Atherosclerosis is a chronic inflammatory disease of the arteries that represents the root cause of the majority of heart attacks and strokes. Work in my laboratory aims to identify the primary agents responsible for promoting the inflammatory signals that underpin this disease, with a particular emphasis on investigation of the mechanisms connecting innate immune receptor signalling with the acute phase response and lipid metabolism.
Our recent work focuses on the mechanisms by which pathogen-associated molecular patterns (PAMPs, which are molecules expressed by microbes but not human cells that are detected by pattern-recognition receptors of the innate immune system), modify systemic inflammatory tone and regulate lipid metabolism at the cellular and systemic levels. Specific interests include: (i) the mechanisms by which innate immune receptor signalling regulates macrophage cholesterol and fatty acid uptake, synthesis and efflux in the context of foam cell formation, (ii) the regulation of innate immune function by factors associated with the Western diet, (iii) the contribution of commensal microbiota-derived PAMPs to the regulation of systemic inflammatory tone and (iv) the means of communication and lipid exchange between hepatocytes and macrophages during the acute phase response. We are currently investigating the contribution made by each of these pathways to atherosclerosis using a variety of models including in vitro cell culture and studies in human subjects.
Our aim is to use an improved understanding of these pathways to develop novel therapeutic approaches for the treatment or prevention of atherosclerosis and related metabolic diseases. We therefore have an active interest in the discovery and pre-clinical testing of novel anti-inflammatory and lipid regulatory lead molecules derived from high throughput screening of our natural product libraries for inhibitors or stimulants of specific pathways identified in our mechanistic studies (see Nutraceutical Discovery Resource pages).