Grant: Undergraduate Student Research Awards (USRA)

"Molecular strategies to treat Cystic Fibrosis (CF) lung disease, such as gene therapy, have the potential to effectively treat all patients with CF. Those strategies require precise identification of cellular targets for treatment. However, the cellular bases of CF lung disease are not understood and there is controversy on which airway cell types contribute to pathology. Traditionally, CFTR was believed to be expressed primarily in airway epithelial ciliated cells and submucosal gland serous cells. This hypothesis was challenged by two reports using scRNA-seq analysis of airway epithelia reporting a new cell type, the pulmonary ionocyte, that constitute just ~1% of all airways epithelial cells but contribute ~60% of CFTR-mediated ion transport. Moreover, cell culture preparations from Foxi1-/- ferrets that lack ionocytes display abnormal Na+ and Cl- transport, resulting in increased airway liquid viscosity and reduced mucociliary clearance, implicating ionocytes as a major contributor to CF. However, subsequent studies reported that the club cell was proposed to be the main site of CFTR-mediated transport. Our results show that ionocyte secrete HCO3- but do not contribute to airway liquid secretion. Thus, there is controversy on the role of ionocytes and club cells in CF. Hypothesis: ionocytes produce HCO3- required for mucin expansion to ensure adequate viscosity, while club cells contribute to fluid secretion and airway hydration."