The successful and rapid translation of fundamental discoveries into better health for our citizens requires a clinical and translational science network that is robust, multidisciplinary, and national in scope. The mission of the Clinical and Translational Science Institute of Southeastern Wisconsin, a unique academic- community partnership between five area academic institutions and three hospitals, is to develop an integrated, shared home for clinical and translational research and research training, hallmarked by a borderless, collaborative, synergistic, and investigator/community/patient-friendly research environment that is functionally integrated into regional and national CTSA networks with the goal of enhancing the transit of therapeutic, diagnostic, and preventive interventions along the developmental pipeline. In the initial five years following the creation of our CTSI, remarkable progress has been made in the multilevel integration of the eight area institutions that comprise the CTSI, the creation of cross-institutional masters and doctoral programs in clinical and translational science, the formation of a bioinformatics focus on clinical and translational research, the development of an increasingly penetrant infrastructure that supports and facilitates the performance of clinical and translational research, including biostatics and trial design and execution, regulatory compliance, translational unit support, and integration into the regional community. Following this initial success, CTSA2.0 proposes to 1) empower our CTSA hub to play a major role in the clinical and research agenda of the nation, by engaging with regional and national CTSA networks in multi-site studies, expanding our partnership to involve additional NIH, NSF, and industry-funded centers and programs, and identifying and replacing bottlenecks and inefficiencies in our clinical and translational research enterprise with innovative and effective solutions; 2) maximize the translational capability and impact of our CTSA hub and its investigators, through the expanded development of a translational workforce trained in team science, engagement of communities of stakeholders in our communities, catalyzing multi-disciplinary team science using innovative approaches, and delivering efficient and timely services to support the conduct of high quality and safe research; and 3) create a mutual learning ?health-care enterprise-CTSA-eco system? that broadens the range and influence of our translational research engine to involve new health systems and patient stakeholder in generating and testing hypotheses, by completing and operationalizing our Biomedical Informatics Connectome which links clinical data in our health systems to our clinical data warehouse that is accessible to investigators and stakeholders, integrating research into clinical practices of our health systems, and providing the opportunity to every patient to benefit from and contribute to advancing health through participation in translational research. These goals and program relates directly to the NIH mission for the CTSAs ? to remove impediments to the translation of fundamental discoveries into better health for our citizens