Newcastle University

Applied Immunobiology and Transplantation

The Applied Immunobiology and Transplanation Research Group is made up of a number of organ focused laboratory teams including Liver, Renal and Lung Immunobiology. The environment within the group favour close-working between these teams to evaluate a number of basic mechanisms and therapeutic interventions relevent to Respiratory Medicine, Liver Medicine, Renal Medicine and transplant Medicine.

Research Achievements

Core members of this group have recently:

• Demonstrated that chemokine binding to heparan sulphate is essential for transendothelial leukocyte migration in inflammation. This is being developed for anti-inflammatory therapy.
• Shown that non GAG-binding chemokines can antagonise inflammation. We are developing this for high impact publication and for patent application
• Demonstrated of importance of the aEß7 integrin in tubilitus during renal allograft rejection. We were the first group to demonstrate the persistence of these cells within epithelial tissues following acute rejection
• Defined the importance of T cell-induced renal epithelial cell to fibroblast transition for chronic allograft dysfunction. We are currently exploring whether this mechanism is common for chronic fibrosis in other organs including liver and lung and are also determining how this transition to function-damaging mesenchymal cells can be reversed.
• Developed and evaluated the first animal model of the human disease primary biliary cirrhosis and we used this model to define a mechanism for the breakdown of tolerance to the (Newcastle-defined) autoantigen in primary biliary cirrhosis, pyruvate dehydrogenase complex (PDC). We have shown that immunogenic PDC is released from mitochondria into the cytoplasm and onto the cell surface during early stages of apoptosis and are investigating the role of xenobiotic modification of PDC in the breakdown of immune tolerance. The group is also exploring intrahepatic routes to immune tolerance in order to prevent the progression of this disease.
• Defined the roles played by brain-death associated acute hypertension and chronic hypotension during lung vascular and epithelial damage before transplantation. We are developing strategies to prevent this damage in order to increase the availability of donor tissues

Research Strategy

The 5 core members of our group have an existing and successful network of collaborative grants, co-supervision of staff and research students, and co-authored publication. This enables us rapidly to adapt our work to new challenges and to apply our methodology across the full range of our activities. We plan to build on this synergistic collaboration by core funding through application to The British Heart Foundation, The Roche Organ Transplant Research Fund, The Wellcome Trust and the Medical Research Council. We will continue actively to seek commercial applications for our work and regularly explore the possibility of patenting our ideas. We have identified five associate members of our group. The core members currently have limited formal collaboration with these staff but we have had detailed discussion and see opportunities to establish natural common areas of joint research. All of our research is nationally competitive and most has a clear impact at the international level. Our goal is to increase our international recognition and to achieve 5* status across our work.

Further information about this area of research can be found on the Institute of Cellular Medicine website.

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