Newcastle University

Applied Immunobiology and Transplantation

Our group of clinical and basic scientists shares a common interest in the mechanisms of tissue injury produced by immunological diseases, and has a particular research focus on the failure of transplanted organs.

The group developed in parallel with Newcastle’s comprehensive clinical transplant programme and its research expertise spans the full range of commonly transplanted organs, including heart, lung, kidney, liver and pancreas.

Although the early outcome of organ transplantation is now generally very good, long-term preservation of graft function remains a major problem with only between 25 and 65% of transplanted organs surviving for 10 years. Transplantation provides a unique opportunity to study mechanisms of tissue damage, from the earliest processes related to the stresses of transplant surgery, to infection, drug toxicity and antigen-specific inflammatory processes which can lead to long-term graft failure as a consequence of tissue remodelling and fibrosis. Improved understanding of these processes has already revolutionised the management of graft loss as a consequence of acute inflammation, but no reliable treatments are currently available to improve the prospect for long-term graft survival.

The group uses a full range of in vivo and in vitro modelling combined with tissue, cell and molecular analysis to investigate processes including:

• the role of toll-like receptors, LPS and complement in graft injury (Dark, Kirby, Marchbank, Sheerin, de Soyza)
• ex vivo donor organ perfusion to improve the function of marginal organs (Fisher, Dark, Corris)
• mechanisms of B cell-mediated antigen presentation and epitope spreading (Knight, Jones)
• manipulation of chemokine-proteoglycan interactions to reduce tissue inflammation (Kirby, Ali)
• local differentiation of effector and regulatory immune cells within allograft tissues (Kirby, Sheerin)
• the innate and adaptive immune response to allogeneic islets (Shaw)
• the potential of cytokines and lymphocytes to damage graft function by the induction of epithelial to mesenchymal transition (Kirby, Burt, Fisher,Sheerin)
• the potential of xenobiotics to trigger autoimmune liver disease (Jones, Kirby)
• the role of antibiotic therapy in management of graft infection and chronic tissue damage (including a drug trial in lung transplant patients) (Corris, Ward, Fisher)

Insights provided by the study of tissue rejection after transplantation have also been translated by the group to further studies of autoimmune diseases including rheumatoid arthritis, primary biliary cirrhosis and primary sclerosing cholangitis.