The overarching goal of the Health Literacy (HL) Core of the Louisiana Clinical and Translational Science Center (LA CaTS) is to infuse HL, and drivers of health into clinical research to improve health outcomes among Louisiana’s most at-risk population. During the previous funding cycles, the Core was highly effective in embedding HL principles in clinical research projects both within and outside LA CaTS institutions to increase patients’ ability to obtain, understand, and use health information and services as well as participate in clinical trials. The HL Core has enabled collaboration between LA CaTS investigators and Federally Qualified Health Centers, as well as faith-based and civic organizations, in order to infuse HL principles in public health outreach projects targeting at-risk populations across the state. We have expanded our regional and national collaborations with the University of Texas at Houston CTSA. Specific aims for this next cycle are designed to expand our network to more investigators within and outside LA CaTS institutions to include HL principles and drivers of health in their clinical research to improve health outcomes. Specific Aim 1: Enhance and expand trust-building relationships with communities to understand their specific needs, obstacles to healthcare access, and target strategies to improve health outcomes. Specific Aim 2: Collaborate with investigators at LA CaTS institutions to improve patients’ understanding and use of new health technologies that improve management of chronic diseases, medication adherence, preventive care and recruitment in clinical trials, particularly in rural areas. Specific Aim 3: Network within LA CaTS, with CTRs, CTSAs in our region and nationally, and with health agencies within the state, to expand recruitment in clinical trials to Louisiana’s rural and at-risk populations with chronic diseases and barriers to healthcare access . We will accomplish these aims by: 1) expanding HL training to include literacy appropriate use of health technologies such as patient health education on digital platforms, patient electronic portals and digital apps to increase ongoing engagement with at-risk populations; 2) advising investigators in developing and sustaining trust in relationships with various populations, community clinics, and agencies to address health challenges and improve participation in clinical trials and health outcomes; 3) continue to collaborate with investigators within LA CaTS to include participants representative of Louisiana’s population. These aims are designed to include a wide net of stakeholders to design and evaluate acceptable and feasible research strategies to improve access, understanding, and use of health information and services to improve the health of Louisiana’s population with chronic disease.