PROJECT SUMMARY/ABSTRACT This renewal application (RFA-HD-21-017) is for support of the Child Health Research Center (CHRC) at 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 junior faculty level, our program supports a mentored career development pathway for 3 Scholars per year for 2-3 years by leveraging a wealth of biomedical resources across the Washington University School of Medicine campus. As we have done for the past 26 years, the long-term objective of our Center is to develop Scholars who focus their research efforts on pediatric disease-oriented biology by applying recent advances in the basic sciences, including developmental biology, cell biology, immunology, genetics/genomics, and systems biology. The specific aims of this proposal include: (1) providing protected, mentored research experiences with well-established investigators encompassing a wide range of disciplines across Washington University School of Medicine and within the Department of Pediatrics; (2) obligatory educational programs in laboratory management, scientific rigor, statistics, grantsmanship and responsible conduct of research; (3) personalized coursework based on each Scholar’s area of investigation (e.g., bioinformatics, statistics, advanced imaging); (4) ongoing feedback to the Scholars, mentors and CHRC leadership; and (5) promoting the development of Scholars who are women and are from communities traditionally underrepresented in medicine and science. The program has a stellar track record, by far exceeding national benchmarks (”K12 to K08/23” conversion rate of 73% and an outstanding “K to R conversion” rate of 60%; national average <38%), and will ultimately close the knowledge gap between basic scientists and pediatric clinicians. Gary A. Silverman, MD, PhD, will continue to serve as Program Director, and David Hunstad, MD, will continue to serve as Training Director. The CHRC and its Scholars will utilize dozens of institutional state-of-the-art core facilities that provide, for example, genomic and metagenomic sequencing, transcriptomics, metabolomics, mass spectrometry, bioinformatics, cryo-EM and other advanced imaging, CRISPR genome editing and animal model development, to facilitate the study of pediatric disease states. The long-term goals of the CHRC are being realized as its Scholars contribute to our understanding of child health and disease for decades to come, while evolving into the next generation of scientific leaders, role models, and mentors for subsequent generations of pediatric physician-scientists.