OVERALL ABSTRACT The overarching Goal of the Washington University Rheumatic Diseases Research Resource-based Center (WU-RDRRC) is to advance research in rheumatic diseases by providing the infrastructure, resources and opportunities for multiple levels of inquiry and translating those discoveries into treatments for delivery to patients. The WU-RDRRC seeks to advance the health of patients with rheumatic disease by supporting enabling technology and promoting the basic and translational research interests of its members. These interests are organized around three major themes: (1) Basic mechanisms of inflammation and autoimmunity; (2) Translational genomics and biomarker discovery; and (3) Musculoskeletal and Regenerative Medicine. Our Central Hypothesis is that translational endeavors in rheumatic diseases research require a team approach performed in a vibrant environment supported by a cross-disciplinary team of experts and state-of- the-art services. Our Focus is to promote interactive approaches that will accelerate the pace of innovative discoveries and translate findings to improvements in treatments for patients with rheumatic diseases. To accomplish our goals we propose the following: 1) A Translational Research Core (TRC) that comprises separate but related services devoted to supporting translational research endeavors: i) an integrated rheumatic disease registry and biospecimen repository (Biobank) that can be searched through electronic biomedical data management systems to allow annotation, tracking and sharing of tissue and databases; ii) a Genomics & Bioinformatics Facility (GBF) powered by the most up-to-date Next-Generation Sequencing technologies and bioinformatics tools to enhance the secure use and analysis of human genomic data and iii) an ImmunoMonitoring Facility (IMF) that offers access to mass cytometry for analysis of human samples. 2) A Genome Engineering Core (GEC) that facilitates functional studies through the use of technological advances such as CRISPR/Cas9 to generate mutant cell lines and knockout/knock-in mice and induced Pluripotent Stem Cells (iPSCs); and 3) A Cellular Imaging Core (CIC) that provides state-of-the-art imaging technologies for building models of health and disease. The Administrative Core promotes collaborative and synergistic interactions in rheumatic diseases research across multiple disciplines and fosters the mentoring of new investigators interested in rheumatic disease-related research.

OVERALL PROJECT NARRATIVE State-of-the-art technologies afforded by the WU-RDRRC will advance our understanding of the pathogenesis of rheumatic diseases through high impact basic and translational research endeavors conducted by cross- disciplinary teams of experts. Findings will potentially translate to improvements in treatment options for patients suffering from various rheumatic diseases.