Work in the Mullighan lab examines the genetic basis of leukemia, particularly high risk acute lymphoblastic leukemia. We use high resolution genomic profiling including next generation sequencing to comprehensively identify all genetic alterations contributing to leukemogenesis and treatment failure. This work is coupled to the development of mouse models that faithfully recapitulate human leukemia in order to validate the role of mutations in leukemogenesis, and to generate platforms for testing of targeted therapies. Recent areas of interest include immature T-lineage ALL, BCR-ABL1 positive leukemia, BCR-ABL1-like ALL and hypodiploid ALL. These studies have identified multiple new targets of genetic alterations, several of which have been translated to the clinic as new diagnostic approaches and targets for therapy. The laboratory has close collaboration with the Children's Oncology Group and the St Jude Children's Research Hospital Pediatric Cancer Genome Project.