A5084917293- Cystic Fibrosis Research Advances
- Neonatal Respiratory Health Research
- Pneumonia and Respiratory Infections
- Respiratory viral infections research
- Smoking Behavior and Cessation
- Asthma and respiratory diseases
- CRISPR and Genetic Engineering
- Bacterial Infections and Vaccines
- Tracheal and airway disorders
- Antimicrobial Peptides and Activities
- Inhalation and Respiratory Drug Delivery
- Pediatric health and respiratory diseases
- Epigenetics and DNA Methylation
- Genetics and Neurodevelopmental Disorders
- COVID-19 Clinical Research Studies
- RNA Interference and Gene Delivery
- Inflammasome and immune disorders
- interferon and immune responses
- Histone Deacetylase Inhibitors Research
- IL-33, ST2, and ILC Pathways
- Tissue Engineering and Regenerative Medicine
- 3D Printing in Biomedical Research
- Blood groups and transfusion
- Studies on Chitinases and Chitosanases
- Heme Oxygenase-1 and Carbon Monoxide
The Ohio State University
2018-2025
Queensland University of Technology
2015
Abstract Robust in vitro lung models are required for risk assessment to measure key events leading respiratory diseases. Primary normal human bronchial epithelial cells (NHBE) represent a good model but obtaining well-differentiated 3D cultures can be challenging. Here, we evaluated the ability expand primary NHBE different culture conditions while maintaining their characteristics such as ciliated and goblet cells, ion channel function. Differentiated were optimally obtained with...
Significance We report the discovery of fundamental roles for noncanonical inflammasome molecule Caspase-4/11 in promoting pathological inflammatory and prothrombotic pathways severe acute respiratory syndrome coronavirus 2 (SARS–CoV-2) infections. Our work demonstrates that Caspase-11 has a broader role immune responses beyond its previously appreciated effects bacterial Further, we show Caspase-11–deficient mice infected with SARS–CoV-2 fare significantly better terms overall illness, lung...
Background: Secondhand smoke exposure (SHSe) is a public health threat for people with cystic fibrosis (CF) and other lung diseases. Primary smoking reduces CFTR channel function, the causative defect in CF. We reported that SHSe worsens respiratory nutritional outcomes CF by disrupting immune responses metabolic signaling. Recently, electronic cigarette (e-cigs) usage caregivers peers has increased rapidly, causing new secondhand e-cig vape exposures. vaping associated immunologic deficits...
Traditionally, whooping cough or pertussis caused by the obligate human pathogen Bordetella ( Bp ) is described as an acute disease with severe symptoms. However, many individuals who contract are either asymptomatic show very mild symptoms and yet can serve carriers sources of bacterial transmission. Biofilms important survival mechanism for bacteria in infections disease. determinants that drive biofilm formation humans ill-defined. In current study, we infection well-differentiated...
Cigarette smoking is known to disrupt the normal mucociliary function of lungs, whereas effect electronic nicotine delivery systems (ENDS) not completely understood. This study aimed compare effects acute exposure primary human bronchial epithelial (NHBE) 3D cultures at air-liquid interface combustible cigarette and ENDS preparations on function, including ion channel ciliary beat frequency (CBF), airway surface liquid (ASL) height. Differentiated NHBE were exposed whole smoke-conditioned...
Respiratory viruses, such as influenza, decrease airway cilia function and expression, which leads to reduced mucociliary clearance inhibited overall immune defense. Ubiquitination is a posttranslational modification using E3 ligases, plays role in the assembly disassembly of cilia. We examined membrane-associated RING-CH (MARCH) family ligases during influenza infection determined that MARCH10, specifically expressed ciliated epithelial cells, significantly decreased mice, human lung...
Mutations in the CFTR gene lead to cystic fibrosis, a genetic disease associated with chronic infection and inflammation ultimately respiratory failure. The most common CF-causing mutation is F508del modulators (correctors potentiators) are being developed rescue its trafficking activity defects. However, there currently no that stabilize rescued membrane F508del-CFTR which endocytosed quickly degraded resulting shorter half-life than wild-type (WT). We previously reported extracellular...
Single-stranded DNA (ssDNA) templates along with Cas9 have been used for gene insertion but suffer from low efficiency. Here, we show that ssDNA chemical modifications in 10-17% of internal bases (eDNA) is compatible the homologous recombination machinery. Moreover, eDNA improve by 2-3 fold compared to unmodified and end-modified airway basal stem cells (ABCs), hematopoietic progenitor (HSPCs), T-cells endothelial cells. Over 50% alleles showed three clinically relevant loci (CFTR, HBB,...
Abstract Single-stranded DNA (ssDNA) templates along with Cas9 have been used for knocking-in exogenous sequences in the genome but suffer from low efficiency. Here, we show that ssDNA chemical modifications 12–19% of internal bases, which denote as enhanced (esDNA), improve knock-in (KI) by 2–3-fold compared to end-modified airway basal stem cells (ABCs), CD34 + hematopoietic (CD34 cells), T-cells and endothelial cells. Over 50% alleles showed KI three clinically relevant loci (CFTR, HBB...
BackgroundThe conducting airway epithelium is repaired by tissue specific stem cells (TSC). In response to mild/moderate injury, each TSC repairs a discrete area of the epithelium. contrast, severe epithelial injury stimulates migration and expands cell's reparative domain. Lung transplantation (LTx) can cause moderate/severe remodeled contains chimeric mixture donor recipient cells. These studies supported hypothesis, LTx resulting in chimerism. We tested this hypothesis cystic fibrosis...
Cigarette smoking is a risk factor for several lung diseases, including chronic obstructive pulmonary disease, cardiovascular and cancer. The potential health effects of use electronic nicotine delivery systems (ENDS) unclear. This study utilized fully differentiated primary normal human bronchial epithelial (NHBE) cultures in repeat-dose exposure to evaluate compare the effect combustible cigarette ENDS preparations. We show that 1-h daily NHBE over 10-day period whole smoke-conditioned...
Acute exposure to cigarette smoke alters gene expression in several biological pathways such as apoptosis, immune response, tumorigenesis and stress among others. However, the effects of electronic nicotine delivery systems (ENDS) on early changes is relatively unknown. The objective this study was evaluate toxicogenomic using a fully-differentiated primary normal human bronchial epithelial (NHBE) culture model after an acute ENDS preparations.
Globally, over 800 000 children under five die each year from infectious diseases caused by Streptococcus pneumoniae. To understand genetic relatedness between isolates, study transmission routes, assess the impact of human interventions e.g. vaccines, and determine infection sources, genotyping methods are required. The 'gold standard' method, Multi-Locus Sequence Typing (MLST), is useful for long-term global studies. Another Variable Number Tandem Repeat Analysis (MLVA), has emerged as a...
ABSTRACT Cystic fibrosis (CF) is caused by mutations in the cystic transmembrane conductance regulator ( CFTR ) gene. Although many people with CF (pwCF) are treated using modulators, some non-responsive due to their genotype or other uncharacterized reasons. Autologous airway stem cell therapies, which cDNA has been replaced, may enable a durable therapy for all pwCF. Previously, CRISPR-Cas9 two AAVs was used sequentially insert halves of and an enrichment cassette into locus. However,...
Abstract SARS-CoV-2 is a worldwide health concern, and new treatment strategies are needed 1 . Targeting inflammatory innate immunity pathways holds therapeutic promise, but effective molecular targets remain elusive. Here, we show that human caspase-4 (CASP4), its mouse homologue, caspase-11 (CASP11), upregulated in infections, CASP4 expression correlates with severity of infection humans. SARS-CoV-2-infected Casp11 -/- mice were protected from severe weight loss lung pathology, including...
The analysis of ribosomal RNA (rRNA) gene patterns (ribotyping) has been used to differentiate strains within bacterial species. We this method investigate two outbreaks campylobacter enteritis that occurred recently in Melbourne, Australia. first outbreak involved seven patients although isolates from only five were available for typing. second consisted three infected with human immunodeficiency virus (HIV) on the same ward a hospital. Analysis rRNA revealed identical outbreak, suggesting...