Theme 2: Glucocorticoid-induced molecules in the control of inflammation and arthritis.

Arthritis and Rheumatology Group

Head – Prof Eric Morand

Email: eric.morand@med.monash.edu.au

Ph: 9594 3564

Fax: 9594 6512

1. Actions of MIF in inflammation

Rheumatoid arthritis is a common idiopathic autoimmune disease affecting over 200,000 people in Australia. Cytokines are important therapeutic targets in arthritis. The Monash group has identified the cytokine macrophage migration inhibitory factor (MIF) as a key cytokine in arthritis, and is actively developing anti-MIF therapies for future use in patients with this disease.

The mechanism of action of MIF is not fully understood, but we have recently reported a probable mechanism for the interaction between MIF and glucocorticoids. Further dissection of the molecular pathways involved in MIF-glucocorticoid interactions will involve signal transduction studies, siRNA, reporter constructs, and similar technologies being applied to human and animal cells in vitro. 

2. Rheumatoid synovial gene expression and signalling

 We have obtained a data set from human rheumatoid arthritis joint (synovial) cells in which the expression of MIF has been silenced using siRNA. This will identify a set of genes regulated by MIF which require investigation for function. The project will translate novel microarray data into confirmed expression data using real-time PCR and functional assays in human cells.

3. MIF and Lupus

(Eric Morand and Michael Hickey)

Lupus (systemic lupus erythematosus, or SLE) is a systemic autoimmune inflammatory disease of unknown aetiology. The role of MIF in lupus is now emerging as a result of work in this lab at Monash. The availability at Monash of MIF gene deficient lupus-prone mice is a world-first, and permits the examination of the contribution of MIF to this disease. Specifically, we will examine the mechanisms of reduced renal inflammation in MIF deficient lupus mice and examine the microcirculation of these mice in the skin, kidney and brain. 

4. Annexin I and inflammatory signal transduction

Annexin I is a gene induced by glucocorticoids (“steroids”) which is essential for the anti-inflammatory effect of these commonly used drugs. We have recently demonstrated major effects of annexin I on intracellular signal transduction events involved in inflammatory responses. The elucidation of these pathways is likely to lead to a definitive understanding of the role of annexin I in the control of cell activation. This project will utilise state of the art signal transduction research technologies which would be widely applicable in any future research positions and therefore represents an excellent training position.

5. GILZ and arthritis

Glucocorticoid-induced leucine zipper (GILZ) is a poorly understood glucocorticoid-induced regulatory protein involved in the control of other signal transduction pathways. We have recently determined the regulation of this protein by annexin I. Examination of the actions of GILZ in human rheumatoid tissues has not been undertaken. This project will apply the examination of GILZ to human arthritic tissues and cells, and will utilize signal transduction, siRNA, reporter constructs, and similar technologies.