"We'll take people whose 9p21 region of the genome says they're at risk for coronary artery disease, and then compare the stem cells from that individual to a healthy elderly person who may also have risk in that region, but somehow doesn't have the disease," said Samuel Levy, the study's lead investigator and director of genomic sciences with STSI. "The crux of our research is to figure out which genes, or which other parts of the genome, are interacting with the 9p21 region. There are no genes in the 9p21 region, which is a big part of our challenge."
The "disease in a dish" heart study brings together two emerging research strategies that to date have largely developed separately induced pluripotent stem cells to create relevant cells, and a sophisticated genome editing technology, which acts like scissors to cut and replace pieces of the genome. The research will also leverage extensive data from genome-wide association studies.
"Genome editing allows us to do an experiment no one has ever tried that is, if you change someone's genetics, can you make their cells revert away from acquiring a disease?" said Levy. "Using zinc finger nucleases (ZFNs), that act like molecular scissors, we can actually take this risk region out of a person's genome and see what happens to his cells if that region is present or absent. This editing allows us to basically recreate the disease or take it away."
Scientists will take skin or blood cells from participants and reprogram them to create induced pluripotent stem cells, which have the capacity to become any cell type in the body. These stem cells will then be transformed into three different types of heart artery-lining cells: smooth muscle cells, endothelial cells and cardio myocytes.
Researchers will characterize participants' artery-l
|Contact: Mika Ono|
Scripps Research Institute