The overarching goal of the Center for Pacific Innovations, Knowledge, and Opportunities (PIKO) is to develop a robust infrastructure for clinical and translational research (CTR), intending to mitigate health disparities in Indigenous Pacific People (IPP), defined as Native Hawaiians, Other Pacific Islanders, and Filipinos, as well as in other underserved populations (e.g., immigrants, homeless, and sexual and gender minorities). To achieve this goal, a Pilot Project Program (PPP) will be designed to provide funding, on a competitive basis, to Junior Investigators (JI) and Established Investigators (EI) who are seeking to make significant changes to their research program. They will come from the faculty of the University of Hawaii, Hawaii Pacific University, and Chaminade University of Honolulu. Funding will be prioritized toward innovative, high quality, and impactful T1–T5 CTR pilot projects, with an emphasis on T3-T5, that accelerate the translation of clinical and biomedical research into better patient care and improved public health for IPP and other underserved populations. The provision of support for pilot projects is expected to result in heightened research productivity and increased competitiveness for mainstream extramural funding for JI/EI. Also, given the serious concerns about the aging of the NIH-funded scientific workforce, and the dearth of IPP principal investigators, we will actively encourage applications from IPP JI/EI. Thus, the PPP Core objective will be achieved through the following Specific Aims: Specific Aim 1: Solicit, review, and fund meritorious pilot projects by developing eligibility criteria, and managing solicitation procedures and application submission processes; and by establishing review criteria and managing review, funding-decision, and award-approval processes. Specific Aim 2: Provide post-award oversight and evaluation of pilot projects by monitoring and evaluating the performance, progress, productivity, and return on investment of the awardees; and by assuring awardees comply with federal policies, rules, and guidelines for conducting CTR. By the end of five years, the PIKO PPP Core will have funded 35 to 45 JI/EI to conduct culturally responsive and scientifically rigorous CTR pilot projects focused on improving the health of IPP and other medically underserved and vulnerable populations. Preliminary data from these pilot projects will be used to secure federal and national grant funding. Most of the funded JI/EI will be from IPP backgrounds, thereby increasing the number of IPP investigators successfully competing for NIH or other extramural funding.