Professor David Greaves

Fellow and Tutor in Medicine

University Lecturer

Subjects: 
Medicine
Qualifications: 
BSc, PhD, MA

Prof Greaves read Microbiology at Bristol BSc (First Class honours) and was awarded a PhD in Biophysics and Biophysics and Molecular Biology at King’s College London (Winner of the Tadion-Rideal Medal). Postdoctoral research was undertaken at the Netherlands Cancer Institute in Amsterdam, the National Institute for Medical Research at Mill Hill in London and the Sir William Dunn School of Pathology in Oxford before being awarded a British Heart Foundation Basic Science Lectureship and subsequent election to a University Lectureship in Cell Pathology. In 2010 David Greaves was awarded the title of Professor of Inflammation Biology by the University of Oxford.

Faculty profile

Undergraduate teaching 

The Hertford Medicine teaching team is led by Professor David R. Greaves, an expert on inflammatory mediators and the resolution of inflammation. Prof. Greaves tutors first year Biochemistry & Medical Genetics, second year Principles of Pathology and third year modules in Cardiovascular Pathology and Inflammation Biology.

Postgraduate teaching 

Prof Greaves is the Course Director of the British Heart Foundation Oxford 4-year DPhil course in Cardiovascular Science, which funds four 4-year DPhil studentships a year and he currently supervises two DPhil students in his laboratory.

Research 

Inflammation Biology – Acute Inflammation is the response of vascularised tissues to injury and infection. It is characterised by the rapid recruitment of plasma proteins and inflammatory cells called neutrophils from the bloodstream. This process is usually short lived and is followed by a period of inflammation resolution when with dead microbes, cell debris and apoptotic neutrophils are removed by cells called macrophages.

Chronic inflammation is characterised by continuing inflammation and the build up of large numbers of macrophages and T lymphocytes in diseased tissues such as the joints in rheumatoid arthritis. Work in my laboratory is aimed at understanding the key molecules that recruit and retain macrophages at sites of chronic inflammation and understanding the key mediators that initiate inflammation resolution. Recent work from the Greaves Lab on the resolution of inflammation has identified two new approaches to the development of novel anti-inflammatory drugs.

Cardiovascular disease – Angina, heart attacks and ischaemic strokes are all caused by the same underlying pathological process in arteries, atherosclerosis. Atherosclerosis is characterised by the build up of cholesterol containing lipoproteins and macrophages within the lining of major arteries. Professor Greaves and collaborators within the Department of Cardiovascular Medicine are studying the molecular mechanisms that regulate the very earliest stages of atherosclerosis and investigating factors with atherosclerotic plaques that affect macrophage differentiation. In collaboration with Professor Ed Fisher at new York University we are examining models of atherosclerotic plaque regression with a special emphasis on how macrophage responses to chemokines can be modified by diabetes and hypertension.

Publications 

Professor David R. Greaves (selected recent papers from over 100 peer-reviewed articles)

Macrophage Differentiation and Function in Atherosclerosis: Opportunities for Therapeutic Intervention?
Williams HJ, Fisher EA, Greaves DR.
J Innate Immun. 2012 Apr 27.  Review

NF-?B-mediated degradation of the coactivator RIP140 regulates inflammatory responses and contributes to endotoxin tolerance.
Ho PC, Tsui YC, Feng X, Greaves DR, Wei LN.
Nat Immunol. 2012 Mar 4;13(4):379-86. doi: 10.1038/ni.2238.

Anti-inflammatory effects of nicotinic acid in human monocytes are mediated by GPR109A dependent mechanisms.
Digby JE, Martinez F, Jefferson A, Ruparelia N, Chai J, Wamil M, Greaves DR, Choudhury RP.
Arterioscler Thromb Vasc Biol. 2012 Mar;32(3):669-76.

Fractalkine: a survivor's guide: chemokines as antiapoptotic mediators.
White GE, Greaves DR.
Arterioscler Thromb Vasc Biol. 2012 Mar;32(3):589-94. Review.

Generation of anti-inflammatory adenosine by leukocytes is regulated by TGF-ß.
Regateiro FS, Howie D, Nolan K, Agorogiannis E, Greaves DR, Cobbold SP, Waldmann H.
Eur J Immunol. 2011 Oct;41(10):2955-65. doi: 10.1002/eji.201141512.

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.
White GE, McNeill E, Christou I, Channon KM, Greaves DR.
Mol Pharmacol. 2011 Aug;80(2):328-36.

TGF-ß limits IL-33 production and promotes the resolution of colitis through regulation of macrophage function.
Rani R, Smulian AG, Greaves DR, Hogan SP, Herbert DR.
Eur J Immunol. 2011 Jul;41(7):2000-9. doi: 10.1002/eji.201041135.

Chemerin contributes to inflammation by promoting macrophage adhesion to VCAM-1 and fibronectin through clustering of VLA-4 and VLA-5.
Hart R, Greaves DR.
J Immunol. 2010 Sep 15;185(6):3728-39.

Chemerin peptides promote phagocytosis in a ChemR23- and Syk-dependent manner.
Cash JL, Christian AR, Greaves DR.
J Immunol. 2010 May 1;184(9):5315-24.

Inflammatory cell recruitment in cardiovascular disease: murine models and potential clinical applications.
McNeill E, Channon KM, Greaves DR.
Clin Sci (Lond). 2010 Mar 9;118(11):641-55. Review.

PPARgamma activation in adipocytes is sufficient for systemic insulin sensitization.
Sugii S, Olson P, Sears DD, Saberi M, Atkins AR, Barish GD, Hong SH, Castro GL, Yin YQ, Nelson MC, Hsiao G, Greaves DR, Downes M, Yu RT, Olefsky JM, Evans RM.
Proc Natl Acad Sci U S A. 2009 Dec 29;106(52):22504-9.

Fractalkine has anti-apoptotic and proliferative effects on human vascular smooth muscle cells via epidermal growth factor receptor signalling.
White GE, Tan TC, John AE, Whatling C, McPheat WL, Greaves DR.
Cardiovasc Res. 2010 Mar 1;85(4):825-35.

Anti-inflammatory effects of nicotinic acid in adipocytes demonstrated by suppression of fractalkine, RANTES, and MCP-1 and upregulation of adiponectin.
Digby JE, McNeill E, Dyar OJ, Lam V, Greaves DR, Choudhury RP.
Atherosclerosis. 2010 Mar;209(1):89-95.

Vagus nerve activity augments intestinal macrophage phagocytosis via nicotinic acetylcholine receptor alpha4beta2.
van der Zanden EP, Snoek SA, Heinsbroek SE, Stanisor OI, Verseijden C, Boeckxstaens GE, Peppelenbosch MP, Greaves DR, Gordon S, De Jonge WJ.
Gastroenterology. 2009 Sep;137(3):1029-39, 1039.e1-4.

Synthetic chemerin-derived peptides suppress inflammation through ChemR23.
Cash JL, Hart R, Russ A, Dixon JP, Colledge WH, Doran J, Hendrick AG, Carlton MB, Greaves DR.
J Exp Med. 2008 Apr 14;205(4):767-75. Epub 2008 Apr 7.

Distinct cell-specific control of autoimmunity and infection by FcgammaRIIb.
Brownlie RJ, Lawlor KE, Niederer HA, Cutler AJ, Xiang Z, Clatworthy MR, Floto RA, Greaves DR, Lyons PA, Smith KG.
J Exp Med. 2008 Apr 14;205(4):883-95.

The duffy antigen/receptor for chemokines exists in an oligomeric form in living cells and functionally antagonizes CCR5 signaling through hetero-oligomerization.
Chakera A, Seeber RM, John AE, Eidne KA, Greaves DR.
Mol Pharmacol. 2008 May;73(5):1362-70.

Galectin-3 is an amplifier of inflammation in atherosclerotic plaque progression through macrophage activation and monocyte chemoattraction.
Papaspyridonos M, McNeill E, de Bono JP, Smith A, Burnand KG, Channon KM, Greaves DR.
Arterioscler Thromb Vasc Biol. 2008 Mar;28(3):433-40.