Illuminating the function of polycystins as ciliary mechanotransducers in cardiac development

Key Words: Congenital heart disease, cilia, calcium signaling, polycystin, cardiac development, zebrafish, microscopy

My project seeks to understand and cure congenital heart disease, a birth defect which affects the heart. Congenital heart disease is the most common birth defect, affects about 1% of all live births and is the leading cause of birth defect related infant death in the U.S. There is no cure for congenital heart disease and the causes behind it are unclear. In a growing number of cases, genetic studies have traced congenital heart disease to defects in the structure and function of cilia, hair-like organelles that are found on nearly all developing organs including the heart. Using zebrafish as a model for cardiac development, I have obtained preliminary evidence that cilia act as “antennae” to sense and translate biomechanical cues into calcium signals that sculpt the heart during early embryogenesis. My proposed research seeks to investigate this by measuring and manipulating calcium signals in cilia during heart development using cutting edge microscopy technologies. Completion of this study will advance our understanding of how cilia regulate cardiac development and cause congenital heart disease when gone awry. If successful, this work will also identify key molecular players in these processes and may lead to the development of novel cilia-based diagnostics and therapeutics for congenital heart disease. This research aligns with the mission of the Charles Hood Foundation as it aims to improve the lives of children with congenital heart disease.