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Will host rotation students in 2023-24
Assistant Professor
7108 Marsico Hall

Research

Respiratory Diseases, Virus, & Immunity

We study lung diseases, respiratory viral infections and how innate defense mechanisms affect viral spread.

Muco-obstructive lung diseases are characterized by chronic airway mucus obstruction and impaired mucociliary clearance. Although the underlying mechanisms vary between diseases, lung conditions like asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis (CF) share common features that include mucus hyperproduction, chronic inflammation, and susceptibility to disease exacerbations following viral infections. For people suffering from muco-obstructive diseases, respiratory viral infections can worsen mucus burden, dysregulate inflammation, and cause secondary bacterial infection, leading to prolonged recovery periods associated with severe bronchiolitis or pneumonia. However, not all viruses infecting the respiratory system will have the same deleterious effects.

In collaboration with virologists, we study host-pathogen interactions for a variety of coronaviruses (SARS-CoV-2, 229E, NL63, OC43, and HKU1), respiratory syncytial virus (RSV), and parainfluenza (Sendai virus). We use a combination of in vitro and in vivo models of muco-obstructive lung diseases to study the different stages of host-virus interactions, including mucus penetration, cell attachment, viral entry and egress, immune response, and pathogenesis.

Specific projects are listed below:

  • Does mucus consistently provide a physical barrier against respiratory viruses?
  • How does chronic inflammation observed in muco-obstructive lung diseases affect respiratory viral infections?
  • Can pharmacological agents used to treat chronic lung diseases improve viral clearance?
  • Can the study of virus infection lead us to specific new targets that will enable DNA/mRNA transfer for gene editing and/or gene therapy?

Understanding the specific interactions between respiratory viruses and their hosts is crucial for developing effective strategies for prevention, treatment, and control. Our studies aim to uncover new insights into these interactions to facilitate the development of antiviral drugs, vaccines, and public health measures to combat respiratory virus infections, particularly for those with muco-obstructive diseases.

Publications

Selected Publications

  • Okuda K, Shaffer KM, Ehre C. Mucins and CFTR: Their Close Relationship. Int J Mol Sci. 2022. PMID: 36142171
  • Kato, T, Asakura, C.E. Edwards, H. Dang, Y. Mikami, K. Okuda, G. Chen, L. Sun, R.C. Gilmore, P.E. Hawkins, G. De la Cruz, M.R. Cooley, A.B. Bailey, S.M. Hewitt, D.S. Chertow, NIH COVID-19 Autopsy Consortium, A.C. Borczuk, S. Salvatore, F.J. Martinez, L.B. Thorne, F.B. Askin, C. Ehre, S.H. Randell, W.K. O’Neal, R.S. Baric, R.C. Boucher. Prevalence and Mechanisms of Mucus Accumulation in COVID-19 Lung Disease. AJRCCM 2022. PMID: 35816430
  • 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. PNAS 04/2022. PMID: 35476513
  • 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.
  • 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. PNAS 2022.
  • B. Morrison, K.M. Shaffer, K.C. Araba, M.R. Markovetz, N.L. Quinney, S. Hao, M.F. Delion, A.L. Flen, L.C. Morton, J. Liao, D.B. Hill, M.L. Drumm, W.K. O’Neal, M. Kesimer, M. Gentzsch and C. Ehre. Treatment of Cystic Fibrosis Airway Cells with CFTR Modulators Reverses Aberrant Mucus Properties via Hydration. ERJ. 2022.
  • Carpenter J., Yang W., Richa G., Yuanli L., Prashamsha H., Durai B. S., Boris R., Lisa M., C. Ridley, W. K. O’Neal, M. P. Buisine, C. Ehre, D. J. Thornton, and M.t Kesimer. Assembly and organization of the N-terminal region of mucin MUC5AC: Indications for structural and functional distinction from MUC5B. PNAS. 2021
  • J. Hou, S. Chiba, P. Halfmann, C. Ehre, M. Kuroda, K. H Dinnon, S. R. Leist, Al. Schäfer, N. Nakajima, K. Takahashi, R. E. Lee, T. M. Mascenik, C. E. Edwards, L. V. Tse, R. C. Boucher, S. H. Randell, T. Suzuki, L. E. Gralinski, Y. Kawaoka and R. S. Baric. SARS-CoV-2 D614G Variant Exhibits Enhanced 1 Replication ex vivo and Earlier Transmission in vivo. Science 2020.
  • Ehre C., Baric. R., Boucher R.C., SARS-CoV-2 infected airway ciliated cells. NEJM 2020.
  • Morrison, M. Markovetz, C. Ehre. Mucus, Mucins and Cystic Fibrosis. Invited Review Article. Pediatric Pulmonology. 2019 Nov. PMID: 31715083
  • Ehre, Z. L. Rushton, B. Wang, C. Morrison, L. N. Hothem, N. C. Fontana, D. Villalon, W. R. Thelin, C. R. Esther Jr., D. B. Hill, B. R. Grubb, A. Livraghi-Butrico, S. H. Donaldson, R. C. Boucher. Improving Inhaled Mucolytics to Treat Airway Obstructive Diseases. AJRCCM 2019 Jan. PMID: 30212240

Link to my bibliography

My Bibliography – NCBI (nih.gov)

Affiliations

Marsico Lung Institute: Welcome to the Marsico Lung Institute/UNC Cystic Fibrosis Center | Marsico Lung Institute

Pediatric Pulmonology: Research Programs | Department of Pediatrics (unc.edu)

UNC Children’s Research Institute (CRI): About the Children’s Research Institute – UNC Children’s Research Institute

Department of Microbiology & Immunology: Department of Microbiology and Immunology | Department of Microbiology and Immunology (unc.edu)

Biological and Biomedical Sciences Program (BBSP): UNC BBSP