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Objective To describe the roles community members can and should play in, and an asset-based strategy used by Chicago’s South Side Health and Vitality Studies for, building sustainable, large-scale community health research infrastructure. The Studies are a family of research efforts aiming to produce actionable knowledge to inform health policy, programming, and investments for the region. Methods Community and university collaborators, using a consensus-based approach, developed shared theoretical perspectives, guiding principles, and a model for collaboration in 2008, which were used to inform an asset-based operational strategy. Ongoing community engagement and relationship-building support the infrastructure and research activities of the Studies. Results Key steps in the asset-based strategy include: 1) continuous community engagement and relationship building, 2) identifying community priorities, 3) identifying community assets, 4) leveraging assets, 5) conducting research, 6) sharing knowledge and 7) informing action. Examples of community member roles, and how these are informed by the Studies’ guiding principles, are provided. Conclusions Community and university collaborators, with shared vision and principles, can effectively work together to plan innovative, large-scale community-based research that serves community needs and priorities. Sustainable, effective models are needed to realize NIH’s mandate for meaningful translation of biomedical discovery into improved population health.

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