A5048118890- Cardiac electrophysiology and arrhythmias
- Ion channel regulation and function
- Cardiomyopathy and Myosin Studies
- Erythrocyte Function and Pathophysiology
- Cardiac Arrhythmias and Treatments
- Cardiovascular Effects of Exercise
- Atrial Fibrillation Management and Outcomes
- Receptor Mechanisms and Signaling
- Pancreatic function and diabetes
- Cardiovascular Function and Risk Factors
- Neuroscience and Neuropharmacology Research
- MicroRNA in disease regulation
- Cardiac Fibrosis and Remodeling
- Cardiac pacing and defibrillation studies
- Ion Transport and Channel Regulation
- Mitochondrial Function and Pathology
- Neuroscience and Neural Engineering
- Circular RNAs in diseases
- Cellular transport and secretion
- Cardiac Ischemia and Reperfusion
- SARS-CoV-2 and COVID-19 Research
- Signaling Pathways in Disease
- Cardiac Imaging and Diagnostics
- Nitric Oxide and Endothelin Effects
- Connexins and lens biology
The Ohio State University
2015-2024
The Ohio State University Wexner Medical Center
2015-2024
Penn State Milton S. Hershey Medical Center
2024
Lung Institute
2011-2021
Bühler (United Kingdom)
2011-2018
Hong Kong University of Science and Technology
1996-2017
University of Hong Kong
1996-2017
Columbia University
2007-2017
University of Victoria
2017
Western University
2017
AimsThe complex architecture of the human atria may create physical substrates for sustained re-entry to drive atrial fibrillation (AF). The existence sustained, anatomically defined AF drivers in humans has been challenged partly due lack simultaneous endocardial–epicardial (Endo–Epi) mapping coupled with high-resolution 3D structural imaging.
We identify a human mutation (E1053K) in the ankyrin-binding motif of Na v 1.5 that is associated with Brugada syndrome, fatal cardiac arrhythmia caused by altered function 1.5. The E1053K abolishes binding to ankyrin-G, and also prevents accumulation at cell surface sites ventricular cardiomyocytes. Ankyrin-G are both localized intercalated disc T-tubule membranes cardiomyocytes, coimmunoprecipitates 190-kDa ankyrin-G from detergent-soluble lysates rat heart. These data suggest associates...
Recent reports of SARS-CoV-2 Omicron variant sub-lineages, BA.1, BA.1.1, and BA.2, have reignited concern over potential escape from vaccine- infection-induced immunity. We examine the sensitivity these sub-lineages other major variants to neutralizing antibodies mRNA-vaccinated boosted individuals, as well recovered COVID-19 patients, including those infected with Omicron. find that all especially BA.1 exhibit substantial immune is largely overcome by mRNA vaccine booster doses. While...
220-kDa ankyrin-B is required for coordinated assembly of Na/Ca exchanger, Na/K ATPase, and inositol trisphosphate (Ins P 3 ) receptor at transverse-tubule/sarcoplasmic reticulum sites in cardiomyocytes. A loss-of-function mutation identified an extended kindred causes a dominantly inherited cardiac arrhythmia, initially described as type 4 long QT syndrome. Here we report the identification eight unrelated probands harboring mutations, including four previously undescribed whose clinical...
The National Heart, Lung, and Blood Institute Office of Rare Diseases at the Institutes Health organized a workshop (September 14 to 15, 2006, in Bethesda, Md) advise on new research directions needed for improved identification treatment rare inherited arrhythmias. These included following: (1) Na+ channelopathies; (2) arrhythmias due K+ channel mutations; (3) other arrhythmogenic mechanisms. Another major goal was provide recommendations support, enable, or facilitate improve future...
We report identification of an ankyrin-B-based macromolecular complex Na/K ATPase (alpha 1 and alpha 2 isoforms), Na/Ca exchanger 1, InsP3 receptor that is localized in cardiomyocyte T-tubules discrete microdomains distinct from classic dihydropyridine receptor/ryanodine “dyads.” E1425G mutation ankyrin-B, which causes human cardiac arrhythmia, also blocks binding ankyrin-B to all three components the complex. The markedly reduced adult ankyrin-B+/− cardiomyocytes, may explain elevated...
Ion channel function is fundamental to the existence of life. In metazoans, coordinate activities voltage-gated Na(+) channels underlie cellular excitability and control neuronal communication, cardiac excitation-contraction coupling, skeletal muscle function. However, despite decades research linkage dysfunction with arrhythmia, epilepsy, myotonia, little progress has been made toward understanding processes that regulate this family proteins. Here, we have identified β(IV)-spectrin as a...
AimsThe shRNA-mediated loss of expression the desmosomal protein plakophilin-2 leads to sodium current (INa) dysfunction. Whether pkp2 gene haploinsufficiency INa deficit in vivo remains undefined. Mutations are detected arrhythmogenic right ventricular cardiomyopathy (ARVC). Ventricular fibrillation and sudden death often occur 'concealed phase' disease, prior overt structural damage. The mechanisms responsible for these arrhythmias remain poorly understood. We sought characterize...
Sinus node dysfunction (SND) is a major public health problem that associated with sudden cardiac death and requires surgical implantation of artificial pacemakers. However, little known about the molecular cellular mechanisms cause SND. Most SND occurs in setting heart failure hypertension, conditions are marked by elevated circulating angiotensin II (Ang II) increased oxidant stress. Here, we show oxidized calmodulin kinase (ox-CaMKII) biomarker for patients dogs disease determinant mice....
During the classic "fight-or-flight" stress response, sympathetic nervous system activation leads to catecholamine release, which increases heart rate and contractility, resulting in enhanced cardiac output. Catecholamines bind β-adrenergic receptors, causing cAMP generation of PKA, phosphorylates multiple targets muscle, including ryanodine receptor/calcium release channel (RyR2) required for muscle contraction. PKA phosphorylation RyR2 enhances activity by sensitizing cytosolic calcium...
The identification of nearly a dozen ion channel genes involved in the genesis human atrial and ventricular arrhythmias has been critical for diagnosis treatment fatal cardiovascular diseases. In contrast, very little is known about genetic molecular mechanisms underlying sinus node dysfunction (SND). Here, we report mechanism SND. We mapped two families with highly penetrant severe SND to ANK2 (ankyrin-B/AnkB) locus. Mice heterozygous AnkB phenocopy displayed bradycardia rate variability....
Voltage-gated Nav channels are required for normal electrical activity in neurons, skeletal muscle, and cardiomyocytes. In the heart, Nav1.5 is predominant channel, Nav1.5-dependent regulates rapid upstroke of cardiac action potential. requires precise localization at specialized cardiomyocyte membrane domains. However, molecular mechanisms underlying channel trafficking heart unknown. this paper, we demonstrate that ankyrin-G targeting heart. Cardiomyocytes with reduced display expression,...
Background— Mutations in the ankyrin-B gene ( ANK2 ) cause type 4 long-QT syndrome and have been described kindreds with other arrhythmias. The frequency of variants large populations molecular mechanisms underlying variability clinical phenotypes are not established. More importantly, there is no cellular explanation for range severity cardiac associated specific variants. Methods Results— We performed a comprehensive screen (control, congenital arrhythmia, drug-induced syndrome) different...
The best understood "fight or flight" mechanism for increasing heart rate (HR) involves activation of a cyclic nucleotide-gated ion channel (HCN4) by beta-adrenergic receptor (betaAR) agonist stimulation. HCN4 conducts an inward "pacemaker" current (I(f)) that increases the sinoatrial nodal (SAN) cell membrane diastolic depolarization (DDR), leading to faster SAN action potential generation. Surprisingly, knockout mice were recently shown retain physiological HR with isoproterenol (ISO),...