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，海马通路， 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。的 本申请的目的是深入了解心脏的分子特性， 由河马信号调节的组织。核心假设是希波 信号传导是一种负调控途径， 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 新生儿心脏为了确定自主Wnt Hippo交互是否发生在 心肌细胞核来控制重要的基因，并调查是否海马 以可逆的方式起作用。该项目在概念和技术上都具有创新性。 待测试的概念包括心肌细胞生物学的新想法和尖端技术 基因组编辑和询问技术来解决假设。意义 因为没有治疗心肌细胞丧失引起的心力衰竭的方法。 设计产生新的心肌细胞的方法是非常重要的。

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.