Grant: Doctoral: Vanier Canada Graduate Scholarships

Blood stem cells are very rare cells that generate mature blood cells over the lifetime of an organism. They are used clinically to regenerate a new blood system in cancer patients requiring very intensive chemotherapy, or who have innate deficiencies in blood formation. They are also thought to be the cells from which leukemia initially develops. Studies in mice have suggested that these cells undergo defined changes during development. One of these changes is their ability to expand their own numbers, which appears to be greater in the blood stem cells present before birth as compared to those present in adults. Interestingly, it has long been recognized that pediatric and adult leukemias also differ in their behavior. Our lab has recently identified a molecular control pathway that regulates the developmental change in blood stem cell expansion potential in mice. My studies will determine whether a similar developmental change occurs in human blood stem cells and whether it involves the same mechanism. To do this, I will use a new approach to measure their expansion in mice transplanted with different sources of human blood stem cells that have been individually tagged beforehand with unique DNA "barcodes". Knowledge of the mechanism that makes fetal blood stem cells more potent should open a new avenue for expanding human blood stem cells for clinical applications where their numbers are limiting. I will also determine whether the pathway I will investigate affects their ability to give rise to cancer. These investigations will deepen our understanding of the origins of childhood leukemias, and potentially pave the way to new therapies for incurable cancers that currently afflict many Canadians.