A5061703216- Neonatal Respiratory Health Research
- Cystic Fibrosis Research Advances
- Asthma and respiratory diseases
- Respiratory viral infections research
- Tracheal and airway disorders
- CRISPR and Genetic Engineering
- Barrier Structure and Function Studies
- Cholesterol and Lipid Metabolism
- RNA Interference and Gene Delivery
- Inhalation and Respiratory Drug Delivery
- Genomics and Rare Diseases
- Respiratory and Cough-Related Research
- Pediatric health and respiratory diseases
- Hedgehog Signaling Pathway Studies
- IL-33, ST2, and ILC Pathways
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Genetics and Neurodevelopmental Disorders
- Drug Transport and Resistance Mechanisms
- Veterinary Medicine and Surgery
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Neurogenetic and Muscular Disorders Research
- thermodynamics and calorimetric analyses
- Genomic variations and chromosomal abnormalities
- Developmental Biology and Gene Regulation
- Neonatal and Maternal Infections
The University of Western Australia
2014-2024
The Kids Research Institute Australia
2014-2023
Princess Margaret Hospital for Children
2022-2023
Perth Children's Hospital
2022-2023
Hurley Medical Center
2022
Treatment Action Group
2020-2021
Pediatrics and Genetics
2020
University of British Columbia
2020
Centre for Global Health Research
2015
Abstract Modulation of airway surface liquid (ASL) pH has been proposed as a therapy for cystic fibrosis (CF). However, evidence that ASL is reduced in CF limited and conflicting. The technical challenges associated with measuring vivo have precluded accurate measurements humans. In order to address this deficiency, was measured children using novel luminescent technology integrated fibre-optic probes. Here we show similar without CF. Findings were supported by highly controlled direct...
Neutrophil elastase is the most significant predictor of bronchiectasis in early-life cystic fibrosis; however, causal link between neutrophil and airway damage not well understood. Matrix metalloproteinases (MMPs) play a crucial role extracellular matrix modelling are activated by elastase. The aim this study was to assess if MMP activation positively correlates with activity, disease severity young children fibrosis.Total MMP-1, MMP-2, MMP-7, MMP-9, tissue inhibitor metalloproteinase...
Current limitations to primary cell expansion led us test whether airway epithelial cells derived from healthy children and those with asthma cystic fibrosis (CF), co-cultured an irradiated fibroblast feeder in F-medium containing 10 µM ROCK inhibitor could maintain their lineage during this is influenced by underlying disease status. Here, we show that conditionally reprogrammed (CRAECs) can be established both diseased phenotypes. CRAECs expanded, cryopreserved phenotypes over at least 5...
Bronchial epithelial tight junctions (TJ) have been extensively assessed in healthy airway epithelium. However, no studies yet the effect of human rhinovirus (HRV) infection on expression and resultant barrier function childhood asthma.To investigate impact HRV TJ cells (AECs) children with without asthma. Furthermore, to test hypothesis that integrity is compromised a greater extent by AECs from asthmatic children.Primary were obtained asthma, differentiated into air-liquid interface (ALI)...
Summary Background The airway epithelium forms an effective immune and physical barrier that is essential for protecting the lung from potentially harmful inhaled stimuli including viruses. Human rhinovirus ( HRV ) infection a known trigger of asthma exacerbations, although mechanism by which this occurs not fully understood. Objective To explore relationship between apoptotic, innate inflammatory responses to in epithelial cells AEC s) obtained children with non‐asthmatic controls. In...
Vitamin D deficiency is associated with disease severity in asthma. We tested whether there a causal association between vitamin deficiency, airway smooth muscle (ASM) mass, and the development of hyperresponsiveness (AHR). A physiologically relevant mouse model was developed by raising BALB/c mice on D-deficient or -replete diets. AHR assessed measuring lung function responses to increasing doses inhaled methacholine. Five-micron sections from formalin-fixed lungs were used for ASM...
Apically located tight junctions in airway epithelium perform a fundamental role controlling macromolecule migration through paracellular spaces. Alterations their expression may lead to disruptions barrier integrity, which subsequently facilitates entry of potential bacterial and other pathogens into the host. Furthermore, there is emerging evidence that integrity certain inflammatory diseases be altered. However, little consensus on way this assessed measured type cells used achieve...
No studies have assessed the effects of human rhinovirus (HRV) infection on epithelial tight junctions (TJs) and resultant barrier function.To correlate viral with TJ disassembly, integrity, function.Human airway cells were infected HRV minor serotype 1B (HRV-1B) at various 50% tissue culture infectivity doses (TCID50) over 72 hours. replication was by quantitative-polymerase chain reaction (qPCR) while cell viability apoptosis proliferation apoptotic assays, respectively. Protein expression...
Induced sputum sampling holds promise as a method for obtaining samples representative of the lower airways in young children. Collection induced children differs from older and adults' pharyngeal suctioning is often required. Our aim was to determine sensitivity specificity with without airway clearance techniques detect pathogens less than age 7 cystic fibrosis.Microbiological culture results were compared between 61 paired bronchoalveolar lavage fluid fibrosis. The first cohort received...
Abnormal wound repair has been observed in the airway epithelium of patients with chronic respiratory diseases, including asthma. Therapies focusing on repairing vulnerable airways, particularly early life, present a potentially novel treatment strategy. We report defective lower epithelial cell to strongly associate common pre–school-aged and school-aged wheezing phenotypes, characterized by aberrant migration patterns reduced integrin α5β1 expression. Next generation sequencing identified...
Abstract Background Over 400 million people worldwide are living with a rare disease. Next Generation Sequencing (NGS) identifies potential disease causative genetic variants. However, many identified as variants of uncertain significance (VUS) and require functional laboratory validation to determine pathogenicity, this creates major diagnostic delays . Methods In study we test rapid variant assessment pipeline using CRISPR homology directed repair introduce single nucleotide into inducible...
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There are an estimated > 400 million people living with a rare disease globally, genetic variants the cause of approximately 80% cases. Next Generation Sequencing (NGS) rapidly identifies however they often unknown significance. Low throughput functional validation in specialist laboratories is current ad hoc approach for variants, which creating major bottlenecks patient diagnosis. This study investigates application CRISPR gene editing followed by genome wide transcriptomic profiling to...
Abstract Background Primary hyperaldosteronism caused by adrenal neoplasia has been well described in cats. Multiple corticosteroid abnormalities occur a subset of affected cats, but characterizations this syndrome are limited to several case reports. Objectives To describe series cats with tumors secreting aldosterone and additional corticosteroids. Animals Ten multiple adrenocortical tumors. Methods Retrospective series. Medical records both progesterone were identified. Data concerning...
In cats, nonthyroidal illness affects serum thyroid hormone concentrations. Serum thyroxine (T4 ) and triiodothyronine (T3 concentrations commonly decrease, whereas free T4 (fT4 vary unpredictably. Limited information exists regarding effects on thyrotropin (thyroid-stimulating [TSH]) in cats with syndrome (NTIS).To characterize alterations function that develop NTIS to correlate these severity outcome of the illness.Two hundred twenty-two 380 clinically normal similar age sex.Prospective,...
The airway epithelium of children with wheeze is characterized by defective repair that contributes to disease pathobiology. Dysregulation developmental processes controlled Notch has been identified in chronic asthma. However, its role epithelial cells young wheeze, particularly during repair, yet be determined. We hypothesized dysregulated primary (pAEC) contributing repair. This study investigated transcriptional and protein expression function pAEC isolated from without wheeze. Primary...
Abstract Background Genomic sequencing in congenital heart disease (CHD) patients often discovers novel genetic variants, which are classified as variants of uncertain significance (VUS). Functional analysis each VUS is required specialised laboratories, to determine whether the causative or not, leading lengthy diagnostic delays. We investigated stem cell cardiac modelling and transcriptomics for purpose variant classification using a GATA4 (p.Arg283Cys) patient with CHD. Methods performed...
Dysregulated airway epithelial repair following injury is a proposed mechanism driving posttransplant bronchiolitis obliterans (BO), and its clinical correlate syndrome (BOS). This study compared gene cellular characteristics of in large (LAEC) small (SAEC) cells transplant patients.Subjects were recruited at the time routine bronchoscopy posttransplantation included patients with without BOS. Airway obtained from bronchial bronchiolar brushing performed under radiological guidance these...
Abstract An estimated 3.5–5.9% of the global population live with rare diseases, and approximately 80% these diseases have a genetic cause. Rare can be difficult to diagnose, patients experiencing diagnostic delays 5–30 years. Next generation sequencing has improved clinical rates 33–48% however novel potentially disease causative variant is often identified. These variants require validation pathogenicity in specialist laboratories, resulting delay that on average lasts five In interim,...