Harnessing the gut microbiome to improve stem cell transplantation

Aspects of this project would be suitable for Honours, Masters, MPhil, MD and PhD students. Email the supervisor to discuss suitability.

Background

Haematopoietic stem cell transplantation (HSCT) is considered the gold standard procedure for the treatment of high-risk blood cancers. However, graft-versus-host disease (GVHD) remains a barrier to the success of this life-saving immunotherapy. GVHD occurs in 50-70% of transplanted patients, of which 20% will develop severe GVHD which is unresponsive to therapy and is eventually fatal. Thus there is an urgent need for new treatments. Systemic exposure to gut microbes (and their derivatives) which are normally sequestered in the lumen, are initiated by chemotherapy/radiation treatment prior to transplant and can have profound effects on GVHD severity. Antibiotic-based approaches to deplete the microbiome and prevent acute GVHD have been partially successful, however increasing antibiotic resistance and the realization that many bacteria have important anti-inflammatory properties severely limits this approach.

Aim

This project aims to improve our fundamental understanding of microbial-host interactions which regulate protective and pathogenic mechanisms after transplant.

Methods

This project will involve animal work, high-parameter flow cytometry, advanced bacterial genomic sequencing, metabolomics, confocal microscopy, molecular and microbiological techniques; with the validation of findings in clinical samples.

Project Potential

This research will generate new knowledge and lead to the identification of novel strategies to prevent and/or treat acute gastrointestinal GVHD.