Think about the last time you heard someone searching for a compatible bone marrow donor. Hematopoietic stem cells (HSCs) are rare cells that can fully reconstitute the blood system after bone marrow transplantation. The donor has to immune-matched and it is unlikely that two unrelated individuals will be matched. Is there an alternative way to create these valuable blood cells? In 2006, a group of Japanese scientists found a way to create pluripotent stem cells by "reprogramming" any cell in the body. These are called induced pluripotent stem cells (iPSCs) and they can give rise to any tissue in the body. Our lab is working to generate immune-matched blood cells from pluripotent stem cells.
Just as iPSCs from healthy individuals can be used to create healthy matched blood cells, iPSCs from patients with blood disorders make diseased blood cells. We can collect bone marrow cells from patients, but there are often too few of these cells to help us understand what goes wrong in these diseases. We are using iPSCs from patients with blood disorders to uncover causes of these diseases and to discover candidate therapeutics using high-throughput drug screens. This allows us to screen thousands of chemical compounds at a time to find ones that can rescue the cellular defect. Our previous work has identified a small molecule therapeutic for Diamond Blackfan anemia - a rare inherited bone marrow disorder. This molecule turns on a cellular pathway called autophagy. It is a damage control pathway that allows cells to recycle damaged components. We would like to understand the role that this pathway plays in normal blood and in diseases, such as anemias.