Professor Jackson is Director of the Centre for Research in Translational Biomedicine and Deputy Head (Research) of the School of Biomedical Sciences at Plymouth University. He was previously a research leader at the University of the West of England, Bristol and the Medical School, Cardiff University. He has over 200 publications in the area of infection and immunity and has particular expertise in the cell and molecular responses to pathogenic molecules such as lipopolysaccharide. He has a particular interest in inflammatory responses to infection and mechanisms controlling them. This has led to the identity of phospholipid modifying enzymes (acyltransferases) that he has shown to have novel roles in the inflammatory response and may provide new therapeutic targets for conditions such as sepsis.
Abstract of Seminar
Sepsis is a major cause of morbidity and mortality worldwide, with over 200,000 deaths annually in Europe alone. Sepsis is initiated by the activation of phagocytic cells by molecules such as lipopolysaccharide (LPS) to produce an overwhelming innate immune response through the induction of excessive cytokine release. This can ultimately lead to damaged blood vessels, a decrease in vascular resistance and subsequent failure of organs that contribute to the lethality of sepsis. Clinically, sepsis has proven very difficult to treat and many therapies aimed at individual inflammatory components have failed to deliver significant improvements in mortality or morbidity. Understanding the mechanisms that regulate the production of inflammatory mediators in response to bacterial products such as LPS is crucial in the development of novel effective therapies for sepsis.
It has been shown that macrophage phospholipid composition is important for the inflammatory responses of these cells. We identified a phospholipid modifying enzyme (Lysophosphatidylcholine acyltransferase (LPCAT)) that could regulate the release of inflammatory cytokines from cells following stimulation with LPS by controlling the translocation of the LPS receptor, TLR-4, into lipid raft domains. This talk will outline how we have used small inhibitory RNAs to show that suppression of LPCAT-2 significantly down-regulates LPS-induced inflammatory cytokines. These effects were not specific to LPS as other bacterial ligand-induced responses were also markedly reduced by the suppression of LPCAT-2. However, the suppression of LPCAT2 had no effect on responses to TLR-independent ligands. The findings provide an insight into the LPCAT isoform that modulates inflammatory responses and may be useful in elucidating novel pathways of regulation of inflammation and identifying novel targets for anti-inflammatory therapy for conditions such as sepsis.