Current projects include:
Developmental Context of Leukemogenesis
The developmental context of the cell of origin in leukemia has often been disregarded, although it is likely to play an important role in the resulting malignancy. In our Down syndrome associated leukemogenesis model, we established that leukemic transformation driven by mutations in GATA1 and STAG2 does not occur in adult hematopoietic stem cells, but is developmentally restricted to fetal and early postnatal stages (Science, 2021). We are interested in characterizing the molecular program of leukemic susceptibility through single cell transcriptional and epigenetic profiling and broadening this phenomenon to other models of childhood and adult leukemias.
Therapy Resistance in Childhood Leukemia
We are extending our CRISPR/Cas9 genome editing approach to model chromosomal translocations and gene fusions that are frequently observed in childhood leukemia. Some of these genetic perturbations are associated with therapy resistance. We are interested in characterizing why these leukemias are resistant to standard chemotherapy and how we can identify and develop therapeutic targets against them.
Functional Genomics to Identify Genetic Vulnerabilities
We are utilizing CRISPR/Cas9 functional screens in primary leukemia patient samples to uncover genetic vulnerabilities in childhood and adult leukemia. Conducting these systematic screens directly in human primary samples will lead to the identification of highly relevant therapeutic targets in a system that we believe is superior to previously used cell lines and genetic mouse models.