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Associate Professor

Specialty Areas:

Mucus biophysical properties, role of the Pericilliary Layer (PCL), and mechanisms of mucociliary clearance in the airways

Selected Bibliography:

  1. Hill DB*, Button B*, Rubinstein M, Boucher RC. Physiology and Pathophysiology of Human Airway Mucus. Physiol Rev. 2022 Oct 1;102(4):1757-1836. doi: 10.1152/physrev.00004.2021. PMID: 35001665. *Co-first authors.
  2. Biering SB, Sarnik SA, Wang E, Zengel JR, Leist SR, Schäfer A, Sathyan V, Hawkins P, Okuda K, Tau C, Jangid AR, Duffy CV, Wei J, Gilmore RC, Alfajaro MM, Strine MS, Nguyenla X, Van Dis E, Catamura C, Yamashiro LH, Belk JA, Begeman A, Stark JC, Shon DJ, Fox DM, Ezzatpour S, Huang E, Olegario N, Rustagi A, Volmer AS, Livraghi-Butrico A, Wehri E, Behringer RR, Cheon DJ, Schaletzky J, Aguilar HC, Puschnik AS, Button B, Pinsky BA, Blish CA, Baric RS, O’Neal WK, Bertozzi CR, Wilen CB, Boucher RC, Carette JE, Stanley SA, Harris E, Konermann S, Hsu PD. Genome-wide bidirectional CRISPR screens identify mucins as host factors modulating SARS-CoV-2 infection. Nat Genet. 2022 Aug;54(8):1078-1089. doi: 10.1038/s41588-022-01131-x. PMID: 35879412. PMCID: PMC9355872.
  3. Figueira MF, Ribeiro CMP, Button BMucus-targeting therapies of defective mucus clearance for cystic fibrosis: A short review. Curr Opin Pharmacol. 2022 Aug;65:102248. doi: 10.1016/j.coph.2022.102248. PMID: 35689870.
  4. Kato T, Radicioni G, Papanikolas MJ, Stoychev GV, Markovetz MR, Aoki K, Porterfield M, Okuda K, Barbosa Cardenas SM, Gilmore RC, Morrison CB, Ehre C, Burns KA, White KK, Brennan TA, Goodell HP, Thacker H, Loznev HT, Forsberg LJ, Nagase T, Rubinstein M, Randell SH, Tiemeyer M, Hill DB, Kesimer M, O’Neal WK, Ballard ST, Freeman R, Button B, Boucher RC. Mucus concentration-dependent biophysical abnormalities unify submucosal gland and superficial airway dysfunction in cystic fibrosis. Sci Adv. 2022 Apr;8(13):eabm9718. doi: 10.1126/sciadv.abm9718. PMID: 35363522.
  5. Rogers TD, Button B, Kelada SNP, Ostrowski LE, Livraghi-Butrico A, Gutay MI, Esther CR Jr, Grubb BR. Regional Differences in Mucociliary Clearance in the Upper and Lower Airways. Front Physiol. 2022 Mar 9;13:842592. doi: 10.3389/fphys.2022.842592. PMID: 35356083; PMCID: PMC8959816.
  6. Dahl DK, Whitesell AN, Sharma-Huynh P, Maturavongsadit P, Janusziewicz R, Fox RJ, Loznev HT, Button B, Schorzman AN, Zamboni W, Ban J, Montgomery SA, Carey ET, Rahima Benhabbour S. A mucoadhesive biodissolvable thin film for localized and rapid delivery of lidocaine for the treatment of vestibulodynia. Int J Pharm. 2022 Jan 25;612:121288. doi: 10.1016/j.ijpharm.2021.121288. PMID: 34800616. PMCID: PMC8753993.
  7. van Heusden C, Grubb BR, Button B, Lazarowski ER. Airway Epithelial Nucleotide Release Contributes to Mucociliary Clearance. Life (Basel). 2021 May 11;11(5):430. doi: 10.3390/life11050430. PMID: 34064654; PMCID: PMC8151306.
  8. Bennett WD, Henderson AG, Ceppe A, Zeman KL, Wu J, Gladman C, Fuller F, Gazda S, Button B, Boucher RC, Donaldson SH. Effect of hypertonic saline on mucociliary clearance and clinical outcomes in chronic bronchitis. ERJ Open Res. 2020 Aug 11;6(3):00269-2020. doi: 10.1183/23120541.00269-2020. PMID: 32802823. PMCID: PMC7418818.
  9. Danahay HL, Lilley S, Fox R, Charlton H, Sabater J, Button B, McCarthy C, Collingwood SP, Gosling M. TMEM16A Potentiation: A Novel Therapeutic Approach for the Treatment of Cystic Fibrosis. Am J Respir Crit Care Med. 2020 Apr 15;201(8):946-954. doi: 10.1164/rccm.201908-1641OC. PMID: 31898911. PMCID: PMC7159426.
  10. Ramsey KA, Chen ACH, Radicioni G, Lourie R, Martin M, Broomfield A, Sheng YH, Hasnain SZ, Radford-Smith G, Simms LA, Burr L, Thornton DJ, Bowler SD, Livengood S, Ceppe A, Knowles MR, Noone PG, Donaldson SH, Hill DB, Ehre C, Button B, Alexis NE, Kesimer M, Boucher RC, McGuckin MA. Airway Mucus Hyperconcentration in Non-Cystic Fibrosis Bronchiectasis. Am J Respir Crit Care Med. 2020 Mar 15;201(6):661-670. doi: 10.1164/rccm.201906-1219OC. PMID: 31765597. PMCID: PMC7068838.
  11. van Heusden C, Button B, Anderson WH, Ceppe A, Morton LC, O’Neal WK, Dang H, Alexis NE, Donaldson SH, Stephan H, Boucher RC, Lazarowski ER. Inhibition of ATP hydrolysis restores airway surface liquid production in cystic fibrosis airway epithelia. Am J Physiol Lung Cell Mol Physiol. 2020 Feb 1;318(2):L356-L365. doi: 10.1152/ajplung.00449.2019. PMID: 31800264. PMCID: PMC7052677.
  12. Brinks V, Lipinska K, de Jager M, Beumer W, Button B, Livraghi-Butrico A, Henig N, Matthee B. The Cystic Fibrosis-Like Airway Surface Layer Is not a Significant Barrier for Delivery of Eluforsen to Airway Epithelial Cells. J Aerosol Med Pulm Drug Deliv. 2019 Oct;32(5):303-316. doi: 10.1089/jamp.2018.1502. PMID: 31120356. PMCID: PMC6781260.
  13. Chen G, Sun L, Kato T, Okuda K, Martino MB, Abzhanova A, Lin JM, Gilmore RC, Batson BD, Volmer AS, Dang H, Deng Y, Randell SH, Button B, Livraghi-Butrico A, Kesimer M, Ribeiro CMP, O’Neal WK, Boucher RC. IL-1β dominates the promucin secretory cytokine profile in cystic fibrosis. J Clin Invest. 2019 Oct 1;129(10):4433-4450. doi: 10.1172/JCI125669. PMID: 31524632. PMCID: PMC6763234.
  14. Goodell HP, Shenoy SK, Shenkute NT, Lackey E, Dennis RG, Button B. Adhesive and Cohesive Peel Force Measurement of Human Airway Mucus. Bio Protoc. 2019 Jul 5;9(13). doi: 10.21769/BioProtoc.3287. PMID: 31687423. PMCID: PMC6827558.
  15. Henderson AG, Anderson WH, Ceppe A, Coakley RD, Button B, Alexis NE, Peden DB, Lazarowski ER, Davis CW, Fuller F, Almond M, Qaqish B, Kesimer M, Boucher RC. Mucus hydration in subjects with stable chronic bronchitis: A comparison of spontaneous and induced sputum. COPD. 2018 Dec;15(6):572-580. doi: 10.1080/15412555.2019.1566892. PMID: 30712400. PMCID: PMC6428611.
  16. Hill DB, Long RF, Kissner WJ, Atieh E, Garbarine IC, Markovetz MR, Fontana NC, Christy M, Habibpour M, Tarran R, Forest MG, Boucher RC, Button B. Pathological Mucus and Impaired Mucus Clearance in Cystic Fibrosis Patients Results from Increased Concentration, not altered pH. Eur Respir J. 2018 Dec 6;52(6). doi: 10.1183/13993003.01297-2018. PMID: 30361244. PMCID: PMC6446239.
  17. Button B, Goodell HP, Atieh E, Chen YC, Williams R, Shenoy S, Lackey E, Shenkute N, Cai L, Dennis R, Boucher RC, Rubinstein M. Roles of mucus adhesion and cohesion in cough clearance. Proc Natl Acad Sci U S A. 2018 Dec 4;115(49):12501-12506. doi: 10.1073/pnas.1811787115. PMID: 30420506. PMCID: PMC6298066.
  18. Rogers TD, Ostrowski LE, Livraghi-Butrico A, Button B, Grubb BR. Mucociliary Clearance in Mice Measured by Tracking Trans-tracheal Fluorescence of Nasally Aerosolized Beads. Sci Rep. 2018 Oct 3;8(1):14744. doi: 10.1038/s41598-018-33053-2. PMID: 30282981. PMCID: PMC6170422.
  19. Goralski JL, Wu D, Thelin WR, Boucher RC, Button B. The in vitro effect of nebulized hypertonic saline on human bronchial epithelium. Eur Respir J. 2018 May 17;51(5). doi: 10.1183/13993003.02652-2017. PMID: 29599187. PMCID: PMC6000726.
  20. Wu D, Boucher RC, Button B, Elston T, Lin CL. An integrated mathematical epithelial cell model for airway surface liquid regulation by mechanical forces. J Theor Biol. 2018 Feb 7;438:34-45. doi: 10.1016/j.jtbi.2017.11.010. PMID: 29154907. PMCID: PMC5764545.
  21. Schultz A, Puvvadi R, Borisov SM, Shaw NC, Klimant I, Berry LJ, Montgomery ST, Nguyen T, Kreda SM, Kicic A, Noble PB, Button B, Stick SM. Airway surface liquid pH is not acidic in children with cystic fibrosis. Nat Commun. 2017 Nov 10;8(1):1409. doi: 10.1038/s41467-017-00532-5. PMID: 29123085. PMCID: PMC5680186.
  22. Esther CR Jr, Hill DB, Button B, Shi S, Jania CM, Duncan EA, Doerschuk CM, Chen G, Ranganathan S, Stick SM, Boucher RC. The sialic acid to urea ratio as a measure of airway surface hydration. Am J Physiol Lung Cell Mol Physiol. 2017 Mar 1;312(3):L398-404. doi: 10.1152/ajplung.00398.2016. PMID: 28062483. PMCID: PMC5374301.
  23. Anderson WH, Coakley RD, Button B, Henderson AG, Zeman KL, Alexis NE, Peden DB, Lazarowski ER, Davis CW, Bailey S, Fuller F, Almond M, Qaqish B, Bordonali E, Rubinstein M, Bennett WD, Kesimer M, Boucher RC. The relationship of mucus concentration (hydration) to mucus osmotic pressure and transport in chronic bronchitis. Am J Respir Crit Care Med. 2015 Jul 15;192(2):182-90. doi: 10.1164/rccm.201412-2230OC. PMID: 25909230; PMCID: PMC4532825.
  24. Chhetri RK, Blackmon RL, Wu WC, Hill DB, Button B, Casbas-Hernandez P, Troester MA, Tracy JB, Oldenburg AL. Probing biological nanotopology via diffusion of weakly constrained plasmonic nanorods with optical coherence tomography. Proc Natl Acad Sci U S A. 2014 Oct 14;111(41):E4289-97. doi: 10.1073/pnas.1409321111. PMID: 25267619; PMCID: PMC4205670.
  25. Henderson AG, Ehre C, Button B, Abdullah LH, Cai LH, Leigh MW, DeMaria GC, Matsui H, Donaldson SH, Davis CW, Sheehan JK, Boucher RC, Kesimer M. Cystic fibrosis airway secretions exhibit mucin hyperconcentration and increased osmotic pressure. J Clin Invest. 2014 Jul;124(7):3047-60. doi: 10.1172/JCI73469. PMID: 24892808; PMCID: PMC4072023.
  26. Button B, Okada SF, Frederick CB, Thelin WR, Boucher RC. Mechanosensitive ATP release maintains proper mucus hydration of airways. Sci Signal. 2013 Jun 11;6(279):ra46. doi: 10.1126/scisignal.2003755. PMID: 23757023; PMCID: PMC3791865.
 
 
 
 
Brian Button