Define new biological and genomic markers as predictive , diagnostic and therapeutic tools for use in haematopoietic stem cell transplantation (HSCT) ;to aid in the prevention of life threatening complications which occur post HSCT and which may ultimately be used in the development of new clinical strategies for improving the outcome and quality of life of patients.
Develop a unique training programme in genomics and immunobiology of transplantation aimed at generating highly trained scientists with the ability to manage complex projects including bioinformatics and understand the importance of the new challenges of the science of individualised patient medicine.
Develop methods for the assessment of acute and chronic graft versus host disease (GvHD) and transplant related complications by predicting outcome on an individual patient basis.
Improve the understanding of the immuno-pathophysiology of chronic GvHD.
Improve the assessment of chimerism and mechanisms of tolerance .
Improve the understanding of the natural killer (NK) cell repertoire reconstitution and NK cell-mediated GvL effects in HSCT.
Improve the understanding of the mechanism and potential of new therapies for GvHD, such as extracorporeal phototherapy (ECP).
Investigate the role of receptor polymorphisms in the non-adaptive immune system in predicting GvH and GvL responses
Develop early diagnostic markers of GvHD, bacterial viral infection and adverse drug reactions, via gene expression profiling and, testing of markers for histopathological damage, e.g. apoptosis, heat shock protein 70 (Hsp70) expression and dendritic cell chimerism .
Use MHC gene expression profiling to identify new genes associated with GvHD and GvL responses which can then be used in the overall assessment of patient and donor genotype for occurrence of GvHD and relapse.
Identify novel peptides and use currently patented peptides, e.g. WO02/022656 heat shock protein 70 (Hsp70) peptide, of value in diagnosis, with future potential for vaccination therapies; characterisation of Heat shock protein peptides via expression on patient blasts and eliciting a GvL response and expressed on GvHD patient biopsies and in vitro patient skin explants. In comparative studies heat shock protein associated peptides will be analysed in a specific autoimmune disease and following UVA exposure during extracorporeal phototherapy (ECP) for GvHD via studies on allorecognition.
Assess the role of individual NK cell repertoires, measured at the level of genetic polymorphism and NK cell receptor reconstitution kinetics, for anti-leukaemic responses in killer inhibitory receptor (KIR) epitope-matched as well as mismatched transplant settings.