Hippo-YAP signaling in cardiac regenerative repair

Baylor College Of Medicine, Houston TX

Investigators

Abstract

Project Summary This R01 application will investigate a novel signaling pathway, the Hippo-YAP pathway, in mammalian heart injury. The long-term goal is to develop new treatments for patients with heart failure by generating treatments that promote a productive response to injury. The objectives of this application are to gain insights into gene therapy strategies that knock down Hippo signaling in cardiac tissue following myocardial infarction. The central hypothesis is that our Hippo knockdown gene therapy approaches can be modulated to improve cardiac function safely and efficiently in mice models of ischemic heart failure. The specific aims are to investigate the YAP-mediated mechanisms for induction of regenerative repair and to create a multi-omic map of the post-myocardial infarction heart. Further preclinical refinement of our gene therapy knockdown strategy is a required and important step to bring the approach to the clinic. The project is conceptually and technically innovative. Concepts to be tested include new ideas in cardiac biology and cutting-edge single-cell genomics technologies to address hypotheses. The significance is high because there are no treatments for heart failure, and devising ways to improve patient outcomes is highly significant.