PROJECT SUMMARY The Sample Processing and Immunoassay REsearch SPIRE Core (Core C) serves the RDRCC research community as a centralized resource for preparation and storage of clinically derived samples, for conducting a range of standard and innovative assays on clinically-derived material, and for serving as a conduit to other relevant Institutional research Cores. Over decades, this core has facilitated, through disease-specific Centers of Excellence, the generation of large specimen bio-repositories obtained from well-pedigreed patient cohorts. This well-established Core, by providing biospecimen acquisition, processing, storage, and retrieval services, has become a critical partner in enabling discovery at the translational interface, and in attracting the interest of a growing group of researchers from inside and outside the institution. In a survey of the research community, this Core was viewed as a major resource, broadly enabling scholarship on well-defined patient cohorts followed prospectively, with the storage of high-quality samples. The high-quality assay services provided by Core C have resulted in numerous peer-reviewed publications, abstracts and investigator-initiated grant proposals. The assay capabilities in the Core play a critical role in pathway validation in human rheumatic disease cohorts. The aims of this proposal are to sustain, grow and evolve this vital resource. We have added high-dimensional metabolic analysis of immune cell populations by Dr. Jonathan Powell, and assays of immune effector function. Core leaders have established interactions to guide investigators to the necessary institutional expertise and resources that provide single cell analysis, sequence-based assays of immune activity, and advanced data analysis and interpretation. Core C will be directed by Drs. Casciola-Rosen and Darrah. Dr. Casciola-Rosen brings decades of experience and rigor in running a highly effective and budget-stable research Core, and in autoantibody discovery. Dr. Darrah recently assumed leadership of the Flow Core, and also brings experience in sequence-based immune-based assays. Drs. Andrade and Gutierrez, both of whom have many years of experience working with this Core team, will provide additional leadership. Dr. Powell leads the high-dimensional immunometabolism analysis.