Novel mechanisms that regulate macrophage activation and inflammatory cell recruitment

Inflammation is a localised, response to injury or infection characterised by the sequential release of inflammatory mediators and the recruitment of circulating leukocytes. Recruited leukocytes become activated at the site of inflammation and release further pro- and anti- inflammatory mediators. Sites of acute inflammation are characterised by the rapid recruitment of neutrophils whereas sites of chronic inflammation are characterised by the continuing recruitment of monocytes that differentiate into macrophages. Macrophage activation is a hallmark of many forms of chronic inflammation including atherosclerosis, the underlying pathological process in major arteries that leads to heart attacks and strokes (1).

My laboratory is studying the role played by a family of inflammatory mediators called chemokines in the recruitment and activation of macrophages and smooth muscle cells in chronic inflammation. We have developed methods to reduce CC chemokine activity in vivo (2) and we are developing new reagents to block activation via the CX3CR1 chemokine receptor which has been implicated in the development of atherosclerotic lesions (3).

Recently we have begun to study endogenous anti-inflammatory pathways that regulate inflammatory cell recruitment and activation, including the macrophage nicotinic acetylcholine receptor and a G-protein coupled receptor called ChemR23. These studies may identify targets for the development of novel anti-inflammatory drugs.

Applicants should have a genuine interest in inflammation biology and/or cardiovascular disease. The successful applicant will develop a specific research project in the area of regulation of leukocyte recruitment or the regulation of macrophage responses to chemokines.

More information about applying for this and other Dunn School studentships can be found here

References

1. Greaves, D. R., and Channon, K. M. (2002) Trends Immunol 23(11), 535-541

2. Bursill, C. A., et al. (2004) Circulation 110(16), 2460-2466

3. Bursill, C. A., Channon, K. M., and Greaves, D. R. (2004) Curr Opin Lipidol 15(2), 145-149