The John M. Maris lab is interested in the childhood cancer neuroblastoma, particularly in translating our understanding of molecular pathogenesis towards improved survival rates. We seek to discover genetic events that initiate neuroblastoma tumorigenesis, acquired aberrations that are critical for developing a highly malignant phenotype, and utilizing these data to both predict outcome and identify rationale therapeutic targets. We have used classic and modern genetic approaches to discover susceptibility genes for both inherited and sporadic forms of the disease. We have defined the acquired genomic events that are associated with clinical phenotype, and showed that deletions of chromosome arm 11q are highly predictive of death from tumor progression. Detection of this abnormality is now used worldwide to assign therapy intensity, and we designed a neuroblastoma-specific diagnostic chip to simplify the process. Finally, we have identified several promising molecular targets that might be exploited in high-risk neuroblastoma patients (cure rate currently 30-40%). We use an integrative strategy, combining genomic and functional strategies to prioritize molecular targets. We have moved several of these through preclinical evaluation programs and into Phase 1 and/or Phase 2 clinical trials with plans to test several of these approaches in randomized Phase 3 trials in the next few years. It is our hope that a comprehensive approach to this important pediatric cancer will result in more precise therapy and improved cure rates with less long-term morbidity.