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Assistant Professor

Specialty Area:

Mucin Gene and Glycoprotein Expression Patterns

Research Focus:

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. Dr. Ehre also studies the infection pathway of SARS-CoV-2 and is investigating new therapies to block viral entry into airway cells.

Biophysical & Biochemical Properties of Mucus

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.

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.

Fig 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).

Fig 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).

Fig 2. (A) 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.

Fig 2. (A) 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.

SARS-CoV-2 & Therapies

In a laboratory setting, the SARS-CoV-2 virus was inoculated into human bronchial epithelial cells. This was done in a biosafety level (BSL) 3 laboratory with a MOI of 3. These cells were then examined 96hrs post-infection, using scanning electron microscopy, and recolorized. An en face image (Panel A) shows infected ciliated cells with strand of mucus (yellow) attached to cilia tips (blue). Higher power magnification image (Panel B) shows the structure and density of SARS-CoV-2 virions (red) produced by human airway epithelia. Virus production was approximately 3×106 PFU/ml, consistent with a high number of virions produced and released per cell.

Recolorized low mag
Panel A
Recolorized high mag
Panel B

We Are Hiring

The Ehre lab has open positions for postdoctoral fellows and research technicians. Interested applicants should send a CV, cover letter, and contact information for three references to camille_ehre@med.unc.edu.


Selected Bibliography:

  1. Donoghue LJ, Markovetz MR, Morrison CB, Chen G, McFadden KM, Sadritabrizi T, Gutay MI, Kato T, Rogers TD, Snead JY, Livraghi-Butrico A, Button B, Ehre C, Grubb BR, Hill DB, Kelada SNP. BPIFB1 loss alters airway mucus properties and diminishes mucociliary clearance. Am J Physiol Lung Cell Mol Physiol. 2023 Dec 1;325(6):L765-L775. doi: 10.1152/ajplung.00390.2022. PMID: 37847709.
  2. Mikami Y, Grubb BR, Rogers TD, Dang H, Asakura T, Kota P, Gilmore RC, Okuda K, Morton LC, Sun L, Chen G, Wykoff JA, Ehre C, Vilar J, van Heusden C, Livraghi-Butrico A, Gentzsch M, Button B, Stutts MJ, Randell SH, O’Neal WK, Boucher RC. Chronic airway epithelial hypoxia exacerbates injury in muco-obstructive lung disease through mucus hyperconcentration. Sci Transl Med. 2023 Jun 7;15(699):eabo7728. doi: 10.1126/scitranslmed.abo7728. PMID: 37285404. PMCID: PMC10664029.
  3. Ehre C, Hansson GC, Thornton DJ, Ostedgaard LS. Mucus aberrant properties in CF: Insights from cells and animal models. J Cyst Fibros. 2023 Mar;22 Suppl 1:S23-S26. doi: 10.1016/j.jcf.2022.08.019. PMID: 36117114. PMCID: PMC10018425.
  4. Kato T, Asakura T, Edwards CE, Dang H, Mikami Y, Okuda K, Chen G, Sun L, Gilmore RC, Hawkins P, De la Cruz G, Cooley MR, Bailey AB, Hewitt SM, Chertow DS, Borczuk AC, Salvatore S, Martinez FJ, Thorne LB, Askin FB, Ehre C, Randell SH, O’Neal WK, Baric RS, Boucher RC; NIH COVID-19 Autopsy Consortium. Prevalence and mechanisms of mucus accumulation in COVID-19 lung disease. Am J Respir Crit Care Med. 2022 Dec 1;206(11):1336-1352. doi: 10.1164/rccm.202111-2606OC. PMID: 35816430. PMCID: PMC9746856.
  5. Hoang ON, Ermund A, Jaramillo AM, Fakih D, French CB, Flores JR, Karmouty-Quintana H, Magnusson JM, Fois G, Fauler M, Frick M, Braubach P, Hales JB, Kurten RC, Panettieri R, Vergara L, Ehre C, Adachi R, Tuvim MJ, Hansson GC, Dickey BF. Mucins MUC5AC and MUC5B Are Variably Packaged in the Same and in Separate Secretory Granules. Am J Respir Crit Care Med. 2022 Nov 1;206(9):1081-1095. doi: 10.1164/rccm.202202-0309OC. PMID: 35776514. PMCID: PMC9704839.
  6. Markovetz MR, Garbarine IC, Morrison CB, Kissner WJ, Seim I, Forest MG, Papanikolas MJ, Freeman R, Ceppe A, Ghio A, Alexis NE, Stick SM, Ehre C, Boucher RC, Esther CR, Muhlebach MS, Hill DB. Mucus and mucus flake composition and abundance reflect inflammatory and infection status in cystic fibrosis. J Cyst Fibros. 2022 Nov;21(6):959-966. doi: 10.1016/j.jcf.2022.04.008. PMID: 35437233.
  7. Okuda K, Shaffer KM, Ehre C. Mucins and CFTR: Their Close Relationship. Int J Mol Sci. 2022 Sep 6;23(18):10232. doi: 10.3390/ijms231810232. PMID: 36142171. PMCID: PMC9499620.
  8. Tse LV, Meganck RM, Araba KC, Yount BL, Shaffer KM, Hou YJ, Munt JE, Adams LE, Wykoff JA, Morowitz JM, Dong S, Magness ST, Marzluff WF, Gonzalez LM, Ehre C, Baric RS. Genomewide CRISPR knockout screen identified PLAC8 as an essential factor for SADS-CoVs infection. Proc Natl Acad Sci U S A. 2022 May 3;119(18):e2118126119. doi: 10.1073/pnas.2118126119. PMID: 35476513. PMCID: PMC9170153.
  9. Wykoff JA, Shaffer KM, Araba KC, Markovetz MR, Patarin J, Robert de Saint Vincent M, Donaldson SH, Ehre C. Rapid Viscoelastic Characterization of Airway Mucus using a Benchtop Rheometer. J Vis Exp. 2022 Apr 21;(182). doi: 10.3791/63876. PMID: 35532240.
  10. Morrison CB, Edwards CE, Shaffer KM, Araba KC, Wykoff JA, Williams DR, Asakura T, Dang H, Morton LC, Gilmore RC, O’Neal WK, Boucher RC, Baric RS, Ehre C. SARS-CoV-2 infection of airway cells causes intense viral and cell shedding, two spreading mechanisms affected by IL-13. Proc Natl Acad Sci U S A. 2022 Apr 19;119(16):e2119680119. doi: 10.1073/pnas.2119680119. PMID: 35353667. PMCID: PMC9169748.
  11. Kato T, Radicioni G, Papanikolas MJ, Stoychev GV, Markovetz MR, Aoki K, Porterfield M, Okuda K, Barbosa Cardenas SM, Gilmore RC, Morrison CB, Ehre C, Burns KA, White KK, Brennan TA, Goodell HP, Thacker H, Loznev HT, Forsberg LJ, Nagase T, Rubinstein M, Randell SH, Tiemeyer M, Hill DB, Kesimer M, O’Neal WK, Ballard ST, Freeman R, Button B, Boucher RC. Mucus concentration-dependent biophysical abnormalities unify submucosal gland and superficial airway dysfunction in cystic fibrosis. Sci Adv. 2022 Apr;8(13):eabm9718. doi: 10.1126/sciadv.abm9718. PMID: 35363522.
  12. Morrison CB, Shaffer KM, Araba KC, Markovetz MR, Wykoff JA, Quinney NL, Hao S, Delion MF, Flen AL, Morton LC, Liao J, Hill DB, Drumm ML, O’Neal WK, Kesimer M, Gentzsch M, Ehre CTreatment of cystic fibrosis airway cells with CFTR modulators reverses aberrant mucus properties via hydration. Eur Respir J. 2022 Feb 3;59(2):2100185. doi: 10.1183/13993003.00185-2021. PMID: 34172469. PMCID: PMC8859811.
  13. Howard RL, Markovetz M, Wang Y, Ehre C, Sheikh SZ, Allbritton NL, Hill DB. Biochemical and rheological analysis of human colonic culture mucus reveals similarity to gut mucus. Biophys J. 2021 Dec 7;120(23):5384-5394. doi: 10.1016/j.bpj.2021.10.024. PMID: 34695384. PMCID: PMC8715165.
  14. Carpenter J, Wang Y, Gupta R, Li Y, Haridass P, Subramani DB, Reidel B, Morton L, Ridley C, O’Neal WK, Buisine MP, Ehre C, Thornton DJ, Kesimer M. Assembly and organization of the N-terminal region of mucin MUC5AC: Indications for structural and functional distinction from MUC5B. Proc Natl Acad Sci U S A. 2021 Sep 28;118(39):e2104490118. doi: 10.1073/pnas.2104490118. PMID: 34548396; PMCID: PMC8488587.
  15. Toyonaga T, Araba KC, Kennedy MM, Keith BP, Wolber EA, Beasley C, Steinbach EC, Schaner MR, Jain A, Long MD, Barnes EL, Herfarth HH, Isaacs KL, Hansen JJ, Kapadia MR, Guillem JG, Gulati AS, Sethupathy P, Furey TS, Ehre C, Sheikh SZ. Increased colonic expression of ACE2 associates with poor prognosis in Crohn’s disease. Sci Rep. 2021 Jun 29;11(1):13533. doi: 10.1038/s41598-021-92979-2. PMID: 34188154; PMCID: PMC8241995.
  16. Escobar YH, Morrison CB, Chen Y, Hickman E, Love CA, Rebuli ME, Surratt JD, Ehre C, Jaspers I. Differential responses to e-cig generated aerosols from humectants and different forms of nicotine in epithelial cells from non-smokers and smokers. Am J Physiol Lung Cell Mol Physiol. 2021 Jun 1;320(6):L1064-L1073. doi: 10.1152/ajplung.00525.2020. PMID: 33825493. PMCID: PMC8285624.
  17. Kato T, Mikami Y, Sun L, Rogers TD, Grubb BR, Morrison CB, Ehre C, Sears PR, Ostrowski LE, Randell SH, Boucher RC. Reuse of Cell Culture Inserts for in vitro Human Primary Airway Epithelial Cell Studies. Am J Respir Cell Mol Biol. 2021 Jun;64(6):760-764. doi: 10.1165/rcmb.2021-0033LE. PMID: 33788673. PMCID: PMC8456889.
  18. Hou YJ, Chiba S, Halfmann P, Ehre C, Kuroda M, Dinnon KH 3rd, Leist SR, Schäfer A, Nakajima N, Takahashi K, Lee RE, Mascenik TM, Graham R, Edwards CE, Tse LV, Okuda K, Markmann AJ, Bartelt L, de Silva A, Margolis DM, Boucher RC, Randell SH, Suzuki T, Gralinski LE, Kawaoka Y, Baric RS. SARS-CoV-2 D614G variant exhibits efficient replication ex vivo and transmission in vivo. Science. 2020 Dec 18;370(6523):1464-1468. doi: 10.1126/science.abe8499. PMID: 33184236. PMCID: PMC7775736.
  19. Ehre C. SARS-CoV-2 Infection of Airway Cells. N Engl J Med. 2020 Sep 3;383(10):969. doi: 10.1056/NEJMicm2023328. PMID: 32877585. PMCID: PMC7484746.
  20. Danahay H, Fox R, Lilley S, Charlton H, Adley K, Christie L, Ansari E, Ehre C, Flen A, Tuvim MJ, Dickey BF, Williams C, Beaudoin S, Collingwood SP, Gosling M. Potentiating TMEM16A does not stimulate airway mucus secretion or bronchial and pulmonary arterial smooth muscle contraction. FASEB Bioadv. 2020 Jul 1;2(8):464-477. doi: 10.1096/fba.2020-00035. PMID: 32821878; PMCID: PMC7429354.
  21. Ramsey KA, Chen ACH, Radicioni G, Lourie R, Martin M, Broomfield A, Sheng YH, Hasnain SZ, Radford-Smith G, Simms LA, Burr L, Thornton DJ, Bowler SD, Livengood S, Ceppe A, Knowles MR, Noone PG, Donaldson SH, Hill DB, Ehre C, Button B, Alexis NE, Kesimer M, Boucher RC, McGuckin MA. Airway Mucus Hyperconcentration in Non-Cystic Fibrosis Bronchiectasis. Am J Respir Crit Care Med. 2020 Mar 15;201(6):661-670. doi: 10.1164/rccm.201906-1219OC. PMID: 31765597. PMCID: PMC7068838.
  22. Lewis BW, Vo T, Choudhary I, Kidder A, Bathula C, Ehre C, Wakamatsu N, Patial S, Saini Y. Ablation of IL-33 Suppresses Th2 Responses but Is Accompanied by Sustained Mucus Obstruction in the Scnn1b Transgenic Mouse Model. J Immunol. 2020 Mar 15;204(6):1650-1660. doi: 10.4049/jimmunol.1900234. PMID: 32060135. PMCID: PMC7714586.
  23. Ehre C. [Mucus buildup: the starting point of cystic fibrosis lung disease pathogenesis]. Med Sci (Paris). 2019 Dec;35(12):1217-1220. doi: 10.1051/medsci/2019234. PMID: 31903945.
  24. Morrison CB, Markovetz MR, Ehre C. Mucus, mucins, and cystic fibrosis. Pediatr Pulmonol. 2019 Nov;54 Suppl 3:S84-S96. doi: 10.1002/ppul.24530. PMID: 31715083. PMCID: PMC6853602.
  25. Markovetz MR, Subramani DB, Kissner WJ, Morrison CB, Garbarine IC, Ghio A, Ramsey KA, Arora H, Kumar PA, Nix DB, Kumagai T, Krunkosky TM, Krause DC, Radicioni G, Alexis NE, Kesimer M, Tiemeyer M, Boucher RC, Ehre C, Hill DB. Endotracheal Tube Mucus as a Source of Airway Mucus for Rheological Study. Am J Physiol Lung Cell Mol Physiol. 2019 Oct 1;317(4):L498-L509. doi: 10.1152/ajplung.00238.2019. PMID: 31389736. PMCID: PMC6842913.
  26. Esther CR Jr, Muhlebach MS, Ehre C, Hill DB, Wolfgang MC, Kesimer M, Ramsey KA, Markovetz MR, Garbarine IC, Forest MG, Seim I, Zorn B, Morrison CB, Delion MF, Thelin WR, Villalon D, Sabeter JR, Turkovic L, Ranganathan S, Stick SM, Boucher RC, on behalf of AREST CF. Mucus accumulation in the lungs precedes structural changes and infection in children with cystic fibrosis. Sci Transl Med. 2019 Apr 3;11(486). doi: 10.1126/scitranslmed.aav3488. PMID: 30944166. PMCID: PMC6566903.
  27. 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/Healthy 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.
  28. 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.
  29. Bauer AK, Umer M, Richardson VL, Cumpian AM, Harder AQ, Khosravi N, Azzegagh Z, Hara NM, Ehre C, Mohebnasab M, Caetano MS, Merrick DT, van Bokhoven A, Wistuba II, Kadara H, Dickey BF, Velmurugan K, Mann PR, Lu X, Barón AE, Evans CM, Moghaddam SJ. Requirement for MUC5AC in KRAS-dependent lung carcinogenesis. JCI Insight. 2018 Aug 9;3(15). doi: 10.1172/jci.insight.120941. PMID: 30089720. PMCID: PMC6129115.
  30. Meng H, Lockshin C, Jain S, Shaligram U, Martinez J, Genkin D, Hill DB, Ehre C, Clark D, Hoppe H. Clinical application of polysialylated therapeutic proteins. Recent Pat Drug Deliv Formul. 2018;12(3):212-222. doi: 10.2174/1872211312666180717164758. PMID: 30019653.
  31. Reighard KP*, Ehre C*, Rushton Z, Ahonen M, Hill DB, Schoenfisch M. Role of nitric oxide-releasing chitosan oligosaccharides on mucus viscoelasticity. ACS Biomater Sci Eng. 2017;3(6):1017–26. doi: 10.1021/acsbiomaterials.7b00039. PMID: 30320206. PMCID: PMC6178828.
  32. Ramsey KA, Rushton ZL, Ehre C. Mucin agarose gel electrophoresis: Western blotting for high-molecular-weight glycoproteins. J Vis Exp. 2016 Jun 14;(112). doi: 10.3791/54153. PMID: 27341489. PMCID: PMC4927784.
  33. Ehre C, Ridley C, Thornton DJ. Cystic fibrosis: an inherited disease affecting mucin-producing organs. Int J Biochem Cell Biol. 2014 Jul;52:136-45. doi: 10.1016/j.biocel.2014.03.011. Review. PMID: 24685676. PMCID: PMC4449140.
  34. Henderson AG, Ehre C, Button B, Abdullah LH, Cai LH, Leigh MW, DeMaria GC, Matsui H, Donaldson SH, Davis CW, Sheehan JK, Boucher RC, Kesimer M. Cystic fibrosis airway secretions exhibit mucin hyperconcentration and increased osmotic pressure. J Clin Invest. 2014 Jul;124(7):3047-60. doi: 10.1172/JCI73469. PMID: 24892808. PMCID: PMC4072023.
  35. Ehré C. [Mucus clearance in the respiratory tract: a new concept?]. Med Sci (Paris). 2013 Feb;29(2):144-6. doi: 10.1051/medsci/2013292010. French. PMID: 23452599.
  36. Ehre C, Worthington EN, Liesman RM, Grubb BR, Barbier D, O’Neal WK, Sallenave JM, Pickles RJ, Boucher RC. Overexpressing mouse model demonstrates the protective role of Muc5ac in the lungs. Proc Natl Acad Sci U S A. 2012 Oct 9;109(41):16528-33. doi: 10.1073/pnas.1206552109. Erratum in: Proc Natl Acad Sci U S A. 2014 Apr 15;111(15):5753. PMID: 23012413. PMCID: PMC3478656.
Camille Ehre