All of Us Southern Network v.2.0 - 2. Abstract The All of Us Southern Network (AoUSN) has been enrolling in the All of Us Research Program since 2018. It consists of sites in Alabama, Mississippi, and Louisiana, led by a team at the University of Alabama at Birmingham (UAB). The Network motivated by the idea that All of Us represents a unique opportunity to ensure that advances in precision medicine will benefit all people, and that there are large populations in our region who have been historically underrepresented in biomedical research. Our participating sites have extensive experience in earning trust and engaging individuals throughout the region, and we are well positioned to ensure that they are included in the All of Us Research Program. In addition to UAB, participating sites include UAB branch campuses in Huntsville, Selma, and Montgomery, AL; Cooper Green Mercy Health Services Authority in Birmingham; University of Alabama in Tuscaloosa; University of South Alabama in Mobile; University of Mississippi Medical Center in Jackson, MS; Louisiana State University Health Sciences Center (LSUHSC) and Tulane University in New Orleans, LA. Two of these sites, UAB, and LSUHSC, are also active in the Nutrition for Precision Health program. Dr. Stephen Sodeke from Tuskegee University serves as a Bioethics Consultant. The AoUSN has been a leader nationally in enrollment of individuals underrepresented in biomedical research, especially in terms of race, geography, and income. We were highly successful in enrollments pre-COVID-19, though it took some time for the Network to recover full capacity when enrollments resumed. The AoUSN is currently functioning in an extension phase from July 2023 - February 2024. During this time, it has consistently exceeded recruitment goals, reflecting in part the initiation of multiple innovations that will continue to expand through the funding period of the new OTA. These include: inpatient enrollment at UAB and several collaborating sites; establishment of a new site affiliated with UAB in Dothan, AL; opening “pop-up” enrollment sites throughout the region; use of several mobile clinical research units to reach participants in rural areas; use of Computer-Assisted Telephone Interviews (CATI) to facilitate retention; development of a relationship with Lakeshore Foundation in Birmingham, AL to engage and enroll persons with disabilities. We expect to continue and expand upon these innovations in the next five years. Inpatient enrollment has proved to be especially productive and efficient in terms of staff resources and will be expanded at UAB and at partner sites that have inpatient units. Our experience in setting up a new site in Dothan, AL prepares us to establish additional sites in larger cities in our region. We currently have four mobile units, including one exclusively dedicated to All of Us, and have another on order that will be dedicated to enrollment in rural areas of Alabama, Mississippi, and Louisiana. We have a new engagement lead (due to the untimely death of Dr. Shauntice Allen, our former Engagement Lead), Dr. Dina Avery, who has extensive connections with community leaders in our region and will work in an integrated manner with our outreach and enrollment teams to facilitate our ability to enroll participants in new areas. We have several active pilots intended to improve our ability to retain participants, including use of retention navigators and providing financial incentives for retention. Each of the AoUSN sites is prepared to enroll children (including four with affiliated dedicated children’s hospitals) and will support participant reassessments once these components are launched. In conclusion, the AoUSN remains committed to the principles of the All of Us Research Program, and especially its goal of partnering with diverse communities to ensure broad inclusion in the program. Precision medicine is a major theme in UAB and our affiliated institutions, and we see A