Selected Publications

• White Gemma E, McNeill Eileen, Christou Ivy, Channon Keith M, and Greaves David R (2011) Site-directed mutagenesis of the CC chemokine binding protein 35K-Fc reveals residues essential for activity and mutations that increase the potency of CC chemokine blockade. Mol Pharmacol, 80(2):328-36.

• Cash Jenna L, Christian Annabel R, and Greaves David R (2010) Chemerin peptides promote phagocytosis in a ChemR23- and Syk-dependent manner. J Immunol, 184(9):5315-24.

• Hart Rosie and Greaves David R (2010) Chemerin contributes to inflammation by promoting macrophage adhesion to VCAM-1 and fibronectin through clustering of VLA-4 and VLA-5. J Immunol, 185(6):3728-39.

• McNeill Eileen, Channon Keith M, and Greaves David R (2010) Inflammatory cell recruitment in cardiovascular disease: murine models and potential clinical applications. Clin Sci (Lond), 118(11):641-55.

• Bursill C A, McNeill E, Wang L, Hibbitt O C, Wade-Martins R, Paterson D J, Greaves D R, and Channon K M (2009) Lentiviral gene transfer to reduce atherosclerosis progression by long-term CC-chemokine inhibition. Gene Ther, 16(1):93-102.

Prof David R Greaves

Inflammation is the response of vascularised tissues to injury, irritation and infection. The initial inflammatory response is localised to the site of injury and characterised by the rapid recruitment of plasma proteins and inflammatory cells from the bloodstream. Acute inflammation lasts only a few days while chronic inflammation lasting months and years is a defining feature of many important human diseases including rheumatoid arthritis, inflammatory bowel disease and coronary heart disease.

The Greaves 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 are particularly interested in the role chemokines play in atherosclerosis - a disease process that occurs in arteries causing angina, heart attacks, strokes and peripheral arterial disease.

Recent work in the Greaves Lab has identified a new endogenous anti-inflammatory pathway in which peptides derived from a plasma protein called chemerin potently reduce inflammatory cell recruitment in models of acute inflammation. Remarkably these peptides can also enhance macrophage clearance of apoptotic cells at sites of inflammation as well as reducing the local production of chemokines and other inflammatory mediators.  These studies have identified new avenues for the development of anti-inflammatory drugs.

Research Techniques
• In vivo gene transfer using adenovirus and lentivirus vectors
• Measuring chemokine and cytokine production
• Macrophage phagocytosis assays
• Models of peritoneal inflammation
• Macrophage activation assays
• Detecting apoptotic cells
• Cell signalling assays
• Chemotaxis assays

David Greaves is the Reader in Molecular Pathology at the Sir William Dunn School of Pathology and he is a tutorial fellow of Hertford College. Dr Greaves trained in Bristol and King’s College London before working at the Netherlands Cancer Institute in Amsterdam and the National Institute for Medical Research in London where he studied the transcriptional regulation of the beta globin gene locus and developed the first animal model of sickle cell disease.

Dr Greaves moved to the Dunn School of Pathology in 1993 where he has worked on many different aspects of macrophage biology including the role of macrophage scavenger receptors in atherosclerosis and developing macrophage-specific gene targeting systems. Dr Greaves’ contributions to the study of chemokine biology include the initial cloning and characterisation of the CCR6 chemokine receptor, the first description of the CX3C chemokine fractalkine and developing new methods for broad-spectrum CC chemokine blockade.

Dr Greaves is Programme Director of the Oxford BHF 4-year PhD studentship scheme, he is the organiser of the second year BM Principles of Pathology course and he runs the Final year Honours School theme Vascular Biology and Vascular Pathology.

In 2007 Dr Greaves won a University of Oxford teaching excellence award for his innovations in teaching pathology and experimental medicine. In January 2009 Dr Greaves was invited by the second year medical students at Oxford University to give the inaugural MedSoc Lecture.