FHFs and Cardiac Electrophysiology

FHF 和心脏电生理学

基本信息

批准号：
9751374
负责人：
Glenn I Fishman
金额：
$ 79.27万
依托单位：
NEW YORK UNIVERSITY SCHOOL OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-08-01 至 2022-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9751374
关键词：
Acceleration Action Potentials Acute Arrhythmia Awareness Back Binding Biophysics Brain Brugada syndrome Calcium Carbenoxolone Cardiac Cardiac Electrophysiologic Techniques Cardiac Myocytes Cardiomyopathies Cause of Death Cells Cellular Structures Cessation of life Complex Computer Simulation Coupling Cytoplasmic Tail Data Developed Countries Developing Countries Disease Electrocardiogram FGF12 gene Failure Family member Fever Fiber Fibroblast Growth Factor Flecainide Formulation Generations Genetically Engineered Mouse Health Heart Heart Abnormalities Heart Atrium Heart Diseases Heart Hypertrophy Heritability Human Hyperthermia Individual Infection Inherited Ion Channel Ischemia Kinetics Knowledge Laboratories Measures Modeling Molecular Molecular Structure Mus Mutant Strains Mice Mutation Myocardial Ischemia Myocardium Neonatal Nifedipine Organ Pathology Periodicity Phenotype Predictive Factor Property Protein Family Protein Isoforms Proteins Research Risk Role Safety Seizures Series Sodium Sodium Channel Study models Suggestion Syndrome Tachyarrhythmias Tachycardia Temperature Testing Tissues United States Ventricular Ventricular Arrhythmia design epileptic encephalopathies experimental study genetic association heart rhythm indium arsenide induced pluripotent stem cell loss of function new therapeutic target patch clamp predictive test response simulation stoichiometry sudden cardiac death voltage

项目摘要

PROJECT SUMMARY Heart disease remains the leading cause of death in the United States and other developed countries. Half of these deaths occur suddenly, typically from ventricular tachyarrhythmias that arise in the setting of acute ischemia, acquired heart disease or inherited syndromes including channelopathies and cardiomyopathies. Despite decades of research, major gaps exist in our understanding of the molecular mechanisms responsible for normal cardiac rhythmicity, as well as abnormalities that increase the risk of rhythm disturbances. Our laboratory has identified molecules, known as fibroblast growth factor homologous factors (FHFs), that potently regulate heart rhythm. In the absence of FHFs, hearts develop significant conduction disease and arrhythmias. In this application we propose a series of experiments designed to understand the mechanisms through which deficiency of FHF proteins results in these disease manifestions.

项目概要心脏病仍然是美国和其他发达国家的主要死亡原因。一半这些死亡突然发生，通常是由于急性发作时出现的室性快速心律失常所致。缺血、获得性心脏病或遗传综合征，包括离子通道病和心肌病。尽管经过了数十年的研究，我们对造成这种现象的分子机制的理解仍存在重大差距。正常的心律，以及增加心律紊乱风险的异常。我们的实验室已鉴定出称为成纤维细胞生长因子同源因子 (FHF) 的分子，该分子可有效调节心律。在没有 FHF 的情况下，心脏会出现严重的传导疾病和心律失常。在此应用中，我们提出了一系列实验，旨在了解其机制 FHF 蛋白的缺乏会导致这些疾病的表现。