David Greaves

Macrophages – In the Greaves Laboratory we study macrophage biology. Macrophages are cells of the innate immune system found in virtually every tissue in the body. Originally it was thought that all tissue resident macrophages were derived from circulating white blood cells called monocytes. For some macrophage-like cells such as dendritic cells in the large intestine this remains true, but we now appreciate that most of the macrophages we find in tissues were seeded during foetal life and are maintained by self-renewal. We can recognise macrophages in tissues by using antibodies that recognise macrophage expressed proteins such as F4/80 or CD68. Work in the Greaves Lab has used the gene regulatory elements of the human CD68 gene to drive reporter gene expression that allows us to follow migration and persistence within different tissues.

Phagocytosis – One of the most fascinating aspects of macrophage cell biology is the way these immune cells reorganise their cytoskeleton to engulf large particles such as bacteria, yeast particles, even dead and dying cells of the same size. In the Greaves Lab we use a wide range of techniques to study macrophage phagocytosis. In recent work we have shown that a membrane protein expressed on the surface of macrophages at sites of inflammation called GPR84 can enhance macrophage phagocytosis of different ‘phagocytic meals’. With our collaborators in the Department of Chemistry we are synthesising and testing a range of small molecules that bind and activate the GPR84 receptor to increase macrophage phagocytosis.

Drug repurposing – Inflammation is a driver of human disease and an unmet clinical need exists for new and better anti-inflammatory medicines. Because macrophages are a key cell type in the pathology of both acute and chronic inflammatory disease, they are an appealing therapeutic target for developing anti-inflammatory medicines. Drug repurposing, the use of existing medicines for new indications, is an attractive and pragmatic strategy for the discovery of novel anti-inflammatory medicines. In the Greaves Lab we have set out to identify novel drug repurposing candidates with anti-inflammatory activity in macrophages by looking for inhibition of macrophage NF-κB activity. We are currently studying FDA approved medicines that inhibit NF-kB activity in macrophages and reduce inflammatory cytokine production in tissue culture and in animal models of acute inflammation.

The Greaves Lab is a potential host laboratory for graduate students on the following Doctoral Training Centres (DTCs):

• Wellcome Trust Chemistry in Cells – project title: Evolution of the GPR84 receptor – a conserved function in immune defence against bacteria?
• BBSRC Doctoral Training Centre – project title: Evolution of the GPR84 receptor – a conserved function in immune defence?