Influenza virus infection, monocytes, macrophages and their roles in lung fibrosis

Supervisor: Professor Ling-Pei Ho

Lung fibrosis (specifically, idiopathic pulmonary fibrosis or IPF) is a devastating disease with a very poor outcome.  Treatment is limited and not proven to prevent progression, merely to slow disease. Acute exacerbations of the condition are associated with diffuse lung injury and 60-80% mortality, and there is a pressing need to address the cause of these periods of accelerated fibrosis.  Our studies in IPF patients suggest that monocytes have pro-fibrogenic characteristics and may contribute to progression and acceleration of lung fibrosis.

This DPhil project will examine the hypothesis that influenza viral infection modifies the baseline composition of resident lung macrophages, depleting pre-existing tolerogenic alveolar macrophages to allow replacement by long-lived, pro-fibrogenic monocyte-derived macrophages.  Using established bleomycin model and matched human lung samples, the project will use single cell RNA sequencing and mass cytometry (CYTOF) to comprehensively characterise the subsets and functions of circulating monocytes and lung macrophages during fibrogenesis and concomitant influenza infection.  Relevant genetically modified mice and CRISPR/cas9 technology will be used to target genes uncovered in these studies in order to examine how they contribute to fibrosis.

The project will complement other studies in the group geared towards identifying new cellular pathways for therapeutic targets in acute exacerbation of IPF.

For further information, please contact:  Prof Ling-Pei Ho