The Center for Pacific Innovations, Knowledge, and Opportunities (PIKO) will build a statewide clinical and translational research (CTR) infrastructure to improve the health of Indigenous Pacific People (IPP) – defined as Native Hawaiians, Other Pacific Islanders, and Filipinos. IPP comprise 40% of Hawaii’s population and have disproportionately high rates of physical and mental health conditions compared to Whites and Asians. They also make up a majority of Hawaii’s other medically underserved and vulnerable populations. PIKO represents a partnership between the University of Hawaii (lead), Hawaii Pacific University, Chaminade University of Honolulu, and a statewide network of practice-based organizations (PBO) and community-based organizations (CBO). PIKO emphasizes the T3 (efficacy studies) to T5 (adoption and institutionalization) domains of CTR where the social determinants of health are strongly operative. PIKO takes a team-science approach to transform current CTR paradigms and to accelerate CTR advances to improve IPP health. PIKO comprises seven Cores: Administrative; Professional Development; Pilot Projects Program; Biostatistics, Epidemiology, and Research Design; Community Engagement and Outreach; Clinical Research and Regulatory Support; and Tracking and Evaluation. The University of Hawaii committed $2 million over 5 years to PIKO. The Overall Specific Aims are: Specific Aim 1: Build a robust CTR infrastructure by establishing and implementing CTR activities within and across PIKO partnering institutions; by leveraging resources and expertise of other research infrastructure programs; by creating CTR registries of academic mentors, community leaders, junior investigators, and study participants; and by implementing efficient and effective administrative operations and communication strategies. Specific Aim 2: Strengthen and diversify the CTR workforce by identifying IPP and non-IPP investigators for CTR careers; by enhancing the mentoring and professional development of CTR investigators and community leaders; by supporting culturally responsive and scientifically meritorious CTR pilot projects; and by engaging PBO/CBO to actively participate on all aspects of CTR. Specific Aim 3: Disseminate and implement CTR findings by providing strategic investments in PBO/CBO to strengthen trust-based relationships; by strengthening a statewide network of PBO/CBO to serve as dissemination and implementation partners; by convening an annual conference that brings together CTR investigators and PBO/CBO stakeholders to share best practices, discoveries, and dissemination and implementation strategies; and by leveraging data science strategies to disseminate data and findings that are user-friendly, easy to understand, and accessible. By the end of this 5-year project, PIKO will have promoted high-impact transformative CTR to improve the health of IPP and other marginalized communities in Hawaii.