Skip to main content

Associate Professor

Specialty Areas:

Murine models of inflammatory and obstructive lung diseases, lung mucosal immunology, mucin biology.

Chronology:

BS Cum Laude: University of Milan, 1996; PhD: University of Milan, 2001; Post-doctoral fellowship: University of North Carolina at Chapel Hill, 2005; Research Associate: University of North Carolina at Chapel Hill, 2013; Research Assistant Professor of Medicine: University of North Carolina at Chapel Hill, 2014-present

Research Focus:

I am currently involved in numerous projects aimed at understanding the molecular mechanisms involved in the derangement of mucus clearance and how its impairment impact other components of the airway mucosal immune system. Over the years, I have a developed a keen interest in using mouse models as a tool to understand the pathogenesis of obstructive lung disease, identify unique targets and test novel therapeutic approaches for translational research. As the Co-director or the Marsico Lung Institute Mouse Models Core, I have extensive personal experience in colony management, pharmacological treatment, and phenotyping of different mouse models of inflammatory and muco-obstructive lung diseases.

Selected Bibliography:

  1. Grubb BR, Livraghi-Butrico A. Animal models of cystic fibrosis in the era of highly effective modulator therapies. Curr Opin Pharmacol. 2022 May 13;64:102235. doi: 10.1016/j.coph.2022.102235. Epub ahead of print. PMID: 35576754.
  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. Kim N, Kwak G, Rodriguez J, Livraghi-Butrico A, Zuo X, Simon V, Han E, Shenoy SK, Pandey N, Mazur M, Birket SE, Kim A, Rowe SM, Boucher R, Hanes J, Suk JS. Inhaled gene therapy of preclinical muco-obstructive lung diseases by nanoparticles capable of breaching the airway mucus barrier. Thorax. 2021 Oct 25:thoraxjnl-2020-215185. doi: 10.1136/thoraxjnl-2020-215185. Epub ahead of print. PMID: 34697091.
  4. Xu J, Livraghi-Butrico A, Hou X, Rajagopalan C, Zhang J, Song J, Jiang H, Wei HG, Wang H, Bouhamdan M, Ruan J, Yang D, Qiu Y, Xie Y, Barrett R, McClellan S, Mou H, Wu Q, Chen X, Rogers TD, Wilkinson KJ, Gilmore RC, Esther CR Jr, Zaman K, Liang X, Sobolic M, Hazlett L, Zhang K, Frizzell RA, Gentzsch M, O’Neal WK, Grubb BR, Chen YE, Boucher RC, Sun F. Phenotypes of CF rabbits generated by CRISPR/Cas9-mediated disruption of the CFTR gene. JCI Insight. 2021 Jan 11;6(1):e139813. doi: 10.1172/jci.insight.139813. PMID: 33232302. PMCID: PMC7821608.
  5. Sigmon JS, Blanchard MW, Baric RS, Bell TA, Brennan J, Brockmann GA, Burks AW, Calabrese JM, Caron KM, Cheney RE, Ciavatta D, Conlon F, Darr DB, Faber J, Franklin C, Gershon TR, Gralinski L, Gu B, Gaines CH, Hagan RS, Heimsath EG, Heise MT, Hock P, Ideraabdullah F, Jennette JC, Kafri T, Kashfeen A, Kulis M, Kumar V, Linnertz C, Livraghi-Butrico A, Lloyd KCK, Lutz C, Lynch RM, Magnuson T, Matsushima GK, McMullan R, Miller DR, Mohlke KL, Moy SS, Murphy CEY, Najarian M, O’Brien L, Palmer AA, Philpot BD, Randell SH, Reinholdt L, Ren Y, Rockwood S, Rogala AR, Saraswatula A, Sassetti CM, Schisler JC, Schoenrock SA, Shaw GD, Shorter JR, Smith CM, St Pierre CL, Tarantino LM, Threadgill DW, Valdar W, Vilen BJ, Wardwell K, Whitmire JK, Williams L, Zylka MJ, Ferris MT, McMillan L, Manuel de Villena FP. Content and Performance of the MiniMUGA Genotyping Array: A New Tool To Improve Rigor and Reproducibility in Mouse Research. Genetics. 2020 Dec;216(4):905-930. doi: 10.1534/genetics.120.303596. PMID: 33067325; PMCID: PMC7768238.
  6. Hou YJ, Okuda K, Edwards CE, Martinez DR, Asakura T, Dinnon KH 3rd, Kato T, Lee RE, Yount BL, Mascenik TM, Chen G, Olivier KN, Ghio A, Tse LV, Leist SR, Gralinski LE, Schäfer A, Dang H, Gilmore R, Nakano S, Sun L, Fulcher ML, Livraghi-Butrico A, Nicely NI, Cameron M, Cameron C, Kelvin DJ, de Silva A, Margolis DM, Markmann A, Bartelt L, Zumwalt R, Martinez FJ, Salvatore SP, Borczuk A, Tata PR, Sontake V, Kimple A, Jaspers I, O’Neal WK, Randell SH, Boucher RC, Baric RS. SARS-CoV-2 Reverse Genetics Reveals a Variable Infection Gradient in the Respiratory Tract. Cell. 2020 Jul 23;182(2):429-446.e14. doi: 10.1016/j.cell.2020.05.042. PMID: 32526206; PMCID: PMC7250779.
  7. 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.
  8. Chen G, Sun L, Kato T, Okuda K, Martino MB, Abzhanova A, Lin JM, Gilmore RC, Batson BD, O’Neal YK, Volmer AS, Dang H, Deng Y, Randell SH, Button B, Livraghi-Butrico A, Kesimer M, Ribeiro CM, 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.
  9. Yin W, Livraghi-Butrico A, Sears PR, Rogers TD, Burns KA, Grubb BR, Ostrowski LE. Mice with a Deletion of Rsph1 Exhibit a Low Level of Mucociliary Clearance and Develop a PCD Phenotype. Am J Respir Cell Mol Biol. 2019 Sep;61(3):312-321. doi: 10.1165/rcmb.2017-0387OC. PMID: 30896965. PMCID: PMC6839924.
  10. 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.
  11. Okuda K, Chen G, Subramani DB, Wolf M, Gilmore RC, Kato T, Radicioni G, Kesimer M, Chua M, Dang H, 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.
  12. 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. PMID: 30282981. PMCID: PMC6170422.
  13. 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.
  14. Chen G, Volmer AS, Wilkinson KJ, Deng Y, Jones LC, Yu D, Bustamante-Marin XM, Burns KA, Grubb BR, O’Neal WK, Livraghi-Butrico A, Boucher RC. Role of Spdef in the regulation of Muc5b expression in the airways of naïve and muco-obstructed mice. Am J Respir Cell Mol Biol. 2018 Sep;59(3):383-396. PMID: 29579396. PMCID: PMC6189647.
  15. Ghosh A, Coakley RC, Mascenik T, Rowell TR, Davis ES, Rogers K, Webster MJ, Dang H, Herring LE, Sassano MF, Livraghi-Butrico A, Van Buren SK, Graves LM, Herman MA, Randell SH, Alexis NE, Tarran R. Chronic e-cigarette exposure alters the human bronchial epithelial proteome. Am J Respir Crit Care Med 2018 Jul 1;198(1):67-76. PMID: 29481290. PMCID: PMC6034122.
  16. Duncan GA, Kim N, Colon-Cortes Y, Rodriguez J, Mazur M, Birket SE, Rowe SM, West NE, Livraghi-Butrico A, Boucher RC, Hanes J, Aslanidi G, Suk JS. An adeno-associated viral vector capable of penetrating the mucus barrier to inhaled gene therapy. Mol Ther 2018 June 15;9:296-304. PMID: 30038933. PMCID: PMC6054694.
  17. Saini Y, Lewis BW, Yu D, Dang H, Livraghi-Butrico A, Del Piero F, O’Neal WK, Boucher RC. Effect of LysM+ macrophage depletion on lung pathology in mice with chronic bronchitis. Physiol Rep. 2018 Apr;6(8):e13677. PMID: 29667749. PMCID: PMC5904692.
  18. Livraghi-Butrico A, Wilkinson KJ, Volmer AS, Gilmore RC, Rogers TD, Caldwell RA, Burns KA, Esther CR Jr, Mall MA, Boucher RC, O’Neal WK, Grubb BR. Lung disease phenotypes caused by over-expression of combinations of alpha, beta, and gamma subunits of the epithelial sodium channel in mouse airways. Am J Physiol Lung Cell Mol Physiol 2018 Feb 1;314(2):L318-L331. PMID: 29074490. PMCID: PMC5866504.
  19. Donoghue LJ, Livraghi-Butrico A, McFadden KM, Thomas JM, Chen G, Grubb BR, O’Neal WK, Boucher RC, Kelada SNP. Identification of trans protein QTL for secreted airway mucins in mice and a causal role for Bpifb1. Genetics 2017 Oct;207(2):801-812. PMID: 28851744. PMCID: PMC5629340.
  20. Livraghi-Butrico A, Grubb BR, Wilkinson KJ, Volmer AS, Burns KA, Evans CM, O’Neal WK, Boucher RC. Contribution of mucus concentration and secreted mucins Muc5ac and Muc5b to the pathogenesis of muco-obstructive lung disease. Mucosal Immunol 2017;10(2):395-407. PMID: 27435107. PMCID: PMC5250616.
  21. Sesma JI, Weitzer CD, Livraghi-Butrico A, Dang H, Donaldson S, Alexis NE, Jacobson KA, Harden TK, Lazarowski ER. UDP-glucose promotes neutrophil recruitment in the lung. Purinergic Signal 2016 Dec;12(4):627-635. PMID: 27421735. PMCID: PMC5124001.
  22. Grubb BR, Livraghi-Butrico A, Rogers TD, Yin W, Button B, Ostrowski LE. Reduced mucociliary clearance in old mice is associated with a decrease in Muc5B mucin. Am J Physiol Lung Physiol 2016 May 1;310(9):L860-7. PMID: 26968767. PMCID: PMC4867354.
  23. Saini Y, Wilkinson KJ, Terrell KA, Burns KA, Livraghi-Butrico A, Doerschuk CM, O’Neal WK, Boucher RC. Neonatal pulmonary macrophage depletion coupled to defective mucus clearance increases susceptibility to pneumonia and alters pulmonary immune responses. Am J Respir Cell Mol Biol 2016 Feb;54(2):210-21. PMID: 26121027. PMCID: PMC4821038.
  24. Saini Y, Dang H, Livraghi-Butrico A, Kelly EJ, Jones LC, O’Neal WK, Boucher RC. Gene expression in whole lung and pulmonary macrophages reflects the dynamic pathology associated with airway surface dehydration. BMC Genomics 2014 Sep 10;15:726. PMID: 25204199. PMCID: PMC4247008.
  25. Roy MG*, Livraghi-Butrico A*, Fletcher AA*, McElwee MM, Evans SE, Boerner RM, Alexander SN, Bellinghausen LK, Song AS, Petrova YM, Tuvim MJ, Adachi R, Romo I, Bordt AS, Bowden MG, Sisson JH, Woodruff PG, Thornton DJ, Rousseau K, De la Garza MM, Moghaddam SJ, Karmouty-Quintana H, Blackburn MR, Drouin SM, Davis CW, Terrell KA, Grubb BR, O’Neal WK, Flores SC, Cota-Gomez A, Lozupone CA, Donnelly JM, Watson AM, Hennessy CE, Keith RC, Yang IV, Barthel L, Henson PM, Janssen WJ, Schwartz DA, Boucher RC, Dickey BF, Evans CM. Muc5b is required for airway defense. Nature 2014 Jan 16;505(7483):412-6. PMID: 24317696. PMCID: PMC4001806.
  26. Livraghi-Butrico A, Kelly EJ, Wilkinson KJ, Rogers TD, Gilmore RC, Harkema JR, Randell SH, Boucher RC, O’Neal WK, Grubb BR. Loss of Cftr function exacerbates the phenotype of Na+ hyperabsorption in murine airways. Am J Physiol Lung Cell Mol Physiol 2013 Apr 1;304(7):L469-80. PMID: 23377346. PMCID: PMC3627939.
  27. Livraghi-Butrico A, Kelly EJ, Klem ER, Dang H, Wolfgang MC, Boucher RC, Randell SH, O’Neal WK. Mucus clearance, MyD88-dependent and MyD88-independent immunity modulate lung susceptibility to spontaneous bacterial infection and inflammation. Mucosal Immunol 2012 Jul 5(4):397-408. PMID: 22419116. PMCID: PMC3377774.
  28. Livraghi-Butrico A, Grubb BR, Kelly EJ, Wilkinson KJ, Yang H, Geiser M, Randell SH, Boucher RC, O’Neal WK. Genetically determined heterogeneity of lung disease in a mouse model of airway mucus obstruction. Physiol Genomics 2012 Apr 15;44(8):470-84. PMID: 22395316. PMCID: PMC3339860.
  29. Livraghi A, Grubb BR, Hudson EJ, Wilkinson KJ, Sheehan JK, Mall MA, O’Neal WK, Boucher RC, Randell SH. Airway and lung pathology due to mucosal surface dehydration in β-Epithelial Na+ Channel-overexpressing mice: role of TNF-alpha and IL-4R-alpha signaling, influence of neonatal development, and limited efficacy of glucocorticoid treatment. J. Immunol 2009 Apr 1;182(7):4357-67. PMID: 19299736. PMCID: PMC2659461.
  30. Mall MA, Harkema JR, Trojanek JB, Treis D, Livraghi A, Schubert S, Zhou Z, Kreda SM, Tilley SL, Hudson EJ, O’Neal WK, Boucher RC. Development of chronic bronchitis and emphysema in beta-epithelial Na+ channel-overexpressing mice. Am J Respir Crit Care Med. 2008 Apr 1;177(7):730-42. PMID: 18079494. PMCID: PMC2277210.
  31. Livraghi A, Mall M, Paradiso AM, Boucher RC, Ribeiro CM. Modeling dysregulated Na+ absorption in airway epithelial cells with mucosal nystatin treatment. Am J Respir Cell Mol Biol 2008 Apr;38(4):423-34. PMID: 17989361. PMCID: PMC2274946.
Alessandra Livraghi-Butrico