PROJECT SUMMARY / ABSTRACT This is the second renewal application for support of the Pediatric physician-scientist T32 training program at the Washington University School of Medicine. Pediatric physician-scientists play a crucial role in advancing knowledge that improves child health. To meet the ongoing national need to replenish the Pediatric physician-scientist pipeline at the clinical post-postdoctoral fellowship level, our program supports a mentored career development pathway for 4 Scholars per year for up to 2 years by leveraging a wealth of biomedical resources within the Washington University School of Medicine, our Child Health Research Center and the Medical Center campus. As we have done for the past 15 years, the long-term objective of our program is to develop Trainees that focus their research efforts on Pediatric disease-oriented biology by applying recent advances in the basic and translational sciences; such as developmental biology, cell biology, immunology, genetics/genomics, and systems biology. The specific aims of this proposal include: 1) protected mentored research experiences with well-established investigators encompassing a wide range of disciplines within the Washington University School of Medicine and the Department of Pediatrics, 2) obligatory educational programs in laboratory management, scientific rigor, statistics, grantsmanship, responsible conduct of research, and biomedical informatics 3) individualized specific coursework based on the Trainees’ areas of investigation, 4) continuous feedback to the Trainees, mentors and program leadership, and 5) the development of Trainees who are women and underrepresented minorities. The program, now fifteen years old, has an excellent track record by exceeding national benchmarks (15-year T to K conversion rate = 52%; this cycle = 57%), and will ultimately close the knowledge gap between basic/translational scientists and pediatric clinicians. Gary A. Silverman, M.D., Ph.D. serves as the Program Director, and David Hunstad, M.D. serves as the Training Director. The Trainees will continue to utilize our institutionally-funded state-of-art core facilities that provide, for example, whole genome/exome DNA sequencing, bioinformatics, cryo-EM imaging, genome editing and model animal development, to facilitate the study of Pediatric disease states. The long-term goals of this program are being realized as its Trainees contribute to our understanding of human developmental diseases for decades to come, while evolving into the next generation of scientific leaders, role models and mentors for subsequent generations of Pediatric physician- scientists.