Cherokee INSPIRE (Indigenous and Native Science Program for Igniting Research & Education) - Project Summary Cherokee INSPIRE (Indigenous and Native Science Program for Igniting Research & Education) will provide multiple pathways to increase representation of American Indian and Alaska Native (AI/AN) students in science, technology, engineering, and mathematics (STEM)-related careers and research. Cherokee INSPIRE will be led by Cherokee Nation and their Sequoyah High School (SHS), a Bureau of Indian Education (BIE) school. Additional program partners include the University of Oklahoma Health Sciences Center (OUHSC), the Oklahoma State University Center for Health Sciences (OSU-CHS) - Office of American Indians in Medicine and Science, and the OSU College of Osteopathic Medicine (OSU-COM) at Cherokee Nation. OSU-COM at Cherokee Nation is the only tribally affiliated medical school in the nation. Cherokee INSPIRE aims to 1) develop a replicable science curricula that integrates Western Science and Indigenous Knowledge and Science (IKS), 2) implement hands-on research and STEM projects within core science classes that will include community mentorship and digital and Indigenous storytelling as novel modes of student learning, 3) establish a multilevel mentorship and research program. In Specific Aim 1, SHS teachers, students, and staff will partner with Indigenous community elders and experts in Indigenous science development to create curricula for their STEM courses that integrates IKS with Western Science, and which also aligns with Next Generation Science Standards (NGSS). Each year, an IKS theme will be selected to guide the transformation of courses in different subfields (biology, earth science, etc.). Digital storytelling, storyboarding, podcasting, and social media platforms will capture stories, experiences, and knowledge related to science, medicine, technology, and environmental balance, which will help inform and create educational resources for the curriculum. In Specific Aim 2, Cherokee INSPIRE students will conduct research and hands-on projects within core science classes, encouraging student-driven inquiry and critical thinking. Finaly, in Specific Aim 3, a formal mentorship program will be created using a Peer-Onsite-Distance (POD) model and incorporate students, teachers, faculty, and staff from SHS, OUHSC, OSU-CHS, OSU-COM at Cherokee Nation, as well as STEM professionals from various departments within the Cherokee Nation. Mentorship PODS will encompass multiple forms of mentorship interactions (peer-peer, near-peer, intergenerational, and reverse peer). Each semester, high school students in mentorship PODs will complete a scientific poster that will be presented at a newly developed Cherokee INSPIRE SHS Research Showcase. Fostering a greater AI/AN presence in STEM, with a specific eye toward creating communities of learning will impact current health and educational disparities. Tribal communities and health systems have designated these disparities as a high priority, and our proposed pathways with respective activities will provide immediate and long-term impacts via reciprocal mentorship networks, enhanced community partnerships, and integrated place-based curriculum.