A5054846185- Cardiac electrophysiology and arrhythmias
- Ion channel regulation and function
- CRISPR and Genetic Engineering
- Receptor Mechanisms and Signaling
- RNA and protein synthesis mechanisms
- Advanced Memory and Neural Computing
- Neuroscience and Neural Engineering
- Aortic Disease and Treatment Approaches
- Cardiomyopathy and Myosin Studies
- Microtubule and mitosis dynamics
- ECG Monitoring and Analysis
- Connective tissue disorders research
- Diet, Metabolism, and Disease
- Cannabis and Cannabinoid Research
- Cardiac Structural Anomalies and Repair
- Electrostatic Discharge in Electronics
- Mass Spectrometry Techniques and Applications
- Adenosine and Purinergic Signaling
- Pluripotent Stem Cells Research
Cardiovascular Institute of the South
2023-2024
Stanford University
2023-2024
Simon Fraser University
2020-2024
hERG channel dysfunction causes long QT syndrome and arrhythmia. Activator compounds have been of significant interest due to their therapeutic potential. We used the whole organ zebrafish heart model demonstrate antiarrhythmic benefit activator, RPR260243. The activator abbreviated APD increased refractoriness, combined effect which rescued induced ventricular Our findings show that targeted slowing deactivation enhancement protective currents caused by RPR260243 may provide an effective approach.
Human Ether-à-go-go (hERG) channels contribute to cardiac repolarization, and inherited variants or drug block are associated with long QT syndrome type 2 (LQTS2) arrhythmia. Therefore, hERG activator compounds present a therapeutic opportunity for targeted treatment of LQTS. However, limiting concern is over-activation resurgent current during the action potential abbreviated repolarization. Activators that slow deactivation gating (type I), such as RPR260243, may enhance repolarizing...
Abstract Aims Long QT syndrome type 2 (LQTS2) is associated with inherited variants in the cardiac human ether-à-go-go-related gene (hERG) K+ channel. However, pathogenicity of hERG channel often uncertain. Using CRISPR–Cas9 gene-edited hiPSC-derived cardiomyocytes (hiPSC-CMs), we investigated pathogenic mechanism underlying LQTS-associated R56Q variant and its phenotypic rescue by using Type 1 activator, RPR260243. Methods results The above approaches enable characterization unclear...
Marfan syndrome (MFS) is a hereditary condition caused by mutations in the FBN1 gene. Genetic locus impact function of encoded protein, Fibrillin 1, structural molecule forming microfibrils found connective tissue. MFS patients develop severe cardiovascular complications including thoracic aortic aneurysm and dissection, which predispose them to an enhanced risk premature death. Here, we generated two induced pluripotent stem cell (iPSC) lines harboring gene (p.C1942C>A c.1954 T>C), directly...
Mathematical models of voltage-gated ion channels are used in basic research, industrial and clinical settings. These range complexity, but typically contain numerous variables representing the proportion a given state, parameters describing voltage-dependent rates transition between states. An open problem is selecting appropriate degree complexity structure for an channel model data availability. Here, we simplify cardiac human Ether-à-go-go related gene (hERG) potassium channel, which carries
The human ether-à-go-go-related gene (KCNH2)-encoded protein hERG constitutes the α subunit of Kv11.1 channel and contributes to
Abstract Mathematical models of voltage-gated ion channels are used in basic research, industrial and clinical settings. These range complexity, but typically contain numerous variables representing the proportion a given state, parameters describing voltage-dependent rates transition between states. An open problem is selecting appropriate degree complexity structure for an channel model data availability. Here, we simplify cardiac human Ether-à-go-go Related Gene (hERG) potassium channel,...
Clustered regularly interspaced short palindromic repeats (CRISPR) in animal models enable precise genetic manipulation for the study of physiological phenomena. Zebrafish have been used as an effective model to numerous questions related heritable disease, development, and toxicology at whole-organ -organism level. Due well-annotated mapped zebrafish genome, tools gene editing developed. However, efficacy generating ease detecting knock-in edits using CRISPR is a limiting factor. Described...
Clustered regularly interspaced short palindromic repeats (CRISPR) in animal models enable precise genetic manipulation for the study of physiological phenomena. Zebrafish have been used as an effective model to numerous questions related heritable disease, development, and toxicology at whole-organ -organism level. Due well-annotated mapped zebrafish genome, tools gene editing developed. However, efficacy generating ease detecting knock-in edits using CRISPR is a limiting factor. Described...
We generated two induced pluripotent stem cell (iPSC) lines from peripheral blood mononuclear cells (PBMCs) of breast cancer patients carrying germline ATM mutations, a gene associated with 7% prevalence in cancer. These iPSC displayed typical morphology, expressed pluripotency markers, maintained stable karyotype, and retained the ability to differentiate into three germ layers. patient-specific hold great potential for mechanistic investigations development drug screening strategies aimed...