ABSTRACT The basis of molecular epidemiologic research lies in the combination of biospecimens and linked subject data. Over the past two phases of our COBRE Center for Molecular Epidemiology, we have created a unique Biorepository and Biorespecimen Resource Facility Core with a state-of-the-art and internationally competitive infrastructure incorporating advanced robotic and bioinformatic systems. Careful handling of biologic samples with well-integrated de-identified specimen coding, tracking, and data systems are essential for applying cutting-edge technologies to rapidly advance our understanding of the molecular basis of complex disease interactions. The Core has handled over 400,000 diverse samples, created over 270,000 aliquots, and assembled and distributed over 50,000 specimen sets to specialized laboratories. Reflecting the high value of the Core to the insitutional research mission, the Biospecimen Resource Facility – containing over 615,000 samples – expanded into a larger, on-site, and newly renovated space with modernized security and back-up systems for long-term biospecimen storage. An advanced laboratory information management and biospecimen tracking system has been implemented, and our automated equipment has been upgraded for even higher throughput sample processing with flexible configuration to assimilate future technological advancements. The wealth of experience, optimized protocols, and efficient systems management approaches in the Biorepository Core allow the support of a broad range of downstream analyses including novel chemical assays, genome wide analyses, metabolomics, and metagenomics. The Core has continued to expand its ability to accommodate diverse specimen types and applications including processing, archiving, and isolations for single cell genomics applications. In Phase III, we will: expand our biorepository services (Aim 1); grow our user base by creating and disseminating materials about our offerings (Aim 2); and extend and adapt our array of services for the wider research community, while continuously evaluating our performance and repertoire of services and developing a strategic plan to achieve long-term sustainability (Aim 3). By providing a centralized and integrated biorepository resource, including study design consultation, we will continue to i) enable efficient, appropriate, and safe collection and storage of biomaterials, ii) utilize quality-controlled sample processing, archiving, and extraction procedures, iii) provide access to experienced investigators with decades of experience in human sample storage and use, and iv) facilitate collaboration and integration across projects and investigators. In Phase III, we will refine our marketing and financial plans for sustainability, and train investigators on ways to expedite research translation and commercialization. Thus, we will continue this vital and successful Core to support new initiatives seeded by the Pilot Project Program, along with...