We aim to develop an innovative approach to generate, at high-throughput, isogenic induced pluripotent stem cells (iPSCs), and use their differentiated progeny to understand the impact of human genetic variation on the risk of developing coronary artery disease (CAD). A genomic variant associated with CAD, myocardial infarction (Ml), abdominal aortic aneurysm, and intracranial aneurysm is found in a stretch of chr9p21 devoid of known genes. We will use this locus as a model for our study;while focusing on 9p21, our overall approach will be broadly applicable to the study of HLBS diseases of complex genetic architecture.
|Yu, Chen; Liu, Yanxia; Ma, Tianhua et al. (2015) Small molecules enhance CRISPR genome editing in pluripotent stem cells. Cell Stem Cell 16:142-7|
|Yu, Chen; Liu, Kai; Tang, Shibing et al. (2014) Chemical approaches to cell reprogramming. Curr Opin Genet Dev 28:50-6|
|Zhang, Yu; Li, Wenlin; Laurent, Timothy et al. (2012) Small molecules, big roles -- the chemical manipulation of stem cell fate and somatic cell reprogramming. J Cell Sci 125:5609-20|