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, Chris Buckley and Steve Watson and Dr. Helen McGettrick, studying processes linked to development of chronic inflammatory pathology (such as atherosclerosis and rheummatoid arthritis) and to thrombo-inflammatory disorders. 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 Institute of Cardiovascular Sciences and the Institute of Inflammation and Ageing.