Airway Surface Liquid (ASL) physiology in health and how it fails in major airways diseases, e.g. the "dehydration hypothesis as relates to CF" (Figure 1).
Airway epithelial Na+ transport, including studies of normal regulation of airway epithelial Na+ transport, and role of Na+ transport in airways disease, including mouse models over-expressing subunits of the epithelial Na+ channel (ENaC) (Figures 2, 3).
Extracellular nucleotides and their role in airways homeostasis, including the role of P2 receptors in airway epithelial function, extracellular nucleotidases; and measuring the rates of metabolism of nucleotides and nucleotide release from cells.
Gene therapy for CF lung disease, particularly focusing on investigations of barriers to gene transfer, and improved vector targeting.
Clinical studies: a current area of interest focuses on Na+ channel blockers and hypertonic saline (Figures 4-6).
Fig 1. CF Airways Disease: The "Dehydration" Hypothesis. Annual Review of Medicine, 2007.
Fig 2. The βENaC Mouse Model: A Phenocopy of CF Lung Disease. Nature Medicine, 2007.
Fig 3. Survival Curves and Causes of Death of Scnn1b (βENaC) Mice. Nature Medicine, 2004.
Fig 4. CF Produces Heterogeneous Structural and 'Basal' Mucus Clearance Lung Defects. NEJM, 2006.
Fig 5. Therapeutic Strategies to Rehydrate CF Airway Surfaces. Curr Opin Pharm, 2010.
Fig 6. Airway Surface Liquid Height in Human Bronchial Epithelial Culture Response to Aerosolized Hypertonic Saline +/- Long-Acting Na+ Channel Blocker.
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Esther CR Jr, Hill DB, Button B, Shi S, Jania CM, Duncan EA, Doerschuk CM, Chen G, Ranganathan S, Stick SM, Boucher RC. The sialic acid to urea ratio as a measure of airway surface hydration. Am J Physiol Lung Cell Mol Physiol. 2017 Mar 1;312(3):L398-404. doi: 10.1152/ajplung.00398.2016. PMID: 28062483. PMCID: PMC5374301.
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Saini Y, Wilkinson KJ, Terrell KA, Burns KA, Livraghi-Butrico A, Doerschuk CM, O'Neal WK, Boucher RC. Neonatal pulmonary macrophage depletion coupled to defective mucus clearance increases susceptibility to pneumonia and alters pulmonary immune responses. Am J Respir Cell Mol Biol. 2016 Feb;54(2):210-21. doi: 10.1165/rcmb.2014-0111OC. Epub 2015 Jun 29. PubMed PMID: 26121027. PubMed Central PMCID: PMC4821038.
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