The major goal of my laboratory is the molecular characterization of malignant childhood cancers to identify drug targets and improve treatment options. Our focus is mainly on pediatric brain tumors such as medulloblastoma, glioblastoma, and ependymoma. Recently, we have demonstrated how to leverage epigenetic information such as DNA methylation and enhancer profiling in pediatric brain tumors and normal human tissues to identify clinically relevant tumor subgroups, oncogenic enhancers, transcription factors, and pathways amenable to pharmacologic targeting. To reveal regulatory circuitries disturbed in childhood brain tumors, we generate and integrate public high-dimensional data from primary tumors and patient-derived cell lines. We are specifically interested in the analysis of somatic and germline DNA mutations, chromatin and DNA modifications, transcription factor binding, and gene expression. To identify molecular mechanisms that contribute to tumor development and maintenance, we also develop hypotheses driven computational tools for the integrative analysis of different layers of genetic and epigenetic information. As we recognized that our epigenetic mapping studies can identify effective drug targets, we now aim to profile the three-dimensional chromosome conformation of tumor genomes and to reveal molecular mechanisms potentially causing disturbed enhancergene interactions and de-regulation of gene expression and biochemical pathways.