Grant: Doctoral: Vanier Canada Graduate Scholarships

Understanding the complex molecular machinery that allows blood stem cells to increase their numbers is important for many reasons. These include a need to develop better methods to treat patients with defective, injured or diseased blood cell outputs. In addition, there is a critical need to develop more effective and less toxic methods of treating leukemia, which depend on similar mechanisms for their growth as do normal blood stem cells. Because blood stem cells are extremely rare and change in subtle ways during development, progress in understanding how to expand them has been slow. This project will exploit recent technical advances that make it possible to identify new pathways that control normal human blood stem cell responses to external factors. I will use established methods to isolate highly purified living blood stem cells from normal tissues. I will then monitor their survival, rate of division, and retention of stem cell properties in single-cell cultures established in a microchip system that allows each cell to be exposed to different factors. In parallel, I will determine which genes the cells have been stimulated to express and, from that information, make inferences about the molecular components of the cell's response machinery which can then be subjected to more rigorous biological tests. The information gained will lead to new methods for growing blood stem cells outside of the body with retention of their full regenerative ability. Based on promising preliminary results already obtained and my proposed use of even more powerful analytical tools, I expect this project will advance the longstanding and significant goal of improving the clinical utility of blood stem cells for transplantation and other applications in regenerative medicine. Further, this research should also provide a better basis for understanding how blood stem cells become leukemic and hence identify new targets for therapy.