Research Topics
Genomes and Genes | Richard BoucherSummaryAffiliation: University of North Carolina Country: USA Publications
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Publications
Cystic fibrosis airway epithelial Ca2+ i signaling: the mechanism for the larger agonist-mediated Ca2+ i signals in human cystic fibrosis airway epitheliaCarla M Pedrosa Ribeiro
Cystic Fibrosis/Pulmonary Research and Treatment Center, University of North Carolina at Chapel Hill, North Carolina 27599-7248, USA
J Biol Chem 280:10202-9. 2005..Greater ER-derived Ca(2+)(i) signals may provide a compensatory mechanism to restore, at least acutely, mucus clearance in CF airways...- Anaerobic killing of mucoid Pseudomonas aeruginosa by acidified nitrite derivatives under cystic fibrosis airway conditionsSang Sun Yoon
Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267-0524, USA
J Clin Invest 116:436-46. 2006..In summary, selective killing by HNO2 may provide novel insights into the important clinical goal of eradicating mucoid P. aeruginosa from the CF airways... - The relative roles of passive surface forces and active ion transport in the modulation of airway surface liquid volume and compositionR Tarran
Cystic Fibrosis/Pulmonary Research and Treatment Center, The University of North Carolina at Chapel Hill, 27599, USA
J Gen Physiol 118:223-36. 2001..These data favor the active ion transport/volume model hypothesis to describe ASL physiology... - Molecular insights into the physiology of the 'thin film' of airway surface liquidR C Boucher
Cystic Fibrosis Pulmonary Research and Treatment Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 7248, USA
J Physiol 516:631-8. 1999..e. the 'insensible water loss', consequent to conditioning inspired air. How airway epithelia perform both functions, and co-ordinate them in health and disease, is the subject of this review... - Regulation of airway surface liquid volume by human airway epitheliaR C Boucher
Cystic Fibrosis Pulmonary Research and Treatment Center, 7011 Thurston Bowles Building, CB 7248, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 7248, USA
Pflugers Arch 445:495-8. 2003..Thus, insights into these systems may offer novel therapeutic opportunities to correct this physiologic dysfunction of airway epithelia... - Relationship of airway epithelial ion transport to chronic bronchitisRichard C Boucher
Cystic Fibrosis Pulmonary Research and Treatment Center, University of North Carolina at Chapel Hill, CB number 7248, 7011 Thurston Bowles, Chapel Hill, NC 27599 7248, USA
Proc Am Thorac Soc 1:66-70. 2004.... - Cystic fibrosis: a disease of vulnerability to airway surface dehydrationRichard C Boucher
Cystic Fibrosis Pulmonary Research and Treatment Center and the UNC Virtual Lung Group, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
Trends Mol Med 13:231-40. 2007..Recent clinical studies indicate that inhalation of hypertonic saline osmotically draws sufficient water onto CF airway surfaces to provide clinical benefit... - New concepts of the pathogenesis of cystic fibrosis lung diseaseR C Boucher
Cystic Fibrosis Pulmonary Research and Treatment Center, 7011 Thurston Bowles Building, CB 7248, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
Eur Respir J 23:146-58. 2004..e. blockers of Na+ transport, initiators of Cl- transport and osmolytes, are reviewed, as are strategies that may be required to use volume-restoring agents safely in patients with cystic fibrosis... - Evidence for airway surface dehydration as the initiating event in CF airway diseaseR C Boucher
CF Pulmonary Research and Treatment Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 7248, USA
J Intern Med 261:5-16. 2007..Clinical trials of inhaled hypertonic saline have demonstrated therapeutic benefit of manoeuvres designed to rehydrate CF airway surfaces... - Regulation and functional significance of airway surface liquid pHR D Coakley
The Cystic Fibrosis Pulmonary Research and Treatment Center, University of North Carolina at Chapel Hill Chapel Hill, North Carolina 27599 7248, USA
JOP 2:294-300. 2001.... - Airway surface dehydration in cystic fibrosis: pathogenesis and therapyRichard C Boucher
Cystic Fibrosis Pulmonary Research and Treatment Center, University of North Carolina at Chapel Hill, North Carolina 27599, USA
Annu Rev Med 58:157-70. 2007..Thus, rehydration therapies may slow the progression of CF lung disease in patients with established bacterial infection and may prevent the onset of CF lung disease if initiated early in life... - An overview of the pathogenesis of cystic fibrosis lung diseaseR C Boucher
Cystic Fibrosis Pulmonary Research and Treatment Center, 7011 Thurston Bowles Building, CB 7248, School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
Adv Drug Deliv Rev 54:1359-71. 2002..These plugs become the nidus for persistent bacterial airway infections that ultimately lead to a markedly anaerobic luminal environment... - Normal and cystic fibrosis airway surface liquid homeostasis. The effects of phasic shear stress and viral infectionsRobert Tarran
Cystic Fibrosis/Pulmonary Research and Treatment Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7248, USA
J Biol Chem 280:35751-9. 2005.... - Regulation of airway tight junctions by proinflammatory cytokinesCarolyn B Coyne
Cystic Fibrosis/Pulmonary Research and Treatment Center, The University of North Carolina at Chapel Hill, 27599, USA
Mol Biol Cell 13:3218-34. 2002..These data indicate that the TJ of airway epithelia exposed to chronic inflammation may exhibit parallel changes in the barrier function to both solutes and ions... - CFTR delivery to 25% of surface epithelial cells restores normal rates of mucus transport to human cystic fibrosis airway epitheliumLiqun Zhang
CF Pulmonary Research and Treatment Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
PLoS Biol 7:e1000155. 2009.... - Adenosine deaminase 1 and concentrative nucleoside transporters 2 and 3 regulate adenosine on the apical surface of human airway epithelia: implications for inflammatory lung diseasesAndrew J Hirsh
Cystic Fibrosis Pulmonary Research and Treatment Center, University of North Carolina, Chapel Hill, North Carolina 27599, USA
Biochemistry 46:10373-83. 2007..This study shows that adenosine elimination on human airway epithelia is mediated by ADA1, CNT2, and CNT3, which constitute important regulators of adenosine-mediated inflammation... - Mechanical ventilation alters airway nucleotides and purinoceptors in lung and extrapulmonary organsChristelle D Douillet
Department of Surgery, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7228, USA
Am J Respir Cell Mol Biol 32:52-8. 2005..MV alters the BAL adenyl-nucleotide profile and purinoceptor patterns in lung, liver, and kidney. PEEP normalizes the BAL nucleotide profile and receptor patterns in lung and extrapulmonary tissues... - Rationale for hypertonic saline therapy for cystic fibrosis lung diseaseRobert Tarran
Cystic Fibrosis Pulmonary Research and Treatment Center, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599 7248, USA
Semin Respir Crit Care Med 28:295-302. 2007.... - Regulation of murine airway surface liquid volume by CFTR and Ca2+-activated Cl- conductancesRobert Tarran
Cystic Fibsosis Pulmonary Research and Treatment Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
J Gen Physiol 120:407-18. 2002..g., mucosal nucleotides). We conclude that both CaCC and the Ca(2+) signal are increased in CF airway epithelia, and that they contribute to acute but not basal regulation of ASL height... - Thrombin promotes release of ATP from lung epithelial cells through coordinated activation of rho- and Ca2+-dependent signaling pathwaysLucia Seminario-Vidal
Department of Cell and Molecular Physiology, University of North Carolina, Chapel Hill, North Carolina 27599, USA
J Biol Chem 284:20638-48. 2009.... - Human alveolar type II cells secrete and absorb liquid in response to local nucleotide signalingPeter F Bove
Department of Medicine, Cystic Fibrosis Pulmonary Research and Treatment Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
J Biol Chem 285:34939-49. 2010..Collectively, our studies suggest that human AT2 cells in vitro have the capacity to absorb or secrete liquid in response to local alveolar conditions... - Acute mechanism of medium chain fatty acid-induced enhancement of airway epithelial permeabilityCarolyn B Coyne
Cystic Fibrosis/Pulmonary Research and Treatment Center, 7123A Thurston Bowles Bldg, CB no. 7248, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7248, USA
J Pharmacol Exp Ther 305:440-50. 2003..These data suggest that C10 and C12 exert their acute effects on airway TJs via a Ca(2+)-independent mechanism of action and may alter junctional permeability via direct effects on the claudin family of TJ proteins... - Abnormal surface liquid pH regulation by cultured cystic fibrosis bronchial epitheliumRaymond D Coakley
Cystic Fibrosis/Pulmonary Research and Treatment Center, School of Medicine, University of North Carolina, Chapel Hill, NC 27599-7248, USA
Proc Natl Acad Sci U S A 100:16083-8. 2003.... - Mathematical model of nucleotide regulation on airway epithelia. Implications for airway homeostasisPeiying Zuo
Department of Mathematics, University of North Carolina, Chapel Hill, North Carolina 27599, USA
J Biol Chem 283:26805-19. 2008..These new insights into the biochemical processes supporting ASL nucleotide regulation illustrate the potential of this mathematical model for fundamental and clinical research... - Thin-film measurements of airway surface liquid volume/composition and mucus transport rates in vitroRobert Tarran
Cystic Fibrosis/Pulmonary Research and Treatment Center, University of North Carolina, Chapel Hill, NC, USA
Methods Mol Med 70:479-92. 2002 - Glycocalyx restricts adenoviral vector access to apical receptors expressed on respiratory epithelium in vitro and in vivo: role for tethered mucins as barriers to lumenal infectionJaclyn R Stonebraker
Cystic Fibrosis/Pulmonary Research and Treatment Center, University of North Carolina at Chapel Hill, 7021 Thurston Bowles, Chapel Hill, NC 27759-7248, USA
J Virol 78:13755-68. 2004.... - The epithelium as a target for therapy in cystic fibrosisWilliam R Thelin
Cystic Fibrosis Pulmonary Research and Treatment Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
Curr Opin Pharmacol 7:290-5. 2007..Although still in the development phase, these approaches, used by themselves or in combination, show great promise in the treatment of CF... - A physical linkage between cystic fibrosis airway surface dehydration and Pseudomonas aeruginosa biofilmsHirotoshi Matsui
Cystic Fibrosis/Pulmonary Research and Treatment Center, University of North Carolina, Chapel Hill, NC 27599, USA
Proc Natl Acad Sci U S A 103:18131-6. 2006..aeruginosa biofilms in CF via changes in the hydration-dependent physical-chemical properties of mucus and suggest that the thickened mucus gel model will be useful to develop therapies of P. aeruginosa biofilms in CF airways... - Front-runners for pharmacotherapeutic correction of the airway ion transport defect in cystic fibrosisMark T Clunes
Cystic Fibrosis Pulmonary Research and Treatment Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United States
Curr Opin Pharmacol 8:292-9. 2008..If mucociliary clearance can be stimulated sufficiently from an early age, then there is the possibility that secondary lung infection may be eradicated from the syndrome of CF disease... - Nucleotides induce IL-6 release from human airway epithelia via P2Y2 and p38 MAPK-dependent pathwaysChristelle D Douillet
Division of Trauma and Critical Care, Department of Surgery, University of North Carolina at Chapel Hill, 4008 Burnett-Womack, Chapel Hill, NC 27599-7228, USA
Am J Physiol Lung Cell Mol Physiol 291:L734-46. 2006..This effect is dependent on transcription and translation. Our findings were confirmed in an in vivo model, thus demonstrating a novel mechanism of nucleotide-induced IL-6 secretion by airway epithelia... - The DeltaF508 mutation results in loss of CFTR function and mature protein in native human colonMarcus Mall
School of Medicine, University of North Carolina at Chapel Hill, NC 27599, USA
Gastroenterology 126:32-41. 2004..However, data with respect to the processing block of DeltaF508 protein in native epithelia are limited and conflicting... - Airway and lung pathology due to mucosal surface dehydration in {beta}-epithelial Na+ channel-overexpressing mice: role of TNF-{alpha} and IL-4R{alpha} signaling, influence of neonatal development, and limited efficacy of glucocorticoid treatmentAlessandra Livraghi
Cystic Fibrosis Pulmonary Research and Treatment Center, The University of North Carolina at Chapel Hill, 27599, USA
J Immunol 182:4357-67. 2009..Thus, manipulation of multiple pathways will likely be required to treat the complex pathogenesis caused by airway surface dehydration... - Role of endoplasmic reticulum stress in cystic fibrosis-related airway inflammatory responsesCarla M P Ribeiro
Cystic Fibrosis Pulmonary Research and Treatment Center and the Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
Proc Am Thorac Soc 7:387-94. 2010.... - Mechanosensitivity of mouse tracheal ciliary beat frequency: roles for Ca2+, purinergic signaling, tonicity, and viscosityScot L Winters
Department of Medicine, Cystic Fibrosis Pulmonary Research and Tteatment Center, University of North Carolina, Chapel Hill, NC 27599 7248, USA
Am J Physiol Lung Cell Mol Physiol 292:L614-24. 2007.... - Physiological regulation of ATP release at the apical surface of human airway epitheliaSeiko F Okada
Cystic Fibrosis Pulmonary Research and Treatment Center, University of North Carolina, Chapel Hill, NC, USA
J Biol Chem 281:22992-3002. 2006.... - The cystic fibrosis transmembrane conductance regulator impedes proteolytic stimulation of the epithelial Na+ channelMartina Gentzsch
Cystic Fibrosis Pulmonary Research and Treatment Center, University of North Carolina, Chapel Hill, North Carolina 27599, USA
J Biol Chem 285:32227-32. 2010..Our results identify limiting proteolytic cleavage of ENaC as a mechanism by which CFTR down-regulates Na(+) absorption... - Osmolytes and ion transport modulators: new strategies for airway surface rehydrationJennifer L Goralski
Division of Pulmonary and Critical Care Medicine, University of North Carolina at Chapel Hill, 130 Mason Farm Road, CB 7020, Chapel Hill, NC 27599 7020, United States
Curr Opin Pharmacol 10:294-9. 2010..Combinations of these therapies may result in a synergistic improvement in airway hydration, and thus, restore MCC. Active ongoing phase II and III trials of new pharmacotherapeutics are covered in this review... - Receptor-promoted exocytosis of airway epithelial mucin granules containing a spectrum of adenine nucleotidesSilvia M Kreda
Cystic Fibrosis Pulmonary Research and Treatment Center, University of North Carolina at Chapel Hill, 4029A Thurston Bowles Building, Chapel Hill, NC 27599 7248, USA
J Physiol 588:2255-67. 2010.... - Purinergic receptors in airway epitheliaEduardo R Lazarowski
Cystic Fibrosis Pulmonary Research and Treatment Center, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
Curr Opin Pharmacol 9:262-7. 2009..Agonist occupation of the P2Y2 receptor promotes inhibition of Na+ absorption as well as CFTR-dependent and CFTR-independent Cl- secretion, ciliary beating, and mucin secretion... - Similarities between UDP-glucose and adenine nucleotide release in yeast: involvement of the secretory pathwayCharles R Esther
Division of Pediatric Pulmonology, University of North Carolina, Chapel Hill, North Carolina 27599, USA
Biochemistry 47:9269-78. 2008..These studies demonstrate the involvement of the secretory pathway in nucleotide and nucleotide sugar efflux in yeast and offer a powerful model system for further investigation... - Role of mechanical stress in regulating airway surface hydration and mucus clearance ratesBrian Button
Cystic Fibrosis Research and Treatment Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 7248, USA
Respir Physiol Neurobiol 163:189-201. 2008.... - Sodium channels and cystic fibrosisScott H Donaldson
Cystic Fibrosis Research and Treatment Center, 6007B Thurston Bowles Building, CB 7248, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
Chest 132:1631-6. 2007..The development of treatment strategies that address this defect is a logical and promising means of preventing or delaying the onset of this lethal lung disease... - Modelling dysregulated Na+ absorption in airway epithelial cells with mucosal nystatin treatmentAlessandra Livraghi
University of North Carolina at Chapel Hill, Cystic Fibrosis Pulmonary Research and Treatment Center, CB 7248 Thurston Bowles Bldg, Room 6029, Chapel Hill, NC 27599, USA
Am J Respir Cell Mol Biol 38:423-34. 2008..We conclude that mucosal Nys treatment of HBEs provides a simple in vitro model to recapitulate the Na(+) and volume hyperabsorptive features of CF airway epithelia... - Azithromycin treatment alters gene expression in inflammatory, lipid metabolism, and cell cycle pathways in well-differentiated human airway epitheliaCarla Maria P Ribeiro
Cystic Fibrosis Center, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America
PLoS ONE 4:e5806. 2009.... - Mass spectrometric analysis of biomarkers and dilution markers in exhaled breath condensate reveals elevated purines in asthma and cystic fibrosisCharles R Esther
Division of Pediatric Pulmonology, Chapel Hill, North Carolina, USA
Am J Physiol Lung Cell Mol Physiol 296:L987-93. 2009..These results show that mass spectrometric analyses can be applied to measurement of purines in EBC and demonstrate that EBC adenosine-to-urea and AMP-to-urea ratios are potential noninvasive biomarkers of airways disease... - Coordinated release of nucleotides and mucin from human airway epithelial Calu-3 cellsSilvia M Kreda
Cystic Fibrosis Pulmonary Research and Treatment Center, The University of North Carolina at Chapel Hill, 7017 Thurston Bowles Building, Chapel Hill, NC 27599 7248, USA
J Physiol 584:245-59. 2007..Our data suggest that nucleotide release is a mechanism by which mucin-secreting goblet cells produce paracrine signals for mucin hydration within the ASL... - Effective mucus clearance is essential for respiratory healthScott H Randell
Department of Cell and Molecular Physiology, University of North Carolina at Chapel Hill, USA
Am J Respir Cell Mol Biol 35:20-8. 2006 - Regulation of normal and cystic fibrosis airway surface liquid volume by phasic shear stressRobert Tarran
Cystic Fibrosis Pulmonary Research and Treatment Center, University of North Carolina, Chapel Hill, North Carolina 27599 7248, USA
Annu Rev Physiol 68:543-61. 2006..We also discuss (a) how derangement of the ADO-CFTR pathway renders CF airways vulnerable to viral infections that deplete ASL volume and produce mucus stasis, and (b) potential shear stress-dependent therapies for CF... - In vivo airway surface liquid Cl- analysis with solid-state electrodesRay A Caldwell
Cystic Fibrosis Pulmonary Research and Treatment Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
J Gen Physiol 119:3-14. 2002..3 +/- 7.1 mM, n = 5) and monkey (128.5 +/- 6.8 mM, n = 3). The measured [Cl-], in excess of 100 mM throughout all airway regions tested in multiple species, is consistent with the isotonic volume hypothesis to describe ASL physiology... - Metabolism of P2 receptor agonists in human airways: implications for mucociliary clearance and cystic fibrosisMaryse Picher
Cystic Fibrosis Pulmonary Research and Treatment Center, School of Medicine, University of North Carolina, 7010 Thurston Bowles Building, Chapel Hill, NC 27599, USA
J Biol Chem 279:20234-41. 2004..This study demonstrates that the duration of nucleotide-mediated MCC is limited by epithelial ectonucleotidases throughout human airways, with the efficiency of this mechanism enhanced in chronic inflammatory lung diseases, including CF... - C-Mannosylation of MUC5AC and MUC5B Cys subdomainsJuan Perez-Vilar
Cystic Fibrosis Pulmonary Research and Treatment Center, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
Glycobiology 14:325-37. 2004..C-mannosylation is likely required for proper folding of the Cys subdomains and/or for some aspect of ER export during mucin biosynthesis... - Effect of ventilatory rate on airway cytokine levels and lung injuryPreston B Rich
Departments of Surgery, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 7228, USA
J Surg Res 113:139-45. 2003.... - Adenosine triphosphate is released during injurious mechanical ventilation and contributes to lung edemaPreston B Rich
Department of Surgery, Univeristy of North Carolina School of Medicine, Chapel Hill, 27599 7228, USA
J Trauma 55:290-7. 2003..It is unknown whether adenosine triphosphate (ATP) is released in vivo during mechanical ventilation (MV). We hypothesized that stress from high-pressure MV would increase airway ATP, contributing to MV-associated lung edema... - Role of claudin interactions in airway tight junctional permeabilityCarolyn B Coyne
Cystic Fibrosis Pulmonary Research and Treatment Center, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
Am J Physiol Lung Cell Mol Physiol 285:L1166-78. 2003..These suggest that airway TJs are regulated by claudinclaudin interactions that confer the selectivity of the junction... - Polarized distribution of HCO3- transport in human normal and cystic fibrosis nasal epitheliaAnthony M Paradiso
Cystic Fibrosis Pulmonary Research and Treatment Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 7248, USA
J Physiol 548:203-18. 2003.... - Ecto 5'-nucleotidase and nonspecific alkaline phosphatase. Two AMP-hydrolyzing ectoenzymes with distinct roles in human airwaysMaryse Picher
Cystic Fibrosis Pulmonary Research and Treatment Center, School of Medicine, University of North Carolina, Chapel Hill, North Carolina 27599, USA
J Biol Chem 278:13468-79. 2003..Collectively, these experiments support a major role for extracellular nucleotide catalysis and for ecto 5'-NT and NS AP in the regulation of adenosine concentrations on airway surfaces... - Human airway ecto-adenylate kinase. A mechanism to propagate ATP signaling on airway surfacesMaryse Picher
Cystic Fibrosis Pulmonary Research and Treatment Center, School of Medicine, University of North Carolina, Chapel Hill, North Carolina 27599, USA
J Biol Chem 278:11256-64. 2003..Our data suggest a role for this nucleotide entrapment cycle in the propagation of purine-mediated mucociliary clearance on human airway epithelial surfaces... - A proteomic analysis of human cilia: identification of novel componentsLawrence E Ostrowski
Cystic Fibrosis Pulmonary Research and Treatment Center, The University of North Carolina, School of Medicine, Chapel Hill, North Carolina 27599 7248, USA
Mol Cell Proteomics 1:451-65. 2002..These studies represent the first proteomic analysis of the human ciliary axoneme and have identified many potentially novel components of this complex organelle... - In vivo microdialysis for determination of nasal liquid ion compositionBarbara R Grubb
Cystic Fibrosis Pulmonary Research and Treatment Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
Am J Physiol Cell Physiol 282:C1423-31. 2002..7 +/- 0.4 mM) was significantly less in normal than in CF mice (16.6 +/- 4 mM). IVMD accurately samples nasal liquid for ionic composition. The ionic composition of nasal liquid in the normal and CF mice is similar... - Respiratory syncytial virus infection of human airway epithelial cells is polarized, specific to ciliated cells, and without obvious cytopathologyLiqun Zhang
Cystic Fibrosis Pulmonary Research and Treatment Center, University of North Carolina, Chapel Hill, North Carolina 27599 7248, USA
J Virol 76:5654-66. 2002..Since rgRSV appears to breach the lumenal barriers encountered by other gene transfer vectors in the airway, this virus may be a good candidate for the development of a gene transfer vector for CF lung disease... - Increased airway epithelial Na+ absorption produces cystic fibrosis-like lung disease in miceMarcus Mall
Cystic Fibrosis Pulmonary Research and Treatment Center, School of Medicine, The University of North Carolina at Chapel Hill, 7011 Thurston Bowles Building, Chapel Hill, North Carolina 27599 7248, USA
Nat Med 10:487-93. 2004..We conclude that increasing airway Na(+) absorption initiates cystic fibrosis-like lung disease and produces a model for the study of the pathogenesis and therapy of this disease... - Reduced three-dimensional motility in dehydrated airway mucus prevents neutrophil capture and killing bacteria on airway epithelial surfacesHirotoshi Matsui
Cystic Fibrosis Pulmonary Research and Treatment Center and Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC 27599, USA
J Immunol 175:1090-9. 2005..We conclude that concentrated ("thick") mucus inhibits neutrophil migration and killing and is a key component in the failure of defense against chronic airways infection in CF... - SERCA pump inhibitors do not correct biosynthetic arrest of deltaF508 CFTR in cystic fibrosisBarbara R Grubb
Cystic Fibrosis Pulmonary Research and Treatment Center, 7011 Thurston Bowles Bldg, CB 7248, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 7248, USA
Am J Respir Cell Mol Biol 34:355-63. 2006.... - Reevaluating gel-forming mucins' roles in cystic fibrosis lung diseaseJuan Perez-Vilar
The Cystic Fibrosis Pulmonary Research and Treatment Center, School of Medicine, University of North Carolina at Chapel Hill, CB7248, 4011 Thurston Bowles Bldg, Chapel Hill, NC 27599, USA
Free Radic Biol Med 37:1564-77. 2004..These novel interactions would create an atypical mucin network with abnormal viscoelastic and adhesive properties... - Mucin granules are in close contact with tubular elements of the endoplasmic reticulumJuan Perez-Vilar
Cystic Fibrosis Pulmonary Research and Treatment Center, School of Medicine, University of North Carolina at Chapel Hill, 27599 7248, USA
J Histochem Cytochem 53:1305-9. 2005..This meshwork could be identified in fixed native human bronchial goblet cells labeled with an anti-calreticulin antibody. The potential biological significance of this ER network for mucin secretion is discussed... - Chronic airway infection/inflammation induces a Ca2+i-dependent hyperinflammatory response in human cystic fibrosis airway epitheliaCarla M Pedrosa Ribeiro
Cystic Fibrosis Center and Department of Medicine, University of North Carolina, Chapel Hill, North Carolina 27599, USA
J Biol Chem 280:17798-806. 2005..However, in CF airways, the Ca(2+)(i)-mediated hyperinflammation may be ineffective in promoting the eradication of infection in thickened mucus and, consequently, may have adverse effects in the lung... - Mucin granule intraluminal organization in living mucous/goblet cells. Roles of protein post-translational modifications and secretionJuan Perez-Vilar
Cystic Fibrosis Pulmonary Research and Treatment Center, University of North Carolina, Chapel Hill, North Carolina 27599 7248, USA
J Biol Chem 281:4844-55. 2006.... - pH-dependent intraluminal organization of mucin granules in live human mucous/goblet cellsJuan Perez-Vilar
Cystic Fibrosis Pulmonary Research and Treatment Center, School of Medicine, University of North Carolina, Chapel Hill, North Carolina 27599 7248, USA
J Biol Chem 280:16868-81. 2005..An intraluminal acidic pH, maintained by the vacuolar H+-ATPase, is one of the critical factors for secretory protein binding to the immobile phase and also for its organization... - Neutrophil elastase activates near-silent epithelial Na+ channels and increases airway epithelial Na+ transportRay A Caldwell
Cystic Fibrosis Pulmonary Research and Treatment Center, University of North Carolina, Chapel Hill, NC 27599 7248, USA
Am J Physiol Lung Cell Mol Physiol 288:L813-9. 2005..The hNE-induced increase of near-silent ENaC activity in CF airways could contribute to Na(+) hyperabsorption, reduced airway surface liquid height, and dehydrated mucus culminating in inefficient mucociliary clearance... - Voltage-dependent anion channel-1 (VDAC-1) contributes to ATP release and cell volume regulation in murine cellsSeiko F Okada
Cystic Fibrosis Pulmonary Research and Treatment Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
J Gen Physiol 124:513-26. 2004..However, the observation that VDAC-1 knockout cells released a significant amount of ATP suggests that other molecules also play a role in this function... - Patterns of epithelial cell invasion by different species of the Burkholderia cepacia complex in well-differentiated human airway epitheliaUte Schwab
Cystic Fibrosis Pulmonary Research and Treatment Center, The University of North Carolina at Chapel Hill, 27599 7248, USA
Infect Immun 70:4547-55. 2002..Strain J-1 penetrated the epithelium both by cell destruction and paracytosis. These studies suggest that the distinct invasion pathways employed by B. cepacia may account for differences in virulence between B. cepacia genomovars... - Mucus clearance and lung function in cystic fibrosis with hypertonic salineScott H Donaldson
University of North Carolina at Chapel Hill Cystic Fibrosis Research and Treatment Center, Chapel Hill 27599, USA
N Engl J Med 354:241-50. 2006..Through osmotic forces, hypertonic saline may increase the volume of airway surface liquid, restore mucus clearance, and improve lung function... - Design, synthesis, and structure-activity relationships of novel 2-substituted pyrazinoylguanidine epithelial sodium channel blockers: drugs for cystic fibrosis and chronic bronchitisAndrew J Hirsh
Parion Sciences Inc, 2525 Meridian Parkway, Suite 260, Durham, North Carolina 27713, USA
J Med Chem 49:4098-115. 2006..Lead compound 32 was 102-fold more potent and 5-fold less reversible than amiloride and displayed the lowest IC(50) value ever reported for an ENaC blocker... - Evaluation of second generation amiloride analogs as therapy for cystic fibrosis lung diseaseAndrew J Hirsh
Parion Sciences Inc, 2525 Meridian Parkway, Suite 260, Durham, NC 27713, USA
J Pharmacol Exp Ther 311:929-38. 2004..More potent, less absorbable, third generation ENaC blockers will be required for an effective aerosol CF pharmacotherapy... - The mitochondrial barriers segregate agonist-induced calcium-dependent functions in human airway epitheliaCarla M Pedrosa Ribeiro
Cystic Fibrosis Pulmonary Research and Treatment Center and Department of Medicine, The University of North Carolina at Chapel Hill, NC 27599 7248, USA
J Gen Physiol 122:377-87. 2003.... - Update on pathogenesis of cystic fibrosis lung diseaseScott H Donaldson
Department of Medicine, University of North Carolina at Chapel Hill, 27599, USA
Curr Opin Pulm Med 9:486-91. 2003..Various hypotheses have attempted to explain the apparent breach of innate defenses in CF, although a definitive explanation has been elusive... - Development of chronic bronchitis and emphysema in beta-epithelial Na+ channel-overexpressing miceMarcus A Mall
Pediatric Pulmonology and Cystic Fibrosis Center, Department of Pediatrics III, University of Heidelberg, Im Neuenheimer Feld 153, 69120 Heidelberg, Germany
Am J Respir Crit Care Med 177:730-42. 2008..Previous studies have shown that airway surface dehydration in beta-epithelial Na(+) channel (betaENaC)-overexpressing mice caused a chronic lung disease with high neonatal pulmonary mortality and chronic bronchitis in adult survivors... - Pharmacological properties of N-(3,5-diamino-6-chloropyrazine-2-carbonyl)-N'-4-[4-(2,3-dihydroxypropoxy)phenyl]butyl-guanidine methanesulfonate (552-02), a novel epithelial sodium channel blocker with potential clinical efficacy for cystic fibrosis lung dAndrew J Hirsh
Parion Sciences Inc, 2525 Meridian Pkwy, Suite 260, Durham, NC 27713, USA
J Pharmacol Exp Ther 325:77-88. 2008..In summary, the preclinical data support the clinical use of 552-02 +/- hypertonic saline for CF lung disease...
Research Grants
- SCCOR in Host Factors in Chronic Lung DiseaseRichard Boucher; Fiscal Year: 2007..The long term objective of this project is to understand how these two layers are maintained and work together to protect the lung and thus help design better therapies. (End of Abstract) ..
- PULMONARY EPITHELIA IN HEALTH AND DISEASERichard Boucher; Fiscal Year: 2007..g., COPD, CF, and asthma, and lead to novel therapies to hydrate airway surfaces to clear the mucus plugs/plaques that produce airways obstruction and infection in these major pulmonary diseases. ..
- PULMONARY, CRITICAL CARE, AND MOLECULAR TRAININGRichard Boucher; Fiscal Year: 2007..End of Abstract) ..
- Mucus Clearance in Acute COPD ExacerbationsRichard Boucher; Fiscal Year: 2006..The ultimate goals for the U.S. COPD patient population are to generate a mechanistic understanding of a major component of an AE and provide the mechanistic basis for novel therapies of AEs. ..
- The Role of Anaerobic Bacterial Infection in Cystic FibrosisRichard C Boucher; Fiscal Year: 2010..S. (Richard Boucher) have explored this hypothesis and produced the following preliminary data: 1) anaerobes are present in the ..