Southern California Superfund Research and Training Program for PFAS Assessment, Remediation, and Prevention (ShARP) - The overall goal of Southern California Superfund Research and Training Program for PFAS Assessment, Remediation, and Prevention (ShARP) is to develop problem-based, solution-oriented scientific knowledge and innovative technologies to address the issue of poly- and perfluoroalkyl substances (PFAS) water contamination in Superfund and other sites. PFAS are a class of persistent and ubiquitous chemicals contaminating more than 3,000 sites across the U.S., including at least 245 EPA-identified Superfund sites. PFAS exposure can affect liver health and partly explain the excess burden of metabolic dysfunction-associated steatotic liver disease (MASLD) in the U.S. We will strengthen the Superfund Research Program (SRP) and complement current SRP Centers by establishing the first Center that specifically addresses PFAS in relation to their effects on liver disease. The Center will lead four highly interactive Research Projects that integrate biomedical and environmental engineering research related to the SRP mandates with the following objectives: (1) Develop advanced techniques to evaluate the effect of PFAS on liver disease (mandate 1) and the molecular mechanisms of PFAS hepatotoxicity (mandate 2) in human 3D liver spheroid models (Project 1) and in human longitudinal studies (Project 2); (2) Develop novel PFAS characterization techniques on samples from environmental reservoirs (water, soil, and air) and a predictive PFAS groundwater model for mobilization of PFAS plumes from a PFAS-contaminated Superfund site because of groundwater recharge (mandate 3/Project 3); and (3) Develop advanced processes for microbial, chemical, and thermal defluorination to allow definitive PFAS treatment, with application to Superfund sites (mandate 4/Project 4). The Research Programs are led by collaborative multidisciplinary teams and supported by four Cores: The Community Engagement Core (CEC) will foster communication and support the translation of Center research findings to inform prevention strategies. The Data Management and Analysis Core (DMAC) will optimize the use of the complex data generated by the research projects and serves as an incubator to accelerate cross-project integration and discoveries. The Research Experience and Training Coordination Core (RETCC) will support the training of the next generation of scientists in environmental health and engineering, translational research and community engagement. The Administrative Core supports the translation of the Center’s research findings to key SRP end-users. In summary, our system-based integrated approaches, the central role of the communities, the strong institutional support, and our team’s successful experience working together, will enable us to address urgent concerns regarding water quality and human health in populations affected by PFAS exposures and Superfund sites. PAGE