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Alessandra Livraghi-Butrico, PhD

Associate Professor of Medicine
7211 Marsico Hall

Research

Research in the Livraghi-Butrico lab focuses on 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. In our lab, these studies nicely complement studies performed in available human specimens or simplified in vitro systems (e.g., primary cultures of airway epithelial cells differentiated at the air-liquid interface). Current research activities in the lab cover three main areas:

  • Mouse models of defective airway mucus clearance are used to study responses to environmental and infectious challenges, to develop models of chronic airway infections, and to test efficiency and pharmacokinetic properties of mucokinetic/mucolytic/gene-editing therapies.
  • Genetically engineered mouse models are used to study the contribution of specific components of the airway mucus clearance system (mucins secretion and assembly, ion, transport, cilia) in determining measurable phenotypes in both naïve and experimentally challenged conditions.
  • Germ-free and specific pathogen-free mice are used to study the influence of age and host microbiota in the composition and function of airway mucus. These studies, funded by a recently awarded NHLBI R01, are complemented by efforts to define the pediatric airway epithelial landscape in healthy humans.

Selected Bibliography: 

  1. Kim N., Rodriguez J., Livraghi-Butrico A., Shenoy S., Mazur M., Birket S.E., Rowe S.M., Boucher R.C., Hanes J., Suk J.S. Inhaled gene therapy of preclinical muco-obstructive lung diseases by nanoparticles capable of breaching the airway mucus barrier”. 2022 Aug;77(8):812-820
  2. Rogers T.D., Button B., Kelada S.N.P., Ostrowski L.E., Livraghi-Butrico A., Gutay M.I., Esther, C.R.Jr, Grubb, B.R. Regional Differences in Mucociliary Clearance in the Upper and Lower Airways. Frontiers in Physiology. 2022;13 09 March 9; 13:842592.
  3. Xu J.*, Livraghi-Butrico A.*, Hou X.*, Rajagopalan C.*, Zhang J., Song J., Jiang H., Wei H-G., Wang H., Bouhamdan M., Ruan ,Yang D., Qiu Y., Youming X., Barrett R., 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. *Co-first authors, #Co-senior authors.
  4. Okuda K., Chen G., Subramani D.B., Wolf M., Gilmore R.C., Kato T., Radicioni G., Kesimer M., Chua M., Dang H., 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/Healthy Human Airways.Am J Respir Crit Care Med. 2019 Mar 15;199(6):715-727.
  5. 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.
  6. 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.
  7. 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.
  8. Donoghue L.J.*, Livraghi-Butrico*, McFadden K.M., Thomas J.M., Chen G., Grubb B.R., O’Neal W.K., Boucher R.C., Kelada S.N.P. Identification of transProtein QTL for Secreted Airway Mucins in Mice and a Causal Role for Bpifb1. Genetics. 2017 Oct;207(2):801-812. *Co-first authors
  9. Livraghi-Butrico, 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 Mar;10(2):395-407.
  10. 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.
  11. Livraghi-Butrico, 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.
  12. 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.
  13. 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.
  14. 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-α and IL-4Rα signaling, influence of neonatal development, and limited efficacy of glucocorticoid treatment. J Immunol. 2009 Apr 1;182(7):4357-67.

 

Affiliations:

Marsico Lung Institute/Cystic Fibrosis Center

Department of Microbiology and Immunology

Alessandra Livraghi-Butrico