Richard Boucher

Summary

Affiliation: University of North Carolina
Country: USA

Publications

  1. ncbi request reprint Cystic fibrosis airway epithelial Ca2+ i signaling: the mechanism for the larger agonist-mediated Ca2+ i signals in human cystic fibrosis airway epithelia
    Carla 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
  2. pmc Anaerobic killing of mucoid Pseudomonas aeruginosa by acidified nitrite derivatives under cystic fibrosis airway conditions
    Sang 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
  3. pmc The relative roles of passive surface forces and active ion transport in the modulation of airway surface liquid volume and composition
    R 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
  4. pmc Molecular insights into the physiology of the 'thin film' of airway surface liquid
    R 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
  5. ncbi request reprint Regulation of airway surface liquid volume by human airway epithelia
    R 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
  6. ncbi request reprint Relationship of airway epithelial ion transport to chronic bronchitis
    Richard 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
  7. ncbi request reprint Cystic fibrosis: a disease of vulnerability to airway surface dehydration
    Richard 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
  8. ncbi request reprint New concepts of the pathogenesis of cystic fibrosis lung disease
    R 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
  9. ncbi request reprint Evidence for airway surface dehydration as the initiating event in CF airway disease
    R 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
  10. ncbi request reprint Regulation and functional significance of airway surface liquid pH
    R 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

Research Grants

  1. The Role of Anaerobic Bacterial Infection in Cystic Fibrosis
    Richard C Boucher; Fiscal Year: 2010
  2. SCCOR in Host Factors in Chronic Lung Disease
    Richard Boucher; Fiscal Year: 2007
  3. PULMONARY EPITHELIA IN HEALTH AND DISEASE
    Richard Boucher; Fiscal Year: 2007
  4. PULMONARY, CRITICAL CARE, AND MOLECULAR TRAINING
    Richard Boucher; Fiscal Year: 2007
  5. Mucus Clearance in Acute COPD Exacerbations
    Richard Boucher; Fiscal Year: 2006

Detail Information

Publications78

  1. ncbi request reprint Cystic fibrosis airway epithelial Ca2+ i signaling: the mechanism for the larger agonist-mediated Ca2+ i signals in human cystic fibrosis airway epithelia
    Carla 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...
  2. pmc Anaerobic killing of mucoid Pseudomonas aeruginosa by acidified nitrite derivatives under cystic fibrosis airway conditions
    Sang 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...
  3. pmc The relative roles of passive surface forces and active ion transport in the modulation of airway surface liquid volume and composition
    R 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...
  4. pmc Molecular insights into the physiology of the 'thin film' of airway surface liquid
    R 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...
  5. ncbi request reprint Regulation of airway surface liquid volume by human airway epithelia
    R 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...
  6. ncbi request reprint Relationship of airway epithelial ion transport to chronic bronchitis
    Richard 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
    ....
  7. ncbi request reprint Cystic fibrosis: a disease of vulnerability to airway surface dehydration
    Richard 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...
  8. ncbi request reprint New concepts of the pathogenesis of cystic fibrosis lung disease
    R 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...
  9. ncbi request reprint Evidence for airway surface dehydration as the initiating event in CF airway disease
    R 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...
  10. ncbi request reprint Regulation and functional significance of airway surface liquid pH
    R 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
    ....
  11. ncbi request reprint Airway surface dehydration in cystic fibrosis: pathogenesis and therapy
    Richard 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...
  12. ncbi request reprint An overview of the pathogenesis of cystic fibrosis lung disease
    R 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...
  13. pmc Normal and cystic fibrosis airway surface liquid homeostasis. The effects of phasic shear stress and viral infections
    Robert 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
    ....
  14. pmc Regulation of airway tight junctions by proinflammatory cytokines
    Carolyn 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...
  15. pmc CFTR delivery to 25% of surface epithelial cells restores normal rates of mucus transport to human cystic fibrosis airway epithelium
    Liqun Zhang
    CF Pulmonary Research and Treatment Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
    PLoS Biol 7:e1000155. 2009
    ....
  16. ncbi request reprint Adenosine deaminase 1 and concentrative nucleoside transporters 2 and 3 regulate adenosine on the apical surface of human airway epithelia: implications for inflammatory lung diseases
    Andrew 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...
  17. ncbi request reprint Mechanical ventilation alters airway nucleotides and purinoceptors in lung and extrapulmonary organs
    Christelle 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...
  18. ncbi request reprint Rationale for hypertonic saline therapy for cystic fibrosis lung disease
    Robert 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
    ....
  19. pmc Regulation of murine airway surface liquid volume by CFTR and Ca2+-activated Cl- conductances
    Robert 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...
  20. pmc Thrombin promotes release of ATP from lung epithelial cells through coordinated activation of rho- and Ca2+-dependent signaling pathways
    Lucia 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
    ....
  21. pmc Human alveolar type II cells secrete and absorb liquid in response to local nucleotide signaling
    Peter 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...
  22. ncbi request reprint Acute mechanism of medium chain fatty acid-induced enhancement of airway epithelial permeability
    Carolyn 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...
  23. pmc Abnormal surface liquid pH regulation by cultured cystic fibrosis bronchial epithelium
    Raymond 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
    ....
  24. pmc Mathematical model of nucleotide regulation on airway epithelia. Implications for airway homeostasis
    Peiying 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...
  25. ncbi request reprint Thin-film measurements of airway surface liquid volume/composition and mucus transport rates in vitro
    Robert Tarran
    Cystic Fibrosis Pulmonary Research and Treatment Center, University of North Carolina, Chapel Hill, NC, USA
    Methods Mol Med 70:479-92. 2002
  26. pmc 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 infection
    Jaclyn 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
    ....
  27. ncbi request reprint The epithelium as a target for therapy in cystic fibrosis
    William 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...
  28. pmc A physical linkage between cystic fibrosis airway surface dehydration and Pseudomonas aeruginosa biofilms
    Hirotoshi 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...
  29. pmc Front-runners for pharmacotherapeutic correction of the airway ion transport defect in cystic fibrosis
    Mark 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...
  30. ncbi request reprint Nucleotides induce IL-6 release from human airway epithelia via P2Y2 and p38 MAPK-dependent pathways
    Christelle 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...
  31. ncbi request reprint The DeltaF508 mutation results in loss of CFTR function and mature protein in native human colon
    Marcus 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...
  32. pmc 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 treatment
    Alessandra 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...
  33. pmc Role of endoplasmic reticulum stress in cystic fibrosis-related airway inflammatory responses
    Carla 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
    ....
  34. ncbi request reprint Mechanosensitivity of mouse tracheal ciliary beat frequency: roles for Ca2+, purinergic signaling, tonicity, and viscosity
    Scot 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
    ....
  35. pmc Physiological regulation of ATP release at the apical surface of human airway epithelia
    Seiko F Okada
    Cystic Fibrosis Pulmonary Research and Treatment Center, University of North Carolina, Chapel Hill, NC, USA
    J Biol Chem 281:22992-3002. 2006
    ....
  36. pmc The cystic fibrosis transmembrane conductance regulator impedes proteolytic stimulation of the epithelial Na+ channel
    Martina 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...
  37. doi request reprint Osmolytes and ion transport modulators: new strategies for airway surface rehydration
    Jennifer 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...
  38. pmc Receptor-promoted exocytosis of airway epithelial mucin granules containing a spectrum of adenine nucleotides
    Silvia 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
    ....
  39. pmc Purinergic receptors in airway epithelia
    Eduardo 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...
  40. pmc Similarities between UDP-glucose and adenine nucleotide release in yeast: involvement of the secretory pathway
    Charles 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...
  41. pmc Role of mechanical stress in regulating airway surface hydration and mucus clearance rates
    Brian 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
    ....
  42. ncbi request reprint Sodium channels and cystic fibrosis
    Scott 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...
  43. pmc Modelling dysregulated Na+ absorption in airway epithelial cells with mucosal nystatin treatment
    Alessandra 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...
  44. pmc Azithromycin treatment alters gene expression in inflammatory, lipid metabolism, and cell cycle pathways in well-differentiated human airway epithelia
    Carla 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
    ....
  45. pmc Mass spectrometric analysis of biomarkers and dilution markers in exhaled breath condensate reveals elevated purines in asthma and cystic fibrosis
    Charles 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...
  46. pmc Coordinated release of nucleotides and mucin from human airway epithelial Calu-3 cells
    Silvia 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...
  47. pmc Effective mucus clearance is essential for respiratory health
    Scott 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
  48. ncbi request reprint Regulation of normal and cystic fibrosis airway surface liquid volume by phasic shear stress
    Robert 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...
  49. pmc In vivo airway surface liquid Cl- analysis with solid-state electrodes
    Ray 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...
  50. ncbi request reprint Metabolism of P2 receptor agonists in human airways: implications for mucociliary clearance and cystic fibrosis
    Maryse 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...
  51. ncbi request reprint C-Mannosylation of MUC5AC and MUC5B Cys subdomains
    Juan 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...
  52. ncbi request reprint Effect of ventilatory rate on airway cytokine levels and lung injury
    Preston 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
    ....
  53. ncbi request reprint Adenosine triphosphate is released during injurious mechanical ventilation and contributes to lung edema
    Preston 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...
  54. ncbi request reprint Role of claudin interactions in airway tight junctional permeability
    Carolyn 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...
  55. pmc Polarized distribution of HCO3- transport in human normal and cystic fibrosis nasal epithelia
    Anthony 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
    ....
  56. ncbi request reprint Ecto 5'-nucleotidase and nonspecific alkaline phosphatase. Two AMP-hydrolyzing ectoenzymes with distinct roles in human airways
    Maryse 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...
  57. ncbi request reprint Human airway ecto-adenylate kinase. A mechanism to propagate ATP signaling on airway surfaces
    Maryse 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...
  58. ncbi request reprint A proteomic analysis of human cilia: identification of novel components
    Lawrence 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...
  59. ncbi request reprint In vivo microdialysis for determination of nasal liquid ion composition
    Barbara 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...
  60. pmc Respiratory syncytial virus infection of human airway epithelial cells is polarized, specific to ciliated cells, and without obvious cytopathology
    Liqun 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...
  61. ncbi request reprint Increased airway epithelial Na+ absorption produces cystic fibrosis-like lung disease in mice
    Marcus 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...
  62. ncbi request reprint Reduced three-dimensional motility in dehydrated airway mucus prevents neutrophil capture and killing bacteria on airway epithelial surfaces
    Hirotoshi 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...
  63. pmc SERCA pump inhibitors do not correct biosynthetic arrest of deltaF508 CFTR in cystic fibrosis
    Barbara 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
    ....
  64. ncbi request reprint Reevaluating gel-forming mucins' roles in cystic fibrosis lung disease
    Juan 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...
  65. ncbi request reprint Mucin granules are in close contact with tubular elements of the endoplasmic reticulum
    Juan 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...
  66. ncbi request reprint Chronic airway infection/inflammation induces a Ca2+i-dependent hyperinflammatory response in human cystic fibrosis airway epithelia
    Carla 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...
  67. ncbi request reprint Mucin granule intraluminal organization in living mucous/goblet cells. Roles of protein post-translational modifications and secretion
    Juan 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
    ....
  68. ncbi request reprint pH-dependent intraluminal organization of mucin granules in live human mucous/goblet cells
    Juan 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...
  69. ncbi request reprint Neutrophil elastase activates near-silent epithelial Na+ channels and increases airway epithelial Na+ transport
    Ray 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...
  70. pmc Voltage-dependent anion channel-1 (VDAC-1) contributes to ATP release and cell volume regulation in murine cells
    Seiko 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...
  71. pmc Patterns of epithelial cell invasion by different species of the Burkholderia cepacia complex in well-differentiated human airway epithelia
    Ute 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...
  72. ncbi request reprint Mucus clearance and lung function in cystic fibrosis with hypertonic saline
    Scott 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...
  73. ncbi request reprint Design, synthesis, and structure-activity relationships of novel 2-substituted pyrazinoylguanidine epithelial sodium channel blockers: drugs for cystic fibrosis and chronic bronchitis
    Andrew 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...
  74. ncbi request reprint Evaluation of second generation amiloride analogs as therapy for cystic fibrosis lung disease
    Andrew 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...
  75. pmc The mitochondrial barriers segregate agonist-induced calcium-dependent functions in human airway epithelia
    Carla 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
    ....
  76. ncbi request reprint Update on pathogenesis of cystic fibrosis lung disease
    Scott 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...
  77. pmc Development of chronic bronchitis and emphysema in beta-epithelial Na+ channel-overexpressing mice
    Marcus 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...
  78. doi request reprint 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 d
    Andrew 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 Grants10

  1. The Role of Anaerobic Bacterial Infection in Cystic Fibrosis
    Richard C Boucher; Fiscal Year: 2010
    ..S. (Richard Boucher) have explored this hypothesis and produced the following preliminary data: 1) anaerobes are present in the ..
  2. SCCOR in Host Factors in Chronic Lung Disease
    Richard 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) ..
  3. PULMONARY EPITHELIA IN HEALTH AND DISEASE
    Richard 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. ..
  4. PULMONARY, CRITICAL CARE, AND MOLECULAR TRAINING
    Richard Boucher; Fiscal Year: 2007
    ..End of Abstract) ..
  5. Mucus Clearance in Acute COPD Exacerbations
    Richard 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. ..