Investigators: Anthony Kicic, Luke Garratt, Stephen Stick
External collaborators: Assistant Professor Rabindra Tirouvanziam (Emory University)
Hallmarks of cystic fibrosis (CF) airway disease include bronchiectasis, airway inflammation by infiltrating polymorphonuclear neutrophils (PMNs) and recurring infection. In prior landmark CF studies, we showed that bronchiectasis begins very early and coincides with high activity of neutrophil elastase (NE) from PMNs in the airway fluid. We aim to characterise how PMN reprogramming and chronic PMN inflammation are linked in early CF lung disease. We will conduct a mechanistic study of PMN function in early CF at unprecedented detail, leveraging:
- renewed understanding of PMN dysfunction in CF;
- novel in vitro model to recapitulate epithelial reprogramming;
- world-leading AREST-CF longitudinal cohort, which includes computed tomography (CT) data and airway fluid,
- gold-standard primary airway epithelial cultures obtained for an established in vitro model of bacterial, viral or hypoxic stimuli, respiratory insults highly relevant to early CF.
Project outcomes will fill a vital knowledge gap, significantly advancing therapeutic approaches for controlling airway inflammation, the major cause of morbidity and mortality in CF.