Novel Therapeutics for Long QT Syndrome

项目总结： 心肌细胞离子通道功能异常可导致长QT综合征等心律失常。 在使用药物方法的初步实验中，我们发现Sigma 1受体的激活可以 减轻人诱导多能干细胞(IPSC)和小鼠模型的细胞表型 遗传性心律失常。这项研究的目标是检查潜在的分子机制。 Sigma受体1激活对心脏离子通道调节、作用表型的有利作用 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。我们会 使用人类IPSC和啮齿动物模型来实现我们的目标。此外，我们还将设计和开发新的 更适合于心律失常的Sigma 1受体激动剂，利用我们在 药物化学。因此，我们的翻译研究将为药物开发提供新的机遇。 遗传性综合症。

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.