Understanding infectious respiratory complications after stem cell transplantation

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, this results in patients becoming critically immunocompromised after transplant such that infection with common respiratory viruses can be life threatening. Respiratory syncytial virus (RSV) in particular can result in pneumonitis, respiratory failure and death in up to 50% of infected patients. With no vaccines and a lack of efficacious antivirals, new treatment options are needed. Given the paucity of mechanistic data to guide clinical studies or define the basis of disease, we established a murine model of RSV infection after SCT using pneumonia virus of mice (PVM), the murine homologue of human RSV. Using this model, the aim of this research is to investigate fundamental immunological mechanisms, which underlie this post-transplant complication. This will lead to the delineation of critical mechanisms and identification of therapeutic targets to alleviate infection-driven post-transplant mortality. This project will involve animal work, high-parameter flow cytometry, single-cell transcriptomics, molecular and viral techniques, with the validation of findings in clinical samples.

KEY PAPERS 

Varelias A, et al. Lung parenchyma–derived IL-6 promotes IL-17A–dependent acute lung injury after allogeneic stem cell transplantation. Blood. 2015. 125(15):2435-44.