A5009157699- Asthma and respiratory diseases
- Pediatric health and respiratory diseases
- Neonatal Respiratory Health Research
- Iron Metabolism and Disorders
- Allergic Rhinitis and Sensitization
- IL-33, ST2, and ILC Pathways
- Eosinophilic Esophagitis
- Bacterial Infections and Vaccines
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Legionella and Acanthamoeba research
- MicroRNA in disease regulation
- Respiratory and Cough-Related Research
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Antibiotic Resistance in Bacteria
- Histone Deacetylase Inhibitors Research
- Respiratory Support and Mechanisms
- Redox biology and oxidative stress
- Peptidase Inhibition and Analysis
- Extracellular vesicles in disease
- S100 Proteins and Annexins
- Respiratory viral infections research
- Inhalation and Respiratory Drug Delivery
- Pneumonia and Respiratory Infections
- Cystic Fibrosis Research Advances
- Urticaria and Related Conditions
QIMR Berghofer Medical Research Institute
2020-2024
Hunter Medical Research Institute
2011-2021
University of Newcastle Australia
2007-2017
Severe, steroid-resistant asthma is the major unmet need in therapy. Disease heterogeneity and poor understanding of pathogenic mechanisms hampers identification therapeutic targets. Excessive nucleotide-binding oligomerization domain-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome concomitant IL-1β responses occur chronic obstructive pulmonary disease, respiratory infections, neutrophilic asthma. However, direct contributions to pathogenesis, involved, potential for...
A subset of patients with stable asthma has prominent neutrophilic and reduced eosinophilic inflammation, which is associated attenuated airways hyper-responsiveness (AHR). Haemophilus influenzae been isolated from the asthmatics; however, nature association between infection development not understood. Our aim was to investigate effects H. respiratory on hallmark features in a mouse model allergic disease (AAD). BALB/c mice were intraperitoneally sensitized ovalbumin (OVA) intranasally...
<h3>Background</h3> 20–30% of patients with asthma have neutrophilic airway inflammation and reduced responsiveness to steroid therapy. They often chronic bacterial colonisation <i>Haemophilus influenzae</i> is one the most commonly isolated bacteria. The relationship between development steroid-resistant unclear. <h3>Objectives</h3> To investigate <i>H respiratory infection using mouse models ovalbumin (OVA)-induced allergic airways disease. <h3>Methods</h3> BALB/c mice were intratracheally...
<h3>Background</h3> Steroid-insensitive endotypes of asthma are an important clinical problem and effective therapies required. They associated with bacterial infection non-eosinophilic inflammatory responses in the asthmatic lung. Macrolide therapy is steroid-insensitive endotypes, such as asthma. However, whether effects macrolides due to antimicrobial or anti-inflammatory mechanisms not known. <h3>Objective</h3> To determine assess efficacy macrolide (ie, clarithromycin) non-macrolide...
Nontypeable Haemophilus influenzae (NTHi) is a prevalent bacterium found in variety of chronic respiratory diseases. The role this the pathogenesis lung inflammation not well defined. In study we examined effect NTHi on two important inflammatory processes 1), oxidative stress and 2), protease expression. Bronchoalveolar macrophages were obtained from 121 human subjects, blood neutrophils 15 human-lung fibroblast epithelial cell lines 16 subjects. Cells stimulated with to measure reactive...
Pathogenic bacterial infections of the lung are life threatening and underpin chronic diseases. Current treatments often ineffective potentially due to increasing antibiotic resistance impairment innate immunity by disease processes steroid therapy. Manipulation miRNA directly regulating anti-microbial machinery immune system may boost host defence responses. Here we demonstrate that miR-328 is a key element response pulmonary infection with non-typeable haemophilus influenzae...
Abstract Background and objective Chronic obstructive pulmonary disease ( COPD ) is characterized by progressive airflow limitation inflammation. Airway bacterial colonization increased in ; however, the role of potentially pathogenic non‐pathogenic bacteria pathogenesis unclear. This study presence a well‐characterized cohort adults with healthy controls. Methods Adults n = 70) controls 51) underwent clinical assessment sputum induction. Sputum was dispersed, total differential cell counts...
Rationale and Objectives: Iron availability metabolism are important in the pathogenesis of bacterial infections. More recently, links have been reported between iron severity viral In this study, we characterize a crucial relationship IAV infection disease. Methods: Iron-related gene expression was assessed human airway epithelial cells (AEC) infected with IAV. AECs were cultured ferric iron, iron-loaded transferrin, or chelator, deferoxamine (DFO), prior to Mice placed on high diet for 8...
Background and Purpose Chronic obstructive pulmonary disease (COPD) is a major cause of illness death, often induced by cigarette smoking (CS). It characterized inflammation fibrosis that impairs lung function. Existing treatments aim to control symptoms but have low efficacy, there are no broadly effective treatments. A new potential target the ectoenzyme, semicarbazide‐sensitive mono‐amine oxidase (SSAO; also known as vascular adhesion protein‐1). SSAO elevated in smokers' serum...
Abstract Background and objective Chronic obstructive pulmonary disease (COPD) is the third leading cause of illness death worldwide. Current treatments aim to control symptoms with none able reverse or stop its progression. We explored major molecular changes in COPD pathogenesis. Methods employed quantitative label‐based proteomics map lung tissue proteome cigarette smoke‐induced experimental that induced over 8 weeks progresses 12 weeks. Results Quantification 7324 proteins enabled...
Background Emerging evidence suggests that non-olfactory tissues and cells can express olfactory receptors (ORs), however, the exact function of ectopic OR expression remains unknown. We have previously shown in mouse models a unique cooperation between interferon-γ (IFN-γ) lipopolysaccharide (LPS) drives activation pulmonary macrophages leads to induction pathogenic responses respiratory tract. Further, through gene array studies, we by these molecules results selective number ORs. In this...
H. influenzae is a host adapted human mucosal pathogen involved in variety of acute and chronic respiratory tract infections, including Chronic Obstructive Pulmonary Disease (COPD) asthma, all which rely on ability to efficiently establish continuing interactions with the host. Here we report characterization novel molybdenum enzyme, TorZ/MtsZ that supports cells during growth oxygen-limited environments. Strains lacking showed reduced survive contact epithelial as shown by...
Background Viral and bacterial respiratory tract infections in early-life are linked to the development of allergic airway inflammation asthma. However, mechanisms involved not well understood. We have previously shown that neonatal infant, but adult, chlamydial lung mice permanently alter inflammatory phenotype physiology increase severity disease by increasing interleukin (IL)-13 expression, mucus hyper-secretion hyper-responsiveness. This occurred through different with infection at ages....
Defective chloride transport in airway epithelial cells (AECs) and the associated lung disease are main causes of morbidity early mortality cystic fibrosis (CF). Abnormal iron homeostasis presence lipid peroxidation products, indicative oxidative stress, features CF disease.Here, we report that AECs (IB3-1) susceptible to ferroptosis, a type cell death with accumulation peroxidation. Compared isogenic CFTR corrected (C38), IB3-1 showed increased susceptibility upon exposure form ferric...
Section:ChooseTop of pageAbstract <<Materials and MethodsResultsDiscussionReferencesCITING ARTICLES
Haemophilus influenzae (Hi) infections are associated with recurring acute exacerbations of chronic respiratory diseases in children and adults including otitis media, pneumonia, obstructive pulmonary disease asthma. Here, we show that persistence recurrence Hi closely linked to metabolic properties, where preferred growth substrates aligned the metabolome human airway epithelial surfaces include lactate, pentoses, nucleosides, but not glucose is typically used for studies vitro . Enzymatic...
Abstract Background and Objective Neutrophil elastase (NE), is an important host defence against lung pathogens. Maintaining a homeostatic balance between proteases such as NE anti‐proteases secretory leukocyte protease inhibitor (SLPI), to prevent tissue damage. In the cystic fibrosis (CF) lung, elevated levels impaired anti‐protease defences contribute destruction. Methods We assessed function sputum SLPI from Pseudomonas aeruginosa infected non‐infected CF patients (median age 20 years at...
Peptide methionine sulfoxide reductases (Msrs) are enzymes that repair ROS-damage to sulfur-containing amino acids such as methionine, ensuring functional integrity of cellular proteins. Here we have shown unlike the majority pro- and eukaryotic Msrs, peptide reductase (MsrAB) from human pathobiont Haemophilus influenzae (Hi) is required for hypochlorite damage cell envelope proteins, but more importantly, were able demonstrate MsrAB plays a role in modulating host immune response Hi...