The great benefit of haematopoietic stem cell transplantation for cancer patients comes from the ability of the new immune system to recognise and kill tumour cells. However, this graft-versus-leukaemia (GVL) effect is frequently accompanied by an undesired complication that results from the transplanted immune cells also targeting/damaging healthy organs (graft-versus-host disease, GVHD). Separation of GVL from GVHD has been frustrated by insufficient knowledge of the biological differences between the two processes.
This project is designed to test the hypothesis that the immune responses after transplantation are heterogeneous and tissue-specific, and that it is possible to uncouple their protective (anti-tumour and anti-viral) and pathogenic (GVHD-inducing) effects. Using cutting edge transcriptomic methodologies, we will compare how immune cells in the bone marrow function in the presence of tumour and identify the differences with those cells that cause injury in healthy tissues. Targeted gene editing of the immune cells will be used to distinguish the cellular programs critical for GVL versus GVHD.
The PhD student will be expected to develop skills in flow cytometry, cell sorting, single-cell RNA-sequencing and bioinformatics. The results from this project will help promote the development of new precision therapies for the enhancement of GVL and suppression of GVHD. More detailed information about the research project is available on request from [email protected]