PROJECT SUMMARY/ABSTRACT This proposal is the third renewal application for support of the Pediatric Physician-Scientist T32 training program in the Department of Pediatrics (DOP) at Washington University School of Medicine (WUSM). 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 Trainees per year (typically for 2 years each) by leveraging a wealth of biomedical research resources across the WUSM campus, the DOP and our Child Health Research Center (NICHD CHRCDA K12). For the past 20 years and going forward, the long-term objective of this program is to develop Trainees who 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, multi-omics systems biology, and bioinformatics. The specific aims of this proposal include: 1) a protected mentored research experience with a well-established investigator across a wide range of disciplines related to child health within WUSM and the DOP, 2) obligatory educational programs in laboratory management, scientific rigor, statistics, grantsmanship, responsible conduct of research, and biomedical informatics, 3) individualized coursework based on the Trainees area of investigation (e.g., genetics, cell biology, computational biology), 4) continuous feedback to the Trainee, mentor and program leadership, and 5) a flexible environment that facilitates the development of Trainees who are women and are under-represented minorities. The program, now 20 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., and David Hunstad, M.D. again serve as the Program Director, and the Training Director, respectively. Our Trainees will continue to utilize a vast array of institutionally funded, state-of-the-art research core facilities that provide, for example, whole-genome/exome DNA sequencing, single-cell RNA sequencing, induced pluripotent stem cells and organoids, bioinformatics, cryo-EM and other advanced imaging, CRISPR-CAS9 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 development and childhood 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.