Basic and Clinical Studies of Cystic Fibrosis

Summary

Principal Investigator: Raymond A Frizzell
Abstract: The Cystic Fibrosis Research Center at the University of Pittsburgh currently has 55 members in eight departments and garners nearly $10 M in external grants and contracts to support its CF research efforts. These are focused in three major areas: The Center has a strong basic science component that addresses the Cell and Molecular Biology of CF, and is supported by NIH, NSF and Cystic Fibrosis Foundation (CFF) grants. Investigators in this group make extensive use of differentiated, primary human bronchial epithelia (HBE) for their work. They employ the methods of biochemistry, molecular biology, cell biology and electrophysiology to study CFTR and ENaC functions in epithelial membranes, how these pathways contribute to normal airway function, how they are trafficked between various compartments of the protein secretory and recycling pathways, and how pharmacological manipulation of channel biogenesis (correction) or channel activity (potentiation) influence HBE function. Studies of Lung Infection and Inflammation focus on the pulmonary inflammatory response to bacterial infection in HBE and animal models. These studies aim to improve our understanding of CF disease pathogenesis, define bio-markers for clinical trials, and identify targets for anti-inflammatory therapy. The Clinical Studies group translates basic findings into new therapies. It develops and evaluates methods to improve airway drug delivery and isotopic clearance assays that assess transmural airway liquid movements in vivo, to test therapeutics that target the core defect in CF. The proposed Research and Translational Core Center will be directed by Dr. Raymond Frizzell while Dr. Joseph Pilewski will serve as Associate Director. The Center is comprised of three scientific cores: Human Airway Cell and Assays (Frizzell, PI), Clinical Studies/Outcomes (Pilewski, PI), and Imaging (Watkins, PI). The Core Center will operate a Pilot and Feasibility Program to bring new investigators into CF research. This Center emphasizes the translation of basic knowledge into applied therapeutics.
Funding Period: 2005-09-15 - 2015-05-31
more information: NIH RePORT

Top Publications

  1. ncbi Quantitative imaging of airway liquid absorption in cystic fibrosis
    Landon W Locke
    Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA
    Eur Respir J 44:675-84. 2014
  2. pmc Novel keto-phospholipids are generated by monocytes and macrophages, detected in cystic fibrosis, and activate peroxisome proliferator-activated receptor-γ
    Victoria J Hammond
    School of Medicine, Cardiff University, Heath Park Campus, Cardiff CF14 4XN, United Kingdom
    J Biol Chem 287:41651-66. 2012
  3. pmc Syndecan-2 is a novel target of insulin-like growth factor binding protein-3 and is over-expressed in fibrosis
    Ximena D Ruiz
    Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America
    PLoS ONE 7:e43049. 2012
  4. pmc Activation of the epithelial sodium channel (ENaC) by the alkaline protease from Pseudomonas aeruginosa
    Michael B Butterworth
    Department of Cell Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA
    J Biol Chem 287:32556-65. 2012
  5. pmc Pharmacological rescue of the mutant cystic fibrosis transmembrane conductance regulator (CFTR) detected by use of a novel fluorescence platform
    John P Holleran
    Department of Cell Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America
    Mol Med 18:685-96. 2012
  6. pmc Phosphorylation-dependent 14-3-3 protein interactions regulate CFTR biogenesis
    Xiubin Liang
    Department of Cell Biology and Physiology, University of Pittsburgh, Pittsburgh, PA 15261, USA
    Mol Biol Cell 23:996-1009. 2012
  7. pmc Calcium-induced folding and stabilization of the Pseudomonas aeruginosa alkaline protease
    Liang Zhang
    Department of Cell Biology and Physiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA
    J Biol Chem 287:4311-22. 2012
  8. pmc Localized expression of tenascin in systemic sclerosis-associated pulmonary fibrosis and its regulation by insulin-like growth factor binding protein 3
    Monique Brissett
    University of Pittsburgh, Department of Medicine, Pittsburgh, Pennsylvania 15231, USA
    Arthritis Rheum 64:272-80. 2012
  9. pmc Lysophosphatidic acid increases soluble ST2 expression in mouse lung and human bronchial epithelial cells
    Jing Zhao
    Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA
    Cell Signal 24:77-85. 2012
  10. pmc Galectin-7 modulates the length of the primary cilia and wound repair in polarized kidney epithelial cells
    Christine Rondanino
    Renal Electrolyte Div, Dept of Medicine, Univ of Pittsburgh School of Medicine, PA 15261, USA
    Am J Physiol Renal Physiol 301:F622-33. 2011

Research Grants

  1. DIABETES AND ENDOCRINOLOGY RESEARCH CENTER
    Domenico Accili; Fiscal Year: 2013
  2. EARLY EVENTS IN ALZHEIMER PATHOGENESIS
    SUE TILTON GRIFFIN; Fiscal Year: 2013
  3. Inflammatory responses of vascular cells
    Paul L Fox; Fiscal Year: 2013

Detail Information

Publications58

  1. ncbi Quantitative imaging of airway liquid absorption in cystic fibrosis
    Landon W Locke
    Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA
    Eur Respir J 44:675-84. 2014
    ..However, mucus effects become negligible in the presence of an osmotic stimulus. Functional imaging of DTPA absorption provides a quantifiable marker of immediate response to treatments that promote airway surface liquid hydration...
  2. pmc Novel keto-phospholipids are generated by monocytes and macrophages, detected in cystic fibrosis, and activate peroxisome proliferator-activated receptor-γ
    Victoria J Hammond
    School of Medicine, Cardiff University, Heath Park Campus, Cardiff CF14 4XN, United Kingdom
    J Biol Chem 287:41651-66. 2012
    ..The lipids are a new family of bioactive mediators from the 12/15-LOX pathway that may contribute to its known anti-inflammatory actions in vivo...
  3. pmc Syndecan-2 is a novel target of insulin-like growth factor binding protein-3 and is over-expressed in fibrosis
    Ximena D Ruiz
    Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America
    PLoS ONE 7:e43049. 2012
    ..This is the first report describing elevated levels of SDC2 in fibrosis. Increased SDC2 expression is due, at least in part, to the activity of two pro-fibrotic factors, TGFβ and IGFBP-3...
  4. pmc Activation of the epithelial sodium channel (ENaC) by the alkaline protease from Pseudomonas aeruginosa
    Michael B Butterworth
    Department of Cell Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA
    J Biol Chem 287:32556-65. 2012
    ..Based on these data, patho-mechanisms associated with AP in the CF lung are proposed wherein secretion of AP leads to decreased airway surface liquid volume and a corresponding decrease in mucocilliary clearance of pulmonary pathogens...
  5. pmc Pharmacological rescue of the mutant cystic fibrosis transmembrane conductance regulator (CFTR) detected by use of a novel fluorescence platform
    John P Holleran
    Department of Cell Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America
    Mol Med 18:685-96. 2012
    ..These findings indicate that the FAP-tagged constructs faithfully report mutant CFTR correction activity and that this approach should be useful as a screening assay in diseases that impair protein trafficking to the cell surface...
  6. pmc Phosphorylation-dependent 14-3-3 protein interactions regulate CFTR biogenesis
    Xiubin Liang
    Department of Cell Biology and Physiology, University of Pittsburgh, Pittsburgh, PA 15261, USA
    Mol Biol Cell 23:996-1009. 2012
    ..Thus 14-3-3 binding to phosphorylated CFTR augments its biogenesis by reducing retrograde retrieval of CFTR to the endoplasmic reticulum. This mechanism permits cAMP/PKA stimulation to make more CFTR available for anion secretion...
  7. pmc Calcium-induced folding and stabilization of the Pseudomonas aeruginosa alkaline protease
    Liang Zhang
    Department of Cell Biology and Physiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA
    J Biol Chem 287:4311-22. 2012
    ..These results provide a basis for the Ca(2+)-mediated regulation of AP and suggest mechanisms by which Ca(2+) regulates the RTX family of virulence factors...
  8. pmc Localized expression of tenascin in systemic sclerosis-associated pulmonary fibrosis and its regulation by insulin-like growth factor binding protein 3
    Monique Brissett
    University of Pittsburgh, Department of Medicine, Pittsburgh, Pennsylvania 15231, USA
    Arthritis Rheum 64:272-80. 2012
    ....
  9. pmc Lysophosphatidic acid increases soluble ST2 expression in mouse lung and human bronchial epithelial cells
    Jing Zhao
    Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA
    Cell Signal 24:77-85. 2012
    ..These results unravel a novel sST2 mediated signaling pathway that has physiological relevance to airway inflammation and remodeling...
  10. pmc Galectin-7 modulates the length of the primary cilia and wound repair in polarized kidney epithelial cells
    Christine Rondanino
    Renal Electrolyte Div, Dept of Medicine, Univ of Pittsburgh School of Medicine, PA 15261, USA
    Am J Physiol Renal Physiol 301:F622-33. 2011
    ..We conclude that Gal-7 is selectively targeted to cilia and plays a key role in surface stabilization of glycoconjugates responsible for integrating cilia function with epithelial repair...
  11. pmc External Cu2+ inhibits human epithelial Na+ channels by binding at a subunit interface of extracellular domains
    Jingxin Chen
    Department of Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA
    J Biol Chem 286:27436-46. 2011
    ..We conclude that extracellular Cu(2+) is a potent inhibitor of human ENaC and binds to multiple sites within the extracellular domains including a subunit interface...
  12. pmc CFTR Folding Consortium: methods available for studies of CFTR folding and correction
    Kathryn W Peters
    Department of Cell Biology and Physiology, University of Pittsburgh, Pittsburgh, PA 15261, USA
    Methods Mol Biol 742:335-53. 2011
    ..The Roadmap queries CFTR structure-function relations at levels ranging from purified protein to well-differentiated human airway primary cultures...
  13. pmc Conjugated linoleic acid is a preferential substrate for fatty acid nitration
    Gustavo Bonacci
    Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA
    J Biol Chem 287:44071-82. 2012
    ..These results affirm that metabolic and inflammatory reactions yield electrophilic products that can modulate adaptive cell signaling mechanisms...
  14. pmc Small heat shock proteins target mutant cystic fibrosis transmembrane conductance regulator for degradation via a small ubiquitin-like modifier-dependent pathway
    Annette Ahner
    Department of Cell Biology and Physiology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA
    Mol Biol Cell 24:74-84. 2013
    ..These findings link sHsp-mediated F508del CFTR degradation to its SUMOylation and to STUbL-mediated targeting to the ubiquitin-proteasome system and thereby implicate this pathway in the disposal of an integral membrane protein...
  15. pmc Regulated recycling of mutant CFTR is partially restored by pharmacological treatment
    John P Holleran
    University of Pittsburgh School of Medicine, Department of Cell Biology, BSTS 225, 3500 Terrace St, Pittsburgh, PA 15261, USA
    J Cell Sci 126:2692-703. 2013
    ....
  16. pmc The membrane-associated adaptor protein DOK5 is upregulated in systemic sclerosis and associated with IGFBP-5-induced fibrosis
    Hidekata Yasuoka
    Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
    PLoS ONE 9:e87754. 2014
    ..Our findings suggest that IGFBP-5 induces its pro-fibrotic effects, at least in part, via DOK5. Furthermore, IGFBP-5 and DOK5 are both increased in SSc fibroblasts and tissues and may thus be acting in concert to promote fibrosis. ..
  17. pmc Unique functional properties of conserved arginine residues in the lentivirus lytic peptide domains of the C-terminal tail of HIV-1 gp41
    Anne Sophie Kuhlmann
    From the Center for Vaccine Research and
    J Biol Chem 289:7630-40. 2014
    ..We propose that these arginines may provide unique functions for Env interaction with viral or cellular cofactors that then influence overall Env functional properties. ..
  18. pmc Olives and olive oil are sources of electrophilic fatty acid nitroalkenes
    Marco Fazzari
    Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America Fondazione Ri MED, Palermo, Italy
    PLoS ONE 9:e84884. 2014
    ..Since NO2-FA instigate adaptive anti-inflammatory gene expression and metabolic responses, these redox-derived metabolites may contribute to the cardiovascular benefits associated with the Mediterranean diet. ..
  19. pmc The threads that tie protein-folding diseases
    Jeffrey L Brodsky
    Department of Biological Sciences, A320 Langley Hall, University of Pittsburgh, Pittsburgh, PA 15260, USA
    Dis Model Mech 7:3-4. 2014
    ....
  20. pmc Pseudomonas aeruginosa Cif protein enhances the ubiquitination and proteasomal degradation of the transporter associated with antigen processing (TAP) and reduces major histocompatibility complex (MHC) class I antigen presentation
    Jennifer M Bomberger
    From the Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15219
    J Biol Chem 289:152-62. 2014
    ..Cif is the first bacterial factor identified that inhibits TAP function and MHC class I antigen presentation. ..
  21. pmc Who's really in control: microbial regulation of protein trafficking in the epithelium
    Matthew R Hendricks
    Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
    Am J Physiol Cell Physiol 306:C187-97. 2014
    ....
  22. pmc Effect of apical hyperosmotic sodium challenge and amiloride on sodium transport in human bronchial epithelial cells from cystic fibrosis donors
    Hector Rasgado-Flores
    Department of Physiology and Biophysics, Rosalind Franklin University of Medicine and Science, North Chicago, Illinois
    Am J Physiol Cell Physiol 305:C1114-22. 2013
    ..Amiloride significantly accelerated the recovery of INa following exposure to HS. Our conclusions are that exposure to HS inhibits hBE INa and that amiloride diminishes this effect. ..
  23. pmc Modulation of nitro-fatty acid signaling: prostaglandin reductase-1 is a nitroalkene reductase
    Dario A Vitturi
    Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA
    J Biol Chem 288:25626-37. 2013
    ..These results situate PtGR-1 as a critical modulator of both the steady state levels and signaling activities of fatty acid nitroalkenes in vivo. ..
  24. pmc Cystic fibrosis transmembrane conductance regulator degradation: cross-talk between the ubiquitylation and SUMOylation pathways
    Annette Ahner
    Department of Cell Biology, University of Pittsburgh School of Medicine, PA 15224, USA
    FEBS J 280:4430-8. 2013
    ..It is reasonable to anticipate that further research on SUMO-ubiquitin pathway interactions will identify additional layers of complexity in the process of CFTR biogenesis and quality control. ..
  25. pmc Synaptic Zn2+ inhibits neurotransmitter release by promoting endocannabinoid synthesis
    Tamara Perez-Rosello
    Department of Otolaryngology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA
    J Neurosci 33:9259-72. 2013
    ..We reveal a previously unknown action of synaptic Zn(2+): synaptic Zn(2+) inhibits glutamate release by promoting 2-AG synthesis...
  26. pmc Tgf-β1 inhibits Cftr biogenesis and prevents functional rescue of ΔF508-Cftr in primary differentiated human bronchial epithelial cells
    Steven M Snodgrass
    Division of Pediatric Pulmonology, Children s Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA
    PLoS ONE 8:e63167. 2013
    ..Our data indicate that activation of TGF-β1 signaling may inhibit CFTR function in non-CF individuals and may interfere with therapies directed at correcting the processing defect of ΔF508-CFTR in CF patients...
  27. pmc Characterization and quantification of endogenous fatty acid nitroalkene metabolites in human urine
    Sonia R Salvatore
    Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA 15261, USA
    J Lipid Res 54:1998-2009. 2013
    ..The measurement of this class of mediators can constitute a sensitive noninvasive index of metabolic and inflammatory status...
  28. pmc Lung tissues in patients with systemic sclerosis have gene expression patterns unique to pulmonary fibrosis and pulmonary hypertension
    Eileen Hsu
    University of Pittsburgh, Pittsburgh, Pennsylvania, USA
    Arthritis Rheum 63:783-94. 2011
    ....
  29. pmc Surface tension gradient driven spreading on aqueous mucin solutions: a possible route to enhanced pulmonary drug delivery
    Kevin Koch
    Physics Department, Carnegie Mellon University, Pittsburgh, Pennsylvania 15213, USA
    Mol Pharm 8:387-94. 2011
    ..It is suggested that capillary forces and Marangoni flows driven by soluble surfactants may thereby enhance the uniformity of drug delivery to diseased lungs...
  30. pmc Chaperone displacement from mutant cystic fibrosis transmembrane conductance regulator restores its function in human airway epithelia
    Fei Sun
    Department of Cell Biology and Physiology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA
    FASEB J 22:3255-63. 2008
    ..Thus, PTD-mediated DeltaFRD fragment delivery may provide a therapy for CF...
  31. pmc Prostasin expression is regulated by airway surface liquid volume and is increased in cystic fibrosis
    Mike M Myerburg
    Division of Pulmonary, Allergy, and Critical Care Medicine, Univ of Pittsburgh Medical Center, 628 NW Montefiore Univ Hospital, 3459 Fifth Ave, Pittsburgh, PA 15213, USA
    Am J Physiol Lung Cell Mol Physiol 294:L932-41. 2008
    ....
  32. pmc IL-22 mediates mucosal host defense against Gram-negative bacterial pneumonia
    Shean J Aujla
    Children s Hospital of Pittsburgh, Suite 3765, 3705 Fifth Avenue, Pittsburgh, Pennsylvania 15213, USA
    Nat Med 14:275-81. 2008
    ..These data support the concept that the T(H)17 cell lineage and its effector molecules have evolved to effect host defense against extracellular pathogens at mucosal sites...
  33. ncbi Defining an inhibitory domain in the alpha-subunit of the epithelial sodium channel
    Marcelo D Carattino
    Renal Electrolyte Division, University of Pittsburgh, S931 Scaife Hall, 3550 Terrace St, Pittsburgh, PA 15261, USA
    Am J Physiol Renal Physiol 294:F47-52. 2008
    ..Our findings suggest that this eight-residue tract is a key conserved inhibitory domain that provides epithelial cells with a reserve of inactive channels that can be activated as required by proteases...
  34. ncbi Electrogenic bicarbonate secretion by prairie dog gallbladder
    A James Moser
    Univ of Pittsburgh School of Medicine, 497 Scaife Hall 3550 Terrace St Pittsburgh, PA 15261, USA
    Am J Physiol Gastrointest Liver Physiol 292:G1683-94. 2007
    ..Basolateral HCO(3)(-) entry is mediated by DNDS-sensitive pNBC1, and the driving force for apical anion secretion is provided by K(+) channel activation...
  35. ncbi Epithelial Na+ channels are fully activated by furin- and prostasin-dependent release of an inhibitory peptide from the gamma-subunit
    James B Bruns
    Renal Electrolyte Division, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA
    J Biol Chem 282:6153-60. 2007
    ..Our results suggest that multiple proteases cleave ENaC gamma subunits to fully activate the channel...
  36. ncbi Derlin-1 promotes the efficient degradation of the cystic fibrosis transmembrane conductance regulator (CFTR) and CFTR folding mutants
    Fei Sun
    Department of Cell Biology and Physiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA
    J Biol Chem 281:36856-63. 2006
    ....
  37. pmc Methods for detecting internalized, FM 1-43 stained particles in epithelial cells and monolayers
    C A Bertrand
    Department of Cell Biology and Physiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
    Biophys J 91:3872-83. 2006
    ..This method provides a single technique for quantifying membrane trafficking in both monolayers and unpolarized cells...
  38. ncbi Airway surface liquid volume regulates ENaC by altering the serine protease-protease inhibitor balance: a mechanism for sodium hyperabsorption in cystic fibrosis
    Mike M Myerburg
    Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, Pennsylvania 15213, USA
    J Biol Chem 281:27942-9. 2006
    ....
  39. ncbi The epithelial Na+ channel is inhibited by a peptide derived from proteolytic processing of its alpha subunit
    Marcelo D Carattino
    Renal Electrolyte Division, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA
    J Biol Chem 281:18901-7. 2006
    ..Our results suggest that proteolysis of the alpha subunit activates ENaC by disassociating an inhibitory domain (alphaAsp-206-Arg-231) from its effector site within the channel complex...
  40. ncbi 14-3-3 isoforms are induced by aldosterone and participate in its regulation of epithelial sodium channels
    Xiubin Liang
    Department of Cell Biology and Physiology, University of Pittsburgh School of Medicine, 3500 Terrace Street, Pittsburgh, PA 15261, USA
    J Biol Chem 281:16323-32. 2006
    ..Our studies show that aldosterone increases the expression of 14-3-3beta, which interacts with phospho-Nedd4-2 to block its interaction with ENaC, thus enhancing sodium absorption by increasing apical membrane ENaC density...
  41. ncbi Cysteine string protein monitors late steps in cystic fibrosis transmembrane conductance regulator biogenesis
    Hui Zhang
    Department of Cell Biology and Physiology, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA
    J Biol Chem 281:11312-21. 2006
    ....
  42. pmc An obligatory heterodimer of 14-3-3beta and 14-3-3epsilon is required for aldosterone regulation of the epithelial sodium channel
    Xiubin Liang
    Department of Cell Biology and Physiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA
    J Biol Chem 283:27418-25. 2008
    ....
  43. pmc Regulation of CFTR trafficking by its R domain
    Christopher M Lewarchik
    Department of Cell Biology and Physiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA
    J Biol Chem 283:28401-12. 2008
    ..These observations suggest that the NEG2 region at the C terminus of the R domain allows stabilization of CFTR in a regulated intracellular compartment from which it traffics to the plasma membrane in response to cAMP/PKA stimulation...
  44. pmc Interleukin-17A induces bicarbonate secretion in normal human bronchial epithelial cells
    James L Kreindler
    Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
    Am J Physiol Lung Cell Mol Physiol 296:L257-66. 2009
    ..These data suggest that IL-17A modulates epithelial bicarbonate secretion and implicate a mechanism by which airway surface liquid pH changes may be abnormal in cystic fibrosis...
  45. pmc Measurement of the airway surface liquid volume with simple light refraction microscopy
    Peter R Harvey
    Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA
    Am J Respir Cell Mol Biol 45:592-9. 2011
    ....
  46. pmc Vitamin D3 attenuates Th2 responses to Aspergillus fumigatus mounted by CD4+ T cells from cystic fibrosis patients with allergic bronchopulmonary aspergillosis
    James L Kreindler
    Children s Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA
    J Clin Invest 120:3242-54. 2010
    ..These data provide rationale for a therapeutic trial of vitamin D to prevent or treat ABPA in patients with CF...
  47. 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
    ....
  48. pmc AS160 modulates aldosterone-stimulated epithelial sodium channel forward trafficking
    Xiubin Liang
    Department of Cell Biology and Physiology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA
    Mol Biol Cell 21:2024-33. 2010
    ....
  49. pmc Acute regulation of the epithelial sodium channel in airway epithelia by proteases and trafficking
    MICHAEL M MYERBURG
    Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh Medical Center, Montefiore University Hospital, 3459 Fifth Ave, Pittsburgh, PA 15213, USA
    Am J Respir Cell Mol Biol 43:712-9. 2010
    ..These findings demonstrate that Na(+) absorption in the airway is acutely modulated by the coordinated trafficking of channels to the luminal surface and by the proteolytic activation of ENaC in response to ASL volume expansion...
  50. pmc Reduced histone deacetylase 7 activity restores function to misfolded CFTR in cystic fibrosis
    Darren M Hutt
    Department of Cell Biology, The Scripps Research Institute, La Jolla, California, USA
    Nat Chem Biol 6:25-33. 2010
    ..We suggest that the tunable capacity of HDACs can be manipulated by chemical biology to counter the onset of cystic fibrosis and other human misfolding disorders...
  51. pmc Absorptive clearance of DTPA as an aerosol-based biomarker in the cystic fibrosis airway
    T E Corcoran
    Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA
    Eur Respir J 35:781-6. 2010
    ..The absorption of In-DTPA is increased in the CF airway. Further study is needed to understand the relative roles of fluid absorption, inflammation and other mechanisms potentially affecting epithelial permeability and DTPA absorption...
  52. 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
    ....
  53. pmc Lipocalin 2 is required for pulmonary host defense against Klebsiella infection
    Yvonne R Chan
    Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA
    J Immunol 182:4947-56. 2009
    ..We conclude that lipocalin 2 is a crucial component of mucosal immune defense against pulmonary infection with K. pneumoniae...
  54. pmc SLC26A9 is a constitutively active, CFTR-regulated anion conductance in human bronchial epithelia
    Carol A Bertrand
    Department of Cell Biology and Physiology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA
    J Gen Physiol 133:421-38. 2009
    ....
  55. pmc Rab11b regulates the apical recycling of the cystic fibrosis transmembrane conductance regulator in polarized intestinal epithelial cells
    Mark R Silvis
    Department of Cell Biology and Physiology, University of Pittsburgh School of Medicine, PA 15261, USA
    Mol Biol Cell 20:2337-50. 2009
    ..This is the first report detailing apical CFTR recycling in a native expression system and to demonstrate that Rab11b regulates apical recycling in polarized epithelial cells...
  56. pmc Cysteine string protein promotes proteasomal degradation of the cystic fibrosis transmembrane conductance regulator (CFTR) by increasing its interaction with the C terminus of Hsp70-interacting protein and promoting CFTR ubiquitylation
    Bela Z Schmidt
    Department of Cell Biology and Physiology, University of Pittsburgh, Pittsburgh, Pennsylvania 15261
    J Biol Chem 284:4168-78. 2009
    ..These findings indicate that Csp not only regulates the exit of CFTR from the ER, but that this action is accompanied by Hsc70/Hsp70 and CHIP-mediated CFTR degradation...
  57. ncbi Up-regulation of AMP-activated kinase by dysfunctional cystic fibrosis transmembrane conductance regulator in cystic fibrosis airway epithelial cells mitigates excessive inflammation
    Kenneth R Hallows
    Department of Medicine, University of Pittsburgh School of Medicine, Pennsylvania 15261, USA
    J Biol Chem 281:4231-41. 2006
    ..We propose that therapies to activate AMPK in the CF airway may be beneficial in reducing excessive airway inflammation, a major cause of CF morbidity...

Research Grants30

  1. DIABETES AND ENDOCRINOLOGY RESEARCH CENTER
    Domenico Accili; Fiscal Year: 2013
    ....
  2. EARLY EVENTS IN ALZHEIMER PATHOGENESIS
    SUE TILTON GRIFFIN; Fiscal Year: 2013
    ..The synergy between our aims, approaches, and measures will enable us to meet our goal of defining early cellular interactions toward development of rational interventions in AD. ..
  3. Inflammatory responses of vascular cells
    Paul L Fox; Fiscal Year: 2013
    ..abstract_text> ..