Ex-vivo normothermic perfusion of organs to minimise ischemia reperfusion injury

Transplantation is the gold-standard treatment for patients with end stage diseases. However, the supply of donor organs is limited in number and quality. Ischaemia reperfusion injury (IRI)at the time of lung transplantation may lead to primary graft dysfunction (PGD) in the recipient. PGD carries a significant early mortality risk of ~30% and is also associated with poorer long term outcomes. There is no disease-specific therapeutics available to treat the condition.

The Newcastle transplant group has developed a programme of ex-vivo lung perfusion (EVLP). The use of EVLP provides a unique opportunity to further improve our understanding of leucocyte - endothelial cell interactions underlying IRI and to study how novel therapeutics might ameliorate the innate immune cascade. Our group has already developed important pilot data showing that agonism of sphingosine-1-phosphate (S1P) receptors can augment endothelial barrier function. In this project we will use EVLP to a) modify the potential for leucocyte-vascular endothelium interaction and b) restore the integrity of the vascular permeability barrier to limit the risk of early graft injury. The overall aim of this project is to develop and evaluate novel approaches and technologies that increase the availability of donor organs for human transplantation, while also improving survival of the transplanted organ.

Our approach is comprehensive and multi-disciplinary and will bring together well-established clinical expertise with basic science and industry collaboration (XVIVO, Sweden). XVIVO is a leading company within the field of transplantation. Our Industry collaborators will provide a secondment opportunity, during which the student will gain experience of working across the sector. This project will utilise core research skills in cell biology, immunology, cell migration, flow based adhesion, RNA Seq etc. Utilising EVLP for organ directed reconditioning as a 'drug delivery platform' provides us with a unique opportunity to prevent or limit PGD. This fully funded studentship is available for outstanding candidates aiming to obtain high quality research training in an exciting and very translational subject area.