Center for Mucosal Immunobiology and Rheumatic Disease Pathogenesis

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A substantial cadre of investigators at the University of Colorado are focused on characterizing the molecular origins and causal mechanisms that drive the initiation and preclinical phases of rheumatic and autoimmune diseases. One of the most important outcomes of those efforts has been the demonstration in populations at- risk for future disease that dysbiosis and chronic inflammation at mucosal sites can promote the initial local development of disease-specific loss of tolerance to autoantigens. Ultimately, this process leads to systemic autoimmunity and the development of diseases including rheumatoid arthritis (RA) and spondyloarthroarthritis (SpA). Building on that concept with unique at-risk populations and an extensive programmatic infrastructure, a P30 Rheumatic Disease Research Resource Center (RDRRC) entitled “Center for Mucosal Immunobiology and Rheumatic Disease Pathogenesis” is proposed. Included in the Center are an Administrative Core, a Population and Data Sciences Core, and a Mucosal Immunobiology Core. This Center is specifically designed to facilitate studies of human disease pathogenesis that incorporate the broad range of mucosal and systemic immunologic techniques, as well as develop new approaches, to study these integrated mechanisms in already recruited cohorts of individuals throughout the preclinical and then clinically active phases of disease. The Center includes 43 internal and external members who have in aggregate $77M in related annual direct cost grant funding. In addition to providing access to stored biospecimens and data from ongoing population studies, the Center will provide consultative and member discount mechanisms for all of the critical aspects of cohort development, epidemiologic assessment, data management and data analyses. In addition, the Center will provide members access to technologies that focus on analyses of the microbiome and microbial:cell interactions, as well as informative mucosal and peripheral immune biomarkers. The Center will build on a recent $80M investment from the Dean to fund four other relevant programs with which this Center will interact. Dr. Michael Holers, Professor of Medicine and Immunology, will serve as the Center Director, and Dr. Kristi Kuhn, Associate Professor of Medicine, will serve as the Associate Director. Both will interact with Advisory and Executive Committees, and in the latter will be joined by Core Directors and Co-Directors with domain expertise. As a key component of the mission of the Center, a Pilot & Feasibility Grants Program will be developed with substantial institutional support. Additional Enrichment Program activities will include a seminar series, technology assessment series, and an annual symposium. A major focus will be on early career investigator development through enhanced Core access as well as Grants Review and a Scholars Programs. Social media, web-based outreach and newsletters will provide comprehensive communication. Finally, a Patient Impact Program will be utilized for the assessment and enhanced translation of novel biomarkers and therapeutically relevant RDRRC discoveries into direct patient care with the goal to improve outcomes.