Hippo and Wnt Signaling in Cardiac Regeneration

这个R01应用程序将研究一种新的信号通路，河马途径，在 哺乳动物心脏再生。长期目标是开发新的治疗方法 通过在成人心脏中产生新的心肌细胞来治疗心力衰竭患者。这个 这项应用的目的是深入了解心脏的分子特性 受河马信号调节的组织。核心假设是河马 信号转导是阻止心肌细胞再生的负性调节途径。 成年哺乳动物的心脏。具体目标是确定河马和 WNT通路调节成人心脏修复的方式类似于 新生儿心脏。确定WNT河马是否在 控制重要基因的心肌细胞核并研究河马 以可逆的方式运行。该项目在概念和技术上都是创新的。 将测试的概念包括心肌细胞生物学和尖端技术的新想法 解决假说的基因组编辑和审问技术。它的意义 之所以高，是因为由于心肌细胞丧失而导致的心力衰竭没有治疗方法。 设计产生新的心肌细胞的方法具有非常重要的意义。

This R01 application will investigate a novel signaling pathway, the Hippo pathway, in mammalian heart regeneration. The long-term goal is to develop new treatments for patients with heart failure by generating new cardiomyocytes in the adult heart. The objectives of this application are to gain insight into molecular properties of cardiac tissue that are regulated by Hippo signaling. The central hypothesis is that Hippo signaling is a negative regulatory pathway that prevents cardiomyocyte regeneration in the adult mammalian heart. The specific aims are to determine whether the Hippo and Wnt pathways regulate adult heart repair in a manner similar to the interaction in neonatal hearts. To determine whether an autonomous Wnt Hippo interaction occurs in heart muscle nuclei to control important genes and to investigate whether Hippo functions in a reversible manner. The project is conceptually and technically innovative. Concepts to be tested include new ideas in cardiomyocyte biology and cutting edge genome editing and interrogation technologies to address hypotheses. The significance is high because there are no treatments for heart failure due to cardiomyocyte loss. Devising ways to generate new cardiomyocytes is highly significant.