cystic fibrosis transmembrane conductance regulator

Summary

Summary: A chloride channel that regulates secretion in many exocrine tissues. Abnormalities in the CFTR gene have been shown to cause cystic fibrosis. (Hum Genet 1994;93(4):364-8)

Top Publications

  1. ncbi Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA
    J R Riordan
    Department of Biochemistry, Hospital for Sick Children, Toronto, Ontario, Canada
    Science 245:1066-73. 1989
  2. pmc Lung infections associated with cystic fibrosis
    Jeffrey B Lyczak
    Channing Laboratory, Brigham and Women s Hospital, Harvard Medical School, Children s Hospital, Boston, MA 02115, USA
    Clin Microbiol Rev 15:194-222. 2002
  3. ncbi Cystic fibrosis
    Steven M Rowe
    Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, AL 35294, USA
    N Engl J Med 352:1992-2001. 2005
  4. pmc A CFTR potentiator in patients with cystic fibrosis and the G551D mutation
    Bonnie W Ramsey
    Seattle Children s Hospital and University of Washington School of Medicine, Seattle WA 98105 0371, USA
    N Engl J Med 365:1663-72. 2011
  5. pmc Correction of the F508del-CFTR protein processing defect in vitro by the investigational drug VX-809
    Fredrick Van Goor
    Vertex Pharmaceuticals, San Diego, CA 92121, USA
    Proc Natl Acad Sci U S A 108:18843-8. 2011
  6. pmc Results of a phase IIa study of VX-809, an investigational CFTR corrector compound, in subjects with cystic fibrosis homozygous for the F508del-CFTR mutation
    J P Clancy
    Department of Pediatrics, Cincinnati Children s Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA
    Thorax 67:12-8. 2012
  7. ncbi Peripheral protein quality control removes unfolded CFTR from the plasma membrane
    Tsukasa Okiyoneda
    Department of Physiology, and Groupe de Recherche Axé sur la Structure des Protéine GRASP McGill University, Montreal, Quebec H3G 1Y6, Canada
    Science 329:805-10. 2010
  8. ncbi Characterization and functional implications of the RNA binding properties of nuclear factor TDP-43, a novel splicing regulator of CFTR exon 9
    E Buratti
    International Center for Genetic Engineering and Biotechnology ICGEB 34012 Trieste, Italy
    J Biol Chem 276:36337-43. 2001
  9. ncbi Hsp90 cochaperone Aha1 downregulation rescues misfolding of CFTR in cystic fibrosis
    Xiaodong Wang
    Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
    Cell 127:803-15. 2006
  10. ncbi Cystic fibrosis
    Brian P O'Sullivan
    Department of Pediatrics, University of Massachusetts Medical School, Worcester, MA 01655, USA
    Lancet 373:1891-904. 2009

Detail Information

Publications338 found, 100 shown here

  1. ncbi Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA
    J R Riordan
    Department of Biochemistry, Hospital for Sick Children, Toronto, Ontario, Canada
    Science 245:1066-73. 1989
    ..A deletion of three base pairs that results in the omission of a phenylalanine residue at the center of the first predicted nucleotide-binding domain was detected in CF patients...
  2. pmc Lung infections associated with cystic fibrosis
    Jeffrey B Lyczak
    Channing Laboratory, Brigham and Women s Hospital, Harvard Medical School, Children s Hospital, Boston, MA 02115, USA
    Clin Microbiol Rev 15:194-222. 2002
    ..distribution of the gene product that is defective in CF, the ion channel and regulator, cystic fibrosis transmembrane conductance regulator (CFTR)...
  3. ncbi Cystic fibrosis
    Steven M Rowe
    Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, AL 35294, USA
    N Engl J Med 352:1992-2001. 2005
  4. pmc A CFTR potentiator in patients with cystic fibrosis and the G551D mutation
    Bonnie W Ramsey
    Seattle Children s Hospital and University of Washington School of Medicine, Seattle WA 98105 0371, USA
    N Engl J Med 365:1663-72. 2011
    Increasing the activity of defective cystic fibrosis transmembrane conductance regulator (CFTR) protein is a potential treatment for cystic fibrosis.
  5. pmc Correction of the F508del-CFTR protein processing defect in vitro by the investigational drug VX-809
    Fredrick Van Goor
    Vertex Pharmaceuticals, San Diego, CA 92121, USA
    Proc Natl Acad Sci U S A 108:18843-8. 2011
    ..VX-809 was more efficacious and selective for CFTR than previously reported CFTR correctors. VX-809 represents a class of CFTR corrector that specifically addresses the underlying processing defect in F508del-CFTR...
  6. pmc Results of a phase IIa study of VX-809, an investigational CFTR corrector compound, in subjects with cystic fibrosis homozygous for the F508del-CFTR mutation
    J P Clancy
    Department of Pediatrics, Cincinnati Children s Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA
    Thorax 67:12-8. 2012
    VX-809, a cystic fibrosis transmembrane conductance regulator (CFTR) modulator, has been shown to increase the cell surface density of functional F508del-CFTR in vitro.
  7. ncbi Peripheral protein quality control removes unfolded CFTR from the plasma membrane
    Tsukasa Okiyoneda
    Department of Physiology, and Groupe de Recherche Axé sur la Structure des Protéine GRASP McGill University, Montreal, Quebec H3G 1Y6, Canada
    Science 329:805-10. 2010
    Therapeutic efforts to restore biosynthetic processing of the cystic fibrosis transmembrane conductance regulator lacking the F508 residue (DeltaF508CFTR) are hampered by ubiquitin-dependent lysosomal degradation of nonnative, rescued ..
  8. ncbi Characterization and functional implications of the RNA binding properties of nuclear factor TDP-43, a novel splicing regulator of CFTR exon 9
    E Buratti
    International Center for Genetic Engineering and Biotechnology ICGEB 34012 Trieste, Italy
    J Biol Chem 276:36337-43. 2001
    ..In particular, the highly conserved Phe residues in the first RRM region play a key role in nucleic acid recognition...
  9. ncbi Hsp90 cochaperone Aha1 downregulation rescues misfolding of CFTR in cystic fibrosis
    Xiaodong Wang
    Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
    Cell 127:803-15. 2006
    ..The activity of cargo-associated chaperome components may be a common mechanism regulating folding for ER exit, providing a general framework for correction of misfolding disease...
  10. ncbi Cystic fibrosis
    Brian P O'Sullivan
    Department of Pediatrics, University of Massachusetts Medical School, Worcester, MA 01655, USA
    Lancet 373:1891-904. 2009
    ..We review clinical care for cystic fibrosis and discuss recent advances in the understanding of its pathogenesis, implementation of screening of neonates, and development of therapies aimed at treating the basic defect...
  11. ncbi The Hsc70 co-chaperone CHIP targets immature CFTR for proteasomal degradation
    G C Meacham
    Department of Cell Biology and Cystic Fibrosis Center, University of Alabama Medical Center, 1918 University Boulevard, Birmingham, Alabama 35294 0005, USA
    Nat Cell Biol 3:100-5. 2001
    ..CHIP is a co-chaperone that converts Hsc70 from a protein-folding machine into a degradation factor that functions in endoplasmic-reticulum quality control...
  12. pmc CFTR: folding, misfolding and correcting the ΔF508 conformational defect
    Gergely L Lukacs
    Department of Physiology and GRASP, McGill University, Montreal, Quebec H3E 1Y6, Canada
    Trends Mol Med 18:81-91. 2012
    ..This review discusses recent basic research aimed at elucidating the structural and trafficking defects of ΔF508 CFTR, a prerequisite for the rational design of CF therapy to correct the loss-of-function phenotype...
  13. ncbi ABC transporters: from microorganisms to man
    C F Higgins
    Imperial Cancer Research Fund Laboratories, University of Oxford, John Radcliffe Hospital, England
    Annu Rev Cell Biol 8:67-113. 1992
  14. pmc Rescue of CF airway epithelial cell function in vitro by a CFTR potentiator, VX-770
    Fredrick Van Goor
    Vertex Pharmaceuticals Incorporated, 11010 Torreyana Road, San Diego, CA 92121, USA
    Proc Natl Acad Sci U S A 106:18825-30. 2009
    ..These results support the hypothesis that pharmacological agents that restore or increase CFTR function can rescue epithelial cell function in human CF airway...
  15. pmc Effect of VX-770 in persons with cystic fibrosis and the G551D-CFTR mutation
    Frank J Accurso
    University of Colorado Denver and Children s Hospital, Aurora, CO 80045, USA
    N Engl J Med 363:1991-2003. 2010
    A new approach in the treatment of cystic fibrosis involves improving the function of mutant cystic fibrosis transmembrane conductance regulator (CFTR)...
  16. pmc Guidelines for diagnosis of cystic fibrosis in newborns through older adults: Cystic Fibrosis Foundation consensus report
    Philip M Farrell
    Department of Pediatrics and Population Health Sciences, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
    J Pediatr 153:S4-S14. 2008
    ..Their recommendations, presented herein, involve a combination of clinical presentation, laboratory testing, and genetics to confirm a diagnosis of CF...
  17. ncbi Rescue of DeltaF508-CFTR trafficking and gating in human cystic fibrosis airway primary cultures by small molecules
    Fredrick Van Goor
    Vertex Pharmaceuticals, 11010 Torreyana Road, San Diego, CA 92121, USA
    Am J Physiol Lung Cell Mol Physiol 290:L1117-30. 2006
    ..The CFTR-activating effects of the two mechanisms are additive and support the rationale of a drug discovery strategy based on rescue of the basic genetic defect responsible for CF...
  18. ncbi The delta F508 mutation decreases the stability of cystic fibrosis transmembrane conductance regulator in the plasma membrane. Determination of functional half-lives on transfected cells
    G L Lukacs
    Research Institute, Hospital for Sick Children, Toronto, Canada
    J Biol Chem 268:21592-8. 1993
    Deletion of the phenylalanine at position 508 of the cystic fibrosis transmembrane conductance regulator (CFTR) is the most prevalent mutation in cystic fibrosis (CF)...
  19. ncbi Rescue of ΔF508-CFTR trafficking via a GRASP-dependent unconventional secretion pathway
    Heon Yung Gee
    Department of Pharmacology, Brain Korea 21 Project for Medical Sciences, Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul 120 752, Korea
    Cell 146:746-60. 2011
    ..These findings provide insight into how unconventional protein secretion is activated, and offer a potential therapeutic strategy for the treatment of cystic fibrosis and perhaps diseases stemming from other misfolded proteins...
  20. pmc Syntaxin 6 and CAL mediate the degradation of the cystic fibrosis transmembrane conductance regulator
    Jie Cheng
    Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Mol Biol Cell 21:1178-87. 2010
    ..We have identified STX6 as a new component of the CAL complex that regulates the abundance and function of CFTR at the post-ER level. Our results suggest a therapeutic role of STX6 in enhancing rescued DeltaF508-CFTR...
  21. ncbi Genetic modifiers of lung disease in cystic fibrosis
    Mitchell L Drumm
    Department of Pediatrics, Case Western Reserve University, Cleveland, USA
    N Engl J Med 353:1443-53. 2005
    Polymorphisms in genes other than the cystic fibrosis transmembrane conductance regulator (CFTR) gene may modify the severity of pulmonary disease in patients with cystic fibrosis.
  22. ncbi Cystic fibrosis: a worldwide analysis of CFTR mutations--correlation with incidence data and application to screening
    Joseph L Bobadilla
    Department of Pediatrics, University of Wisconsin, Madison, Wisconsin, USA
    Hum Mutat 19:575-606. 2002
    ..reports from around the world of mutations in the gene of chromosome 7 known as CFTR (cystic fibrosis transmembrane conductance regulator), little attention has been given to integrating these mutant alleles into a global ..
  23. pmc Requirements for efficient correction of ΔF508 CFTR revealed by analyses of evolved sequences
    Juan L Mendoza
    Molecular Biophysics Program, and Department of Physiology, University of Texas Southwestern Medical Center, Dallas, TX 75390 9040, USA
    Cell 148:164-74. 2012
    ..These results provide a mechanistic rationale for the limited efficacy of extant corrector compounds and suggest approaches for identifying compounds that correct both defective steps...
  24. pmc Disruption of the CFTR gene produces a model of cystic fibrosis in newborn pigs
    Christopher S Rogers
    Department of Internal Medicine, Roy J and Lucille A Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
    Science 321:1837-41. 2008
    ..The pig model may provide opportunities to address persistent questions about CF pathogenesis and accelerate discovery of strategies for prevention and treatment...
  25. pmc Disease phenotype of a ferret CFTR-knockout model of cystic fibrosis
    Xingshen Sun
    Department of Anatomy and Cell Biology, Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242, USA
    J Clin Invest 120:3149-60. 2010
    ..The animals described in this study are likely to be useful tools for dissecting CF disease pathogenesis and developing treatments...
  26. ncbi TDP-43 binds heterogeneous nuclear ribonucleoprotein A/B through its C-terminal tail: an important region for the inhibition of cystic fibrosis transmembrane conductance regulator exon 9 splicing
    Emanuele Buratti
    International Centre for Genetic Engineering and Biotechnology, Trieste, Italy
    J Biol Chem 280:37572-84. 2005
    ..factor of yet unknown function that binds to ug-repeated sequences and is responsible for cystic fibrosis transmembrane conductance regulator exon 9 splicing inhibition...
  27. pmc Small-molecule correctors of defective DeltaF508-CFTR cellular processing identified by high-throughput screening
    Nicoletta Pedemonte
    Department of Medicine, UCSF, San Francisco, California 94143 0521, USA
    J Clin Invest 115:2564-71. 2005
    ..Small-molecule correctors may be useful in the treatment of CF caused by the DeltaF508 mutation...
  28. pmc Arsenic promotes ubiquitinylation and lysosomal degradation of cystic fibrosis transmembrane conductance regulator (CFTR) chloride channels in human airway epithelial cells
    Jennifer M Bomberger
    Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15219, USA
    J Biol Chem 287:17130-9. 2012
    ..model organism, that arsenic exposure induced the ubiquitinylation and degradation of cystic fibrosis transmembrane conductance regulator (CFTR), a chloride channel that is essential for the mucociliary clearance of respiratory ..
  29. ncbi Ivacaftor potentiation of multiple CFTR channels with gating mutations
    Haihui Yu
    Vertex Pharmaceuticals Incorporated, Cambridge, MA 02139, USA
    J Cyst Fibros 11:237-45. 2012
    ..The aim of this in vitro study was to determine whether ivacaftor potentiates mutant CFTR with gating defects caused by other CFTR gating mutations...
  30. ncbi CFTR function and prospects for therapy
    John R Riordan
    Department of Biochemistry and Biophysics, Cystic Fibrosis Treatment and Research Center, School of Medicine, University of North Carolina at Chapel Hill, NC 27599, USA
    Annu Rev Biochem 77:701-26. 2008
    Mutations in the gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) epithelial anion channel cause cystic fibrosis (CF)...
  31. ncbi Defective CFTR induces aggresome formation and lung inflammation in cystic fibrosis through ROS-mediated autophagy inhibition
    Alessandro Luciani
    European Institute for Research in Cystic Fibrosis, San Raffaele Scientific Institute, Milan 20132, Italy
    Nat Cell Biol 12:863-75. 2010
    ..CF), a life-threatening genetic disorder caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR)...
  32. ncbi Cystic fibrosis transmembrane conductance regulator intracellular processing, trafficking, and opportunities for mutation-specific treatment
    Mark P Rogan
    Department of Respiratory Medicine, Waterford Regional Hospital, Waterford, Ireland
    Chest 139:1480-90. 2011
    ..and even before the CFTR gene discovery: Will therapies that specifically restore CFTR-mediated chloride secretion slow or arrest the deleterious cascade of events leading to chronic infection, bronchiectasis, and end-stage lung disease?..
  33. pmc Cystic fibrosis population carrier screening: 2004 revision of American College of Medical Genetics mutation panel
    Michael S Watson
    ACMG Cystic Fibrosis Carrier Screening Work Group, American College of Medical Genetics, Bethesda, Maryland 20814, USA
    Genet Med 6:387-91. 2004
  34. pmc Phenylalanine-508 mediates a cytoplasmic-membrane domain contact in the CFTR 3D structure crucial to assembly and channel function
    Adrian W R Serohijos
    Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC 27599, USA
    Proc Natl Acad Sci U S A 105:3256-61. 2008
    ..of phenylalanine-508 (Phe-508) from the N-terminal nucleotide-binding domain (NBD1) of the cystic fibrosis transmembrane conductance regulator (CFTR), a member of the ATP-binding cassette (ABC) transporter family, disrupts both its ..
  35. ncbi 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
    Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene result in defective epithelial cAMP-dependent Cl(-) secretion and increased airway Na(+) absorption...
  36. pmc CFTR channel opening by ATP-driven tight dimerization of its nucleotide-binding domains
    Paola Vergani
    Laboratory of Cardiac Membrane Physiology, The Rockefeller University, New York, New York 10021, USA
    Nature 433:876-80. 2005
    ..b>Cystic fibrosis transmembrane conductance regulator (CFTR), the protein dysfunctional in cystic fibrosis, is unique among ABC proteins in that ..
  37. pmc Correction of both NBD1 energetics and domain interface is required to restore ΔF508 CFTR folding and function
    Wael M Rabeh
    Department of Physiology, McGill University, Montreal, Quebec H3E 1Y6, Canada
    Cell 148:150-63. 2012
    ..thermodynamic instability of the first nucleotide-binding domain (NBD1) of ΔF508 CFTR (cystic fibrosis transmembrane conductance regulator) partly accounts for the mutant channel degradation in the endoplasmic reticulum and is ..
  38. ncbi The short apical membrane half-life of rescued {Delta}F508-cystic fibrosis transmembrane conductance regulator (CFTR) results from accelerated endocytosis of {Delta}F508-CFTR in polarized human airway epithelial cells
    Agnieszka Swiatecka-Urban
    Department of Physiology, Dartmouth Medical School, Hanover, New Hampshire 03755, USA
    J Biol Chem 280:36762-72. 2005
    The most common mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene in individuals with cystic fibrosis, DeltaF508, causes retention of DeltaF508-CFTR in the endoplasmic reticulum and leads to the absence of ..
  39. pmc Gp78 cooperates with RMA1 in endoplasmic reticulum-associated degradation of CFTRDeltaF508
    Daisuke Morito
    Department of Molecular and Cellular Biology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606 8397, Japan
    Mol Biol Cell 19:1328-36. 2008
    ..Hrd1p/Der3p is an ER membrane-spanning ubiquitin ligase that participates in ERAD of the cystic fibrosis transmembrane conductance regulator (CFTR) when CFTR is exogenously expressed in yeast cells...
  40. pmc Cigarette smoke exposure induces CFTR internalization and insolubility, leading to airway surface liquid dehydration
    Lucy A Clunes
    Cystic Fibrosis Pulmonary Research and Treatment Center, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
    FASEB J 26:533-45. 2012
    ..Furthermore, our data suggest that strategies to rehydrate airway surfaces may provide a novel form of therapy for patients with CB...
  41. pmc Consensus on the use and interpretation of cystic fibrosis mutation analysis in clinical practice
    C Castellani
    Cystic Fibrosis Centre, Ospedale Civile Maggiore, Verona, Italy
    J Cyst Fibros 7:179-96. 2008
    ..The importance of communication between clinicians and medical genetic laboratories is emphasized. The results of testing and their implications should be reported in a manner understandable to the clinicians caring for CF patients...
  42. pmc PTC124 is an orally bioavailable compound that promotes suppression of the human CFTR-G542X nonsense allele in a CF mouse model
    Ming Du
    Department of Microbiology and Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, AL 35294, USA
    Proc Natl Acad Sci U S A 105:2064-9. 2008
    ....
  43. ncbi Correction of the Delta phe508 cystic fibrosis transmembrane conductance regulator trafficking defect by the bioavailable compound glafenine
    Renaud Robert
    Physiology Department, McGill University, Montreal, Quebec, H3G 1Y6, Canada
    Mol Pharmacol 77:922-30. 2010
    ....
  44. pmc Statistical evidence for conserved, local secondary structure in the coding regions of eukaryotic mRNAs and pre-mRNAs
    Irmtraud M Meyer
    European Bioinformatics Institute, Wellcome Trust Genome Campus, Cambridge CB10 1SD, UK
    Nucleic Acids Res 33:6338-48. 2005
    ....
  45. pmc A microRNA network regulates expression and biosynthesis of wild-type and DeltaF508 mutant cystic fibrosis transmembrane conductance regulator
    Shyam Ramachandran
    Department of Pediatrics, Interdisciplinary Program in Genetics, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
    Proc Natl Acad Sci U S A 109:13362-7. 2012
    ..Despite the importance of the cystic fibrosis transmembrane conductance regulator (CFTR) channel for epithelial anion transport, how its expression is regulated remains ..
  46. pmc Quercetin increases cystic fibrosis transmembrane conductance regulator-mediated chloride transport and ciliary beat frequency: therapeutic implications for chronic rhinosinusitis
    Shaoyan Zhang
    Gregory Fleming James Cystic Fibrosis Research Center, Birmingham, Alabama, USA
    Am J Rhinol Allergy 25:307-12. 2011
    ..and anti-inflammatory activity and is now recognized as a potent activator of the cystic fibrosis transmembrane conductance regulator (CFTR) anion channel activity in a fashion largely independent of cyclic adenosine ..
  47. pmc Chloride channels as drug targets
    Alan S Verkman
    Departments of Medicine and Physiology, University of California, San Francisco, California 94143 0521, USA
    Nat Rev Drug Discov 8:153-71. 2009
    ..Here, we discuss the broad opportunities that remain in chloride-channel-based drug discovery...
  48. ncbi Association of MBL2, TGF-beta1 and CD14 gene polymorphisms with lung disease severity in cystic fibrosis
    Elisangela Jacinto de Faria
    Department of Medical Genetics, Universidade Estadual de Campinas UNICAMP, State University at Campinas School of Medical Sciences, Campinas, Brazil
    J Bras Pneumol 35:334-42. 2009
    ....
  49. pmc c-Cbl facilitates endocytosis and lysosomal degradation of cystic fibrosis transmembrane conductance regulator in human airway epithelial cells
    Siying Ye
    Department of Physiology, Dartmouth Medical School, Hanover, New Hampshire 03755, USA
    J Biol Chem 285:27008-18. 2010
    b>Cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP-activated Cl(-) channel expressed in the apical membrane of fluid-transporting epithelia...
  50. pmc Dynamic association of proteasomal machinery with the centrosome
    W C Wigley
    Department of Physiology, The University of Texas Southwestern Medical Center, Dallas, Texas 75235, USA
    J Cell Biol 145:481-90. 1999
    ..Thus, the centrosome may act as a scaffold, which concentrates and recruits the systems which act as censors and modulators of the balance between folding, aggregation, and degradation...
  51. ncbi Regulatory insertion removal restores maturation, stability and function of DeltaF508 CFTR
    Andrei A Aleksandrov
    Department of Biomedical Engineering, University of North Carolina Chapel Hill, Chapel Hill, NC 27599, USA
    J Mol Biol 401:194-210. 2010
    The cystic fibrosis transmembrane conductance regulator (CFTR) epithelial anion channel is a large multidomain membrane protein that matures inefficiently during biosynthesis...
  52. ncbi Correctors of protein trafficking defects identified by a novel high-throughput screening assay
    Graeme W Carlile
    Department of Biochemistry, McGill University, McIntyre Medical Building, 3655 Promenade Sir William Osler, Montreal, QC, H3G 1Y6, Canada
    Chembiochem 8:1012-20. 2007
    ..This novel screening approach to protein-trafficking diseases is robust and general, and could enable the selection of molecules that could be translated rapidly to a clinical setting...
  53. ncbi MicroRNA regulation of expression of the cystic fibrosis transmembrane conductance regulator gene
    Austin E Gillen
    Human Molecular Genetics Program, Children s Memorial Research Center, Chicago, IL 60614, USA
    Biochem J 438:25-32. 2011
    The CFTR (cystic fibrosis transmembrane conductance regulator) gene shows a complex temporal and spatial pattern of expression that is controlled by multiple cis-acting elements interacting with the basal promoter...
  54. ncbi The phenotypic consequences of CFTR mutations
    Rebecca K Rowntree
    Paediatric Molecular Genetics, Institute of Molecular Medicine, Oxford University, John Radcliffe Hospital, Oxford, OX3 9DS, UK
    Ann Hum Genet 67:471-85. 2003
    ..Over one thousand mutations have currently been identified in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene that are associated with CF disease...
  55. ncbi Genotype and phenotype in cystic fibrosis
    J Zielenski
    Department of Genetics, The Hospital for Sick Children, Toronto, Ont, Canada
    Respiration 67:117-33. 2000
    ..Expansion of the spectrum of disease associated with the CFTR mutant genes creates a need for revision of the diagnostic criteria for CF and a dilemma for setting nosologic boundaries between CF and other diseases with CFTR etiology...
  56. ncbi Identification of a NBD1-binding pharmacological chaperone that corrects the trafficking defect of F508del-CFTR
    Heidi M Sampson
    Department of Biochemistry, McGill University, Montreal, QC, Canada
    Chem Biol 18:231-42. 2011
    ..We show that RDR1 treatment partially rescues F508del-CFTR function in both cells and in an F508del-CF mouse model. Thus, RDR1 is a pharmacological chaperone of F508del-CFTR and represents a novel scaffold for drug development...
  57. ncbi Sequential quality-control checkpoints triage misfolded cystic fibrosis transmembrane conductance regulator
    J Michael Younger
    Department of Cell and Developmental Biology, UNC Chapel Hill School of Medicine, University of North Carolina, Chapel Hill, NC 27599, USA
    Cell 126:571-82. 2006
    ..Thus, the RMA1 and CHIP E3 ubiquitin ligases act sequentially in ER membrane and cytosol to monitor the folding status of CFTR and CFTR Delta F508...
  58. ncbi CFTR regulates phagosome acidification in macrophages and alters bactericidal activity
    Anke Di
    Dept of Neurobiology, Pharmacology and Physiology, University of Chicago, Chicago, IL 60637, USA
    Nat Cell Biol 8:933-44. 2006
    ..Here, we show that in alveolar macrophages the cystic fibrosis transmembrane conductance regulator Cl- channel (CFTR) participates in phagosomal pH control and has bacterial killing capacity...
  59. ncbi A Golgi-associated PDZ domain protein modulates cystic fibrosis transmembrane regulator plasma membrane expression
    Jie Cheng
    Department of Physiology and Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
    J Biol Chem 277:3520-9. 2002
    We identified a novel cystic fibrosis transmembrane conductance regulator (CFTR)-associating, PDZ domain-containing protein, CAL (CFTR associated ligand) containing two predicted coiled-coiled domains and one PDZ domain...
  60. pmc The endoplasmic reticulum-associated Hsp40 DNAJB12 and Hsc70 cooperate to facilitate RMA1 E3-dependent degradation of nascent CFTRDeltaF508
    Diane E Grove
    Department of Cell and Developmental Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
    Mol Biol Cell 22:301-14. 2011
    ..b>Cystic fibrosis transmembrane conductance regulator (CFTR) biogenesis serves as an excellent model to study this question because folding of ..
  61. pmc Production of CFTR-null and CFTR-DeltaF508 heterozygous pigs by adeno-associated virus-mediated gene targeting and somatic cell nuclear transfer
    Christopher S Rogers
    Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA
    J Clin Invest 118:1571-7. 2008
    ..In addition, because gene-modified mice often fail to replicate human diseases, this approach could be used to generate models of other human genetic diseases in species other than mice...
  62. pmc Genes that determine immunology and inflammation modify the basic defect of impaired ion conductance in cystic fibrosis epithelia
    Frauke Stanke
    Department of Pediatrics, Hannover Medical School, Germany
    J Med Genet 48:24-31. 2011
    ..The cystic fibrosis (CF) basic defect, caused by dysfunction of the apical chloride channel CFTR in the gastrointestinal and respiratory tract epithelia, has not been employed so far to support the role of CF modifier genes...
  63. ncbi Ataluren (PTC124) induces cystic fibrosis transmembrane conductance regulator protein expression and activity in children with nonsense mutation cystic fibrosis
    Isabelle Sermet-Gaudelus
    Hopital Necker Enfants Malades, Paris, France
    Am J Respir Crit Care Med 182:1262-72. 2010
    Nonsense (premature stop codon) mutations in mRNA for the cystic fibrosis transmembrane conductance regulator (CFTR) cause cystic fibrosis (CF) in approximately 10% of patients...
  64. ncbi BAP31 interacts with Sec61 translocons and promotes retrotranslocation of CFTRDeltaF508 via the derlin-1 complex
    Bing Wang
    Department of Biochemistry, McIntyre Medical Sciences Building, McGill University, Montreal, Quebec, H3G 1Y6, Canada
    Cell 133:1080-92. 2008
    ..Thus, BAP31 operates at early steps to deliver newly synthesized CFTRDeltaF508 to its degradation pathway...
  65. ncbi Effectiveness of PTC124 treatment of cystic fibrosis caused by nonsense mutations: a prospective phase II trial
    Eitan Kerem
    Hadassah Hebrew University Hospital, Jerusalem, Israel
    Lancet 372:719-27. 2008
    ..results from nonsense mutations (premature stop codons) in the messenger RNA (mRNA) for the cystic fibrosis transmembrane conductance regulator (CFTR)...
  66. ncbi Curcumin, a major constituent of turmeric, corrects cystic fibrosis defects
    Marie E Egan
    Department of Pediatrics, Yale University School of Medicine, 333 Cedar Street, Post Office Box 208026, New Haven, CT 06520 8026, USA
    Science 304:600-2. 2004
    Cystic fibrosis is caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR)...
  67. pmc Polymorphisms in ADRB2 gene can modulate the response to bronchodilators and the severity of cystic fibrosis
    Fernando A L Marson
    Department of Pediatrics, School of Medical Sciences, University of Campinas, Campinas, SP, Brazil
    BMC Pulm Med 12:50. 2012
    ..In this context, our objective was to verify whether the Arg16Gly and Glu27Gln polymorphisms in ADRB2 gene are associated with severity and with the bronchodilator response in CF patients...
  68. pmc Assessment of cystic fibrosis transmembrane conductance regulator (CFTR) activity in CFTR-null mice after bone marrow transplantation
    Emanuela M Bruscia
    Department of Laboratory Medicine, Yale University School of Medicine, 330 Cedar Street, New Haven, CT 06520, USA
    Proc Natl Acad Sci U S A 103:2965-70. 2006
    ..We investigate whether, after transplantation of cystic fibrosis transmembrane conductance regulator (CFTR)-positive BM-derived cells, BM-derived GI and airway epithelial cells can provide ..
  69. pmc Contribution of casein kinase 2 and spleen tyrosine kinase to CFTR trafficking and protein kinase A-induced activity
    Simão Luz
    University of Lisbon, BioFIG Center for Biodiversity, Functional and Integrative Genomics, 1749 016 Lisbon, Portugal
    Mol Cell Biol 31:4392-404. 2011
    ..These results reinforce the importance of CK2 and the S422 and T1471 residues for regulation of CFTR and uncover a novel regulation of CFTR by SYK, a recognized controller of inflammation...
  70. pmc Transepithelial ion transport is suppressed in hypoxic sinonasal epithelium
    Angela Blount
    Department of Surgery, Division of Otolaryngology Head and Neck Surgery, University of Alabama at Birmingham, Birmingham, Alabama, USA
    Laryngoscope 121:1929-34. 2011
    ..across primary sinonasal epithelial monolayers, 2) expression of the apical Cl(-) channels cystic fibrosis transmembrane conductance regulator (CFTR) and transmembrane protein 16A (TMEM16A), and 3) the pathogenesis of chronic ..
  71. ncbi A pilot clinical trial of oral sodium 4-phenylbutyrate (Buphenyl) in deltaF508-homozygous cystic fibrosis patients: partial restoration of nasal epithelial CFTR function
    R C Rubenstein
    Eudowood Division of Pediatric Respiratory Sciences, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21287, USA
    Am J Respir Crit Care Med 157:484-90. 1998
    ..Side effects due to drug therapy were minimal and comparable in the two groups. These data are consistent with 4PBA therapy inducing CFTR function in the nasal epithelia of deltaF508-homozygous CF patients...
  72. pmc Cystic fibrosis transmembrane conductance regulator (CFTR) potentiator VX-770 (ivacaftor) opens the defective channel gate of mutant CFTR in a phosphorylation-dependent but ATP-independent manner
    Paul D W Eckford
    Programme of Molecular Structure and Function, Research Institute, Hospital for Sick Children, Toronto M5G 1X8, Canada
    J Biol Chem 287:36639-49. 2012
    The cystic fibrosis transmembrane conductance regulator (CFTR) acts as a channel on the apical membrane of epithelia...
  73. ncbi New insights into cystic fibrosis: molecular switches that regulate CFTR
    William B Guggino
    Department of Physiology and Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    Nat Rev Mol Cell Biol 7:426-36. 2006
    b>Cystic fibrosis transmembrane conductance regulator (CFTR), a Cl(-)-selective ion channel, is a prototypic member of the ATP-binding cassette transporter superfamily that is expressed in several organs...
  74. pmc The relative binding affinities of PDZ partners for CFTR: a biochemical basis for efficient endocytic recycling
    Patrick R Cushing
    Department of Biochemistry, Dartmouth Medical School, Hanover, New Hampshire 03755, USA
    Biochemistry 47:10084-98. 2008
    The cystic fibrosis transmembrane conductance regulator (CFTR) is an epithelial chloride channel mutated in patients with cystic fibrosis...
  75. pmc Mechanism-based corrector combination restores ΔF508-CFTR folding and function
    Tsukasa Okiyoneda
    Department of Physiology, McGill University, Montreal, Quebec, Canada
    Nat Chem Biol 9:444-54. 2013
    ..most common cystic fibrosis mutation, ΔF508 in nucleotide binding domain 1 (NBD1), impairs cystic fibrosis transmembrane conductance regulator (CFTR)-coupled domain folding, plasma membrane expression, function and stability...
  76. ncbi Cystic fibrosis transmembrane conductance regulator in the gills of the climbing perch, Anabas testudineus, is involved in both hypoosmotic regulation during seawater acclimation and active ammonia excretion during ammonia exposure
    Yuen K Ip
    Department of Biological Sciences, National University of Singapore, Kent Ridge, Singapore 117543, Republic of Singapore
    J Comp Physiol B 182:793-812. 2012
    This study aimed to clone and sequence the cystic fibrosis transmembrane conductance regulator (cftr) from, and to determine the effects of seawater acclimation or exposure to 100 mmol l⁻¹ NH₄Cl in freshwater on its mRNA and protein ..
  77. pmc Rescuing cystic fibrosis transmembrane conductance regulator (CFTR)-processing mutants by transcomplementation
    Estelle Cormet-Boyaka
    Department of Physiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
    Proc Natl Acad Sci U S A 101:8221-6. 2004
    ..These findings indicate that it may be possible to develop CF therapies (e.g., mini-cDNA constructs for gene therapy) that are tailored to specific disease-causing mutants of CFTR...
  78. ncbi Rescue of DeltaF508 and other misprocessed CFTR mutants by a novel quinazoline compound
    Tip W Loo
    Departments of Medicine and Biochemistry, University of Toronto, Toronto, Ontario M5S 1A8, Canada
    Mol Pharm 2:407-13. 2005
    Cystic fibrosis (CF) is most commonly caused by deletion of Phe508 in the cystic fibrosis transmembrane conductance regulator protein (DeltaF508 CFTR)...
  79. pmc Cadmium regulates the expression of the CFTR chloride channel in human airway epithelial cells
    Jessica Rennolds
    Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, The Ohio State University, Columbus, Ohio 43210, USA
    Toxicol Sci 116:349-58. 2010
    ..Ion channels, including the cystic fibrosis transmembrane conductance regulator (CFTR), play a central role in maintaining fluid homeostasis and lung functions...
  80. ncbi Mouse models of cystic fibrosis: phenotypic analysis and research applications
    Martina Wilke
    Erasmus MC, Biochemistry Department, Rotterdam, The Netherlands
    J Cyst Fibros 10:S152-71. 2011
    ..The recent development of genetically modified pigs and ferrets heralds the application of more advanced animal models to CF research and drug development...
  81. ncbi Accessory protein facilitated CFTR-CFTR interaction, a molecular mechanism to potentiate the chloride channel activity
    S Wang
    Department of Physiology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
    Cell 103:169-79. 2000
    The cystic fibrosis transmembrane conductance regulator (CFTR) gene encodes a chloride channel protein that belongs to the superfamily of ATP binding cassette (ABC) transporters...
  82. pmc CFTR is a negative regulator of NFkappaB mediated innate immune response
    Neeraj Vij
    Department of Pediatric Respiratory Sciences, The Johns Hopkins School of Medicine, Baltimore, Maryland, United States of America
    PLoS ONE 4:e4664. 2009
    ..The mechanism(s) by which CFTR mediates inflammatory signaling is under debate...
  83. pmc DeltaF508 CFTR processing correction and activity in polarized airway and non-airway cell monolayers
    S M Rowe
    Department of Medicine, University of Alabama at Birmingham, 1530 3rd Ave South, Birmingham, AL 35294 0005, United States
    Pulm Pharmacol Ther 23:268-78. 2010
    We examined the activity of DeltaF508 cystic fibrosis transmembrane conductance regulator (CFTR) stably expressed in polarized cystic fibrosis bronchial epithelial cells (CFBE41o(-)) human airway cells and Fisher Rat Thyroid (FRT) cells ..
  84. ncbi Physiological modulation of CFTR activity by AMP-activated protein kinase in polarized T84 cells
    Kenneth R Hallows
    Renal Electrolyte Division, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA
    Am J Physiol Cell Physiol 284:C1297-308. 2003
    The cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP-activated, ATP-gated Cl(-) channel and cellular conductance regulator, but the detailed mechanisms of CFTR regulation and its regulation of other transport proteins ..
  85. pmc Multiple membrane-cytoplasmic domain contacts in the cystic fibrosis transmembrane conductance regulator (CFTR) mediate regulation of channel gating
    Lihua He
    Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, North Carolina 27599, USA
    J Biol Chem 283:26383-90. 2008
    The cystic fibrosis transmembrane conductance regulator (CFTR) is a unique ATP-binding cassette (ABC) ion channel mutated in patients with cystic fibrosis...
  86. pmc Loss of anion transport without increased sodium absorption characterizes newborn porcine cystic fibrosis airway epithelia
    Jeng Haur Chen
    Department of Internal Medicine, University of Iowa, Iowa City, 52242, USA
    Cell 143:911-23. 2010
    ..These results indicate that CFTR provides the predominant transcellular pathway for Cl⁻ and HCO₃⁻ in porcine airway epithelia, and reduced anion permeability may initiate CF airway disease...
  87. pmc Cystic fibrosis: terminology and diagnostic algorithms
    K De Boeck
    Department of Pediatrics, Pediatric Pulmonology, University Hospital of Leuven, Herestraat 49, 3000 Leuven, Belgium
    Thorax 61:627-35. 2006
    ..Non-classic CF includes patients with multiorgan or single organ involvement. Most of these patients have exocrine pancreatic sufficiency and milder lung disease. Algorithms for a structured diagnostic process are proposed...
  88. pmc The porcine lung as a potential model for cystic fibrosis
    Christopher S Rogers
    Department of Internal Medicine, Roy J Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242, USA
    Am J Physiol Lung Cell Mol Physiol 295:L240-63. 2008
    ..Although the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) has been targeted in mice, CF mice fail to develop lung or pancreatic disease like ..
  89. ncbi The DeltaF508 cystic fibrosis mutation impairs domain-domain interactions and arrests post-translational folding of CFTR
    Kai Du
    Hospital for Sick Children Research Institute, Program in Cell and Lung Biology, University of Toronto, Ontario M5G 1X8, Canada
    Nat Struct Mol Biol 12:17-25. 2005
    ....
  90. ncbi Pathophysiology and management of pulmonary infections in cystic fibrosis
    Ronald L Gibson
    Department of Pediatrics, University of Washington School of Medicine, Children s Hospital, Seattle, WA 98125, USA
    Am J Respir Crit Care Med 168:918-51. 2003
    ..In addition, the article discusses infection control policies, therapies to optimize airway clearance and reduce inflammation, and potential future therapies...
  91. ncbi Gentamicin-induced correction of CFTR function in patients with cystic fibrosis and CFTR stop mutations
    Michael Wilschanski
    Department of Pediatrics, Cystic Fibrosis Center, Shaare Zedek Medical Center, Jerusalem, Israel
    N Engl J Med 349:1433-41. 2003
    Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene containing a premature termination signal cause a deficiency or absence of functional chloride-channel activity...
  92. pmc Misfolding diverts CFTR from recycling to degradation: quality control at early endosomes
    Manu Sharma
    Hospital for Sick Children, Program in Cell and Lung Biology, 555 University Ave, Toronto, Ontario M5G 1X8, Canada
    J Cell Biol 164:923-33. 2004
    ....
  93. pmc The Hdj-2/Hsc70 chaperone pair facilitates early steps in CFTR biogenesis
    G C Meacham
    Department of Cell Biology, School of Medicine and Dentistry, University of Alabama Medical Center, Birmingham, AL 35209, USA
    EMBO J 18:1492-505. 1999
    The cystic fibrosis transmembrane conductance regulator (CFTR) is a chloride ion channel constructed from two membrane-spanning domains (MSDs), two nucleotide-binding domains (NBD) and a regulatory (R) domain...
  94. pmc A C-terminal motif found in the beta2-adrenergic receptor, P2Y1 receptor and cystic fibrosis transmembrane conductance regulator determines binding to the Na+/H+ exchanger regulatory factor family of PDZ proteins
    R A Hall
    Howard Hughes Medical Institute, Departments of Medicine and Biochemistry, Duke University Medical Center, Durham, NC 27710, USA
    Proc Natl Acad Sci U S A 95:8496-501. 1998
    ..NHERF also binds to the tail of the cystic fibrosis transmembrane conductance regulator, which ends in D-T-R-L...
  95. pmc A mouse model for the cystic fibrosis delta F508 mutation
    J H van Doorninck
    MGC Department of Cell Biology and Genetics, Erasmus University, Rotterdam, The Netherlands
    EMBO J 14:4403-11. 1995
    Most cystic fibrosis (CF) patients produce a mutant form (delta F508) of the cystic fibrosis transmembrane conductance regulator (CFTR), which is not properly processed in normal cells but is active as a chloride channel in several ..
  96. ncbi Structural analog of sildenafil identified as a novel corrector of the F508del-CFTR trafficking defect
    Renaud Robert
    McIntyre Building, Physiology Department, 3655 Promenade Sir William Osler, Montreal, Quebec, H3G 1Y6, Canada
    Mol Pharmacol 73:478-89. 2008
    The F508del mutation impairs trafficking of the cystic fibrosis transmembrane conductance regulator (CFTR) to the plasma membrane and results in a partially functional chloride channel that is retained in the endoplasmic reticulum and ..
  97. pmc Expression of wild-type CFTR suppresses NF-kappaB-driven inflammatory signalling
    Mairi J Hunter
    Division of Medical Sciences, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK
    PLoS ONE 5:e11598. 2010
    ..CF-inflammation provides one example but its pathogenesis remains controversial. Here, we tested the simple but fundamental hypothesis that wild-type CFTR is needed to suppress NF-kappaB activity...
  98. pmc CFTR regulatory region interacts with NBD1 predominantly via multiple transient helices
    Jennifer M R Baker
    Program in Molecular Structure and Function, The Hospital for Sick Children, 555 University Ave, Toronto, Ontario M5G 1X8, Canada
    Nat Struct Mol Biol 14:738-45. 2007
    The regulatory (R) region of the cystic fibrosis transmembrane conductance regulator (CFTR) is intrinsically disordered and must be phosphorylated at multiple sites for full CFTR channel activity, with no one specific phosphorylation ..
  99. pmc AMPK agonists ameliorate sodium and fluid transport and inflammation in cystic fibrosis airway epithelial cells
    MICHAEL M MYERBURG
    Renal Electrolyte Division, Department of Medicine, University of Pittsburgh School of Medicine, S976 Scaife Hall, 3550 Terrace Street, Pittsburgh, PA 15261, USA
    Am J Respir Cell Mol Biol 42:676-84. 2010
    ....
  100. ncbi A principal role for the proteasome in endoplasmic reticulum-associated degradation of misfolded intracellular cystic fibrosis transmembrane conductance regulator
    Marina S Gelman
    Department of Biological Sciences, Stanford University, Stanford, California 94305 5020, USA
    J Biol Chem 277:11709-14. 2002
    Endoplasmic reticulum-associated degradation of misfolded cystic fibrosis transmembrane conductance regulator (CFTR) protein is known to involve the ubiquitin-proteasome system...
  101. pmc The cystic fibrosis-causing mutation deltaF508 affects multiple steps in cystic fibrosis transmembrane conductance regulator biogenesis
    Patrick H Thibodeau
    Department of Physiology, The University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
    J Biol Chem 285:35825-35. 2010
    The deletion of phenylalanine 508 in the first nucleotide binding domain of the cystic fibrosis transmembrane conductance regulator is directly associated with >90% of cystic fibrosis cases...

Research Grants77

  1. Physiologic membrane traffic regulation: intestinal CFTR
    Nadia Ameen; Fiscal Year: 2006
    ..Both diseases target the small intestine and are linked by the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel...
  2. Pathobiology of Cystic Fibrosis-Related Diabetes in a Ferret Model
    Zoe Stewart; Fiscal Year: 2013
    ..most common lethal autosomal recessive disease in Caucasians, resulting from defects in the cystic fibrosis transmembrane conductance regulator (CFTR) channel...
  3. Iowa Phase II Clinical Trials of Novel Therapies for Lung Diseases (U01
    Lakshmi Durairaj; Fiscal Year: 2012
    ..Disruption of the cystic fibrosis transmembrane conductance regulator chloride channels due to genetic mutations in subjects with CF results in altered fluid and ..
  4. Fatty Acid Defects &Oxidative Stress Modulate Islet Function in Cystic Fibrosis
    Aliye Uc; Fiscal Year: 2013
    ..b>Cystic fibrosis transmembrane conductance regulator (CFTR)-knockout pig and ferret models developed at the University of Iowa have multi-organ ..
  5. CFTR Biogenesis and Function in Epithelia
    Zsuzsa Bebok; Fiscal Year: 2012
    DESCRIPTION (provided by applicant): The cystic fibrosis transmembrane conductance regulator (CFTR) is a chloride channel expressed on the apical surface of epithelial cells and is defective in cystic fibrosis (CF)...
  6. Transcriptional Networks Regulating Luminal Environment in the Epididymis
    Ann Harris; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Functional inactivation (by mutation) of the cystic fibrosis transmembrane conductance regulator (CFTR), a small conductance, cAMP activated chloride ion channel, leads to developmental defects that ..
  7. NAPS2 Continuation Genome Wide Association Study of Pancreatitis
    DAVID CLEMENT WHITCOMB; Fiscal Year: 2011
    ..We also discovered a new class of cystic fibrosis transmembrane conductance regulator (CFTR) variants that alter bicarbonate but not chloride conductance, such that the pancreas ..
  8. Transcriptional Control of Submucosal Gland Formation and Function
    Jeffrey A Whitsett; Fiscal Year: 2013
    ..growth, diferentiation, and gene expression of AECs and SMGs are influenced by the lack of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR)...
  9. Pathogensis of Bacterial corneal infection
    Gerald B Pier; Fiscal Year: 2013
    ..scratch-injured mouse eyes are found inside of cells, and entry requires binding to the cystic fibrosis transmembrane conductance regulator (CFTR)...
  10. MOLECULAR MECHANISMS FOR EXTRACELLULAR PH CONTROL DURING AMELOGENESIS
    MICHAEL LANSDELL PAINE; Fiscal Year: 2013
    ..The third protein is the cystic fibrosis transmembrane conductance regulator (CFTR), which is a chloride channel, is directly associated with AE2 function...
  11. Role of Ion Channel in Mononuclear Phagocyte Activation
    Deborah J Nelson; Fiscal Year: 2012
    ..we demonstrated that murine alveolar macrophages (AMs) but not neutrophils employ the CFTR (Cystic Fibrosis Transmembrane conductance Regulator) Cl- channel as a major shunt mechanism...
  12. Mining open chromatin to define molecular mechanisms of CF modifier genes
    WANDA K O'NEAL; Fiscal Year: 2013
    ..Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene cause CF, a devastating, recessive, monogenic disease...
  13. Spin labeling of MsbA
    Candice S Klug; Fiscal Year: 2012
    ..MsbA with other ABC transporters implicated in various common genetic disorders such as the cystic fibrosis transmembrane conductance regulator, any new functional information gained by studying the easily purified MsbA will be ..
  14. Regulated biosynthesis and function of ABC-transport systems
    Patrick H Thibodeau; Fiscal Year: 2013
    ..salt and water movement across epithelial tissues, is caused by mutations within the cystic fibrosis transmembrane conductance regulator (CFTR)...
  15. Toxic metals and ion channels in cigarette-smoke induced COPD
    ESTELLE A CORMET BOYAKA; Fiscal Year: 2010
    ..CS was shown to reduce the expression of the Cystic Fibrosis Transmembrane conductance Regulator (CFTR)...
  16. CFTR inhibitors for therapy of polycystic kidney disease
    Alan S Verkman; Fiscal Year: 2010
    ..ADPKD) progressive fluid accumulation into cysts requires chloride secretion by the cystic fibrosis transmembrane conductance regulator protein (CFTR), a cAMP-regulated chloride channel, which, when mutated, causes the genetic ..
  17. Optimization of Protein Therapeutics Formulations
    Lawrence J Delucas; Fiscal Year: 2012
    ..as the proteins osteoprotegerin (involved in bone mineralization and osteoporosis), the cystic fibrosis transmembrane conductance regulator protein (CFTR), the nucleotide-binding domain-1 of CFTR and phospholipase-D1 (a human ..
  18. Elucidating the role of a-AP-2 in CFTR endocytosis and function in the intestine
    Anne M Collaco; Fiscal Year: 2013
    ..tissues and polarized intestinal cells to examine how internalization (endocytosis) of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) anion channels and its exocytic insertion back to the apical plasma membrane (..
  19. The Role of the Calcium Activated Potassium Channel, KCa3.1, in the Pathogenesis
    Edward Skolnik; Fiscal Year: 2010
    ..enhanced growth of renal epithelia and the stimulation of apical chloride secretion via the cystic fibrosis transmembrane conductance regulator (CFTR)...
  20. Development of a Humanized Pig Model of Cystic Fibrosis
    Christopher Rogers; Fiscal Year: 2010
    DESCRIPTION (provided by applicant): Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene...
  21. Functional Anatomic Imaging of CF Patients with Early Lung Disease Using microOCT
    Guillermo J Tearney; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR), an anion transporter of chloride and bicarbonate...
  22. Mechanistic Basis Underlying Protein Repair of CFTR Nonsense Mutations
    STEVEN MARK ROWE; Fiscal Year: 2010
    ..in particular, the molecular basis underlying increased response observed for the W1282X cystic fibrosis transmembrane conductance regulator (CFTR) mutation), and identifying pathways to augment rescue of CFTR nonsense codons...
  23. Tissue-specific regulation of a gene essential for airway epithelial function
    Ann Harris; Fiscal Year: 2012
    ..cells and shows a complex expression pattern involving intronic regulatory elements, is the cystic fibrosis transmembrane conductance regulator gene (CFTR)...
  24. Novel function and mechanism of CFTR in heart failure
    DAYUE DARREL DUAN; Fiscal Year: 2012
    The cystic fibrosis transmembrane conductance regulator (CFTR) is a unique member of the ATP-binding cassette (ABC) transporters superfamily, which functions as not only a transport but also a Cl- channel gated by protein kinase-..
  25. Myosin Functions in the Enterocyte
    Mark S Mooseker; Fiscal Year: 2012
    ..g. cystic fibrosis transmembrane conductance regulator, Na+/phosphate exchanger 2b,Toll-like receptor 4) will be explored.
  26. Targeting compartmentalized phosphodiesterases to regulate CFTR function
    WITO H RICHTER; Fiscal Year: 2013
    ..microdomains of signaling, rather than on the global scale, determines the function of the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) in health and disease...
  27. Adaptive glutathione responses to cigarette smoke in COPD
    Brian J Day; Fiscal Year: 2011
    ..The cystic fibrosis transmembrane conductance regulator (CFTR) and breast cancer related protein (BCRP) congenic KO mouse provides a unique animal ..
  28. Regulation of the Endocytic Trafficking of CFTR
    Agnieszka Swiatecka-Urban; Fiscal Year: 2012
    ..Our long-term objective is to elucidate the endocytic trafficking pathways of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) in order to identify a therapeutic target for the fatal disease, cystic fibrosis (CF)..
  29. ER export and the quality control checkpoint during membrane protein biogenesis
    Elizabeth A Miller; Fiscal Year: 2013
    ..Yor1p is broadly related to the human cystic fibrosis transmembrane conductance regulator, CFTR, which causes cystic fibrosis when mutated...
  30. LIVE-CELL IMAGING OF CFTR OLIGOMERIZATION, TRAFFICKING AND INTERACTIONS
    PETER MICHAEL HAGGIE; Fiscal Year: 2012
    The cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP-regulated ion channel present in the apical surface of several epithelia including the airways, pancreas, kidney, sweat glands and gastrointestinal tract...
  31. Functional Relevance of CFTR Trafficking in Vivo to Intestinal Disease
    Nadia A Ameen; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) channels are the major apical exit pathways for anion (chloride and bicarbonate) secretion from the brush border membrane (BBM) in the ..
  32. Islet Biology in Cystic Fibrosis Related Diabetes
    Alvin C Powers; Fiscal Year: 2013
    ..Since the cystic fibrosis transmembrane conductance regulator (CFTR) is expressed and functional in mouse and human pancreatic islet cells, we propose ..
  33. MOLECULAR MECHANISMS OF CFTR FUNCTION
    John R Riordan; Fiscal Year: 2013
    The cystic fibrosis transmembrane conductance regulator (CFTR) plays a critical role in vertebrate epithelial salt and fluid homeostasis and its absence or dysfunction results in cystic fibrosis in humans...
  34. CFTR degradation in the early biogenesis
    Fei Sun; Fiscal Year: 2013
    ..a lethal autosomal recessive inherited disease caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR), which functions as a cAMP- dependent Cl channel at the apical membrane of ..
  35. Chloride secretagogues for acquired CFTR dysfunction in chronic rhinosinusitis
    Bradford Alan Woodworth; Fiscal Year: 2013
    ..Decreased transepithelial Cl- transport secondary to an acquired Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) deficiency may contribute to respiratory epithelial dysfunction by abrogating MCC ..
  36. Microbiome acquistion and the progression of inflammation and airway disease in i
    Barbara I Kazmierczak; Fiscal Year: 2013
    ..Mutations of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) affect its ability to act as a chloride channel...
  37. Role of LMTK2 in CFTR Trafficking
    Neil A Bradbury; Fiscal Year: 2013
    ..CF is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, that encodes for a chloride selective anion channel...
  38. Integration of Genomics with Genetics - Molecular Phenotypes for CF Lung Disease
    Hara Levy; Fiscal Year: 2010
    ..and pancreatic insufficiency attributed to dysfunction of a single gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR)...
  39. The Role of Hepoxilin A3 in Neutrophil Breach of the Infected Airway Mucosa
    Bryan P Hurley; Fiscal Year: 2013
    ..mouse and human lung epithelial cells as well as lung epithelial cells with defective cystic fibrosis transmembrane conductance regulator. The ability of P...
  40. Development of inhibitors of the calcium-activated chloride channel TMEM16a
    Marc O Anderson; Fiscal Year: 2013
    ..An important example of a mis-functioning chloride channel is mutation of the cystic fibrosis transmembrane conductance regulator (CFTR), which causes cystic fibrosis (CF), one of the most common life-limiting genetic ..
  41. Mechanisms and Binding-Sites in Adenylate Kinase-Dependent CFTR Gating
    CHRISTOPH OSKAR RANDAK; Fiscal Year: 2013
    ..The cystic fibrosis transmembrane conductance regulator (CFTR), a regulated chloride channel, is a representative of one of the largest families of ..
  42. Correction of defective deltaF508-CFTR processing in cystic fibrosis
    Gergely L Lukacs; Fiscal Year: 2013
    ..It is caused by mutations in the CF gene, encoding the cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP-regulated chloride channel...
  43. Cell Biology of CFTR in Polarized Epithelia
    James F Collawn; Fiscal Year: 2013
    ..CF is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that encodes a chloride channel...
  44. Molecular Physiology and Pharmacology of CFTR
    SILVIA BOMPADRE; Fiscal Year: 2009
    The Cystic Fibrosis Transmembrane conductance Regulator (CFTR) is a chloride channel that is regulated by phosphorylation and gated by ATP binding and hydrolysis...
  45. Role of ion channels in the development of COPD
    ESTELLE A CORMET-BOYAKA; Fiscal Year: 2013
    ..We have evidence that the expression of the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) is suppressed in human samples from COPD patients and that cigarette smoke reduces ..
  46. Epigenomic Modulation of Cystic Fibrosis
    WILLIAM EDWARD BALCH; Fiscal Year: 2013
    ..CF is caused principally by the Phe 508 deletion in the cystic fibrosis transmembrane conductance regulator (?F508 CFTR), a multi-membrane spanning, cAMP-regulated chloride channel...
  47. The Effects of CFTR Deficiency on Metabolic Bone Disease
    MICHAEL SHANE STALVEY; Fiscal Year: 2013
    ..Recent data suggests that an underlying defect exists in bone metabolism of cystic fibrosis transmembrane conductance regulator (CFTR) deficient mice...
  48. cGMP Metabolism in Resistance to Bacterial Infection
    Kris Steinbrecher; Fiscal Year: 2013
    ..cells, elevates intracellular cGMP and elicits transmembrane ion movement via the cystic fibrosis transmembrane conductance regulator and the Na+/H+ Exchanger 3...
  49. Chromatin Dynamics of the CFTR locus
    MARTIN JOHN WALSH; Fiscal Year: 2013
    ..Since the discovery of the gene responsible for cystic fibrosis (CF) encoding the cystic fibrosis transmembrane conductance regulator (CFTR) protein, several therapeutic approaches have emerged that have extended and enhanced ..
  50. DELTAF508-CFTR TRAFFICKING REGULATED BY 4-PHENYLBUTYRATE
    Ronald C Rubenstein; Fiscal Year: 2012
    The Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) is a multifunctional protein that both transports Cl- across the apical plasma membrane of epithelial cells and regulates ion transport by other proteins, such as the ..
  51. CFTR Delivery to Ciliated Airway Cells by PIV Vectors
    Raymond Pickles; Fiscal Year: 2009
    ..The absent gene product in CF is the cystic fibrosis transmembrane conductance regulator (CFTR) protein that regulates fluid homeostatic mechanisms in the airway epithelium...
  52. Discovering New Regulators of CFTR and Fluid Secretion in Zebrafish
    Michel Bagnat; Fiscal Year: 2009
    ..My focus is on the Cystic Fibrosis Transmembrane conductance Regulator, a chloride channel that is the major regulator of fluid secretion in vertebrates...
  53. Potentiation of Mutant CFTR Activity
    LOUISE CLARE PYLE; Fiscal Year: 2010
    ..The illness is caused by abnormalities in the cystic fibrosis transmembrane conductance regulator (CFTR), a chloride channel that serves a critical role maintaining lung health and ..
  54. Investigation of CFTR on sinus and craniofacial development in a CF porcine model
    Eugene H Chang; Fiscal Year: 2013
    ..This is the first time an animal model will allow us to investigate the role of Cystic Fibrosis Transmembrane conductance Regulator (CFTR) on craniofacial development and sinus pathology in CFTR knockout (CFTR-/-) and wild-..
  55. Biosynthesis and function of ABC transporters
    Patrick H Thibodeau; Fiscal Year: 2010
    ..altered water and salt secretion across epithelial tissues, is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR)...
  56. Mechanisms, Structure, and Regulation of CFTRs NBDs
    David C Gadsby; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): CFTR (cystic fibrosis transmembrane conductance regulator), encoded by the gene mutated in CF patients, is one of 48 human ATP-binding cassette (ABC) proteins...
  57. A Novel HTS Cell-Based Imaging Assay To Identify Chemical Correctors for ??F508-C
    Wook Joon Chung; Fiscal Year: 2009
    ..fibrosis (CF) is a lethal genetic disease caused by mutations in the gene that encodes Cystic Fibrosis Transmembrane conductance Regulator (CFTR)...
  58. MOLECULAR PATHOPHYSIOLOGY OF CYSTIC FIBROSIS
    Tzyh Chang Hwang; Fiscal Year: 2012
    CFTR (Cystic Fibrosis Transmembrane conductance Regulator) is a chloride channel that plays a critical role in mediating epithelial chloride secretion and absorption...
  59. CFTR regulation of thyroid transport
    Peying Fong; Fiscal Year: 2013
    ..Our group recently positively established the presence of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) in thyroid, where it can mediate thyroid anion secretion via an apically localized, ..
  60. The (Mis)Folding Pathway of CFTR: Early Interdomain and Protein Interactions
    ANNA ELIZABETH PATRICK; Fiscal Year: 2012
    ..Cystic fibrosis (CF) is a lethal genetic disease caused by the lack of functional cystic fibrosis transmembrane conductance regulator protein (CFTR)...
  61. Biosynthesis of N-linked Glycoproteins: Two Fates - Folding or Degradation
    William J Lennarz; Fiscal Year: 2010
    ..secretory protein trafficking problems including cystic fibrosis caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR), emphysema and cirrhosis due to ?1-antitrypsin deficiency, and hemophilia in ..
  62. Development of Membrane Protein Structure
    Philip J Thomas; Fiscal Year: 2013
    ..fatal genetic disease, are caused by mutations that interfere with the assembly of the cystic fibrosis transmembrane conductance regulator (CFTR) protein...
  63. GATING OF THE CFTR CL CHANNEL BY ATP HYDROLYSIS
    Tzyh Chang Hwang; Fiscal Year: 1999
    ..goal of this project is to understand how hydrolysis of ATP is coupled to the gating of the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) Cl channel in isolated guinea pig ventricular myocytes and in various cell lines ..
  64. Daily genistein injections stimulate intestinal secretion: How?
    Layla Al Nakkash; Fiscal Year: 2007
    ..a naturally occurring phytoestrogen found in soy, is a known in vitro activator of the cystic fibrosis transmembrane conductance regulator chloride channel (CFTR)...
  65. Clinical and Mechanistic Features of Premature Termination Codon Suppression
    STEVEN MARK ROWE; Fiscal Year: 2010
    ..CF caused by premature stop mutations results in the production of little or no functional cystic fibrosis transmembrane conductance regulator (CFTR)...
  66. GC-C agonists for colitis-induced CRC
    Kunwar Shailubhai; Fiscal Year: 2009
    ..resulting in enhanced production of cyclic guanosine monophosphate (cGMP) and activation of cystic fibrosis transmembrane conductance regulator (CFTR)...
  67. Role of Myosin VI in CFTR Endocytosis in the Intestine
    Nadia Ameen; Fiscal Year: 2007
    ..fill critical gaps in our understanding of the physiologic relevance of trafficking of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel to anion transport in the intestine and its relevance to the ..
  68. Characterization of Pancreatic Disease in a Novel Porcine Cystic Fibrosis Model
    Aliye Uc; Fiscal Year: 2010
    ..We produced pigs (Sus scrofa) with a targeted disruption of both cystic fibrosis transmembrane conductance regulator (CFTR) alleles...
  69. Rescue of CFTR-deltaF508 misfolding by pharmacological and genetic suppressors
    RYAN TYLER; Fiscal Year: 2009
    ..It is caused by mutations in the CF gene, which encodes the cystic fibrosis transmembrane conductance regulator (CFTR), a cell surface localized integral membrane protein that functions as chloride ion ..
  70. Development of Crofelemer to Treat Vibrio cholerae
    Barry Quart; Fiscal Year: 2007
    ..non-absorbed, oligomeric proanthocyanidin, which acts through luminal blockade of the cystic fibrosis transmembrane conductance regulator (CFTR)...
  71. CFTR AND ALIMENTARY EPITHELIAL ACID/ BASE TRANSPORT
    Lane Clarke; Fiscal Year: 2000
    ..human genetic disease, cystic fibrosis (CF), are indicative of the central role that the cystic fibrosis transmembrane conductance regulator (CFTR) plays in gastrointestinal electrolyte transport physiology...
  72. MEMBRANES AND ACTIVE TRANSPORT OF AMINO ACIDS
    GIOVANNA AMES; Fiscal Year: 2001
    The superfamily of translocators, traffic ATPases (or ABC proteins), the cystic fibrosis transmembrane conductance regulator (CFTR), the P- glycoprotein of multidrug resistance (MDR), and bacterial periplasmic permeases...
  73. High-throughput Assay to Identify CFTR Inhibitors
    Rangan Maitra; Fiscal Year: 2009
    ..a microplate-based fluorescent membrane potential assay to identify inhibitors of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR)...
  74. NOVEL NONVIRAL VECTORS FOR GENE TRANSFER
    Thomas Scanlin; Fiscal Year: 2000
    ..have been shown to be effective and efficient for the transfer of reporter genes and the cystic fibrosis transmembrane conductance regulator (CFTR) gene into airway epithelial cells from patients with cystic fibrosis (CF)...
  75. AIRWAY SUBMUCOSAL GLANDS AND CYSTIC FIBROSIS DISEASE
    STEPHEN BALLARD; Fiscal Year: 2009
    Cystic Fibrosis (CF) is caused by deleterious mutations in the gene that codes for the cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP-activated anion channel...
  76. Rapid Cystic Fibrosis DNA Mutation Screening Test
    Wlodek Mandecki; Fiscal Year: 2003
    ..autosomal recessive disease caused by one or more mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) protein...
  77. Agonists of guanylate cyclase receptor for colon cancer
    Kunwar Shailubhai; Fiscal Year: 2002
    ..production of cyclic guanosine monophosphate (cGMP), resulting in activation of cystic fibrosis transmembrane conductance regulator (CFTR)...