After studying engineering and physics as an undergraduate, I opted to follow a research career in the biophysical sciences. My PhD was initially in instrumentation for automated cell characterisation but I quickly moved into cell mechanics and biorheology, and have subsequently gravitated towards studies of the cellular physiology of the cardiovascular system.
As a post-doc, my work at Guy’s and at University of Southern California initially revolved around analysis of the physical properties of red cells, and later leukocytes, that influence their circulation. On returing to UK and St. George’s Hospital Medical School, I applied these analytical approaches to defining biomechanical abnormalities associated with vascular disease.
On moving to Birmingham in 1989, my interest increasingly turned to the cellular adhesive properties of leukocytes and red cells. I established the Cardiovascular Rheology group, and developed novel flow-based culture and adhesion assays incorporating endothelial cells. We characterised for the first time the dynamic adhesive interactions of flowing malarial parasitised red cells. However, work on the mechanisms by which flowing neutrophils bind to ‘vessel’ walls came to take precedence, and we were the first to describe the ability of surface-adherent platelets to capture flowing neutrophils.
At the same time I developed an increasing interest in the role of endothelial cells in regulating neutrophil recruitment. Studies followed, e.g, defining the ability of endothelial cells exposed to hypoxia, cigarette smoke or cytokines to induce neurophil recruitment, and defining the kinetics and molecular mechanisms of each stage of the capture, activation and migration process. More recently I have concentrated on the concept that the local physicochemical environment defines the responsiveness of endothelial cells to inflammatory stimuli, and also the subsequent fate of recruited leukocytes. This has involved development of models in which endothelial cells are conditioned by culture under different flow conditions or with different stromal cells. Initially we defined how these variables modified ability to capture and induce migration of leukocytes. We are currently extending this to include studies of migration through basement membrane into tissue constructs, and evaluation of how stromal cells may influence the fate of recruited leukocytes in inflammed tissue.
Much of the more recent work has been carried out in collaboration with Professors Ed Rainger and Chris Buckley and Dr. Helen McGettrick, studying processes linked to development of chronic inflammatory pathology, especially in atherosclerosis and rheummatoid arthritis. Recently we have worked on linking inflammatory responses with thrombosis and angiogenesis, and examining the potential for stem cells to modulate such responses. In this way we aim to develop an understanding of how these different responses are integrated and may be manipulated to facilitate tissue healing. This work is inter-disciplinary in nature, and e.g., acts as an interface between the Centre for Cardiovascular Sciences and the MRC Centre for Immune Regulation.
Luu NT, Madden J, Calder PC, Grimble RF, Shearman CP, Chan T, Dastur N, Howell WM, Rainger GE, Nash GB, (2007) Dietary supplementation with fish oil modifies the ability of human monocytes to induce an inflammatory response. Journal of Nutrition 137 :2769-74. 137 :2769-74.
Matharu NM, McGettrick HM, Salmon M, Kissane S, Vohra RK, Rainger GE, Nash GB, (2008) Inflammatory responses of endothelial cells experiencing reduction in flow after conditioning by shear stress Journal of Cellular Physiology 216 732-41
McGettrick HM, Hunter K, Moss P, Buckley CD, Rainger GE, Nash GB (2009), Direct observations of the kinetics of migrating T cells suggest active retention by endothelial cells with continual bidirectional migration Journal of Leukocyte Biology 85 1-10
McGettrick HM, Smith E, Filer ADJ, Kissane S, Salmon M, Buckley CD, Rainger GE, Nash GB, (2009) Fibroblasts from different sites may promote or inhibit recruitment of flowing lymphocytes by endothelial cells. European Journal of Immunology 39 113-25
Tull SP, Yates CM, Maskrey BH, O'Donnell VB, Madden J, Grimble RF, Calder PC, Nash GB, Rainger GE, (2009) Omega-3 Fatty acids and inflammation: novel interactions reveal a new step in neutrophil recruitment. PLoS Biology 7 e1000177
McGettrick HM, Buckley CD, Filer A, Ed Rainger G, Nash GB (2010) Stromal cells differentially regulate neutrophil and lymphocyte recruitment through the endothelium. Immunology, 131, 357-730
V.J. Burton, L.M. Butler, H.M. McGettrick, P.C. Stone, H.C. Jeffery, C.O. Savage, G.E. Rainger, G.B. Nash (2011) Delay of migrating leukocytes by the basement membrane deposited by endothelial cells in long-term culture. Exp Cell Res, 317, 276-292
Butler LM, Jeffery HC, Wheat RL, Rae PC, Townsend K, Alkharsah KR, Schulz TF, Nash GB, Blackbourn DJ (2011) Kaposi's sarcoma-associated herpesvirus infection of endothelial cells inhibits neutrophil recruitment through an interleukin-6-dependent mechanism: a new paradigm for viral immune evasion. J Virol 85, 7321-7332
Glen K, Luu NT, Ross E, Buckley CD, Rainger GE, Egginton S, Nash GB (2012) Modulation of functional responses of endothelial cells linked to angiogenesis and inflammation by shear stress: differential effects of the mechanotransducer CD31. J Cell Physiol 227, 2710-2721