PROJECT SUMMARY/ABSTRACT Hematological malignancies are the most common childhood tumors. Despite remarkable advances in survival rates, they remain a leading cause of cancer death. Great progress has been made in understanding the genetic basis of these tumors, which now requires systematic efforts to translate these discoveries into mechanistic insight into the basis of tumorigenesis and advances in diagnostic and therapeutic approaches. Advancing outcomes for children with hematologic malignancies requires training independent investigators with expertise in genomic analysis, experimental modeling, translational science, and preclinical modeling of childhood hematological malignancies (CHM). No other T32 training programs are solely devoted to training in CHM, nor is there a training program that relies on the rich foundation of genomic discoveries from the Pediatric Cancer Genome Project. This training program has been designed to equip the next generation of scientists with the skills and knowledge needed from multifaceted disciplines to become leaders in childhood hematological malignancy research. The T32 has funded eight postdoctoral trainees, and two additional trainees were supported by institutional funds. In the current cycle, continued funding is requested for four postdoctoral trainee T32 positions, and St. Jude Children’s Research Hospital will continue to support one slot to enhance recruitment of an additional trainee from an underrepresented minority background. The program is designed to deliver an individualized and enriched training experience for each trainee through the support of a team of multi- disciplinary faculty with a wide range of expertise, cutting-edge core facilities, and robust training in genomic approaches. Each trainee will have a mentorship team to include scientific and clinical investigators, with oversight provided by an Internal Advisory Committee of dedicated faculty and an External Advisory Board comprised of five national leaders in childhood cancer research and postdoctoral training. Trainees host speakers for a lecture series on CHM topics related to genomics, biostatistics, experimental modeling, genome editing, immunotherapy, and preclinical studies and present their research as part of an annual Training Day attended by faculty and External Advisory Board members. A critical aspect of the program is participation in an interactive grant writing workshop, with the expectation that trainees submit a fellowship application by their second year. All trainees have completed or are enrolled in the workshop, and of the six initial trainees supported, five successfully transitioned to independent funding. All trainees are closely integrated with the rich portfolio of research activities of the St Jude Comprehensive Cancer Center Hematological Malignancies Program, which coordinates the translation of basic science discoveries to clinical trials. This program provides an unrivaled opportunity to train sci...