Modeling clonal hematopoietic disorders in gata2 heterozygosity using color-barcoding and mosaic mutagenesis in zebrafish
EvansMDS Young Investigator Award
Children and young adults with inherited mutations in GATA2 gene have an increased risk of developing blood cancers arising from blood stem cells. To understanding how leukemias initiate from mutated abnormal blood stem cells, I used a system of labeling and tracking individual stem cells in zebrafish. This allows me to follow the changes in their function over time, and in the presence of additional mutations which are required to cause leukemia. I have shown that mutations in gata2 in a zebrafish model result in a small stem cell pool with low index of diversity, making it more unstable and vulnerable to additional genetic mutations. I am currently testing individual mutations found in GATA2 associated leukemias to establish a robust model for future work to define the mechanism by which they cause disease and to use it as a platform for drug screens to find novel therapies.