Tissue wound healing is a normal consequence of injury but if dysregulated, can lead to pathology, as seen in idiopathic pulmonary fibrosis (IPF). IPF is a chronic debilitating lung disease with no cure, characterized by deposition of excessive extracellular matrix in the lung parenchyma. Macrophages are key components of lung defence with central roles in resolution of inflammation and repair. ( O’Callaghan et al., 2024)
The published and preliminary work of Prof. Adam Byrne indicates that pulmonary macrophages are metabolically rewired during fibrosis and furthermore, that these metabolic phenotypes are related to disease severity. (Gesa J. Albers et al., 2024) I hypothesise that metabolic alterations underlie pulmonary macrophage profibrotic phenotypes and that targeting macrophage metabolism is a tractable therapeutic strategy. This project aims to answer the following key question: What are the metabolic phenotype and nutrient dependencies of macrophage and monocytes during lung fibrosis? Developments in this area could lead to the identification of novel therapeutic targets and strategies which would help increase the quality of life of patients suffering with this condition.
I plan on testing this hypothesis using methods such as flow cytometry, Seahorse XF Cell Mito Stress Test Kit assays and qPCR testing.