A5065602013- Neonatal Respiratory Health Research
- Asthma and respiratory diseases
- Respiratory viral infections research
- Tissue Engineering and Regenerative Medicine
- Pediatric health and respiratory diseases
- IL-33, ST2, and ILC Pathways
- Chronic Obstructive Pulmonary Disease (COPD) Research
- COVID-19 Clinical Research Studies
- Energy Harvesting in Wireless Networks
- Immune Cell Function and Interaction
- SARS-CoV-2 and COVID-19 Research
- Venomous Animal Envenomation and Studies
- Marine Invertebrate Physiology and Ecology
- Protist diversity and phylogeny
- Plant and animal studies
- Cancer Cells and Metastasis
- Immune Response and Inflammation
- Inhalation and Respiratory Drug Delivery
- Rabies epidemiology and control
- Endoplasmic Reticulum Stress and Disease
- Viral gastroenteritis research and epidemiology
- Multisensory perception and integration
- Vitamin D Research Studies
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Tracheal and airway disorders
Hunter Medical Research Institute
2017-2023
University of Newcastle Australia
2017-2023
Monash University
2020
Inhaled corticosteroids (ICS) have limited efficacy in reducing chronic obstructive pulmonary disease (COPD) exacerbations and increase pneumonia risk, through unknown mechanisms. Rhinoviruses precipitate most susceptibility to secondary bacterial infections. Here, we show that the ICS fluticasone propionate (FP) impairs innate acquired antiviral immune responses leading delayed virus clearance previously unrecognised adverse effects of enhanced mucus, impaired antimicrobial peptide...
Respiratory viral infections, particularly those caused by rhinovirus, exacerbate chronic respiratory inflammatory diseases such as asthma and obstructive pulmonary disease (COPD). Airway epithelial cells are the primary site of rhinovirus replication responsible initiating host immune response to infection. Numerous studies have reported that anti-viral innate (including type I III interferon) in is less effective or deficient leading conclusion immunity a key determinant severity during...
COVID-19 is complicated by acute lung injury, and death in some individuals. It caused SARS-CoV-2 that requires the ACE2 receptor serine proteases to enter AEC. We determined what factors are associated with expression particularly patients asthma COPD.
Patients with frequent exacerbations represent a chronic obstructive pulmonary disease (COPD) subgroup requiring better treatment options. The aim of this study was to determine the innate immune mechanisms that underlie susceptibility in COPD. We measured sputum expression mediators and bacterial loads samples from patients COPD at stable state during virus-associated exacerbations. In vitro responses rhinovirus infection differentiated primary bronchial epithelial cells (BECs) sampled were...
BackgroundMicrobiota are recognized to play a major role in regulation of immunity through release immunomodulatory metabolites such as short-chain fatty acids (SCFAs). Rhinoviruses (RVs) induce upper respiratory tract illnesses and precipitate exacerbations asthma chronic obstructive pulmonary disease poorly understood mechanisms. Local interactions between SCFAs antiviral immune responses the have not been previously investigated.ObjectiveWe sought investigate whether metabolite...
In asthma, goblet cell numbers are increased within the airway epithelium, perpetuating production of mucus that is more difficult to clear and results in plugging. Notch1, Notch2, or Notch3, a combination these has been shown influence differentiation epithelial cells. How expression specific Notch isoforms differs fully differentiated adult asthmatic epithelium whether influences mucin after currently unknown. We aimed quantify different individuals with severe asthma examine impact...
Abstract Primary air liquid interface (ALI) cultures of bronchial epithelial cells are used extensively to model airway responses. A recent advance is the development conditional reprogramming that enhances proliferative capability. Several different media and protocols utilized, yet even subtle differences may influence cellular We compared morphology functional responses, including innate immune responses rhinovirus infection in conditionally reprogrammed primary (pBECs) differentiated...
Summary SARS-CoV-2 infection causes an inflammatory cytokine storm and acute lung injury. Currently there are no effective antiviral and/or anti-inflammatory therapies. Here we demonstrate that 2019 spike protein subunit 1 (CoV2-S1) induces high levels of NF-κB activations, production pro-inflammatory cytokines mild epithelial damage, in human bronchial cells. CoV2-S1-induced activation requires S1 interaction with ACE2 receptor early endoplasmic reticulum (ER) stress, associated unfolded...
Abstract IL-25 is implicated in the pathogenesis of viral asthma exacerbations. However, effect on antiviral immunity has yet to be elucidated. We observed abundant expression and colocalization receptor at apical surface uninfected airway epithelial cells rhinovirus infection increased expression. Analysis immune transcriptome rhinovirus-infected differentiated asthmatic bronchial (BECs) treated with an anti-IL-25 monoclonal antibody (LNR125) revealed a re-calibrated response defined by...
Background We assessed whether Toll-like receptor (TLR)2 activation boosts the innate immune response to rhinovirus infection, as a treatment strategy for virus-induced respiratory diseases. Methods employed with novel TLR2 agonist (INNA-X) prior infection in mice, and INNA-X differentiated human bronchial epithelial cells derived from asthmatic-donors. viral load, cell recruitment, cytokines, type I III interferon (IFN) production, well lung tissue transcriptome. Results show, vivo , that...
Intra-specific venom variation has the potential to provide important insights into evolution of snake venom, but remains a relatively neglected aspect studies. We investigated from 13 individual coastal taipans Oxyuranus scutellatus four localities on north-east coast Australia, spanning distance 2000 km. The intra-specific in taipan was considerably less than inter-specific between it and other Australian elapids which compared. electrophoretic profile O. visually different six genera...
Early diagnosis of snake envenomation is essential, especially neurotoxicity and myotoxicity. We investigated the diagnostic value serum phospholipase (PLA2) in Australian snakebites. In total, 115 envenomated 80 non-envenomated patients were recruited over 2 years, which an early blood sample was available pre-antivenom. Serum samples analyzed for secretory PLA2 activity using a Cayman sPLA2 assay kit (#765001 Chemical Company, Ann Arbor MI, USA). Venom concentrations measured...
Bronchoconstriction is the main physiological event in asthma, which leads to worsened clinical symptoms and generates mechanical stress within airways. Virus infection primary cause of exacerbations people with however, impact that bronchoconstriction itself on host antiviral responses viral replication currently not well understood. Here we demonstrate how forces generated during may suppress at airway epithelium without any difference replication. Primary bronchial epithelial cells from...
Primary bronchial epithelial cells (pBECs) obtained from donors have limited proliferation capacity. Recently, conditional reprogramming (CR) technique has overcome this and provided the potential for extended passaging subsequent differentiation of at air-liquid interface (ALI). However, there been no donor-specific comparison cell morphology, baseline gene expression, barrier function, antiviral responses compared with their “parent” pBECs, especially asthma. We, therefore, collected...
Abstract Rationale COVID-19 is complicated by acute lung injury, and death in some individuals. It caused SARS-CoV-2 that requires the ACE2 receptor serine proteases to enter airway epithelial cells (AECs). Objective To determine what factors are associated with expression particularly patients asthma chronic obstructive pulmonary disease (COPD). Methods We obtained upper lower AECs from 145 people two independent cohorts, aged 2-89, Newcastle (n=115), Perth (n= 30) Australia. The cohort was...
ABSTRACT Background Patients with frequent exacerbations represent a chronic obstructive pulmonary disease (COPD) sub-group requiring better treatment options. The aim of this study was to determine the innate immune mechanisms that underlie susceptibility in COPD. Methods We measured sputum expression mediators and bacterial loads samples from patients COPD at stable state during virus-associated exacerbations. Ex vivo responses rhinovirus infection differentiated bronchial epithelial cells...
<b>Rationale:</b> Bronchoconstriction (BC) is a hallmark of asthma and generates airway mechanical stress. During exacerbations, BC occurs simultaneously with viral infection; the influence on antiviral responses has not been investigated. We hypothesised that stresses generated during suppress epithelial innate immune following rhinovirus (RV) infection. <b>Methods:</b> Airway cells were obtained from asthmatic donors. Cells cultured differentiated at air-liquid interface then apically...
Abstract Introduction Primary air liquid interface (ALI) cultures of bronchial epithelial cells are used extensively to model airway responses. A recent advance is the development conditional reprogramming that enhances proliferative capability. Several different media and protocols utilized, yet even subtle differences may influence cellular We compared morphology functional responses, including innate immune responses rhinovirus infection in conditionally reprogrammed primary (pBECs)...