International Protease Network

Sutton Arthritis Research Laboratories, Department of Medicine,
University of Sydney
Royal North Shore Hospital, Sydney
Email: cjackson@med.usyd.edu.au
Tel: +61-2-9926 6043
Fax: +61-2-9926 6269
Homepage:

Research

For 10 years we have been interested in the biochemical regulation of matrix metalloproteinases (MMPs) and their roles in numerous pathologies including arthritis, chronic wounds, pregnancy disorders and diabetes. Having recently discovered a link between MMPs and serine proteases we are now also studying the role of the anticoagulant serine protease, activated protein C (APC), in these disorders and its association with MMPs. Specific projects include i) Mechanism of action of APC as a promoter of chronic wound healing. ii) Identification and prevention of gelatinase A activation pathways in rheumatoid arthritis iii) The mechanism of tendon invasion by tenosynovium in rheumatoid arthritis, iv) Mechanisms of bone erosion and matrix breakdown in arthritis., v) The role of activated protein C in the regulation of the function of leukocytes from normal volunteers and from diabetic patients vi) Mechanism of defective trophoblast invasion in human pregnancies that develop pre-eclampsia and vii) The role of MMPs in heart failure in a sheep model.

Collaborations

Prof. Ross Davey, UTS and Dept Oncology, RNSH
Dr Shing Shung To and Prof Hg, Hong Kong PolyTechnic, Hong Kong
Assoc. Prof. Alan Cooper, Dept Dermatology, RNSH
Professor Stephen Hunyor, Cardiac Research Centre, RNSH
Prof Eileen Gallery, Dept Renal Medicine, RNSH
Assoc Prof Jagdeep Nanchahaal, Dept Hand Surgery, RNSH
Dr Stephen Twigg, Royal Prince Alfred Hospital
Dr Yoshifumi Itoh, Kennedy Institute, London

Publications

M. Nguyen, Arkell J and C Jackson. Thrombin rapidly and efficiently activates gelatinase A in human microvascular endothelial cells via a mechanism independent of MT1-MMP. Lab. Invest., 79:467-475, 1999.

M. Nguyen, J. Arkell and C. Jackson, Activated protein C directly activates human endothelial gelatinase A, J. Biol. Chem, 275, 9095-9098, 2000.

C. Jackson, M. Nguyen, J. Arkell and P.Sambrook, Selective matrix metalloproteinase inhibition in rheumatoid arthritis - Targetting gelatinase A activation, Inflamm. Res., 50, 183-186, 2001.

J. Arkell and C. Jackson, Constitutive expression of gelatinase B by cultured early-passage human endothelial cells, Cell Biochem and Function, 21:381-386, 2003.

N. Buisson-Legendre, Sue Smith, Lyn March, and C. Jackson, Activated protein C (APC) is elevated in rheumatoid arthritic synovial joints and correlates with matrix metalloproteinase-2 (MMP-2), Arthritis and Rheumatism, in press.