Novel Therapeutics for Long QT Syndrome

项目摘要： 心肌细胞离子通道功能异常可诱发心律失常，如长QT综合征。 在使用药物方法的初步实验中，我们发现σ 1受体的激活可以 减轻人诱导多能干细胞（iPSC）和小鼠模型中的细胞表型 遗传性心律失常本研究的目的是研究潜在的分子机制， σ受体1激活对心脏离子通道调节表型的有益作用 遗传性心律失常模型中的电位、收缩、线粒体功能和基因表达。我们将 使用人类iPSC和啮齿动物模型来实现我们的目标。此外，我们将设计和开发新的 Sigma 1受体激动剂，更适用于心律失常，利用我们的专业知识， 药物化学因此，我们的转化研究将为药物开发提供新的机遇。 遗传性综合征疾病。

Project Summary: Abnormal ion channel function in heart muscle cells induces cardiac arrhythmias such as long QT syndrome. In preliminary experiments using pharmaceutical approach, we found that activation of Sigma 1 receptor could alleviate the cellular phenotypes in human induced pluripotent stem cell (iPSC) and mouse models of the genetic cardiac arrhythmias. The goal of this study is to examine the molecular mechanism underlying the beneficial effect of Sigma receptor 1 activation on the phenotypes in cardiac ion channel regulation, action potentials, contraction, mitochondrial function and gene expression in the genetic arrhythmia models. We will use human iPSC and rodent models to accomplish our goal. In addition, we will design and develop new Sigma 1 receptor agonists that are more suitable for cardiac arrhythmias, taking advantage of our expertise in medicinal chemistry. Therefore, our translational study will provide new opportunity of drug development for the genetic syndromic disorders.