Publications (2008-present)

Acute administration of ivacaftor to people with cystic fibrosis and a G551D-CFTR mutation reveals smooth muscle abnormalities.
Adam RJ, Hisert KB, Dodd JD, Grogan B, Launspach JL, Barnes JK, Gallagher CG, Sieren JP, Gross TJ, Fischer AJ, Cavanaugh JE, Hoffman EA, Singh PK, Welsh MJ, McKone EF, Stoltz DA.

Airway acidification initiates host defense abnormalities in cystic fibrosis mice.
Shah VS, Meyerholz DK, Tang XX, Reznikov L, Abou Alaiwa M, Ernst SE, Karp PH, Wohlford-Lenane CL, Heilmann KP, Leidinger MR, Allen PD, Zabner J, McCray PB Jr, Ostedgaard LS, Stoltz DA, Randak CO, Welsh MJ.
Science. 2016 Jan 29;351(6272):503-7. doi: 10.1126/science.aad5589.
PMID: 26823428

Acidic pH increases airway surface liquid viscosity in cystic fibrosis.
Tang XX, Ostedgaard LS, Hoegger MJ, Moninger TO, Karp PH, McMenimen JD, Choudhury B, Varki A, Stoltz DA, Welsh MJ.
J Clin Invest. 2016 Mar 1;126(3):879-91. doi: 10.1172/JCI83922. Epub 2016 Jan 25.
PMID: 26808501

Electrolyte transport properties in distal small airways from cystic fibrosis pigs with implications for host defense.
Li X, Tang XX, Vargas Buonfiglio LG, Comellas AP, Thornell IM, Ramachandran S, Karp PH, Taft PJ, Sheets K, Abou Alaiwa MH, Welsh MJ, Meyerholz DK, Stoltz DA, Zabner J.
Am J Physiol Lung Cell Mol Physiol. 2016 Jan 22:ajplung.00422.2015. doi: 10.1152/ajplung.00422.2015. [Epub ahead of print]
PMID: 26801568

Immunohistochemical Detection of Markers for Translational Studies of Lung Disease in Pigs and Humans.
Meyerholz DK, Lambertz AM, Reznikov LR, Ofori-Amanfo GK, Karp PH, McCray PB Jr, Welsh MJ, Stoltz DA.
Toxicol Pathol. 2015 Oct 27. pii: 0192623315609691. [Epub ahead of print]
PMID: 26511846

CFTR in Sarcoplasmic Reticulum of Airway Smooth Muscle: Implications for Airway Contractility.
Cook DP, Rector MV, Bouzek DC, Michalski AS, Gansemer ND, Reznikov LR, Li X, Stroik MR, Ostedgaard LS, Abou Alaiwa MH, Thompson MA, Prakash YS, Krishnan R, Meyerholz DK, Seow CY, Stoltz DA.
Am J Respir Crit Care Med. 2015 Oct 21. [Epub ahead of print]
PMID: 26488271

Sonographic evidence of abnormal tracheal cartilage ring structure in cystic fibrosis.
Diwakar A, Adam RJ, Michalski AS, Tamegnon MM, Fischer AJ, Launspach JL, Horan RA, Kao SC, Chaloner K, Meyerholz DK, Stoltz DA.
Laryngoscope. 2015 Oct;125(10):2398-404. doi: 10.1002/lary.25255. Epub 2015 Mar 30.
PMID: 25827636

Sonographic evidence of abnormal tracheal cartilage ring structure in cystic fibrosis.
Diwakar A, Adam RJ, Michalski AS, Tamegnon MM, Fischer AJ, Launspach JL, Horan RA, Kao SC, Chaloner K, Meyerholz DK, Stoltz DA.
Laryngoscope. 2015 Oct;125(10):2398-404. doi: 10.1002/lary.25255. Epub 2015 Mar 30.
PMID: 25827636

Origins of cystic fibrosis lung disease. 
Stoltz DA, Meyerholz DK, Welsh MJ. 
N Engl J Med. 2015 Jan 22;372(4):351-62. doi: 10.1056/NEJMra1300109. Review. No abstract available. 
PMID: 25607428

pH modulates the activity and synergism of the airway surface liquid antimicrobials β-defensin-3 and LL-37. 
Abou Alaiwa MH, Reznikov LR, Gansemer ND, Sheets KA, Horswill AR, Stoltz DA, Zabner J, Welsh MJ. 
Proc Natl Acad Sci U S A. 2014 Dec 30;111(52):18703-8. doi: 10.1073/pnas.1422091112. Epub 2014 Dec 15.
PMID: 25512526

Medical reversal of chronic sinusitis in a cystic fibrosis patient with ivacaftor. 
Chang EH, Tang XX, Shah VS, Launspach JL, Ernst SE, Hilkin B, Karp PH, Abou Alaiwa MH, Graham SM, Hornick DB, Welsh MJ, Stoltz DA, Zabner J.
Int Forum Allergy Rhinol. 2015 Feb;5(2):178-81. doi: 10.1002/alr.21440. Epub 2014 Oct 31. 
PMID: 25363320

Glycaemic regulation and insulin secretion are abnormal in cystic fibrosis pigs despite sparing of islet cell mass. 
Uc A, Olivier AK, Griffin MA, Meyerholz DK, Yao J, Abu-El-Haija M, Buchanan KM, Vanegas Calderón OG, Abu-El-Haija M, Pezzulo AA, Reznikov LR, Hoegger MJ, Rector MV, Ostedgaard LS, Taft PJ, Gansemer ND, Ludwig PS, Hornick EE, Stoltz DA, Ode KL, Welsh MJ, Engelhardt JF, Norris AW. 
Clin Sci (Lond). 2015 Jan;128(2):131-42. doi: 10.1042/CS20140059. 
PMID: 25142104

Impaired mucus detachment disrupts mucociliary transport in a piglet model of cystic fibrosis.
Hoegger MJ, Fischer AJ, McMenimen JD, Ostedgaard LS, Tucker AJ, Awadalla MA, Moninger TO, Michalski AS, Hoffman EA, Zabner J, Stoltz DA, Welsh MJ. 
Science. 2014 Aug 15;345(6198):818-22. doi: 10.1126/science.1255825.
PMID: 25124441

Antibacterial properties of the CFTR potentiator ivacaftor.
Reznikov LR, Abou Alaiwa MH, Dohrn CL, Gansemer ND, Diekema DJ, Stoltz DA, Welsh MJ.
J Cyst Fibros. 2014 Sep;13(5):515-9. doi: 10.1016/j.jcf.2014.02.004. Epub 2014 Mar 5. 
PMID: 24618508

Assessing mucociliary transport of single particles in vivo shows variable speed and preference for the ventral trachea in newborn pigs.
Hoegger MJ, Awadalla M, Namati E, Itani OA, Fischer AJ, Tucker AJ, Adam RJ, McLennan G, Hoffman EA, Stoltz DA, Welsh MJ. 
Proc Natl Acad Sci U S A. 2014 Feb 11;111(6):2355-60. doi: 10.1073/pnas.1323633111. Epub 2014 Jan 28.
PMID: 24474805

Neonates with cystic fibrosis have a reduced nasal liquid pH; a small pilot study. 
Abou Alaiwa MH, Beer AM, Pezzulo AA, Launspach JL, Horan RA, Stoltz DA, Starner TD, Welsh MJ, Zabner J.
J Cyst Fibros. 2014 Jul;13(4):373-7. doi: 10.1016/j.jcf.2013.12.006. Epub 2014 Jan 11. 
PMID: 24418186

Early airway structural changes in cystic fibrosis pigs as a determinant of particle distribution and deposition. 
Awadalla M, Miyawaki S, Abou Alaiwa MH, Adam RJ, Bouzek DC, Michalski AS, Fuld MK, Reynolds KJ, Hoffman EA, Lin CL, Stoltz DA. Ann Biomed Eng. 2014 Apr;42(4):915-27. doi: 10.1007/s10439-013-0955-7. Epub 2013 Dec 6. 
PMID: 24310865

Genotype-specific alterations in vascular smooth muscle cell function in cystic fibrosis piglets.
Guo JJ, Stoltz DA, Zhu V, Volk KA, Segar JL, McCray PB Jr, Roghair RD. 
J Cyst Fibros. 2014 May;13(3):251-9. doi: 10.1016/j.jcf.2013.10.009. Epub 2013 Oct 31. 
PMID: 24183914

Air trapping and airflow obstruction in newborn cystic fibrosis piglets.
Adam RJ, Michalski AS, Bauer C, Abou Alaiwa MH, Gross TJ, Awadalla MS, Bouzek DC, Gansemer ND, Taft PJ, Hoegger MJ, Diwakar A, Ochs M, Reinhardt JM, Hoffman EA, Beichel RR, Meyerholz DK, Stoltz DA.
Am J Respir Crit Care Med. 2013 Dec 15;188(12):1434-41. doi: 10.1164/rccm.201307-1268OC. 
PMID: 24168209

Tracheomalacia is associated with lower FEV1 and Pseudomonas acquisition in children with CF. 
Fischer AJ, Singh SB, Adam RJ, Stoltz DA, Baranano CF, Kao S, Weinberger MM, McCray PB Jr, Starner TD. 
Pediatr Pulmonol. 2014 Oct;49(10):960-70. doi: 10.1002/ppul.22922. Epub 2013 Oct 25. 
PMID: 24166775

Abundant DNase I-sensitive bacterial DNA in healthy porcine lungs and its implications for the lung microbiome. 
Pezzulo AA, Kelly PH, Nassar BS, Rutland CJ, Gansemer ND, Dohrn CL, Costello AJ, Stoltz DA, Zabner J.
Appl Environ Microbiol. 2013 Oct;79(19):5936-41. doi: 10.1128/AEM.01752-13. Epub 2013 Jul 19. 
PMID: 23872563

Intestinal CFTR expression alleviates meconium ileus in cystic fibrosis pigs. 
Stoltz DA, Rokhlina T, Ernst SE, Pezzulo AA, Ostedgaard LS, Karp PH, Samuel MS, Reznikov LR, Rector MV, Gansemer ND, Bouzek DC, Alaiwa MH, Hoegger MJ, Ludwig PS, Taft PJ, Wallen TJ, Wohlford-Lenane C, McMenimen JD, Chen JH, Bogan KL, Adam RJ, Hornick EE, Nelson GA 4th, Hoffman EA, Chang EH, Zabner J, McCray PB Jr, Prather RS, Meyerholz DK, Welsh MJ. 
J Clin Invest. 2013 Jun;123(6):2685-93. doi: 10.1172/JCI68867. Epub 2013 May 8. 
PMID: 23676501

Adenoviral gene transfer corrects the ion transport defect in the sinus epithelia of a porcine CF model.
Potash AE, Wallen TJ, Karp PH, Ernst S, Moninger TO, Gansemer ND, Stoltz DA, Zabner J, Chang EH. 
Mol Ther. 2013 May;21(5):947-53. doi: 10.1038/mt.2013.49. Epub 2013 Mar 19.
PMID: 23511247

CFTR-deficient pigs display peripheral nervous system defects at birth.
Reznikov LR, Dong Q, Chen JH, Moninger TO, Park JM, Zhang Y, Du J, Hildebrand MS, Smith RJ, Randak CO, Stoltz DA, Welsh MJ. 
Proc Natl Acad Sci U S A. 2013 Feb 19;110(8):3083-8. doi: 10.1073/pnas.1222729110. Epub 2013 Feb 4. 
PMID: 23382208

Computer-aided analysis of airway trees in micro-CT scans of ex vivo porcine lung tissue. 
Bauer C, Adam R, Stoltz DA, Beichel RR. 
Comput Med Imaging Graph. 2012 Dec;36(8):601-9. doi: 10.1016/j.compmedimag.2012.08.001. Epub 2012 Sep 7. 
PMID: 22959430

Expression of human paraoxonase 1 decreases superoxide levels and alters bacterial colonization in the gut of Drosophila melanogaster.
Pezzulo AA, Hornick EE, Rector MV, Estin M, Reisetter AC, Taft PJ, Butcher SC, Carter AB, Manak JR, Stoltz DA, Zabner J. 
PLoS One. 2012;7(8):e43777. doi: 10.1371/journal.pone.0043777. Epub 2012 Aug 30.
PMID: 22952763

Pancreatic and biliary secretion are both altered in cystic fibrosis pigs.
Uc A, Giriyappa R, Meyerholz DK, Griffin M, Ostedgaard LS, Tang XX, Abu-El-Haija M, Stoltz DA, Ludwig P, Pezzulo A, Abu-El-Haija M, Taft P, Welsh MJ. 
Am J Physiol Gastrointest Liver Physiol. 2012 Oct 15;303(8):G961-8. doi: 10.1152/ajpgi.00030.2012. Epub 2012 Aug 30. 
PMID: 22936270

Reduced airway surface pH impairs bacterial killing in the porcine cystic fibrosis lung.
Pezzulo AA, Tang XX, Hoegger MJ, Alaiwa MH, Ramachandran S, Moninger TO, Karp PH, Wohlford-Lenane CL, Haagsman HP, van Eijk M, Bánfi B, Horswill AR, Stoltz DA, McCray PB Jr, Welsh MJ, Zabner J.
Nature. 2012 Jul 4;487(7405):109-13. doi: 10.1038/nature11130. 
PMID: 22763554

Sinus hypoplasia precedes sinus infection in a porcine model of cystic fibrosis. 
Chang EH, Pezzulo AA, Meyerholz DK, Potash AE, Wallen TJ, Reznikov LR, Sieren JC, Karp PH, Ernst S, Moninger TO, Gansemer ND, McCray PB Jr, Stoltz DA, Welsh MJ, Zabner J.
Laryngoscope. 2012 Sep;122(9):1898-905. doi: 10.1002/lary.23392. Epub 2012 Jun 18. 
PMID: 22711071

Pancreatic damage in fetal and newborn cystic fibrosis pigs involves the activation of inflammatory and remodeling pathways. 
Abu-El-Haija M, Ramachandran S, Meyerholz DK, Abu-El-Haija M, Griffin M, Giriyappa RL, Stoltz DA, Welsh MJ, McCray PB Jr, Uc A. 
Am J Pathol. 2012 Aug;181(2):499-507. doi: 10.1016/j.ajpath.2012.04.024. Epub 2012 Jun 8. 
PMID: 22683312

CFTR is required for maximal transepithelial liquid transport in pig alveolar epithelia. 
Li X, Comellas AP, Karp PH, Ernst SE, Moninger TO, Gansemer ND, Taft PJ, Pezzulo AA, Rector MV, Rossen N, Stoltz DA, McCray PB Jr, Welsh MJ, Zabner J. 
Am J Physiol Lung Cell Mol Physiol. 2012 Jul;303(2):L152-60. doi: 10.1152/ajplung.00116.2012. Epub 2012 May 25.
PMID: 22637155

Inhaled hypertonic saline in adults hospitalised for exacerbation of cystic fibrosis lung disease: a retrospective study.
Pezzulo AA, Stoltz DA, Hornick DB, Durairaj L. BMJ Open. 2012 Apr 19;2(2):e000407. doi: 10.1136/bmjopen-2011-000407. Print 2012.
PMID: 22517980

Cystic fibrosis transmembrane conductance regulator intracellular processing, trafficking, and opportunities for mutation-specific treatment. 
Rogan MP, Stoltz DA, Hornick DB. 
Chest. 2011 Jun;139(6):1480-90. doi: 10.1378/chest.10-2077. Review. 
PMID: 21652558

The ΔF508 mutation causes CFTR misprocessing and cystic fibrosis-like disease in pigs. 
Ostedgaard LS, Meyerholz DK, Chen JH, Pezzulo AA, Karp PH, Rokhlina T, Ernst SE, Hanfland RA, Reznikov LR, Ludwig PS, Rogan MP, Davis GJ, Dohrn CL, Wohlford-Lenane C, Taft PJ, Rector MV, Hornick E, Nassar BS, Samuel M, Zhang Y, Richter SS, Uc A, Shilyansky J, Prather RS, McCray PB Jr, Zabner J, Welsh MJ, Stoltz DA. 
Sci Transl Med. 2011 Mar 16;3(74):74ra24. doi: 10.1126/scitranslmed.3001868. 
PMID: 21411740

Concentration of the antibacterial precursor thiocyanate in cystic fibrosis airway secretions. 
Lorentzen D, Durairaj L, Pezzulo AA, Nakano Y, Launspach J, Stoltz DA, Zamba G, McCray PB Jr, Zabner J, Welsh MJ, Nauseef WM, Bánfi B. 
Free Radic Biol Med. 2011 May 1;50(9):1144-50. doi: 10.1016/j.freeradbiomed.2011.02.013. Epub 2011 Feb 18. 
PMID: 21334431

Glucose depletion in the airway surface liquid is essential for sterility of the airways. 
Pezzulo AA, Gutiérrez J, Duschner KS, McConnell KS, Taft PJ, Ernst SE, Yahr TL, Rahmouni K, Klesney-Tait J, Stoltz DA, Zabner J.
PLoS One. 2011 Jan 20;6(1):e16166. doi: 10.1371/journal.pone.0016166.
PMID: 21311590

Loss of anion transport without increased sodium absorption characterizes newborn porcine cystic fibrosis airway epithelia. 
Chen JH, Stoltz DA, Karp PH, Ernst SE, Pezzulo AA, Moninger TO, Rector MV, Reznikov LR, Launspach JL, Chaloner K, Zabner J, Welsh MJ.
Cell. 2010 Dec 10;143(6):911-23. doi: 10.1016/j.cell.2010.11.029. 
PMID: 21145458

Pigs and humans with cystic fibrosis have reduced insulin-like growth factor 1 (IGF1) levels at birth.
Rogan MP, Reznikov LR, Pezzulo AA, Gansemer ND, Samuel M, Prather RS, Zabner J, Fredericks DC, McCray PB Jr, Welsh MJ, Stoltz DA. 
Proc Natl Acad Sci U S A. 2010 Nov 23;107(47):20571-5. doi: 10.1073/pnas.1015281107. Epub 2010 Nov 8. 
PMID: 21059918

Loss of cystic fibrosis transmembrane conductance regulator function produces abnormalities in tracheal development in neonatal pigs and young children. 
Meyerholz DK, Stoltz DA, Namati E, Ramachandran S, Pezzulo AA, Smith AR, Rector MV, Suter MJ, Kao S, McLennan G, Tearney GJ, Zabner J, McCray PB Jr, Welsh MJ.
Am J Respir Crit Care Med. 2010 Nov 15;182(10):1251-61. doi: 10.1164/rccm.201004-0643OC. Epub 2010 Jul 9. 
PMID: 20622026

Cystic fibrosis pigs develop lung disease and exhibit defective bacterial eradication at birth. 
Stoltz DA, Meyerholz DK, Pezzulo AA, Ramachandran S, Rogan MP, Davis GJ, Hanfland RA, Wohlford-Lenane C, Dohrn CL, Bartlett JA, Nelson GA 4th, Chang EH, Taft PJ, Ludwig PS, Estin M, Hornick EE, Launspach JL, Samuel M, Rokhlina T, Karp PH, Ostedgaard LS, Uc A, Starner TD, Horswill AR, Brogden KA, Prather RS, Richter SS, Shilyansky J, McCray PB Jr, Zabner J, Welsh MJ. 
Sci Transl Med. 2010 Apr 28;2(29):29ra31. doi: 10.1126/scitranslmed.3000928. 
PMID: 20427821

Paraoxonase 1, quorum sensing, and P. aeruginosa infection: a novel model. 
Estin ML, Stoltz DA, Zabner J. 
Adv Exp Med Biol. 2010;660:183-93. doi: 10.1007/978-1-60761-350-3_17.
PMID: 20221881

Pathology of gastrointestinal organs in a porcine model of cystic fibrosis.
Meyerholz DK, Stoltz DA, Pezzulo AA, Welsh MJ. 
Am J Pathol. 2010 Mar;176(3):1377-89. doi: 10.2353/ajpath.2010.090849. Epub 2010 Jan 28. 
PMID: 20110417

A common mutation in paraoxonase-2 results in impaired lactonase activity. 
Stoltz DA, Ozer EA, Recker TJ, Estin M, Yang X, Shih DM, Lusis AJ, Zabner J.
J Biol Chem. 2009 Dec 18;284(51):35564-71. doi: 10.1074/jbc.M109.051706. Epub . 
PMID: 19840942

Development of a porcine model of cystic fibrosis. 
Welsh MJ, Rogers CS, Stoltz DA, Meyerholz DK, Prather RS. 
Trans Am Clin Climatol Assoc. 2009;120:149-62.
PMID: 19768173

Disruption of the CFTR gene produces a model of cystic fibrosis in newborn pigs. 
Rogers CS, Stoltz DA, Meyerholz DK, Ostedgaard LS, Rokhlina T, Taft PJ, Rogan MP, Pezzulo AA, Karp PH, Itani OA, Kabel AC, Wohlford-Lenane CL, Davis GJ, Hanfland RA, Smith TL, Samuel M, Wax D, Murphy CN, Rieke A, Whitworth K, Uc A, Starner TD, Brogden KA, Shilyansky J, McCray PB Jr, Zabner J, Prather RS, Welsh MJ. 
Science. 2008 Sep 26;321(5897):1837-41. doi: 10.1126/science.1163600. 
PMID: 18818360

Drosophila are protected from Pseudomonas aeruginosa lethality by transgenic expression of paraoxonase-1.
Stoltz DA, Ozer EA, Taft PJ, Barry M, Liu L, Kiss PJ, Moninger TO, Parsek MR, Zabner J. 
J Clin Invest. 2008 Sep;118(9):3123-31. doi: 10.1172/JCI35147. 
PMID: 18704198

The porcine lung as a potential model for cystic fibrosis. 
Rogers CS, Abraham WM, Brogden KA, Engelhardt JF, Fisher JT, McCray PB Jr, McLennan G, Meyerholz DK, Namati E, Ostedgaard LS, Prather RS, Sabater JR, Stoltz DA, Zabner J, Welsh MJ. Am J Physiol Lung Cell Mol Physiol. 2008 Aug;295(2):L240-63. doi: 10.1152/ajplung.90203.2008. Epub 2008 May 16. Review. 
PMID: 18487356

Production of CFTR-null and CFTR-DeltaF508 heterozygous pigs by adeno-associated virus-mediated gene targeting and somatic cell nuclear transfer. 
Rogers CS, Hao Y, Rokhlina T, Samuel M, Stoltz DA, Li Y, Petroff E, Vermeer DW, Kabel AC, Yan Z, Spate L, Wax D, Murphy CN, Rieke A, Whitworth K, Linville ML, Korte SW, Engelhardt JF, Welsh MJ, Prather RS. 
J Clin Invest. 2008 Apr;118(4):1571-7. doi: 10.1172/JCI34773. 
PMID: 18324337