The program is designed to characterize the functions of respiratory epithelia in health and disease. The specific goals include: (1) a description of pulmonary surface liquid metabolism that integrates the functions of alveolar and of small and large airways surfaces in regulating the ionic, mucin and protein composition and volume of the surface liquid; (2) an elucidation of the mechanisms that control the rate of epithelial activities, focussing upon regulation via cytosolic Ca++ activity, arachidonic acid metabolites, cAMP mediated mechanisms, and energy metabolism; (3) changes in epithelial functions consequent to maturation; and (4) abnormalities in epithelial function in disease, e.g., cystic fibrosis (CF). Where possible the research proposed will focus on human respiratory epithelia and will employ physiologic, biochemical, pharmacologic, ultrastructural, cell biological and clinical approaches. The component projects will: (1) use microelectrode, optical, and biochemical techniques to describe alveolar ion transport activities in adult and fetal animals, and describe the mechanisms that control the functional state and number of ion paths; (2) use cell biological and biochemical approaches to evaluate rates and control of mucin synthesis and secretion in different elements of human airways (gland vs. goblet cell) from normal and diseased subjects; (3) use physiologic and ultrastructural techniques to investigate the modes of protein-translocation across airway epithelia; (4) investigate the control of ion transport in human airways (both large and small airway) focussing on arachidonic acid and cAMP derived products, integrating these studies with others designed to refine tissue culture techniques for the study of human respiratory epithelia; (5) using clinical techniques, investigate in vivo the coordination between secretory elements of nasal mucosa, glands and superficial epithelium, and their contributions to disease, e.g., C.F. Together, these projects will develop a framework for characterizing the functions and control of respiratory epithelial activities which may permit more specific approaches for the diagnosis, treatment and prevention of diseases, e.g., asthma, infection, neonatal distress syndromes, and CF that reflect a dysfunction of this tissue.
| Schultz, André; Puvvadi, Ramaa; Borisov, Sergey M et al. (2017) Airway surface liquid pH is not acidic in children with cystic fibrosis. Nat Commun 8:1409 |
| Blackmon, R L; Kreda, S M; Sears, P R et al. (2017) Direct monitoring of pulmonary disease treatment biomarkers using plasmonic gold nanorods with diffusion-sensitive OCT. Nanoscale 9:4907-4917 |
| Esther Jr, Charles R; Turkovic, Lidija; Rosenow, Tim et al. (2016) Metabolomic biomarkers predictive of early structural lung disease in cystic fibrosis. Eur Respir J 48:1612-1621 |
| Blackmon, Richard L; Kreda, Silvia M; Sears, Patrick R et al. (2016) Diffusion-sensitive optical coherence tomography for real-time monitoring of mucus thinning treatments. Proc SPIE Int Soc Opt Eng 9697: |
| Tyrrell, Jean; Qian, Xiaozhong; Freire, Jose et al. (2015) Roflumilast combined with adenosine increases mucosal hydration in human airway epithelial cultures after cigarette smoke exposure. Am J Physiol Lung Cell Mol Physiol 308:L1068-77 |
| Esther Jr, Charles R; Coakley, Raymond D; Henderson, Ashley G et al. (2015) Metabolomic Evaluation of Neutrophilic Airway Inflammation in Cystic Fibrosis. Chest 148:507-515 |
| Åstrand, Annika B M; Hemmerling, Martin; Root, James et al. (2015) Linking increased airway hydration, ciliary beating, and mucociliary clearance through ENaC inhibition. Am J Physiol Lung Cell Mol Physiol 308:L22-32 |
| Bove, Peter F; Dang, Hong; Cheluvaraju, Chaitra et al. (2014) Breaking the in vitro alveolar type II cell proliferation barrier while retaining ion transport properties. Am J Respir Cell Mol Biol 50:767-76 |
| Esther Jr, Charles R; Boucher, Richard C; Johnson, M Ross et al. (2014) Airway drug pharmacokinetics via analysis of exhaled breath condensate. Pulm Pharmacol Ther 27:76-82 |
| Mellnik, John; Vasquez, Paula A; McKinley, Scott A et al. (2014) Micro-heterogeneity metrics for diffusion in soft matter. Soft Matter 10:7781-96 |
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