Perhaps one of the most remarkable results from the genomic sequencing efforts in cancer over the past several years has been the growing number of mutations in epigenetic regulators in cancer. Detailed mechanistic analysis of epigenetic modifications and the contribution of individual chromatin regulators to these modifications have long been hindered by a lack of effective technologies. With the use of next generation sequencing techniques combined with chromatin immunoprecipitation and genome editing tools it is now possible to comprehensively investigate the molecular mechanisms of epigenetic alterations and define their disease relevance. This is critically important for designing therapeutic targeting of epigenetic modifiers and novel biomarkers that measure their effect and predict responses.
The laboratory combines functional perturbation of chromatin regulators with modern next-generation sequencing tools for chromatin state analysis to identify, mechanistically characterize, and therapeutically validate epigenetic dependencies in cancer. Specifically, we are investigating epigenetic mechanisms of drug resistance in T-cell acute lymphoblastic leukemia and are studying the evolution of epigenetic states in pediatric solid tumors.