Inflammatory Signalling

Our Group is interested in molecular and cellular regulatory mechanisms of inflammatory signal transduction networks and activation of inflammatory cytokine secretion, with a specific focus on vascular cell types.

Current research focuses on three key areas:

1. We develop and perform high throughput functional screens to identify novel proteins, which are involved in the inflammatory activation of various cell types. We have recently generated a unique collection of mouse cDNAs, which cover ~60% of the entire mouse transcriptome and use this research tool to perform unbiast, genome-wide screens. These efforts led to the identification of a number of novel inflammatory regulators, the biology of which is currently being investigated.
   
2. The second area of current activities focuses on the regulation of the Mitogen Activated Protein Kinase and PI3 kinase signalling networks in vascular cells. We have discovered a family of proteins, called tribbles, which are key regulators of these signalling systems. We have shown that tribbles interact with specific members or these pathways and that they are able to control the balance of activation between parallel signalling systems. Current research in this are has a dual focus. We wish to gain an insight into the importance of tribbles proteins in vascular cell function both in health and disease, as well as to understand the molecular basis of tribbles action.
   
3. Whilst inflammation is a coordinated response to infection or injury, it is now understood that this process is dysregulated in chronic disease states such as cardiovascular disease. We are focussed on addressing a fundamental question in inflammation research which remains unresolved: how are leaderless cytokines secreted from the cell? We understand that ATP-mediated P2X7 activation results in inflammatory IL-1beta/IL-18 cytokine secretion from macrophages. Stimulation of P2X7 results in a plethora of rapid cellular responses. However, the signaling events involved in this physiology are complex and cannot be fully explained by our existing knowledge. Our current research uses both mammalian cell and non-mammalian fluorescence reporter models to identify the role of key regulators of cytokine secretion, P2X7 receptor activation and cellular targeting of inflammatory cytokines.