The goals of our studies are to identify genes that control the processes of hematopoiesis and vascular development, understand their functional role, and apply this information to the treatment of defects in blood and blood vessel formation in adults. To achieve these goals, we will obtain lethal mutants generated from the established ENU mutagenesis screen at Baylor, which is directed by our collaborator, Dr. Monica Justice. In collaboration with the Justice lab, we will screen all lethal mutants, determine which have probable defects in blood or blood vessel development, then thoroughly characterize their phenotype and functional defects, using histological, molecular and biochemical approaches. Importantly, the genetic mapping of mutations will be done via the established Mutagenesis Genomics Core in the Justice lab. Information gained from these developmental studies will be applied in the future to the modulation of blood and blood vessel formation in adults, using systems we have already established in our lab. We will determine the role of the identified genes found to play a critical role in the determination or maturation of blood and vascular cells, to direct the fate of adult stem cells and contribute to the regeneration of blood and blood vessels in adults. Thus, our hypothesis is that by screening lethal ENU-induced mutants, we will discover genes involved in blood and blood vessel formation, which modulate the fate of adult stem cells and will prove useful for the treatment of adult hematopoietic and vascular pathologies.
