Professor Jon Gibbins

Biography

Dr. Professor Jon Gibbins is currently working as a Director of the Institute for Cardiovascular and Metabolic Research in the Department of Institute of Caediovascular & Metabolic Research (ICMR), University of Reading , United Kingdom. Platelets play a vital role in the prevention of bleeding on damage to blood vessels. The carefully balanced regulation of platelet function ensures that platelets are normally only activated when they are exposed to extra-cellular matrix proteins such as sub-endothelial collagens or by factors that are generated at sites of tissue damage. The importance of these complex control systems is highlighted in conditions where these go wrong. This can lead to excessive bleeding, or perhaps more commonly thrombosis (causing heart attacks and strokes). The focus of the research in this group is to increase our understanding of the molecular mechanisms that positively and negatively regulate platelet function. As described below, this is currently divided into a number of areas of interest. A major focus of the laboratory is understanding immune-like signalling mechanisms regulate the balance between platelet activation and inhibition. This includes platelet activation via the collagen receptor GPVI, and the inhibition of platelet function by the adhesion receptor PECAM-1. The ability of activated platelets to form a thrombus is mediated by receptors of the integrin family, the affinity of which for their ligands becomes increased during platelet activation (commonly called inside-out signalling). In this way integrins support platelet-platelet interactions and adhesion to components of the damaged vascular wall. We are currently investigating the bi-directional signalling mechanisms employed by platelet integrins. This includes the role of thiol isomerases that we have shown to be recruited to the platelet surface during activation, and their roles in conformational changes that are associated with integrin affinity modulation. We have recently discovered new positive feedback regulatory mechanisms in platelets that are mediated by members of the tachykinin family of peptides that are secreted from platelets during activation. We are currently determining their mechanisms of action and physiologic importance. Through collaboration with the Nutrition Group at the University of Reading we investigate the ability of dietary components to modulate platelet function and signal transduction. Using in vitroand in vivo techniques in humans we have made substantial progress in understanding the effects of some compounds at the molecular level. The University of Reading has developed state of the art proteomics facilities, and we are using these to take a more global perspective on the signalling mechanisms that regulate platelet function. Our strategies are designed to home in on the protein-protein interactions that are essential for platelet function. The driving factor behind our research is the clinical need to prevent and treat thrombosis more effectively. A greater understanding of the molecular mechanisms that regulate platelet function and the specific molecules that are involved will aid in the development of more effective and specific strategies to prevent and treat thrombosis. Our work is supported by research grants from the Medical Research Council, the Biotechnology and Biological Sciences Research Council, the British Heart Foundation and the Wellcome Trust. Research groups / Centres: Thrombosis and haemostasis

Research Interest

Platelets play a vital role in the prevention of bleeding on damage to blood vessels. The carefully balanced regulation of platelet function ensures that platelets are normally only activated when they are exposed to extra-cellular matrix proteins such as sub-endothelial collagens or by factors that are generated at sites of tissue damage. The importance of these complex control systems is highlighted in conditions where these go wrong. This can lead to excessive bleeding, or perhaps more commonly thrombosis (causing heart attacks and strokes). The focus of the research in this group is to increase our understanding of the molecular mechanisms that positively and negatively regulate platelet function. As described below, this is currently divided into a number of areas of interest. A major focus of the laboratory is understanding immune-like signalling mechanisms regulate the balance between platelet activation and inhibition. This includes platelet activation via the collagen receptor GPVI, and the inhibition of platelet function by the adhesion receptor PECAM-1. The ability of activated platelets to form a thrombus is mediated by receptors of the integrin family, the affinity of which for their ligands becomes increased during platelet activation (commonly called inside-out signalling). In this way integrins support platelet-platelet interactions and adhesion to components of the damaged vascular wall. We are currently investigating the bi-directional signalling mechanisms employed by platelet integrins. This includes the role of thiol isomerases that we have shown to be recruited to the platelet surface during activation, and their roles in conformational changes that are associated with integrin affinity modulation. We have recently discovered new positive feedback regulatory mechanisms in platelets that are mediated by members of the tachykinin family of peptides that are secreted from platelets during activation. We are currently determining their mechanisms of action and physiologic importance. Through collaboration with the Nutrition Group at the University of Reading we investigate the ability of dietary components to modulate platelet function and signal transduction. Using in vitro and in vivo techniques in humans we have made substantial progress in understanding the effects of some compounds at the molecular level. The University of Reading has developed state of the art proteomics facilities, and we are using these to take a more global perspective on the signalling mechanisms that regulate platelet function. Our strategies are designed to home in on the protein-protein interactions that are essential for platelet function. The driving factor behind our research is the clinical need to prevent and treat thrombosis more effectively. A greater understanding of the molecular mechanisms that regulate platelet function and the specific molecules that are involved will aid in the development of more effective and specific strategies to prevent and treat thrombosis. Our work is supported by research grants from the Medical Research Council, the Biotechnology and Biological Sciences Research Council, the British Heart Foundation and the Wellcome Trust.