A5068933715- Cardiac electrophysiology and arrhythmias
- Ion channel regulation and function
- Cardiomyopathy and Myosin Studies
- Retinal Development and Disorders
- Neuroscience and Neural Engineering
- Cardiovascular Effects of Exercise
- Advanced biosensing and bioanalysis techniques
- Computational Drug Discovery Methods
- Advanced Drug Delivery Systems
- Viral Infections and Immunology Research
- RNA and protein synthesis mechanisms
- PARP inhibition in cancer therapy
- Pharmacological Receptor Mechanisms and Effects
- Receptor Mechanisms and Signaling
- Congenital heart defects research
- RNA Interference and Gene Delivery
- Virus-based gene therapy research
- Polymer Surface Interaction Studies
UNSW Sydney
2021-2024
Victor Chang Cardiac Research Institute
2018-2024
St Vincent's Clinic
2021-2022
Western Sydney University
2012-2016
Current treatment for congenital long QT syndrome Type 2 (cLQTS2), an electrical disorder that increases the risk of life-threatening cardiac arrhythmias, is aimed at reducing incidence arrhythmia triggers (beta-blockers) or terminating after onset (implantable cardioverter-defibrillator). An alternative strategy to target underlying disease mechanism, which reduced rapid delayed rectifier current (IKr) passed by Kv11.1 channels. Small molecule activators have been identified but extent...
Hydroxychloroquine, chloroquine and azithromycin are three drugs that were proposed to treat coronavirus disease 2019 (COVID-19). While concern already existed around their proarrhythmic potential, there little data regarding how altered physiological states encountered in patients such as febrile state, electrolyte imbalances or acidosis might change risk profiles.Potency of human ether-à-go-go related gene (hERG) block was measured using high-throughput electrophysiology the presence...
Abstract Familial hypertrophic cardiomyopathy (FHC) patients are advised to avoid strenuous exercise due increased risk of arrhythmias. Mice expressing the human FHC-causing mutation R403Q in myosin heavy chain gene ( MYH6 ) recapitulate phenotype, including cytoskeletal disarray and arrhythmia susceptibility. Following vivo administration isoproterenol, mutant mice exhibited tachyarrhythmias, poor recovery fatigue. Arrhythmias were attenuated with β-blocker atenolol protein kinase A...
Drug-induced or acquired long QT syndrome occurs as a result of the unintended disruption cardiac repolarization due to drugs that block ion channels. These side effects have been responsible for withdrawal range from market and are common reason termination development new in preclinical stage. Existing approaches risk prediction expensive overly sensitive meaning recently there renewed efforts, largely driven by comprehensive proarrhythmic assay initiative, develop more accurate methods...
Hypertrophic cardiomyopathy (HCM) is an inherited characterized by left ventricular hypertrophy ≥15 mm in the absence of loading conditions. HCM has a prevalence up to one 200, and can result significant adverse outcomes including heart failure sudden cardiac death. An induced pluripotent stem cell (iPSC) line was generated from peripheral blood mononuclear cells obtained whole 38-year-old female patient with which genetic testing identified well-known pathogenic p.Arg403Gln mutation myosin...
ABSTRACT Hypertrophic cardiomyopathy (HCM) is an inherited heart muscle disease that characterised by left ventricular wall thickening, cardiomyocyte disarray and fibrosis, associated with arrhythmias, failure sudden death. However, it unclear to what extent the electrophysiological disturbances lead death occur secondary structural changes in myocardium or as a result of HCM electrophysiology. In this study, we used induced pluripotent stem cell model R403Q variant myosin heavy chain 7...
Background and Purpose: Hydroxychloroquine chloroquine, alone or in combination with azithromycin, have been proposed as therapies for COVID-19. However, there is currently scant inconsistent data regarding their proarrhythmic potential these patients. Moreover, risk profile the setting of altered physiological states encountered patients COVID-19 (i.e. febrile state, electrolyte imbalances, and/or acidosis) unknown. Experimental approach: Potency hERG block was measured using...
Abstract Cardiac electrical activity is controlled by the carefully orchestrated of more than a dozen different ion conductances. Yet, there considerable variability in cardiac channel expression levels both within and between subjects. In this study we tested hypothesis that variations individuals are not random but rather modules co-expressed genes these make signaling heart robust. Meta-analysis 3653 public RNA-Seq datasets identified strong correlation CACNA1C (L-type calcium current, I...
Abstract Hypertrophic cardiomyopathy (HCM) is an inherited heart muscle disease; characterised by left ventricular wall thickening, cardiomyocyte disarray, and fibrosis, associated with arrhythmias, failure sudden death. However, it unclear to what extent the electrophysiological disturbances that lead death occur secondary structural changes in myocardium, or as a result of intrinsic properties HCM cardiomyocyte. In this study, we used induced pluripotent stem cell model Arg403Gln variant...