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Associate Professor

Research: Mucin biopolymer regulation, gene therapy vector delivery, mechanisms of airway mucociliary clearance

Associate Professor of Biochemistry & Biophysics
Joint appointments with UNC Medicine and BME
PhD – University of Texas Medical Branch

ACCEPTING STUDENTS

RESEARCH

My research has largely focuses on understanding various biochemical and biophysical aspects of the airway mucus clearance system in health and disease. The airway clearance system, the primary innate immune system of the lung, is designed to remove virtually all of the pathogenic particles deposited on the lung surface during normal breathing. It is a multifaceted system in which many aspects of its regulation remain either unknown or poorly understood. The major focus of my lab is to understand the biophysics of the polymer mucus layer, its physical interaction with the underlying epithelial layer, and why lung diseases such as cystic fibrosis (CF) and chronic bronchitis (CB) result in a failure of mucus clearance.

Overall, my ongoing research can be broken down into the following four distinct topics: 1) Role of extracellular nucleotide signal transduction on regulation of epithelial ion transport and airway surface biophysical properties, 2) biochemical identification and function of membrane-bound polymers on the airway epithelial surface and their role in lung defense, 3) understanding the nature of the biophysical interactions of the superficial mucus layer and the underlying epithelial surface in health and disease, and 4) elucidating the mechanisms of mucus clearance by cilia beating and high-velocity airflow (i.e. coughing).

RECENT PUBLICATIONS pubmed.png(click for Full Publication List)

https://www.ncbi.nlm.nih.gov/myncbi/browse/collection/41141209/

  1. 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. Epub 2022 Apr 1. PMID: 35363522.
  2. 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.
  3. 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.
  4. Hill DB*, Button B*, Rubinstein M, Boucher RC. Physiology and Pathophysiology of Human Airway Mucus. Physiol Rev. 2022 Jan 10. doi: 10.1152/physrev.00004.2021. Epub ahead of print. PMID: 35001665. *Co-first authors.
  5. 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.
  6. 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.
  7. 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.
  8. 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.
  9. 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.
  10. 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.
  11. 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.
  12. 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.
  13. 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.
  14. 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.
  15. 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 Nov 12. doi: 10.1073/pnas.1811787115. [Epub ahead of print]. PMID: 30420506.
  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 Oct 25. doi: 10.1183/13993003.01297-2018. [Epub ahead of print]. PMID: 30361244.
  17. 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.
  18. 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.
  19.  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.
  20. Esther CR Jr, Hill DB, Button B, Shi S, Jania C, Duncan EA, Doerschuk CM, Chen G, Ranganathan S, Stick SM, Boucher RC. 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-L404.
  21. Button B, Anderson WH, Boucher RC. Mucus Hyperconcentration as a Unifying Aspect of the Chronic Bronchitic Phenotype. Ann Am Thorac Soc. 2016 Apr;13 Suppl 2:S156-62.
  22. 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.
  23. Button BM, Button B. Structure and function of the mucus clearance system of the lung. Cold Spring Harb Perspect Med. 2013 Aug 1;3(8).
  24. 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
  25. Button B, Cai LH, Ehre C, Kesimer M, Hill DB, Sheehan JK, Boucher RC, Rubinstein M. A periciliary brush promotes the lung health by separating the mucus layer from airway epithelia. Science. 2012 Aug 24;337(6097):937-41

Lab Contact

Lab Room: 6017 Thurston-Bowles Bldg

Phone: 919-966-8073

Photo of
  • Phone Number

    919-966-8073 (Office Phone)

  • Address

    Marsico Lung Institute, UNC Cystic Fibrosis Center

    Thurston-Bowles, Room 6019A

    CB# 7248

    Chapel Hill, NC 27599-7248