Advances in tumor genetics have increasingly linked pediatric neoplasms with disrupted mechanisms of normal development. Medulloblastoma, the most common malignant brain tumor in children, is predominately originated from granule neuron precursors (GNPs) in developing cerebella. Proliferation of cerebellar GNPs is driven by the hedgehog signaling, and uncontrolled proliferation of cerebellar GNPs often results in medulloblastoma formation. Our research seeks to elucidate the cellular and molecular basis for the proliferation and differentiation of cerebellar GNPs during normal development, and investigate how the hedgehog signaling goes awry in cerebellar GNPs, leading to medulloblastoma initiation. 

Tumor development is a multistep process in which tumor cells accumulate genetic and epigenetic mutations/alterations to facilitate tumor progression. These epigenetic/genetic events influence the growth, metastasis and drug responses of tumor cells. We are currently investigating the epigenetic/genetic alterations during the progression of brain tumors including medulloblastoma and neuroblastoma, by NGS and bioinformatic analyses. We hope to define the epigenetic/genetic events critical for brain tumor growth, which may represent novel therapeutic targets for tumor treatment.

Tumor microenvironment including the surrounding blood vessels, immune cells, signaling molecules and the extracellular matrix, plays important role in tumor initiation, progression and metastasis. By using mouse models (genetically engineered mouse models and patient-derived xenograft mouse models), we are examining the cellular composition of tumor microenvironment in medulloblastoma and glioma, and studying the interaction between tumor cells and those supporting cells during brain tumor progression. We hope to find a more effective way to control brain tumor growth, through interfering the communication between tumor cells and their supporting stroma.