Targeting the gut and the microbiome to improve blood cancer treatments

Multiple projects available to suit Honours or PhD students

Stem cell transplantation (SCT) remains the preferred treatment option for the majority of blood cancers providing alloimmunity to eradicate the disease and prevent relapse. However, graft-versus-host disease (GVHD) is a major complication that limits its effectiveness and utility, thus represents a clinical unmet need. Chemotherapy/radiation prior to transplant damages the intestinal epithelium resulting in systemic exposure to microbiota and their by-products, which are normally sequestered in the lumen. The aim of this research is to improve our fundamental understanding of the microbial-host interactions, which regulate protective/pathogenic mechanisms after transplant. This will lead to the identification of new strategies to prevent and/or treat acute gastrointestinal GVHD. This project will involve animal work, high-parameter flow cytometry, bacterial genomic sequencing, metabolomics, spatial transcriptomics, confocal microscopy, molecular and microbiological techniques, with the validation of findings in clinical samples.

KEY PAPERS

Varelias A, et al. Acute graft-versus-host disease is regulated by an IL-17-sensitive microbiome. Blood. 2017. 129(15):2172-85.

Varelias A*, Bunting MD*, et al. Recipient Mucosal-Associated Invariant T Cells control GVHD within the colon. J Clin Invest. 2018. 128(5):1919-36. *Joint first authors.