We are interested in how the innate immune response contributes to the adaptive immune response and, in particular, how it influences chronic allograft vasculopathy (CAV). When an organ is retrieved for transplantation, it undergoes a period of ischaemia when the blood supply is interrupted, followed by reperfusion when the organ is transplanted into the patient. Both of these events are unavoidable and cause some degree of tissue injury which is thought to contribute to poor graft function at a late stage after transplantation.
One theory is that the tissue damage may result in development of antibodies against normal cell structures – autoantibodies – which have been shown to be associated with CAV. Professor Mike Nicholson and Dr Sarah Hosgood have developed a system for perfusing kidneys retrieved from donors that appears to repair some ischaemic damage and improve renal function. Together with Prof. Nicholson, we are using this system to attempt to improve the function of DCD organs.
It is thought that ischaemic injury is caused, in part, by the response of mitochondria to the reduced flow of oxygenated blood. Dr Mike Murphy in the MRC Mitochondrial Biology Unit, Cambridge, has pioneered the development of mitochondria-targeted therapies that have been applied to a wide range of models of human disorders in which mitochondrial oxidative stress plays an important role. One treatment has gone on to phase II trials and a newer compound appears to be protective against cardiac ischaemia-reperfusion injury. We are collaborating with Dr Murphy, testing this approach for ameliorating ischaemic injury both in models of transplant vasculopathy and using the kidney perfusion system.