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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01HL107436-03
Application #
8500436
Study Section
Special Emphasis Panel (ZHL1-CSR-N (F1))
Program Officer
Jaquish, Cashell E
Project Start
2011-07-05
Project End
2016-06-30
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
3
Fiscal Year
2013
Total Cost
$1,678,344
Indirect Cost
$265,143
Name
Scripps Research Institute
Department
Type
DUNS #
781613492
City
La Jolla
State
CA
Country
United States
Zip Code
92037
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Lo Sardo, Valentina; Ferguson, William; Erikson, Galina A et al. (2017) Influence of donor age on induced pluripotent stem cells. Nat Biotechnol 35:69-74
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 28:50-56
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