Research relating to the role of TNF and its receptors has demonstrated the independent regulation and differential functions of TNFRs in myocardium, consistent with TNFR1-mediated tissue injury and cell death and TNFR2-mediated repair. These results are being translated into potential novel therapeutic approaches to reducing graft loss through a number of strategies. Peptides which may act as TNF receptor selective agonists and antagonists are being designed based on existing knowledge of TNF-TNF receptor interactions, in collaboration with Professor Shankar Balasubramanian Department of Chemistry, University of Cambridge. These peptides are currently being tested in receptor binding assays.
In addition, selective TNF receptor antagonists are being tested using in vivo models in collaboration with colleagues at Yale University as part of an academic-commercial partnership. The potential role of TNF in promoting cell growth in malignancy has also been investigated in collaboration with Professor David Neal (Cancer theme). Studies in renal cell carcinoma have demonstrated that TNF, acting through TNFR2, is an autocrine growth factor for renal cell carcinoma, acting via Enothelial/epithelial tyrosine kinase-VEGFR2 cross-talk, providing insights that may inform a more effective therapeutic approach to this disease.
Sub-theme lead: John Bradley
