Overall Abstract The Center for Dietary Supplements and Inflammation (CDSI) COBRE is located at the School of Medicine (SOM), the University of South Carolina (USC), Columbia, SC. SOM is one of the smallest medical schools in the nation located at the Veterans Administration (VA) campus. Thus, the CDSI attracts users from multiple colleges across USC. The scientific mission of the CDSI is to investigate how compounds derived from botanicals and natural products can attenuate inflammation as well as understand the mechanisms that trigger chronic inflammatory diseases. Inflammation plays a critical role in the pathogenesis of not only autoimmune diseases but also a wide range of clinical disorders including cardiovascular diseases, neurodegenerative disorders, obesity, aging, and cancer. Thus, understanding the mode of action of botanicals or their constituents on inflammation could lead to novel treatment modalities with far-ranging clinical implications. To accomplish this goal, we will continue to build on the success of COBRE Phase-1 and Phase-2, further advance the research infrastructure, grow the critical mass of researchers using diverse perspectives, and promote the sustainability of the research cores. In Phases-1 and 2, we have made outstanding progress in the successful transition of 12 of our junior faculty Research Project Leaders (RPLs) into independent NIH/NSF-funded investigators as PIs. Additionally, the CDSI funded 26 Pilot Project leaders (PPLs) who were also highly productive. Also, we were successful in securing NIH Complementary and Alternative Medicine (CAM) Center (PPG/P01) for Epigenetic Regulation of Inflammation, in which ‘graduated’ RPLs served as project leaders, thereby paving the path towards sustainability of CDSI. The Specific Aims include: 1) To support innovative research using the latest technologies and equipment such as Spectral Flow Cytometry, Single-cell RNA-seq and Single-cell Spatial Transcriptomics, natural product library, and high-throughput data analysis, offered at our core facilities. 2) To continue to grow the critical mass of researchers at CDSI by providing support through the Pilot Project Program (PPP) and recruitment of new and early-stage as well as diverse investigators. 3) To sustain a multi-disciplinary, collaborative research program and cores beyond Phase-3. The CDSI will offer two state-of-the-art research core facilities that include a Flow Cytometry, and Cell Analysis (FCCA) Core, and a Bioanalytical Core, to study epigenetic and microbiome regulation of inflammation. The program will be evaluated by an Administrative Core (AC) consisting of nationally recognized scientists. Additionally, through institutional support, several new tenure- track and diverse faculty will be recruited and mentored at USC to further increase the critical mass of users. The long-term objective of the CDSI is to build a self-sustaining, nationally and internationally recognized multi- disciplinary Center for dietary supplements and inflammation research.

Project Narrative Inflammation is the underlying cause of a larger number of clinical disorders. Our Center will pursue multi- disciplinary research to study how compounds found in botanicals can suppress inflammation and identify new pathways that trigger or prevent inflammation by providing state-of-the-art research facilities to investigators.