Dr. Ehre’s laboratory specializes in the biophysical and biochemical properties of mucus, which are affected in various airway diseases such as cystic fibrosis (CF), chronic obstructive pulmonary disease (COPD) and primary ciliary dyskinesia (PCD). Studies conducted in her laboratory utilize cell cultures, human specimen and small animal models.
Mucus is normally produced in the lungs to trap inhaled pathogens (e.g., bacteria, viruses) and particles (e.g., dust, smoke) but, in disease, increased mucus concentration leads to airflow obstruction, bacterial infection and chronic inflammation. Dr. Ehre’s research focuses on understanding the biological alterations of mucus that occur in disease and studying new pharmacological approaches to restore lung health.
Figure 1.Immunolabeling of mucins and DNA in pediatric bronchoalveolar lavages. Confocal images revealing different mucin network topologies between CF and non-CF patients. (Blue=DAPI, Green=MUC5B, Red=MUC5AC).
The viscoelastic properties of mucus rely on the polymeric gel-forming mucins (mostly MUC5AC and MUC5B in the lungs), which are among the largest glycoproteins in the animal world. Working with mucus can be challenging because of the size of these mucin molecules and the complex ultrastructure and intermingled organization of mucin polymers. Dr. Ehre has established a series of assays to study mucin-mucin and mucin-DNA interactions based on confocal imaging, fluorescence-based quantification and multi-angle light scattering analysis, as well as techniques to measure changes in rheology.
Dr. Ehre also conducts preclinical studies testing compounds aimed at improving mucus clearance in the lungs. New pharmacological reagents are initially tested in vitro utilizing primary human bronchial epithelial cells (HBE) and/or human specimen (sputum or bronchoalveolar lavages). Subsequently, drug efficacy and toxicity are tested in vivo using mouse models of airway diseases such as the βENaC model.
Figure 2.Spontaneous formation of mucus plaques and neutrophilic inflammation in βENaC mice, a mouse model mimicking the CF lung disease. (A) AB-PAS stain of βENaC lungs revealing mucus plugs at airway branching. (B) Immunohistochemistry (IHC) displaying PCL collapse and mucin accumulation on airway surfaces (green=Muc5b, Blue=DAPI). (C) Inflammatory cells from a βENaC mouse bronchoalveolar lavage showing a mixture of macrophages and neutrophils. (D) IHC exhibiting inflammatory cells trapped in mucus.
2004 PhD, Pathophysiology, “Regulation of Mucin Secretion from Airway Goblet Cells”
Université Pierre and Marie Curie, Paris (VI), France
2000 MS, Molecular Biology, “Cloning Mega Complexes with Highly Repetitive Sequences”
Université Paul Sabatier, Toulouse (III), France
1998 BS, Physiology and Immunology
Université Paul Sabatier, Toulouse (III), France
2006-present, Research Associate (UNC), Cystic Fibrosis (CF)/Pulmonary Research Treatment Center. Preclinical studies testing pharmacological compounds aimed at removing adherent mucus from the lungs.
2005-2006, Postdoctoral Fellow (UNC), Dr. R.C. Boucher Lab, CF Center. Studied the role of mucins in airway obstruction, infection and inflammation.
2000-2004, Ph.D. student (Paris VI Univ.), Dr. P. Codogno Lab, Department of Physiology and Pathophysiology; in collaboration with Dr. C.W. Davis Lab (UNC), CF Center. Studied the regulation of mucin secretion in the lungs.
1999-2000, Visiting Master Research Fellow (UNC), Dr. B. Sartor Lab, Department of Microbiology & Immunology. Identified inflammatory pathways involved in the pathogenesis of Crohn’s disease.
A.G. Henderson*, C. Ehre*, B. Button, L.H. Abdullah, L. Cai, M.W. Leigh, G. De Maria, H. Matsui, S. H. Donaldson, C.W. Davis, J.K. Sheehan, R.C. Boucher and M. Kesimer. 2014. CF Airway Secretions Exhibit Mucin Hyperconcentration and Increased Osmotic Pressure. J. Clin. Invest. (*co-first authors)
Ehre C., Ridley C., Thornton D.J. 2014. Cystic Fibrosis: an inherited disease affecting mucin-producing organs. IJBCB (in press)
Ehre, C. 2013. [Mucus clearance in the respiratory tract: a new concept?]. Med Sci (Paris) 29:144-146
Kesimer, M., Ehre, C., Burns, K.A., Davis, C.W., Sheehan, J.K., and Pickles, R.J. 2013. Molecular organization of the mucins and glycocalyx underlying mucus transport over mucosal surfaces of the airways. Mucosal Immunol 6:379-392.
Martino, M.B., Jones, L., Brighton, B., Ehre, C., Abdulah, L., Davis, C.W., Ron, D., O'Neal, W.K., and Ribeiro, C.M. 2013. The ER stress transducer IRE1beta is required for airway epithelial mucin production. Mucosal Immunol 6:639-654
Ehre, C., Worthington, E.N., Liesman, R.M., Grubb, B.R., Barbier, D., O'Neal, W.K., Sallenave, J.M., Pickles, R.J., and Boucher, R.C. 2012. Overexpressing mouse model demonstrates the protective role of Muc5ac in the lungs. Proc Natl Acad Sci U S A 109:16528-16533.
Button, B., Cai, L.H., Ehre, C., Kesimer, M., Hill, D.B., Sheehan, J.K., Boucher, R.C., and Rubinstein, M. 2012. A periciliary brush promotes the lung health by separating the mucus layer from airway epithelia. Science 337:937-941.
Roy, M.G., Rahmani, M., Hernandez, J.R., Alexander, S.N., Ehre, C., Ho, S.B., and Evans, C.M. 2011. Mucin Production During Pre- and Post-Natal Mouse Lung Development. Am J Respir Cell Mol Biol.
Zhu, Y., Ehre, C., Abdullah, L.H., Sheehan, J.K., Roy, M., Evans, C.M., Dickey, B.F., and Davis, C.W. 2008. Munc13-2-/- baseline secretion defect reveals source of oligomeric mucins in mouse airways. J Physiol 586:1977-1992.
Nguyen, L.P., Omoluabi, O., Parra, S., Frieske, J.M., Clement, C., Ammar-Aouchiche, Z., Ho, S.B., Ehre, C., Kesimer, M., Knoll, B.J., et al. 2008. Chronic exposure to beta-blockers attenuates inflammation and mucin content in a murine asthma model. Am J Respir Cell Mol Biol 38:256-262.
Ehre, C., Zhu, Y., Abdullah, L.H., Olsen, J., Nakayama, K.I., Nakayama, K., Messing, R.O., and Davis, C.W. 2007. nPKCepsilon, a P2Y2-R downstream effector in regulated mucin secretion from airway goblet cells. Am J Physiol Cell Physiol 293:C1445-1454
Ehre, C., Rossi, A.H., Abdullah, L.H., De Pestel, K., Hill, S., Olsen, J.C., and Davis, C.W. 2005. Barrier role of actin filaments in regulated mucin secretion from airway goblet cells. Am J Physiol Cell Physiol 288:C46-56
Abdullah, L.H., Bundy, J.T., Ehre, C., and Davis, C.W. 2003. Mucin secretion and PKC isoforms in SPOC1 goblet cells: differential activation by purinergic agonist and PMA. Am J Physiol Lung Cell Mol Physiol 285:L149-160
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The University of North Carolina at Chapel Hill
Chapel Hill, NC 27599