A5049641668- Neonatal Respiratory Health Research
- Cystic Fibrosis Research Advances
- Tracheal and airway disorders
- Inhalation and Respiratory Drug Delivery
- Asthma and respiratory diseases
- SARS-CoV-2 and COVID-19 Research
- RNA modifications and cancer
- Respiratory viral infections research
- Congenital Diaphragmatic Hernia Studies
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Pediatric health and respiratory diseases
- Epigenetics and DNA Methylation
- RNA Research and Splicing
- Tissue Engineering and Regenerative Medicine
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Transplantation: Methods and Outcomes
- Viral gastroenteritis research and epidemiology
- Energy Harvesting in Wireless Networks
- Cancer-related molecular mechanisms research
- RNA and protein synthesis mechanisms
- Neuroscience of respiration and sleep
- Animal Virus Infections Studies
- Lung Cancer Treatments and Mutations
- RNA Interference and Gene Delivery
- Glycosylation and Glycoproteins Research
University of North Carolina at Chapel Hill
2016-2025
Lung Institute
2016-2025
Institute of Cell Biology and Neurobiology
2003-2024
Institute of Molecular and Cell Biology
2023
Segeberger Kliniken
2023
UNC Lineberger Comprehensive Cancer Center
2003-2023
Michigan State University
2004-2022
Cystic Fibrosis Research Foundation
2009-2022
University of Missouri Health System
2021
University of Missouri
2021
Gas exchange in the lung occurs within alveoli, air-filled sacs composed of type 2 and 1 epithelial cells (AEC2s AEC1s), capillaries, various resident mesenchymal cells. Here, we use a combination vivo clonal lineage analysis, different injury/repair systems, vitro culture purified cell populations to obtain new information about contribution AEC2s alveolar maintenance repair. Genetic lineage-tracing experiments showed that surfactant protein C-positive (SFTPC-positive) self renew...
The pseudostratified epithelium of the mouse trachea and human airways contains a population basal cells expressing Trp-63 ( p63 ) cytokeratins 5 Krt5 Krt14 . Using KRT5-CreER T2 transgenic line for lineage tracing, we show that generate differentiated during postnatal growth in adult both steady state epithelial repair. We have fractionated by FACS identified 627 genes preferentially expressed subpopulation vs. non-BCs. Analysis reveals potential mechanisms regulating allows comparison with...
Current theories of CF pathogenesis predict different predisposing “local environmental” conditions and sites bacterial infection within airways. Here we show that, in patients with established lung disease, Psuedomonas aeruginosa was located hypoxic mucopurulent masses airway lumens. In vitro studies revealed that CF-specific increases epithelial O2 consumption, linked to increased surface liquid (ASL) volume absorption mucus stasis, generated steep gradients thickened on surfaces prior...
The spike aspartic acid-614 to glycine (D614G) substitution is prevalent in global severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains, but its effects on viral pathogenesis and transmissibility remain unclear. We engineered a SARS-CoV-2 variant containing this substitution. exhibits more efficient infection, replication, competitive fitness primary human airway epithelial cells maintains similar morphology vitro neutralization properties, compared with the ancestral...
The emergence of severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East (MERS)-CoV underscores the threat cross-species transmission events leading to outbreaks in humans. Here we examine disease potential a SARS-like virus, SHC014-CoV, which is currently circulating Chinese horseshoe bat populations. Using SARS-CoV reverse genetics system, generated characterized chimeric virus expressing spike SHC014 mouse-adapted backbone. results indicate that group 2b viruses encoding...
Current theories of CF pathogenesis predict different predisposing “local environmental” conditions and sites bacterial infection within airways. Here we show that, in patients with established lung disease, Psuedomonas aeruginosa was located hypoxic mucopurulent masses airway lumens. In vitro studies revealed that CF-specific increases epithelial O2 consumption, linked to increased surface liquid (ASL) volume absorption mucus stasis, generated steep gradients thickened on surfaces prior...
The airway epithelium occupies a critical environmental interface, protecting the host from wide variety of inhaled insults, including chemical and particulate pollutants pathogens. coordinated regulation ion water transport, mucous secretion, cilia beating underlies mucociliary clearance. Physical trapping removal harmful substances, in combination with baseline or inducible secretion antimicrobial factors, antioxidants, protease inhibitors recruitment nonspecific inflammatory cells...
Outbreaks from zoonotic sources represent a threat to both human disease as well the global economy. Despite wealth of metagenomics studies, methods leverage these datasets identify future threats are underdeveloped. In this study, we describe an approach that combines existing data with reverse genetics engineer reagents evaluate emergence and pathogenic potential circulating viruses. Focusing on severe acute respiratory syndrome (SARS)-like viruses, results indicate WIV1-coronavirus (CoV)...
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The evolutionary origins of Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV) are unknown. Current evidence suggests that insectivorous bats likely to be the original source, as several 2c CoVs have been described from various species in family Vespertilionidae Here, we describe a MERS-like CoV identified Pipistrellus cf. hesperidus bat sampled Uganda (strain PREDICT/PDF-2180), further supporting hypothesis source MERS-CoV. Phylogenetic analysis showed PREDICT/PDF-2180 is...
Head and neck squamous cell carcinoma (HNSCC) is a frequently fatal heterogeneous disease. Beyond the role of human papilloma virus (HPV), no validated molecular characterization disease has been established. Using an integrated genomic analysis validation methodology we confirm four classes HNSCC (basal, mesenchymal, atypical, classical) consistent with signatures established for lung, including deregulation KEAP1/NFE2L2 oxidative stress pathway, differential utilization lineage markers...
Ivacaftor, a CFTR potentiator drug used for cystic fibrosis, destabilizes rescued ΔF508 and interferes with the action of drugs that correct function.
Severe acute respiratory syndrome with high mortality rates (~50%) is associated a novel group 2c betacoronavirus designated Middle East coronavirus (MERS-CoV). We synthesized panel of contiguous cDNAs that spanned the entire genome. Following contig assembly into genome-length cDNA, transfected full-length transcripts recovered several recombinant viruses (rMERS-CoV) contained expected marker mutations inserted component clones. Because wild-type MERS-CoV contains tissue culture-adapted...
Lung squamous cell carcinoma (SCC) is clinically and genetically heterogeneous, current diagnostic practices do not adequately substratify this heterogeneity. A robust, biologically based SCC subclassification may describe variability lead to more precise patient prognosis management. We sought determine if mRNA expression subtypes exist, are reproducible across multiple cohorts, relevant.Subtypes were detected by unsupervised consensus clustering in five published discovery cohorts of...
The combination of irradiated fibroblast feeder cells and Rho kinase inhibitor, Y-27632, conditionally induces an indefinite proliferative state in primary mammalian epithelial cells. These reprogrammed (CRCs) are karyotype-stable nontumorigenic. Because self-renewal is a recognized property stem cells, we investigated whether Y-27632 induced stem-like phenotype. We found that CRCs share characteristics adult exhibit up-regulated expression α6 β1 integrins, ΔNp63α, CD44, telomerase reverse...