A5055201103- Chronic Obstructive Pulmonary Disease (COPD) Research
- Neonatal Respiratory Health Research
- Cystic Fibrosis Research Advances
- Asthma and respiratory diseases
- Pediatric health and respiratory diseases
- Respiratory Support and Mechanisms
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Respiratory viral infections research
- Tracheal and airway disorders
- Inhalation and Respiratory Drug Delivery
- Epigenetics and DNA Methylation
- Glycosylation and Glycoproteins Research
- Respiratory and Cough-Related Research
- Virus-based gene therapy research
- Lung Cancer Diagnosis and Treatment
- RNA Interference and Gene Delivery
- Adenosine and Purinergic Signaling
- Gut microbiota and health
- Genomics and Rare Diseases
- Neuroscience of respiration and sleep
- Pulmonary Hypertension Research and Treatments
- Immunodeficiency and Autoimmune Disorders
- Endoplasmic Reticulum Stress and Disease
- Ion Transport and Channel Regulation
- Smoking Behavior and Cessation
University of North Carolina at Chapel Hill
2016-2025
Lung Institute
2016-2025
Yahoo (United Kingdom)
2024
Communities In Schools of Orange County
2021
University of North Carolina Health Care
2021
Institute of Neurobiology
2020
Duke Medical Center
2020
Atlanta VA Health Care System
2019
Indiana University School of Medicine
2010-2017
Cornell University
2017
The efficiency of first-generation adenoviral vectors as gene delivery tools is often limited by the short duration transgene expression, which can be related to immune responses and toxic effects viral proteins. In addition, readministration usually ineffective unless animals are immunocompromised or a different adenovirus serotype used. Recently, devoid all coding sequences (helper-dependent gutless vectors) have been developed avoid expression mice, liver-directed transfer with AdSTK109,...
YAP is a multifunctional adapter protein and transcriptional coactivator with several binding partners well described in vitro cell culture.To explore vivo requirements for YAP, we generated mice carrying targeted disruption of the Yap gene.Homozygosity tm1Smil allele (Yap ؊/؊ ) caused developmental arrest around E8.5.Phenotypic characterization revealed requirement yolk sac vasculogenesis.Yolk endothelial erythrocyte precursors were specified as shown by histology, PECAM1 immunostaining,...
Airway mucus forms the structural basis of local innate immune defense mechanism. It is an integrated, active, viscoelastic gel matrix evolved to protect exposed lung from physical, chemical, and pathological erosion. Exosomes are biologically active vesicles secreted by different cell types including epithelial, hematopoietic, some tumor cells. They also present in biological fluids such as serum, urine, breast milk, bronchoalveolar lavage fluid. In this study, we demonstrate for first time...
Chronic obstructive pulmonary disease (COPD) is characterized by chronic bronchitic and emphysematous components. In one biophysical model, the concentration of mucin on airway surfaces hypothesized to be a key variable that controls mucus transport in healthy persons versus cessation with muco-obstructive lung diseases. Under this it postulated high produces sputum progression are characteristic bronchitis.We COPD status 917 participants from Subpopulations Intermediate Outcome Measures...
MUC5AC and MUC5B are the predominant gel-forming mucins in mucus layer of human airways. Each mucin has distinct functions site-specific expression. However, regional distribution expression cell types that secrete each normal/healthy airways not fully understood.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a range of symptoms in infected individuals, from mild illness to distress syndrome. A systematic understanding host factors influencing viral infection is critical elucidate SARS-CoV-2-host interactions and the progression Coronavirus disease 2019 (COVID-19). Here, we conducted genome-wide CRISPR knockout activation screens human lung epithelial cells with endogenous expression SARS-CoV-2 entry ACE2 TMPRSS2. We uncovered...
A subset of individuals who recover from coronavirus disease 2019 (COVID-19) develop post-acute sequelae severe acute respiratory syndrome 2 (SARS-CoV-2) (PASC), but the mechanistic basis PASC-associated lung abnormalities suffers a lack longitudinal tissue samples. The mouse-adapted SARS-CoV-2 strain MA10 produces an distress in mice similar to humans. To investigate PASC pathogenesis, studies MA10-infected were extended clinical recovery phases. At 15 120 days after virus clearance,...
Significance Gaining insights into severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) high transmissibility and the role played by inflammatory mediators in viral proliferation are critical to investigating new therapeutic targets against COVID-19. Electron microscopy reveals important SARS-CoV-2 features, including combination of large, rapidly released clusters massive shedding epithelial cells packed with virions. Interleukin-13 (IL-13), a Th2 cytokine up-regulated allergic...
Cystic fibrosis (CF) transmembrane conductance regulator (CFTR)-dependent airway epithelial bicarbonate transport is hypothesized to participate in surface liquid pH regulation and contribute lung defense. We measured ionic composition apical (ASL) on polarized normal (NL) CF primary bronchial cell cultures under basal conditions, after cAMP stimulation, challenge with luminal acid loads. Under epithelia acidified ASL more rapidly than NL epithelia. Two regulatory paths that contributed were...
ATP released from airway epithelial cells promotes purinergic receptor-regulated mucociliary clearance activities necessary for innate lung defense. Cell swelling-induced membrane stretch/strain is a common stimulus that release, but the mechanisms transducing cell swelling into release are incompletely understood. Using knockdown and knockout approaches, we tested hypothesis pannexin 1 mediates hypotonically swollen epithelia investigated regulating this activity. Well differentiated...
Rationale: Chronic obstructive pulmonary disease is a leading cause of death worldwide, but its pathogenesis not well understood. Previous studies have shown that airway surface dehydration in β-epithelial Na+ channel (βENaC)–overexpressing mice caused chronic lung with high neonatal mortality and bronchitis adult survivors.Objectives: The aim this study was to identify the initiating lesions investigate natural progression by dehydration.Methods: Lung morphology, gene expression,...
MUC5AC, a major gel-forming mucin expressed in the lungs, is secreted at increased rates response to infectious agents, implying that mucins exert protective role against inhaled pathogens. However, epidemiological and pathological studies suggest excessive secretion causes airways obstruction inflammation. To determine whether MUC5AC alone produces airway and/or inflammation, we generated mouse model overexpressing Muc5ac mRNA ∼20-fold using rCCSP promoter. The cDNA was cloned from lungs...
Extracellular ATP regulates several elements of the mucus clearance process important for pulmonary host defense. However, mechanisms mediating release onto airway surfaces remain unknown. Mitochondrial voltage-dependent anion channels (mt-VDACs) translocate a variety metabolites, including and ADP, across mitochondrial outer membrane, plasmalemmal splice variant (pl-VDAC-1) has been proposed to mediate translocation plasma membrane. We tested involvement VDAC-1 in series studies murine...
The efficiency of the mucociliary clearance (MCC) process that removes noxious materials from airway surfaces depends on balance between mucin secretion, surface liquid (ASL) volume, and ciliary beating. Effective dispersion into ASL requires salt water secretion onto mucosal surface, but how rate is coordinated with ion and, ultimately, transport rates poorly understood. Several components MCC, including electrolyte transport, are regulated by nucleotides in interacting purinergic...
Novel proteomics platforms, such as the aptamer-based SOMAscan platform, can quantify large numbers of proteins efficiently and cost-effectively are rapidly growing in popularity. However, comparisons to conventional immunoassays remain underexplored, leaving investigators unsure when cross-assay appropriate. The correlation results from with relative protein quantification is explored by SOMAscan. For 63 assessed two chronic obstructive pulmonary disease (COPD) cohorts, subpopulations...