Diagnosis, Prevention, And Treatment Of Cardiovascular Diseases With Genome Editing

项目总结 在过去的6年里，我的独立实验室利用了人类基因组学的新方法， 在基因组编辑技术的支持下，开创了新型的后基因组功能研究 阐明驱动心血管疾病的新机制。我的实验室已经确定了 涉及脂肪代谢、冠心病和糖尿病的特定基因，以及对 非编码DNA变异如何影响这些基因的功能。展望未来，我的研究将需要 疾病建模和治疗性基因组编辑的最新进展的优势-我的进展 实验室发挥了作用--解决了心血管领域的两个模范翻译挑战：(1) 利用治疗性基因组编辑预防冠心病，这是导致死亡的主要原因 世界范围内；以及(2)使用基因组编辑来增强对变体的高通量功能注释 通过临床测序在患者中检测到的不确定意义。

PROJECT SUMMARY For the past 6 years, my independent laboratory has leveraged new approaches in human genomics and pioneered new types of post-genomic functional studies—empowered by genome-editing technologies—to elucidate novel mechanisms that drive cardiovascular diseases. My laboratory has characterized the roles of specific genes involved in lipid metabolism, coronary heart disease, and diabetes, as well yielding insights into how noncoding DNA variation influences the functions of these genes. Going forward, my research will take advantage of recent advances in disease modeling and therapeutic genome editing—advances in which my laboratory played a part—to tackle two exemplary translational challenges in the cardiovascular field: (1) the use of therapeutic genome editing to prevent coronary heart disease, the leading cause of death worldwide; and (2) the use of genome editing to empower high-throughput functional annotation of variants of uncertain significance detected in patients by clinical sequencing.