Research Interest

Allele-Specific Expression can reveal genes which are deregulated by cis-acting non-coding regulatory mutations even when the identify of the specific mutations are unknown.

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.

Single-cell gene expression and chromatin accessibility can reveal novel cell states in neuroblastomas.

Determining how genetic variations contribute to tumor cell heterogeneity and differentiation in neuroblastomas. Neuroblastoma exhibit cellular heterogeneity which is reflective of sympathoadrenal development which suggest that they arise due to defective differentiation of neural crest cells. We are using single cell sequencing technologies to characterize tumor cell subpopulations in high-risk patients and determining how genetic variations contribute to the tumor cell state specification.

CRISPR-Cas9 fused to KRAB domain can be used to perturb regulatory sequence function.

Determining the causes of therapy resistance and relapse of neuroblastomas. Undifferentiated neuroblastoma tumors are typically associated with chemotherapy resistance and high frequency of relapse. We have identified a network of sympathoadrenal transcription factors which regulate tumor cell state specification in neuroblastomas. Now we are using CRISPR interference to decipher their downstream transcriptional dependencies.