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Alessandra Livraghi-Butrico, PhD

Assistant Professor

Specialty Areas:

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


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:

  • Xu, J., Livraghi-Butrico, A., Hou, X., Rajagopalan, C., Zhang, J., Song, J., Jiang, H., Wei, H.G., Wang, H., Bouhamdan, M., Ruan, J., Yang, D., Qiu, Y., Youming, X., Barrett, R.P., McClellan, S.A., Mou, H., Wu, Q., Chen, X., Rogers, T.D., Wilkinson, K.J., Gilmore, R.C., Esther, C.R., Jr., Zaman, K., Liang, X., Sobolic, M., Hazlett, L., Zhang, K., Frizzell, R.A., Gentzsch, M., O’Neal, W.K., Grubb, B.R., Chen, Y.E., Boucher, R.C., 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.
  • Hou, Y.J., Okuda, K., Edwards, C.E., Martinez, D.R., Asakura, T., Dinnon III, K.H., Kato T., Lee, R.E., Yount, B.L., Mascenik, T.M., Chen, G., Olivier, K.N., Ghio, A., Tse, L.V., Leist, S.R., Gralinski, L.E., Schäfer, A., Dang, H., Gilmore, R., Fulcher, L., Livraghi-Butrico, A., Nicely, N.I., Cameron, M., Cameron, C., Kelvin, D.J., de Silva, A., Margolis, D.M., Markmann, A., Bartelt, L., Zumwalt, R., Martinez, F.J., Salvatore, S.P., Borczuk, A.R., Tata, P., Sontake, V., Kimple, A., Jaspers, I., O’Neal, W.K., Randell, S.H., Boucher, R.C., Baric, R.S. 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.
  • 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.
  • Chen, G., Sun, L., Kato, T., Okuda, K., Martino, M.B., Abzhanova, A., Lin, J.M., Gilmore, R.C., Batson, B.D., Volmer, A.S., Dang, H., Deng, Y., Randell, S.H., Button, B., Livraghi-Butrico, A., Kesimer, M., Ribeiro, C.M.P., O’Neal, W.K., Boucher, R.C. 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.
  • Yin, W., Livraghi-Butrico, A., Sears, P.R., Rogers, T.D., Burns, K.A., Grubb, B.R., Ostrowski, L.E. 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.
  • Chen, G., Ribeiro, C.M.P., Sun, L., Okuda, K., Kato, T., Gilmore, R.C., Martino, M.B., Dang, H., Abzhanova, A., Lin, J.M., Hull-Ryde, E.A., Volmer, A.S., Randell, S.H., Livraghi-Butrico, A., Deng, Y., Scherer, P.E., Stripp, B.R., O’Neal, W.K., Boucher, R.C. 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.
  • Okuda, K., Chen, G., Subramani, D.B., Wolf, M., Gilmore, R.C., Kato, T., Radicioni, G., Kesimer, M., Chua, M., Livraghi-Butrico, A., Ehre, C., Doerschuk, C.M., Randell, S.H., Matsui, H., Nagase, T., O’Neal, W.K., Boucher, R.C. 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.
  • Rogers, T.D., Ostrowski, L.E., Livraghi-Butrico, A., Button, B., Grubb, B.R. Mucociliary Clearance in Mice Measured by Tracking Trans-tracheal Fluorescence of Nasally Aerosolized Beads. Sci Rep. 2018 Oct 3;8(1):14744. PMCID: PMC6170422.
  • Ehre, C., Rushton, Z.L., Wang, B., Hothem, L.N., Morrison, C.B., Fontana, N.C., Markovetz, M.R., Delion, M.F., Kato, T., Villalon, D., Thelin, W.R., Esther, C.R., Jr., Hill, D.B., Grubb, B.R., Livraghi-Butrico, A., Donaldson, S.H., Boucher, R.C. 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.
  • Chen, G., Volmer, A.S., Wilkinson, K.J., Deng, Y., Jones, L.C., Yu, D., Bustamante-Marin, X.M., Burns, K.A., Grubb, B.R., O’Neal, W.K., Livraghi-Butrico, A., Boucher, R.C. 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. PMCID: PMC6189647.
  • Ghosh, A., Coakley, R.C., Mascenik, T., Rowell, T.R., Davis, E.S., Rogers, K., Webster, M.J., Dang, H., Herring, L.E., Sassano, M.F., Livraghi-Butrico, A., Van Buren, S.K., Graves, L.M., Herman, M.A., Randell, S.H., Alexis, N.E., 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. PMCID: PMC6034122.
  • Duncan, G.A., Kim, N., Colon-Cortes, Y., Rodriguez, J., Mazur, M., Birket, S., Rowe, S.M., West, N.E., Livraghi-Butrico, A., Boucher, R.C., Hanes, J., Aslanidi, G., Suk, J.S. An adeno-associated viral vector capable of penetrating the mucus barrier to inhaled gene therapy. Mol Ther 2018 June 15;9:296-304. PMCID: PMC6054694.
  • Saini, Y., Lewis, B., Yu, D., Dang, H., Livraghi-Butrico, A., Del Piero, F., O’Neal, W., Boucher R. Effect of LysM+ macrophage depletion on lung pathology in mice with chronic bronchitis. Physiol Rep. 2018 Apr;6(8):e13677. PMCID: PMC5904692.
  • Livraghi-Butrico, A., Wilkinson, K.J., Volmer, A.S., Gilmore, R.C., Rogers, T.D., Caldwell, R.A, Burns, K.A., Esther, C.R. Jr., Mall, M.A., Boucher, R.C., O’Neal, W.K., Grubb, B.R. 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. PMCID: PMC5866504.
  • Donoghue, L.J.*, Livraghi-Butrico, A.*, McFadden, K.M., Thomas, J.M., Chen, G., Grubb, B.R., O’Neal, W.K., Boucher, R.C., Kelada, S.N.P. Identification of trans protein QTL for secreted airway mucins in mice and a causal role for Bpifb1. Genetics 2017 Oct;207(2):801-812. PMCID: PMC5629340.
  • Livraghi-Butrico, A., Grubb, B.R., Wilkinson, K.J., Volmer, A.S., Burns, K.A., Evans, C.M., O’Neal, W.K., Boucher, R.C. 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. PMCID: PMC5250616
  • Sesma, J.I., Weitzer, C.D., Livraghi-Butrico, A., Dang, H., Donaldson, S., Alexis, N.E., Jacobson, K.A., Harden, T.K., Lazarowski, E.R. UDP-glucose promotes neutrophil recruitment in the lung. Purinergic Signal 2016 Dec;12(4):627-635. PMCID: PMC5124001
  • Grubb, B.R, Livraghi-Butrico, A., Rogers, T., Yin, W-N, Ostrowski, L. 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. PMCID: PMC5124001
  • Saini, Y., Wilkinson, K.J., Terrell, K.A., Burns, K.A., Livraghi-Butrico, A., Doerschuk, C.M., O’Neal, W.K., Boucher, R.C. 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. PMCID: PMC4821038
  • Saini, Y., Dang, H., Livraghi-Butrico, A., Kelly, E.J., Jones, L.C., O’Neal, W.K., Boucher, R.C. Gene expression in whole lung and pulmonary macrophages reflects the dynamic pathology associated with airway surface dehydration. BMC Genomics 2014 Sep 10;15:726. PMCID: PMC4247008
  • Roy, M.G.*, Livraghi-Butrico, A.*, Fletcher A.A.*, McElwee M.M., Evans S.E., Boerner R.M., Alexander S.N., Bellinghausen L.K., Song A.S., Petrova Y.M., Tuvim M.J., Adachi R., Romo I., Bordt A.S., Bowden M.G., Sisson J.H., Woodruff, P.G., Thornton, D.J., Rousseau K., De la Garza M.M., Moghaddam S.J., Karmouty-Quintana H., Blackburn, M.R., Drouin S.M., Davis C.W., Terrell K.A., Grubb B.R., O’Neal W.K., Flores S.C., Cota-Gomez, A., Lozupone C.A., Donnelly J.A., Watson, A.M., Hennessy C.E., Keith R.C.,Yang I.V., Barthel, L., Peter M. Henson P.M., Janssen W.J., Schwartz, D.A., Boucher, R.C., Dickey B.F., Evans C.M. Muc5b is required for airway defense. Nature 2014 Jan 16;505(7483):412-6. PMCID: PMC4001806
  • Livraghi-Butrico, A., Kelly E.J., Wilkinson K.J., Rogers T.D., Gilmore R.C, Harkema J.R., Randell S.H., Boucher R.C., O’Neal W.K., Grubb B.R. 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. PMCID: PMC3627939
  • Livraghi-Butrico, A., Kelly, E.J., Klem, E.R., Dang, H., Wolfgang, M.C., Boucher, R.C., Randell, S.H., O’Neal, W.K. 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. PMCID: PMC3377774
  • Livraghi-Butrico, A., Grubb, B.R., Kelly, E.J., Wilkinson, K.J., Yang, H., Geiser, M., Randell, S.H., Boucher, R.C., O’Neal, W.K. Genetically determined heterogeneity of lung disease in a mouse model of airway mucus obstruction. Physiol Genomics 2012 Apr 15;44(8):470-84. PMCID: PMC3339860
  • Livraghi, A., Grubb, B.R., Hudson, E.J., Wilkinson, K.J., Sheehan, J.K., Mall, M.A., O’Neal, W.K., Boucher, R.C., Randell, S.H. 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. PMCID: PMC265946
  • Mall, M.A, Harkema, J.R., Trojanek, J.B., Treis, D., Livraghi, A., Schubert, S., Zhou, Z., Kreda, S.M., Tilley, S.L., Hudson, E.J., O’Neal, W.K., Boucher, R.C. 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. PMCID: PMC2277210
  • Livraghi, A., Mall, M, Paradiso, A.M., Boucher, R.C., Ribeiro, C.M.P. Modeling dysregulated Na+ absorption in airway epithelial cells with mucosal nystatin treatment. Am J Respir Cell Mol Biol 2008 Apr;38(4):423-34. PMCID: PMC2274946
Alessandra Livraghi-Butrico