PROJECT SUMMARY/ABSTRACT – NEUROBIOLOGY AND BRAIN TUMOR PROGRAM Brain tumors are the leading cause of cancer-related death in children. Despite rapid advances in understanding disease biology, treatment approaches are still lacking for some patients and lead to long-term, debilitating side effects in others. The goal of the Neurobiology and Brain Tumor Program (NBTP) is to improve survival and morbidity of children with brain tumors by developing the most effective, least toxic therapies through better understanding of disease pathogenesis and normal brain development. The NBTP Co-leaders (PLs) are Suzanne Baker, PhD (Basic Science Lead), an expert in the molecular pathogenesis of brain tumors, and Giles Robinson, MD (Clinical Research Lead), an expert in risk-stratified therapies based on molecular and clinical tumor subgroups. The PLs strategically structure regular programmatic meetings, seminars, and retreats to bring together experts in fundamental, translational, and clinical brain tumor research, facilitate collaboration, and drive translation of discoveries. NBTP multidisciplinary research efforts align with the St. Jude Comprehensive Cancer Center (SJCCC) Strategic Plan to advance fundamental research, accelerate translation, develop innovative clinical trials to improve cure rates, and understand and reduce toxicity and late effects. Supported by outstanding SJCCC Shared Resources, throughout the current project period, the NBTP illuminated mechanisms of oncogenesis and developmental origins of pediatric brain tumors, altered diagnostic practice worldwide by identifying refined molecular subgroups that are now incorporated into the new World Health Organization tumor classification guidelines, developed innovative clinical trials with risk-stratified design or immunotherapy approaches, and identified mitigating approaches to neurocognitive and long-term effects of therapy. NBTP investigators collaborate extensively with other SJCCC Programs and participat