Arthritis Research

The role of MIF in rheumatoid arthritis

Supervisor: Associate Professor Eric Morand

Rheumatoid arthritis (RA) is the most common autoimmune disease, affecting over 200,000 Australians. The cause of rheumatoid arthritis is not known, but research into its mechanisms have provided dramatic breakthroughs in treatment in recent years. The cytokine MIF (macrophage migration inhibitory factor) was first described in RA tissues by Dr Morand’s group, which continues to be at the forefront of research into this cytokine. Emerging data suggest a unique set of signal transduction pathways is activated by MIF, giving rise to its unique set of biological effects. Current projects focus on the examination of signal transduction events operative in cell activation by MIF, the role of MIF in the regulation of synovial cell proliferation via modulation of p53, and the phenotypic study of arthritis models in MIF -/- mice.

The role of annexin I in rheumatoid arthritis

Supervisor: Associate Professor Eric Morand

As noted above, RA is a complex idiopathic disease characterised by over activity of inflammation. The study of naturally occurring anti-inflammatory molecules provides the potential for development of advanced, effective, safe biological therapies for human disease. Annexin I, formerly known as lipocortin 1, was first reported in RA synovium by Dr Morand, and his group has demonstrated the critical role of this molecule in the regulation of synovial inflammation. The development of annexin I -/- mice by collaborators now allows new projects which can investigate the cellular mechanism of action of annexin I in inflammation.

The role of glucocorticoids in rheumatoid arthritis

Supervisor: Associate Professor Eric Morand

Glucocorticoids (or “steroids”) have been used for the treatment of RA for over fifty years, and indeed their discovery and application to RA gave rise to the 1950 Nobel prize for Medicine. It is less widely appreciated that endogenous adrenal glucocorticoids contribute significantly to the counter-regulation of the immune-inflammatory response. The role of endogenous glucocorticoids in the control of joint inflammation in models of RA, and in humans with RA, has been a focus of Dr Morand’s group’s research interest for several years. Ongoing studies include the examination of interactions between cytokine-activated MAP kinases and glucocorticoid receptor function.

The role of Protease Activated Receptors (PAR's) in rheumatoid arthritis.

Supervisors: Associate Professor Eric Morand & Associate Professor Peter Tipping

PAR's are a family of seven transmembrane, G protein couple receptors, which are activated by proteolytic cleavage of their extra-cellular N terminal. PAR-1 is a member of this family that is cleaved by thrombin, a key molecule in activation of coagulation. PAR-1 activation by thrombin may play an important role in systemic an local inflammatory diseases. The contribution of PAR-1 to inflammation in will be studied in PAR-1 deficient mice using models of systemic inflammation and organ specific cognate and innate immunity. Such studies have been pioneered in the study of glomerulonephritis and will be studied for the first time in models of RA.