ABSTRACT American Indian and Alaska Native (AI/AN) communities have been disproportionately negatively impacted by opioid and stimulant drugs, health conditions that cause chronic pain, and related problems such as trauma, suicide, and alcohol use. These problems are caused by settler colonialism. Therefore, AI/AN communities are best positioned to understand and overcome these challenges using cultural strengths and protective factors. Too often research is driven by funder priorities and led by non-community researchers rather than centered on community objectives and led by local research teams. Thus, AI/AN people may not experience sustained health benefits or have the opportunity to develop and strengthen their own research expertise and infrastructure. In response to the opioid epidemic that is disproportionately harming Native people and calls by AI/AN leaders to support communities in implementing their own solutions, the National Institutes of Health (NIH) invites Tribes and Native American Serving Organizations (T/NASOs) and alley organizations to form The Native Collective Research Effort to Enhance Wellness (N CREW). The objectives of N CREW are to support T/NASOs to conduct community prioritized research, grow their infrastructure, and improve the quality of relevant data for local decision-making. With the support of N CREW, T/NASOs will conduct research and data improvement projects to promote wellbeing and healing from the effects of opioid and stimulant drugs, pain, and related problems, such as suicide, alcohol use, and historical trauma. We will form a key component of the N CREW Native Research Resource Network (NRRN) entitled, “Promoting Community Wellbeing Through Indigenous Science and Healing (PC-WISH).” PC-WISH will partner with other NRRN members to support T/NASOs as they develop and pilot research and data improvement projects. PC-WISH is led by a Multiple Principal Investigator team of three Native Investigators (Abigail Echo- Hawk, Kamilla Venner, Stacy Rasmus), and a non-Native researcher (Michael McDonell), who together have over 50 years of experience leading or partnering with T/NASOs, and a productive history of collaboration with one another. Our team has expertise in research on culturally grounded and adapted prevention, harm reduction, treatment, and recovery interventions for opioids, stimulants, pain, and other problems, as well as leaders in Indigenous data improvement frameworks and research with Urban Indian people. PC-WISH is rooted in the understanding that Indigenous Knowledge is the basis for healing in AI/AN communities. We propose an Indigenous Research and Evaluation Partnership Model based on the metaphor of the seasons of the harvest. Using this model and guided by the principles of Tribal and Community Based Participatory Research, we propose the following aims. We will listen and learn from communities to understand their research and data improvement strengths and resource needs. We will host InterTribal Cafés in the first two quarters of the project to learn and document research readiness. We will use this information to create Partnership Plans that will guide our supports and develop blueprints in collaboration with T/NASOs to guide their formative work. We will develop, implement, and refine research trainings, tools, and knowledge exchange opportunities (e.g., workgroups, ongoing consultation) to support the growth of T/NASO research capacity. We will lead and engage in activities that establish, strengthen, and maintain partnerships, as reciprocal communication is the foundation of effective collaboration. We will evaluate our activities by using the Indigenous Evaluation Framework and host InterTribal Cafés at the end of Phase 1. We will use this feedback to reflect on lessons learned in preparation for Phase 2 of N CREW. We will create a dissemination and resource website to share lessons learned and serve as a resource to T/NASOs in the second phase of this important project. We will partner with T/NASOs to disseminate relevant information to their communities and the field. We will also co- lead cross-N CREW activities in collaboration with other NRRN members. Our work will be impactful because we have a track record of long-term sustained partnerships with Rural and Urban T/NASOs to design, implement, and disseminate intervention research and data improvement projects. We will use culturally grounded or adapted approaches to develop, implement, evaluate, and disseminate our work. Our application is innovative because we have expertise that spans the prevention, harm reduction, treatment, and recovery spectrum. We also have extensive research partnership experience in co- developing interventions grounded in local Indigenous Knowledge and culturally adapting evidence based approaches. Further, we can support T/NASOs who may want to develop and pilot multilevel strengths based interventions (individual, family, community), or interventions across the lifespan. PC-WISH has strong AI/AN leadership and representation and includes the only National Tribal Epidemiology Center that is focused on supporting Urban Indian communities. We will utilize innovative, culturally responsive methods to support T/NASOs in reaching their milestones, coordinate with NRRN partners, and refine our efforts so we are prepared to support the expansion of N CREW research in Phase 2 and beyond.