Screening for Novel Genetic Regulators of
Hematopoietic Stem Cells and Leukemia

Hematopoietic stem cells (HSCs) are rare cells found in the bone marrow with the capacity to differentiate into each of the different types of cells in the blood and renew themselves so that the supply of stem cells never exhausts. HSCs are used clinically for patients requiring a bone marrow transplant. However, questions exist about how these cells function in the normal bone marrow to supply just the right amount of blood cells required by an animal over its lifetime and what genes regulate HSCs during development and in mature bone marrow. It is clear that abnormal regulation of many genes important for normal HSC function can lead to cancers such as leukemia and lymphoma. Therefore, searching for novel genes that regulate normal HSCs will help us understand how leukemia develops when these genes become disregulated and could lead to novel targets for treatment.  This proposal plans to use the zebrafish animal model to perform a genetic screen for modifiers of HSC engraftment after marrow transplantation. Once mutant genes are identified through this process, resources will be mobilized to fully characterize the biology and significance of each gene in normal mammalian cells and in human leukemia and potential targets for leukemia treatment and/or prevention.