Grant: Doctoral: Vanier Canada Graduate Scholarships

Blood stem cells are a rare group of cells that are responsible for maintaining life long blood cell production. They are also the cells that must be present in a transplant to recover blood formation in patient's with innate deficiencies in blood formation or whose cancers can only be cured by an otherwise lethal dose of chemotherapy. Blood stem cells can also initiate leukemia if they acquire certain genetic changes, therefore a further understanding of what controls the normal and abnormal expansion of blood stem cells underpins progress in many areas of medicine. Previous research has established that blood stem cells from fetal compared to adult mice have a number of distinct properties including a higher expansion potential, higher turnover rate and different response to immune-mediating cytokines; however, the mechanistic basis of this difference remains a mystery. A greater understanding of developmental processes governing blood stem cell properties would have valuable clinical applications including the possibility of learning how to make stem cell transplants more effective and enabling the wider use of umbilical cord blood collections for use in adult patients where they are currently inadequate due to small stem cell numbers. Our lab has shown that many of the fetal properties of blood stem cells change abruptly and in unison soon after birth and behave as if these co-ordinated changes are governed by a common mechanism. The goal of my research is therefore to test this hypothesis that there is a developmental mechanism that coordinates the simultaneous change in many key biological properties of blood stem cells. To achieve this goal I will search for some of its critical molecular features and then test their role in this process. If successful, this could provide a new approach to increase the effectiveness of adult blood stem cell transplants and possibly reveal new targets for the treatment of some leukemias.