Alessandra Livraghi-Butrico, PhD

Research Biosketch Personnel Contact

Research Focus

Livraghi
Dr. Alessandra Livraghi-Butrico, Research Associate

My interest in cystic fibrosis and other respiratory diseases caused by impaired mucus clearance dates back to my post-doctoral studies at the UNC CF Center, where I focused on the effects of accelerated Na+ transport and resultant airway surface dehydration on the physiology of cultured human bronchial epithelial cells in vitro. As I became part of the effort to define the development of lung pathology in the βENaC-Tg mouse model, I had the opportunity to further expand my interest in the in vivo effects of airway Na+ hyperabsorption. I am and have been involved in numerous projects involving the βENaC-Tg mouse model which are aimed at understanding the molecular mechanisms involved in the derangement of mucus clearance and how its impairment impacts other components of the airway mucosal immune system. A summary of these studies can be found on our Mouse Models Core page in the “Current projects” section. As a result of these efforts, I have developed a keen interest in using the βENaC-Tg mouse model as a tool for translational research, to identify unique targets and test novel therapeutic approaches for lung diseases characterized by defective mucus clearance, such as CF, chronic bronchitis (CB), and chronic obstructive pulmonary disease (COPD).

Biographical Sketch

Alessandra Livraghi, PhD, Research Associate

Dr. Livraghi received her B.S. in Biology and Biochemistry at the Universita’ degli Studi di Milano (Italy) in 1996. She obtained her Ph.D. degree in 2001, working at the Institute for Experimental Treatment of Cystic Fibrosis, Department of Biotechnology, Hospital S. Raffaele - Universita’ degli Studi di Milano (Milan, Italy). In 2002 she joined the Cystic Fibrosis/Pulmonary Research and Treatment Center at UNC Chapel Hill as a post-doc and in 2005 she became Research Associate.

Education

(1991 - 1996) Universita’ degli Studi di Milano (Milan, Italy), Baccalaureate, Biology and Biochemistry.

(1997 - 2001) Institute for Experimental Treatment of Cystic Fibrosis, Department of Biotechnology, Hospital S Raffaele. Universita’ degli Studi di Milano (Milan, Italy), PhD, Molecular Biology.

(2001 - 2004) Cystic Fibrosis/Pulmonary Research and Treatment Center – UNC Chapel Hill, Post-doctoral training, Airway epithelial biology.

Positions and Employment

(2005- present) Research Associate, Cystic Fibrosis/Pulmonary Research and Treatment Center - University of North Carolina at Chapel Hill.

Other Experience and Honors

(May-July 1999) Recipient of Short Term Fellowship from the European CF Fellowship Program, Department of Dermatology, Christian Albrechts University of Kiel, Kiel, Germany.

(1996-1997) Post-graduate trainee, Cystic Fibrosis group at the Telethon Institute for Gene Therapy (TIGET), H.S. Raffaele, Milan, Italy. Recipient of a fellowship from Associazione Lombarda Fibrosi Cistica (Lombardy Cystic Fibrosis Association).

Professional Affiliations

(2008 – present) American Thoracic Society (ATS).

Courses

Aug 2008 FASEB Summer Conference: “Lung Epithelium in Development and Disease”

Publications

Please see Pubmed feed in the righthand column for links to current publications.

Manuscripts in preparation

Livraghi-Butrico, A., Grubb B. R., Hudson E. J., Wilkinson K. J., Randell S. H., Boucher R. C., and O’Neal W. K., Strain-specific and widespread effects of airway-targeted overexpression of epithelial sodium channel β subunit on airway bioelectrical properties and lung pathology in inbred mice.

Livraghi-Butrico, A., Klem, E.R., Hudson, E.J., Wilkinson K.J., Wolfgang, M.C., O’Neal W.K., Boucher, R.C., and Randell S.H. Airway immune responses and susceptibility to infection in the context of defective mucus clearance: MyD88-dependent and independent signaling and effect of environmental bacteria.

Livraghi-Butrico, A., Hudson E. J., Wilkinson K. J., Randell S. H., O’Neal W. K., Boucher R. C. and Grubb B. R. Increased airway epithelial necrosis and massive neutrophilia in double CF/βENaC mice highlights role for CFTR-mediated Cl- secretion in neonatal airways.

Professional Presentations

Nov 2011 Invited Oral presentation – Livraghi-Butrico A., Duncan E.A., Kelly E.J., Waxer D.L., Gilmore R.C., Evans C.M., Doerschuk C.M., Boucher R.C., O'Neal W.K. Deletion of Muc5b in Scnn1b transgenic mice reduces airway mucus obstruction but perturbs lung immune homeostasis: a new role for secreted mucins? 24th Annual North American Cystic Fibrosis Conference. Anaheim, California

Nov 2011 Invited Oral presentation – Livraghi-Butrico A., Grubb B.R., Kelly E.J., Yang H., Geiser M., Boucher R.C., O'Neal W.K. Identification of congenic variant of Scnn1b transgenic mice reveals contribution of early lesions to the development of obstructive lung disease due to airway surface dehydration. 24th Annual North American Cystic Fibrosis Conference. Anaheim, California

June 2011 Oral presentation – Livraghi-Butrico, A., Duncan, E.A., Saini Y., Dang H., Doerschuk C.M., O’Neal W.K., Boucher R.C. Mechanisms of host defense during mucus obstruction in Scnn1b transgenic mice, a mouse model of COPD. 54th Thomas L. Petty Aspen Lung Conference, "COPD and Lung Cancer A Continuum of Airway Disease", Aurora, Colorado

May 2011 Oral poster presentation – Livraghi-Butrico, A., Kelly, E.J., Erich Klem, Nanette B. Fulcher, Matthew C. Wolfgang, Boucher, R.C., Randell, S.H, O’Neal W.K. Impaired mucus clearance correlates with increased susceptibility to spontaneous bacterial infection/colonization in Scnn1b-transgenic mice. American Thoracic Society International Conference, Denver, Colorado

Oct 2010 Poster presentation – Livraghi-Butrico, A., Kelly, E.J., Erich Klem, Nanette B. Fulcher, Matthew C. Wolfgang, Boucher, R.C., Randell, S.H, O’Neal W.K. Increased susceptibility to bacterial infection/colonization in Scnn1b transgenic mice. 24th Annual North American Cystic Fibrosis Conference. Baltimore, Maryland

Oct 2010 Poster presentation – Livraghi-Butrico, A., Kelly, E.J., Evans, C.E., Boucher, R.C., O’Neal W.K. Deletion of Muc16, Muc5ac, Muc5b in Scnn1b transgenic mice: implications for CF lung disease pathogenesis and therapy. 24th Annual North American Cystic Fibrosis Conference. Baltimore, Maryland

Oct 2010 Poster presentation – Livraghi-Butrico, A., Kelly, E.J., Boucher, R.C., O’Neal W.K., Randell, S.H. Non-redundant role of Toll-like receptor 2 and 4 in host defense and development of lung pathology when mucus clearance is impaired. 24th Annual North American Cystic Fibrosis Conference. Baltimore, Maryland

Oct 2009 Invited Oral presentation - Livraghi A., Hudson E.J., Wilkinson K.J., Boucher R.C., Doerschuk C.M. O'Neal W.K. Identification of congenic Scnn1b-Tg lines markedly susceptible to pulmonary hemorrhage and right ventricular hypertrophy. 23rd Annual North American Cystic Fibrosis Conference. Minneapolis, Minnesota.

Oct 2009 Poster presentation - Livraghi, A., Wilkinson K.J., Hudson, E.J., Randell S.H., Boucher, R.C., O’Neal W.K. Deletion of membrane-tethered mucins 1 and 4 does not alter the phenotype of Scnn1b transgenic mice: implications for airway mucin function. 23rd Annual North American Cystic Fibrosis Conference. Minneapolis, Minnesota.

Oct 2008 Poster presentation - Livraghi, A., Klem, E.R., Hudson, E.J., Wilkinson K.J., Wolfgang, M.C., O’Neal W.K., Boucher, R.C., Randell S.H. Genetic deletion of MyD88-mediated signaling in βENaC-overexpressing mice reduces airway neutrophilia but promotes spontaneous, mucus-associated bacterial infection. 22nd Annual North American Cystic Fibrosis Conference. Orlando, Florida.

Oct 2008 Poster presentation - Livraghi, A., Rogers, T.D., Brighton, B.W., Hudson, E.J., Wilkinson K.J., Boucher, R.C., O’Neal W.K. Grubb, B.R. Increased airway epithelial necrosis and massive neutrophilia in double CF/βENaC mice highlights role for CFTR-mediated Cl- secretion in neonatal airways. 22nd Annual North American Cystic Fibrosis Conference. Orlando, Florida.

Oct 2008 Poster presentation - Murray, S.A., Livraghi A., Sharp, J.E., Grubb, B.R., Hudson E.J., Wilkinson, K.J., Jones, L.C., Boucher R.C., O'Neal W.K. Analysis of genetic modifiers of phenotypic severity in the βENaC mouse model of cystic fibrosis. 22nd Annual North American Cystic Fibrosis Conference. Orlando, Florida.

Aug 2008 Invited Oral presentation - Livraghi, A., Grubb, B.R., Klem, E.R., Hudson, E.J., Wilkinson K.J., Sheehan J.K., Wolfgang, M.C., O’Neal W.K., Boucher, R.C., Randell S.H. Impaired mucus clearance due to airway surface dehydration affects neonatal lung development, immune responses and susceptibility to infection. FASEB Summer Research Conference “Lung Epithelium in Development and Disease”, Saxton Rivers, VT.

Aug 2008 Poster presentation - Livraghi A., Grubb B.R., Klem E.R., Hudson E.J., Wilkinson K.J., Sheehan J.K., Wolfgang M.C., O’Neal W.K., Boucher R.C., Randell S.H. Impaired mucus clearance due to airway surface dehydration affects neonatal lung development, immune responses and susceptibility to infection. 12th annual Research Day UNC Department of Cell & Molecular Physiology (received “best poster” award).

Apr 2008 Invited Oral presentation - Livraghi A., Grubb, B.R., O’Neal W.K., Mall M., Boucher R.C., Randell S.H. Signaling pathways regulating the airway phenotype of mice exhibiting airway surface dehydration. Experimental Biology Meeting 2008, San Diego, CA.

Nov 2007 Invited Oral presentation - Livraghi A. Impaired mucus clearance and airway inflammation in Scnn1b-transgenic mice, a model of airway surface dehydration. Center for Environmental Medicine, Asthma and Lung Biology, UNC School of Medicine.

Oct 2007 Poster presentation - Livraghi A., Grubb, B.R., Hudson E.J., Wilkinson K.J., Mall M., O’Neal W.K., Boucher R.C., Randell S.H. TNFα is not a key mediator of airway inflammation and remodeling in βENaC-transgenic mice. 21st Annual North American Cystic Fibrosis Conference, Anaheim, California.

Oct 2007 Poster presentation - Livraghi A., Grubb B.R., Threadgill, D.W., Mall, M. A., Hudson E.J., Boucher R.C., O'Neal W.K. Assessment of genetic modifiers for phenotypic severity of Scnn1b transgenic mice. 21st Annual North American Cystic Fibrosis Conference, Anaheim, California.

Oct 2007 Poster presentation - Grubb, B.R., Livraghi, A., Rogers, T.D., Wilkinson K.J. Hudson, E.J. Boucher, R.C; O’Neal W.K. Enhancing airway Na+ absorption in CF mice airways results in increased mortality. 21st Annual North American Cystic Fibrosis Conference, Anaheim, California.

Oct 2007 Poster presentation - Jackson P.L., Livraghi A., O’Neal W.K., Noerager B.D., Solomon G.M., McQuaid D.B., Gaggar A., Clancy J.P., Sorscher E.J., Liu G., Abraham E.A., Blalock J.E., Rowe S.M. Novel mediators of persistent neutrophilic inflammation in cystic fibrosis. 21st Annual North American Cystic Fibrosis Conference, Anaheim, California.

Oct 2007 Poster presentation - Mall M, Harkema J.R, Trojanek J.B, Treis D., Schubert S., Zhou Z., Tilley S.L., Livraghi A., O'Neal W.K., Boucher R.C. Initial pulmonary lesions and spontaneous course of lung disease caused by airway surface liquid depletion in βENaC overexpressing mice. 21st Annual North American Cystic Fibrosis Conference, Anaheim, California.

Oct 2007 Poster presentation - Livraghi A., Mall M., Rogers T.D., Hudson E.J., O’Neal W.K, Boucher R.C., Grubb B.R. Generation and phenotypic characterization of transgenic mice over-expressing multiple subunits of EnaC in the airways. 21st Annual North American Cystic Fibrosis Conference, Anaheim, California.

May 2007 Poster presentation - Rowe S.M., Solomon G.M., Livraghi A., O’Neal W.K., Gaggar A., Blalock J.E., Clancy J.P., Sorscher E.J., Abraham E.A., Liu G. Evidence for pathogenic role of HMGB1 in cystic fibrosis. American Thoracic Society International Conference, San Francisco, CA.

Nov 2006 Poster presentation - Livraghi A., Hudson E.J., DeMaria G.C., Sheehan J.K., O’Neal W.K., Boucher R.C., Randell S.H. Absence of IL-4Rα in Scnn1b-transgenic mice enhances neonatal survival but does not mitigate adult lung pathology. 20th Annual North American Cystic Fibrosis Conference, Denver, Colorado.

Nov 2006 Invited Oral presentation - Livraghi, A., O’Neal, W. K.; Mall, M., Boucher, R.C., Grubb, B.R. Enhanced Na+ absorption in the double transgenic ENaC mouse Scnn1b/c correlates with severity of lung pathology 20th Annual North American Cystic Fibrosis Conference, Denver, Colorado.

Oct 2005 Poster presentation - Livraghi A., O’Neal W., Mall M, Boucher R.C., Airway inflammation in Scnn1b transgenic mice. 19th Annual North American Cystic Fibrosis Conference, Baltimore, Maryland.

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Laboratory Personnel

Dr. Livraghi-Butrico is co-director of the CF Center Mouse Models Core. Please follow link for list of personnel.

Contact Information

6029 Thurston-Bowles Bldg.
The University of North Carolina at Chapel Hill
Campus Box #7248
Chapel Hill, NC 27599
Phone: (919) 843-1097
Fax: (919) 966-5178
E-mail: alessandra_livraghi@med.unc.edu

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