The Program Project """"""""Pulmonary Epithelia in Health and Disease"""""""" tests the overall hypothesis that the pulmonary epithelial regulation of surface liquids is critical for the health of the lung. Specific hypotheses will be tested in five projects, focusing on the roles of extracellular triphosphate nucleotide receptors (P2U-Rs), non-CFTR chloride channels, and epithelial Na+ channels (ENaC), that are supported by three Cores. Project I, Regulation of Airways Mucosal Physiology/Defense, R.C. Boucher, Project Leader, proposes to test hypotheses related to the roles of P2U-R and ENaC in regulation of airway surface liquid (ASL) volume and composition, and lung defense, in genetically manipulated mice. Project II, Regulation of Ion Conductances in Airway Epithelia, M.J. Stutts, Project Leader, will test hypotheses related to the theme of nucleotide secretion into airway lumens and CFTR-specific regulation of ENaC. Project III, Human Airway P2U Purinergic Receptors, T.K. Harden, Project Leader, will further expand the theme of P2U-Rs, identifying high affinity agonists/antagonists for P2U-R and exploring the mechanisms of acute and chronic P2U-R desensitization/tachyphylaxis. Project IV, Cl- Secretion and Na+ Absorption by Fetal and Newborn Lung, P.M. Barker, Project Leader, will explore the role of P2U-Rs, ATP release, and identification of Cl- and Na+ channels functional in fetal lung liquid metabolism, focusing on comparative studies in fetal mouse and human pulmonary epithelia. Project V, Human Respiratory Epithelial Function In Vivo, M.R. Knowles, Project Leader, will extend studies of the concepts of airway ATP secretion, acute and chronic effects of ATP/UTP on P2U-R desensitization/tachyphylaxis, and the contributions of abnormal Cl- transport and abnormal Na+ pathogenesis to CF and non-CF lung diseases to human subjects in vivo. The Projects are supported by and Administrative Core (A); an Imaging/Morphology Core (B) with an extensive engineering component; and a Mouse Core (C), for breeding and maintaining knockout and transgenic mice. The PPG asks fundamental questions about pulmonary epithelial physiology/pathophysiology in children and adults, and attacks these questions with a powerful combination of molecular and physiologic techniques in mouse models and man. The goal is to develop a comprehensive understanding of pulmonary epithelial physiology that will generate important new concepts for treatment of airway diseases in children and adults, as well as neonatal pulmonary diseases of prematurity that are a major cause of mortality, especially in minorities.
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| 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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