Taisuke Ishikawa
A5086167197- Cardiac electrophysiology and arrhythmias
- Ion channel regulation and function
- Cardiomyopathy and Myosin Studies
- Cardiovascular Effects of Exercise
- Cardiovascular Conditions and Treatments
- Nuclear Structure and Function
- Receptor Mechanisms and Signaling
- Cardiac Arrhythmias and Treatments
- RNA Research and Splicing
- Cardiac Valve Diseases and Treatments
- Cardiac pacing and defibrillation studies
- RNA and protein synthesis mechanisms
- Cardiovascular Function and Risk Factors
- Mitochondrial Function and Pathology
- Congenital heart defects research
- Neuroscience and Neural Engineering
- Nitric Oxide and Endothelin Effects
- ECG Monitoring and Analysis
- Pulmonary Hypertension Research and Treatments
- Muscle Physiology and Disorders
- Genomics and Rare Diseases
- Erythrocyte Function and Pathophysiology
- Cellular Mechanics and Interactions
- Heat shock proteins research
- Genomics and Chromatin Dynamics
National Cerebral and Cardiovascular Center
2020-2024
Nagasaki University
2014-2020
Rockefeller University
2020
Brigham and Women's Hospital
2020
Federation of American Societies for Experimental Biology
2020
National Institutes of Health
2020
Yale University
2020
Harvard University
2020
Tokyo Medical and Dental University
2007-2018
Industrial Research Institute of Ishikawa
2015-2017
Background— Genetic predisposition to life-threatening cardiac arrhythmias such as congenital long-QT syndrome (LQTS) and catecholaminergic polymorphic ventricular tachycardia (CPVT) represent treatable causes of sudden death in young adults children. Recently, mutations calmodulin ( CALM1 , CALM2 ) have been associated with severe forms LQTS CPVT, occurring very early life. Additional mutation-positive cases are needed discern genotype–phenotype correlations mutations. Methods Results— We...
Recently, we and others reported that early repolarization (J wave) is associated with idiopathic ventricular fibrillation. However, its clinical genetic characteristics are unclear.This study included 50 patients (44 men; age, 45 ± 17 years) fibrillation repolarization, 250 age- sex-matched healthy controls. All of the had experienced arrhythmia events, 8 (16%) a family history sudden death. Ventricular was inducible by programmed electric stimulation in 15 29 (52%). The heart rate slower...
Dilated cardiomyopathy (DCM) is characterized by dilation of left ventricular cavity with systolic dysfunction. Clinical symptom DCM heart failure, often associated cardiac sudden death. About 20-35% patients have apparent family histories and it has been revealed that mutations in genes for sarcomere proteins cause DCM. However, the disease-causing can be found only about 17% Japanese familial Bcl-2-associated athanogene 3 (BAG3) a co-chaperone protein antiapoptotic function, which...
Long QT syndrome (LQTS) is a rare genetic disorder and major preventable cause of sudden cardiac death in the young. A causal variant with large effect size identified up to 80% probands (genotype positive) cascade family screening shows incomplete penetrance variants. Furthermore, proportion cases meeting diagnostic criteria for LQTS remain genetically elusive despite testing established genes negative). These observations raise possibility that common variants small contribute clinical...
Abstract Aims The prognostic value of genetic variants for predicting lethal arrhythmic events (LAEs) in Brugada syndrome (BrS) remains controversial. We investigated whether the functional curation SCN5A variations improves predictability. Methods and results Using a heterologous expression system whole-cell patch clamping, we functionally characterized 22 unknown significance (VUSs) among 55 mutations previously curated using silico prediction algorithms Japanese BrS registry (n = 415)....
Background— Mutations in genes including SCN5A encoding the α-subunit of cardiac sodium channel (hNav1.5) cause Brugada syndrome via altered function ion channels, but more than two-thirds remains pathogenetically elusive. T-tubules and sarcoplasmic reticulum are essential excitation cardiomyocytes, sarcolemmal membrane-associated protein (SLMAP) is a unknown localizing at reticulum. Methods Results— We analyzed 190 unrelated patients for mutations SLMAP . Two missense mutations, Val269Ile...
Calmodulin is a ubiquitous Ca2+ sensor molecule encoded by three distinct calmodulin genes, CALM1-3. Recently, mutations in CALM1-3 have been reported to be associated with severe early-onset long-QT syndrome (LQTS). However, the underlying mechanism through which heterozygous lead LQTS remains unknown, particularly human cardiomyocytes. We aimed establish an disease model CALM2 mutation (LQT15) using induced pluripotent stem cells (hiPSCs) and assess mutant allele-specific ablation genome...
Background: Brugada syndrome (BrS) is characterized by specific alterations on ECG in the right precordial leads and associated with ventricular arrhythmia that may manifest as syncope or sudden cardiac death. The major causes of BrS are mutations SCN5A for a large subunit sodium channel, Nav1.5, but mutation SCN3B small Navβ3, has been recently reported an American patient. Methods Results: A total 181 unrelated patients, 178 Japanese 3 Koreans, who had no SCN5A, were examined direct...
Mutations in LMNA (lamin A/C), which encodes lamin A and C, typically cause age-dependent cardiac phenotypes, including dilated cardiomyopathy, conduction disturbance, atrial fibrillation, malignant ventricular arrhythmias. Although the type of mutations have been reported to be associated with susceptibility arrhythmias, gene-based risk stratification for complications remains unexplored.The multicenter cohort included 77 mutation carriers from 45 families; disorders were retrospectively...
Brugada syndrome (BrS) is characterized by the type 1 ECG pattern. Pathogenic rare variants in SCN5A (mutations) are identified 20% of BrS families whom incomplete penetrance and genotype-negative phenotype-positive individuals observed. E1784K-SCN5A most common mutation identified. We determined association a genetic risk score (BrS-GRS) on phenotype with mutations.Subjects spontaneous pattern or positive/negative drug challenge from cohorts harboring mutations were recruited 16 centers...
Stringent variant interpretation guidelines can lead to high rates of variants uncertain significance (VUS) for genetically heterogeneous disease like long QT syndrome (LQTS) and Brugada (BrS). Quantitative disease-specific customization American College Medical Genetics Genomics/Association Molecular Pathology (ACMG/AMP) address this false negative rate.We compared rare frequencies from 1847 LQTS (KCNQ1/KCNH2/SCN5A) 3335 BrS (SCN5A) cases the International LQTS/BrS Consortia...
Abstract While 3D chromatin organization in topologically associating domains (TADs) and loops mediating regulatory element-promoter interactions is crucial for tissue-specific gene regulation, the extent of their involvement human Mendelian disease largely unknown. Here, we identify 7 families presenting a new cardiac entity associated with heterozygous deletion 2 CTCF binding sites on 4q25, inducing TAD fusion conformation remodeling. The are located desert at 1 Mb from Paired-like...
Ventricular fibrillation (VF), the main cause of sudden cardiac death (SCD), occurs most frequently in acute phase myocardial infarction: a certain fraction VF, however, develops an apparently healthy heart, referred as idiopathic VF. The contribution perturbation fast conduction system ventricle, His-Purkinje system, for VF has been implicated, but underlying mechanism remains unknown. Irx3/IRX3 encodes transcription factor specifically expressed heart. Genetic deletion Irx3 provides mouse...
Dilated cardiomyopathy (DCM) is characterized by a dilated left ventricular cavity with systolic dysfunction manifested heart failure. It has been revealed that mutations in genes for cytoskeleton or sarcomere proteins cause DCM. However, the disease-causing can be found only far less than half of patients family history, indicating there should other disease Formin homology 2 domain containing 3 (FHOD3) sarcomeric protein expressed plays an essential role organization during...
Sick sinus syndrome (SSS) is a common arrhythmia often associated with aging or organic heart diseases but may also occur in familial form variable mode of inheritance. Despite the identification causative genes, including cardiac Na channel (SCN5A), pathogenesis and molecular epidemiology SSS remain undetermined primarily because its rarity.We genetically screened 48 members 15 families for mutations several candidate genes determined functional properties mutant channels using whole-cell...
The effects of furosemide on left atrial pressure (LAP) in dogs with mitral regurgitation (MR) have not been documented a quantitative manner and between different routes administration.To document LAP echocardiographic parameters MR administered IV or PO, order to changes after treatment.Five healthy Beagle (3 males 2 females; aged years) were used.Experimental, cross-over, interventional study. was measured before the administration furosemide, 30 minutes, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24...
Dilated cardiomyopathy (DCM) is characterized by ventricular dilation associated with systolic dysfunction, which could be caused mutations in lamina/C gene (LMNA). LMNA-linked DCM severe males both human patients and a knock-in mouse model carrying homozygous p.H222P mutation (LmnaH222P/H222P). The aim of this study was to investigate the molecular mechanisms underlying gender difference DCM. A whole-exome analysis multiplex family exhibiting revealed DCM-linked LMNA mutation, p.R225X....
Key points The contribution of HCN4 pacemaker channels in the autonomic regulation sino‐atrial node (SAN) has been a matter debate. transgenic overexpression did not induce tachycardia, but reduced heart rate variability, while conditional knockdown gave rise to sinus arrhythmia. response SAN β‐adrenergic stimulation was affected by or channels. When were knocked down, parasympathetic examined cervical vagus nerve (CVNS) enhanced; CVNS induced complete pause. attenuated bradycardia only...
Recent genome-wide association studies have demonstrated an between MYH6, the gene encoding α-myosin heavy chain (α-MHC), and sinus node function in general population. Moreover, a rare MYH6 variant, R721W, predisposing susceptibility to sick syndrome has been identified. However, existence of disease-causing mutations for familial their underlying mechanisms remain unknown.We screened 9 genotype-negative probands with families identified in-frame 3-bp deletion predicted delete one residue...
Mutation in the lamin A/C gene (LMNA) is associated with several cardiac phenotypes, such as conduction disorders (CCD), atrial arrhythmia (AA), malignant ventricular (MVA) and left dysfunction (LVD), leading to sudden death (SCD) and/or end-stage heart failure. We investigated how these phenotypes are each other which of them most important for total mortality. Methods Results: A multicenter registry included 110 LMNA mutation carriers (age, 43±15 years, male: 62%) from 60 families. After...