OVERALL ABSTRACT The WU-RDRRC seeks to advance the health of patients with rheumatic diseases by supporting enabling technology and promoting the members’ basic, clinical, and translational research interests that are organized around three major themes: 1) elucidating basic mechanisms of inflammation and autoimmunity; 2) accelerating clinical/translational research to inform precision medicine; and 3) advancing genome engineering and regenerative medicine to develop new treatment approaches for rheumatic diseases. We posit that translational research endeavors in rheumatic diseases require a team approach cultivated in a vibrant environment and supported by cross-disciplinary groups of experts and cutting-edge technologies. Over the past four years, this operational philosophy and the infrastructure supported by the WU-RDRRC perfectly positioned our investigators to increase the efficiency and impact of their research, allowed them to quickly address emergent issues that arose during the COVID-19 pandemic, and helped a number of young investigators obtain extramural funding and successfully transition to research independence. The WU- RDRRC propose to continue promoting rheumatic disease research by: 1) providing the infrastructure, education, and training needed to assist investigators with the experimental and scientific design of their projects; 2) organizing and supporting Core laboratories that will adopt and apply innovative technologies and expertise that would otherwise be unavailable to investigators in a cost-effective manner; 3) promoting interest in rheumatic diseases research by engaging multidisciplinary teams and bringing together diverse disciplines and clinical divisions to address roadblocks in translational science; 4) fostering the next generation of junior investigators who are interested in the study of rheumatic disease-related areas. To accomplish our goals we propose four cores: 1) a Biobank and Phenotyping Core to collect high-quality biospecimens for downstream molecular analysis; 2) a Genome Engineering Core to generate bioengineered cell-based therapies, knockin/knockout mice for testing in preclinical disease models; 3) a Cellular Imaging Core that offers novel microscopy technologies for building models of health and disease; and 4) an Administrative Core that promotes collaborative and synergistic interactions among rheumatic disease researchers and the mentoring of junior and new investigators interested in rheumatic disease research. In addition, we will address members’ evolving needs by expanding access to novel technologies such as spatial transcriptomics, and the changing societal landscape by incorporating social determinants of health into clinical data collection, and enhancing diversity of trainees entering the physician-scientist pathway.