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The foundation of our work is based upon recent comprehensive next-generation genomic analyses through which we have discovered the genes, pathways, and molecular processes recurrently altered in patients with medulloblastoma. Our current focus is to summarize these somatic alterations in the context of medulloblastoma subgroups and functionally validate candidate driver genes and pathways using a variety of technically advanced in vivo methodologies. In addition, we are working closely with the Division of Neuro-Oncology at St. Jude to improve understanding of how specific genomic variants correlate with the demographic and clinical features of medulloblastoma patients treated on clinical trials conducted at St. Jude Children’s Research Hospital.