Summary In July of 2017, we launched Phase I of the COBRE Center for Translational Pediatric Research at Arkansas Children’s Research Institute in Little Rock, Arkansas. The mission of the center is to use proteogenomic approaches to identify epigenomic mechanisms and therapeutic targets in diseases, including cancer, impacting or translatable to the pediatric population. The unifying theme of research among center members is utilizing systems biology approaches and sophisticated bioinformatics for studying disease mechanism. The goal of Phase I was to establish the foundation of the center, expand the pool of successful investigators with a Faculty Development Plan, and support systems-level core resources. Towards this goal, the center was created with a nucleus of 4 Research Project Leaders and 2 research cores, Proteomics Core and Genomics & Bioinformatics Core. Through use of a mentored Faculty Development Program overseen by the Administrative Core, the junior investigators from Phase I received 9 RPG-level grants, including an U01-award. Additionally, we were able to “graduate” both Phase I research cores to self-sustainability. Collectively, during the past 4 years of Phase I, we have made substantial progress towards establishing a multi-disciplinary, thematic research center through expansion of our center members, transitioning core resources to independence, and extramural funding – demonstrating how the center is moving in the direction of long-term sustainability beyond COBRE support. Building on the momentum of Phase I, our goals in Phase II are to further enhance our institutional research infrastructure by developing our multi-disciplinary, thematic research center through strategic expansion of the critical mass of investigators, investing into research infrastructure, and implementing a plan for long-term center sustainability beyond COBRE support. We will provide structured mentoring and support to an initial group of 5 Research Project Leaders in Phase II. Furthermore, we will expand the pool of investigators in the center through institutional commitments to recruit 4 Assistant and 1 Associate or Full Professor to the center. To support needs of the expanding critical mass of investigators, we will develop a new Proteogenomics Core that is essential for the evolving research mission of the center. This unique core will provide Research Project Leaders and other center members access to experienced personnel for non-standard proteomic, genomic, and epigenomic applications, and access to highly skilled bioinformaticians for cutting-edge data analysis and integration. To support the expansion of investigators and a new research core, the Administrative Core will provide a Faculty Development Plan, Pilot Project Program, operational oversight, and leadership as the center prepares to transition to long-term sustainability. Upon completion of Phase II, we anticipate having a critical mass of junior, mid-career, and senior inves...