Discovering and characterizing non-coding driver mutations in neuroblastomas. Comprehensive genome sequencing of high-risk neuroblastomas has revealed that many tumors lack identifiable and clinically actionable driver mutations in protein-coding genes at the time of initial diagnosis. As a result, precision medicine based on protein-coding mutations has not substantially benefited most patients. The paucity of protein-coding driver mutations also suggests that neuroblastoma tumorigenesis is likely to be driven by genetic variations which perturbs gene-expression. In our lab we develop computational and molecular biology methods to characterize non-coding regulatory mutations in neuroblastomas.
Determining the causes of therapy resistance and relapse of neuroblastomas. Undifferentiated neuroblastoma tumors are typically associated with chemotherapy resistance and a high frequency of relapse. We have identified a network of sympathoadrenal transcription factors that regulate tumor cell state specification in neuroblastomas. Now, we are using CRISPR interference to decipher their downstream transcriptional dependencies.
Molecular mechanism of drug sensitivity. We use CRISPR screening to identify genes that underlie sensitivity to novel drugs in neuroblastoma and other pediatric cancers.
