PROJECT SUMMARY/ABSTRACT – CORE A Phase 1 of COBRE support established the Center for Musculoskeletal Disease Research (CMDR) at the University of Arkansas for Medical Sciences (UAMS). The scientific theme of the CMDR is that identification of molecular contributors to musculoskeletal dysfunction and disease will guide development of effective therapies. The Center achieved key milestones during Phase 1, including mentoring and support of junior investigators to the point of achieving independence, as defined by obtaining R01-level funding. These efforts, combined with recruitment of established investigators, have significantly expanded the number of successful musculoskeletal investigators in our Center. The three CMDR research cores established during Phase 1 also contributed to the success of our junior investigators and other center members and significantly strengthened the biomedical research infrastructure of our institution. An essential component of the effective operation of the CMDR was establishment of the Administrative Core (Core A), which manages the infrastructure, oversight, and day-to-day functioning of the Center. During Phase 2, the Administrative Core will continue to oversee all organizational and budgetary aspects of the CMDR, supported by internal and external advisory committees (Aim 1). In addition, the core will support CMDR growth via mentoring and a structured faculty development plan that will support Project Leaders to point of R01-level funding (Aim 2). The Administrative Core will also recruit and promote the development of new investigators via a Pilot Project Program, targeted recruitment of new investigators, and evaluation of Center progress by the advisory committees (Aim 3). These goals will be accomplished under the leadership of the Center Director and Associate Director who, with the support of experienced mentors and advisory committees, will enable Project Leaders focused on musculoskeletal research to compete effectively for R01-level funding. The Administrative Core will also oversee the operation of four Research Cores providing state-of-the-art services to create new genetic models (Core B), perform specialized skeletal histology and bank human bone tissue (Core C), provide bone imaging and quantification (Core D), and perform bioinformatic analyses of large molecular datasets (Core E). The overall success of this strategy will be gauged by achieving the following milestones within the five years of Phase 2 support: 1) three or more Project Leaders will obtain R01-level research grant support; 2) three or more new Project Leaders will be selected and join the Center; 3) Project Leaders and other Center members will publish between 25 and 50 peer-reviewed publications; and 4) graduated Project Leaders and other members of the Center will develop productive collaborations and submit a center-level grant application, such as a P01 or P30.