Novel Therapeutics for Long QT Syndrome

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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.