes blocks matrix metalloproteinase but not aggrecanase mediated cartilage degradation.
Arthritis Rheum. 56, 1549-1558                    [IF = 7.7]


Rogerson, FM., Stanton, H., East, CJ., Golub, SB.,  Tutolo, L, Farmer PJ. & Fosang, AJ. (2008) Evidence for a novel aggrecan degrading activity in cartilage: studies of mice deficient in both ADAMTS-4 and ADAMTS-5
Arthritis Rheum. 58, 1664-1673                    [IF = 6.8]


Wilson, R., Belluoccio, D., Little, CB., Fosang, AJ. & Bateman, JF (2008) Proteomic characterization of mouse cartilage degradation in vitro
Arthritis Rheum.58, 3120-3131                [IF = 6.8]


Fosang, AJ., Rogerson, FM., East, CJ. & Stanton, H (2008) ADAMTS-5: the story so far
Eur. Cells Mater. 15, 11-26                    [IF = 4.3]


Kannu, P., Bateman, JF., Belluoccio, D., Fosang, AJ. & Savarirayan, R. (2009) Employing molecular genetics of chondrodysplasias to inform the study of osteoarthritis
Arthritis Rheum.60, 325-334                    [IF = 7.3]


Little CB, Barai A, Burkhardt D, Smith SM, Fosang AJ, Werb Z, Shah M & Thompson EW (2009) Matrix metalloproteinase 13-deficient mice are resistant to osteoarthritic cartilage erosion but not chondrocyte hypertrophy or osteophyte development
Arthritis Rheum. 60, 3723-3733                [IF = 7.3]


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                [IF = 8.4]


Fosang, AJ. & Rogerson, FM. (2010) Identifying the human aggrecanase
Osteoarthritis Cartilage 18, 1109-1116            [IF = 4.0]


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., Melrose, J., Little, CB. & Fosang AJ. (2011) Proteoglycan degradation by the ADAMTS family of proteinases
Biochim. Biophys. Acta In Press