A5053835635- Heat shock proteins research
- Immune Response and Inflammation
- Asthma and respiratory diseases
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- RNA and protein synthesis mechanisms
- Genomic variations and chromosomal abnormalities
- Genetics and Neurodevelopmental Disorders
- Respiratory viral infections research
- Pneumonia and Respiratory Infections
- Genomics and Chromatin Dynamics
- Transplantation: Methods and Outcomes
- Adenosine and Purinergic Signaling
- Macrophage Migration Inhibitory Factor
- Medical Imaging and Pathology Studies
- RNA modifications and cancer
- Mycobacterium research and diagnosis
- Cancer-related gene regulation
- Pharmacological Effects and Assays
- Blood Coagulation and Thrombosis Mechanisms
- RNA Research and Splicing
- Neonatal Respiratory Health Research
- Genomics and Rare Diseases
- NF-κB Signaling Pathways
- Eicosanoids and Hypertension Pharmacology
- RNA regulation and disease
Liverpool Hospital
2022-2024
UNSW Sydney
1999-2024
Prince of Wales Hospital
2020-2023
Sydney Children's Hospital
2020-2023
Neuroscience Research Australia
2021-2022
The University of Western Australia
2003-2018
Institute for Respiratory Health
2017-2018
Harry Perkins Institute of Medical Research
2002-2017
Lung Foundation Australia
2014
Royal Perth Hospital
2003-2013
Abstract Around 60% of individuals with neurodevelopmental disorders (NDD) remain undiagnosed after comprehensive genetic testing, primarily protein-coding genes 1 . Large genome-sequenced cohorts are improving our ability to discover new diagnoses in the non-coding genome. Here we identify RNA RNU4-2 as a syndromic NDD gene. encodes U4 small nuclear (snRNA), which is critical component U4/U6.U5 tri-snRNP complex major spliceosome 2 We an 18 base pair region mapping two structural elements...
Abstract Around 60% of individuals with neurodevelopmental disorders (NDD) remain undiagnosed after comprehensive genetic testing, primarily protein-coding genes 1 . Increasingly, large genome-sequenced cohorts are improving our ability to discover new diagnoses in the non-coding genome. Here, we identify RNA RNU4-2 as a novel syndromic NDD gene. encodes U4 small nuclear (snRNA), which is critical component U4/U6.U5 tri-snRNP complex major spliceosome 2 We an 18 bp region mapping two...
Abstract —Despite intense investigation, mechanisms linking the development of occlusive vascular disease with elevated levels homocysteine (HCY) are still unclear. The endothelium plays a key role in regulating thrombogenesis and thrombolysis. We hypothesized that lesions individuals plasma HCY may be related to dysfunction triggered by HCY. investigated effect on human neutrophil adhesion migration through endothelial monolayers. also examined leukocyte mesenteric venules anesthetized...
Cyclophilin 40 (CyP40) is a tetratricopeptide repeat (TPR)-containing immunophilin and modulator of steroid receptor function through its binding to heat shock protein 90 (Hsp90). Critical this are the carboxyl-terminal MEEVD motif Hsp90 TPR domain CyP40. Two different models CyP40-MEEVD peptide interaction were used as basis for comprehensive mutational analysis Hsp90-interacting Using CyP40 construct template, 24 amino acids from flanking acidic basic domains individually mutated by...
Recessive Fanconi anemia (FA) phenotype is used in classification of BRCA1/FANCS, BRCA2/FANCD1 and PALB2/FANCN variants with respect to dominant hereditary breast-ovarian cancer syndrome. We assessed its utility by examining the spectrum phenotypes observed individuals biallelic for BRCA1, BRCA2 or PALB2 pathogenic variants, exploring relationship between presentation allele severity score based on variant molecular features. A data collection instrument comprising 158 Human Phenotype...
Summary Heat shock protein 70 (HSP70) plays a major role in immune responses. Polymorphisms within the gene have been associated with development of septic shock. This study refines region HSP70 and confirms its functionality. Subjects ( n = 31) were grouped into one three haplotypes based on their HSPA1B‐179C>T HSPA1B1267A>G genotypes. Mononuclear cells from these subjects stimulated heat‐killed bacteria (10 7 colony‐forming units/mL Escherichia coli or Streptococcus pneumoniae ) for...
Children's interstitial and diffuse lung disease (chILD) is a complex heterogeneous group of disorders. Gene panel approaches have reported diagnostic yield ~ 12%. No data currently exist using trio exome sequencing as the standard modality. We assessed utility in chILD. prospectively enrolled children meeting specified clinical criteria between 2016 2020 from 16 Australian hospitals. Exome was performed with analysis an initial gene followed by analysis. A subset critically ill infants...
Objective 20-hydroxyeicosatetraenoic acid (20-HETE) is a potent constrictor in small arteries and also has natriuretic properties. Urinary 20-HETE excretion increased adrenocorticotrophic hormone (ACTH)-induced hypertensive rats. In the present study, we investigated effect of specific enzyme inhibitor production, N-hydroxy-N′-(4-butyl-2-methylphenyl) formamidine (HET0016), on glucocorticoid-induced hypertension rats, sodium-independent model. Methods Male Sprague–Dawley rats were treated...
Summary Polymorphisms within the gene encoding macrophage migration inhibitory factor (MIF) have been associated with susceptibility to inflammatory diseases such as rheumatoid arthritis and increased risk of developing sepsis. We investigated effects MIF‐173G>C polymorphism MIF‐794 CATT microsatellite on MIF expression. These are in moderate linkage disequilibrium. Mononuclear cells from healthy donors were stimulated bacterial pathogens sepsis ( Streptococcus pneumoniae or Escherichia...
Heat shock protein 70 (HSP70) has been implicated in infection-related processes and found body fluids during infection. This study aimed to determine whether pleural mesothelial cells release HSP70 response bacterial infection vitro mouse models of serosal In addition, the cytokine effects isoform, Hsp72, on were examined. Further, Hsp72 was measured human effusions levels compared between non-infectious infectious patients diagnostic accuracy fluid traditional parameters. We showed that...
Background β2 adrenergic receptor (ADRβ2) polymorphisms including ADRβ2+46G>A have been reported to cause adverse outcomes in mild asthmatics. The extent which ADRβ2 and particular their haplotypes contribute severe asthma is unknown. Objective To determine the association of with severity. Methods Caucasians (n = 2979) were genotyped for 11 polymorphisms. cohort (mean age 39.6, 60% female) included 2296 non-asthmatics, 386 asthmatics, 172 moderate asthmatics 125 Haplotype frequency...
Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive metabolic disorder caused by variants in the DHCR7 gene. In cholesterol biosynthesis, 7-dehydrocholesterol (7-DHC) converted to enzyme 7-DHC reductase, which encoded gene DHCR7. Thus, elevated indicative of SLOS. Characteristically SLOS usually associated with congenital anomalies, dysmorphisms, and moderate severe neurodevelopmental delay. However, there are rare descriptions individuals milder phenotypes. We report a mild case...
We sequenced the lymphotoxin alpha (LTA) promoter and identified LTA10G>A in strong linkage with LTA252G>A LTA723C>A. Stimulated cells from LTA723AA: LTA252GG:LTA10AA individuals had significantly higher LTA mRNA levels than LTA723CC:LTA252AA:LTA10GG LTA723AA:LTA252AG:LTA10GA individuals, suggesting that this diplotype may contain a functional polymorphism explaining observed disease associations LTA252G>A.