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Richard Boucher, MD

James C. Moeser Eminent Professor of Medicine, Division of Pulmonary Diseases and Critical Care Medicine; Director, Marsico Lung Institute

Specialty Areas: Normal Physiology of Airway Surface Liquids (ASL); ASL System Failure in CF and COPD; Epithelial ion transport in human airways disease; Gene therapy; Airway of mucus biology; development of novel therapies for human lung diseases.

Biography:

Dr. Boucher attended Yale University for his undergraduate education and Columbia College of Physicians and Surgeons for medical school. Following a two-year internship/residency at Columbia Presbyterian Hospital, he joined the India Health Service and was a family medicine physician in Eagle Butte, South Dakota, and San Ildefonso, New Mexico. Dr. Boucher performed his respiratory training at McGill, notably under the tutelage of Dr. James Hogg in the Meakins-Christie Laboratories. After three years of training in Montreal, he joined the faculty of the Adult Pulmonary Medicine Division at The University of North Carolina School of Medicine in Chapel Hill, North Carolina. He has remained there for 43 years, studying the pathogenesis of cystic fibrosis and, more recently, the broad spectrum of muco-obstructive lung diseases. He is presently Director of the Marsico Lung Institute/UNC CF Research Center.

Research Focus: Dr. Boucher has primarily studied the normal physiology of pulmonary surface liquid homeostasis and how these systems fail in lung diseases, e.g., cystic fibrosis (CF). This airways disease research has focused on the ion channels responsible for transepithelial ion transport, e.g., the epithelial Na+ channel (ENaC), CFTR, and the calcium-activated Cl- channel (CaCC, including TMEM16a), the extracellular nucleotide/nucleoside regulatory system that controls the relative activities of the absorptive (ENaC) vs. secretory (CFTR, CaCC) channels, and the mucins that form “mucus.” The research work encompasses experimental systems, including epithelial cell culture systems, mouse models of lung disease, mathematical models (the “virtual lung”) to identify key pathogenetic pathways, in vivo human investigations, including studies of mucus concentrations/composition, and therapies for major human lung diseases. Notably, these research technologies have been focused on the early pathogenesis, diagnosis, and treatment of CF.

 Publications:

  1. 1 Ramsey KA, Chen ACH, Radicioni G, Lourie R, Martin M, Broomfield A, Sheng YH, Hasnain SZ, Radford-Smith G, Simms L, Burr L, Thornton DJ, Bowler SD, Livengood S, Ceppe A, Knowles MR, 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.
  2. McCarron A, Cmielewski P, Reyne N, McIntyre C, Finnie J, Craig F, Rout-Pitt N, Delhove J, Schjenken JE, Chan HY, Boog B, Knight E, Gilmore RC, O’Neal WK, Boucher RC, Parsons D, Donnelley M. Phenotypic characterization and comparison of Phe508del and cystic fibrosis transmembrane conductance regulator (CFTR) knockout rat models of cystic fibrosis generated by CRISPR/Cas9 gene editing. Am J Pathol. 2020 Feb 18. doi: 10.1016/j.ajpath.2020.01.009. [Epub ahead of print]. PMID: 32084371.
  3. Rao W, Wang S, Mahalingam R, Duleba M, Xie J, Gollar K, Niroula S, Qi Y, Neupane R, Liew A, Vincent M, Okuda K, O’Neal WK, Boucher RC, Dickey BF, Wechsler ME, Ibrahim O, Engelhardt JF, Crum CP, Mertens TCJ, Wang W, Jyothula SSK, Karmouty-Quintana H, Parekh KR, Metersky ML, McKeon FD, Xian W. Regenerative metaplastic clones in COPD lung drive inflammation and fibrosis. Cell. 2020.
  4. Goralski JL, Chung SH, Glass TJ, Ceppe AS, Akinnagbe-Zusterzeel EO, Trimble AT, Boucher RC, Soher BJ, Charles HC, Donaldson SH, Lee YZ. Dynamic perfluorinated gas MRI reveals abnormal ventilation despite normal FEV1 in cystic fibrosis. JCI Insight. 2019 Dec 19. doi: 10.1172/jci.insight.133400. PMID: 31855577
  5. van Heusden C, Button B, Anderson WH, Ceppe A, Morton LC, O’Neil W, Dang H, Alexis NE, Donaldson S, 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. 2019 Dec 4. doi: 10.1152/ajplung.00449.2019. PMID: 31800264.
  6. Ramsey KA, Chen ACH, Radicioni G, Lourie R, Martin M, Broomfield A, Sheng YH, Hasnain SZ, Radford-Smith G, Simms L, Burr L, Thornton DJ, Bowler SD, Livengood S, Ceppe A, Knowles MR, 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. 2019 Nov 25. doi: 10.1164/rccm.201906-1219OC. PMID: 31765597.
  7. 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 ClinInvest. 2019 Oct 1;129(10):4433-4450. doi: 10.1172/JCI125669. PMID: 31524632. PMCID: PMC6763234.
  8. Markovetz M, Subramani D, Kissner W, Morrison C, Garbarine I, Ghio A, Ramsey K, Arora H, Kumar P, Nix D, Kumagai T, Krunkosky T, KrauseD , Radicioni G, Alexis N, Kesimer M, Tiemeyer M, Boucher RC, Ehre C, Hill D. Endotracheal tube mucus as a source of airway mucus for rheological study. Am J Physiol Lung Cell Mol Physiol. 2019 Oct 1;317(4):L498-L509. doi: 10.1152/ajplung.00238.2019. PMID: 31389736. PMCID: PMC6842913
  9. Chen G, Ribeiro CMP, Sun L, Okuda K, Kato T, Gilmore RC, Martino MB, Dang H, Abzhanova A, Lin JM, Hull-Ryde EA, Volmer AS, Randell SH, Livraghi-Butrico A, Deng Y, Scherer PE, Stripp BR, O’Neal WK, Boucher RC. XBP1S regulates MUC5B in a promoter variant-dependent pathway in IPF airway epithelia. Am J Respir Crit Care Med. 2019 Jul 15;200(2):220-234. doi: 10.1164/rccm.201810-1972OC. PMID: 30973754. PMCID: PMC6635783.
  10. Boucher RC. Muco-obstructive lung diseases. N Engl J Med. 2019 May 16;380(20):1941-1953. doi: 10.1056/NEJMra1813799. PMID: 31091375.
  11. Esther CR Jr, Muhlebach MS, Ehre C, Hill DB, Wolfgang MC, Kesimer M, Ramsey KA, Markovetz MR, Garbarine IC, Forest MG, Seim I, Zorn B, Morrison CB, Delion MF, Thelin WR, Villalon D, Sabeter JR, Turkovic L, Ranganathan S, Stick SM, Boucher RC, on behalf of AREST CF. Mucus accumulation in the lungs precedes structural changes and infection in children with cystic fibrosis. Sci Transl Med. 2019 Apr 3;11(486). doi: 10.1126/scitranslmed.aav3488. PMID: 30944166. PMCID: PMC6566903.
  12. Sherrard LJ, Einarsson GG, Johnston E, O’Neill K, McIlreavey L, McGrath SJ, Gilpin DF, Downey DG, Reid A, McElvaney GN, Boucher RC, Muhlebach MS, Elborn JS, Tunney MM. Assessment of stability and fluctuations of cultured lower airway bacterial communities in people with cystic fibrosis. J Cyst Fibros. 2019 Mar 21. doi: 10.1016/j.jcf.2019.02.012. [Epub ahead of print]. PMID: 30905581. PMCID: PMC6754815.
  13. Okuda K, Chen G, Subramani DB, Wolf M, Gilmore RC, Kato T, Radicioni G, Kesimer M, Chua M, Livraghi-Butrico A, Ehre C, Doerschuk CM, Randell SH, Matsui H, Nagase T, O’Neal WK, Boucher RC. Localization of secretory mucins MUC5AC and MUC5B in normal human airways. Am J Respir Crit Care Med. 2019 Mar 15;199(6):715-727. doi: 10.1164/rccm.201804-0734OC. PMID: 30352166. PMCID: PMC6423099.
  14. Ehre C, Rushton ZL, Wang B, Hothem LN, Morrison CB, Fontana NC, Markovetz MR, Delion MF, Kato T, Villalon D, Thelin WR, Esther CR Jr., Hill DB, Grubb BR, Livraghi-Butrico A, Donaldson SH, Boucher RC. An improved inhaled mucolytic to treat airway muco-obstructive diseases. Am J Respir Crit Care Med. 2019 Jan 15;199(2):171-180. doi: 10.1164/rccm.201802-0245OC. PMID: 30212240. PMCID: PMC6353008.
  15. Christenson SA, van den Berge M, Faiz A, Bhakta N, Bonser LR, Zlockf LT, Junga KL, Barjaktarevic IZ, Barr RG, Bleecker ER, Boucher RC, Bowler RP, Comellas AP, Curtis JL, Han MK, Hansel NN, Hiemstra PS, Kaner RJ, Krishnan JA, Martinez FJ, O’Neal WK, Paine R III, Timens W, Wells JM, Spira A, Erle DJ, Woodruff PG. An airway IL-17A genomic signature identifies a steroid-unresponsive COPD subgroup. J Clin Invest. 2019 Jan 2;129(1):169-181. doi: 10.1172/JCI121087. PMID: 30383540. PMCID: PMC6307967.
  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. 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.
  19. Kesimer M, Smith B, Ceppe A, Anderson WH, O’Neal W, Barr RG, Woodruff PG, Han MK, Hoffman EA, Martinez F, Curtis J, Paine R III, Cooper CB, Ford AA, Bleecker ER, Boucher RC. Mucin concentrations and peripheral airways obstruction in COPD. Am J Respir Crit Care Med. 2018 Dec 1;198(11):1453-1456. doi: 10.1164/rccm.201806-1016LE. PMID: 30130124. PMCID: PMC6290944.
  20. Ash SY, Harmouche R, Putman RK, Ross JC, Martinez FJ, Choi AM, Bowler RP, Regan EA, Curtis JL, Han MK, Boucher RC, O’Neal WK, Hatabu H9 Lynch DA, Rosas IO, Hunninghake GM, San Jose Estepar R, Washko GR; and COPDGene Investigators. Association between acute respiratory disease events and the MUC5B promoter polymorphism in smokers. Thorax. 2018 Nov;73(11):1071-1074. doi: 10.1136/thoraxjnl-2017-211208. PMID: 29440587. PMCID: PMC6089672.

Dr. Boucher’s Marsico Lung Institute Profile page.

Richard Boucher