Translational Research Program on PFAS and Metabolic Diseases: A Solution Oriented Framework

This R35 application aims to revolutionize precision environmental health in a model research program addressing the complex health risks posed by per- and polyfluoroalkyl substances (PFAS), with a focus on metabolic diseases such as obesity, type 2 diabetes, and metabolic-associated steatotic liver disease (MASLD). PFAS, known as "forever chemicals", are detectable in the blood of nearly all U.S. residents and disrupt metabolic processes through multiple biological pathways. This research will fill critical knowledge gaps by leveraging large-scale epidemiological data, innovative translational models, and multi-omics approaches to identify early biological markers of PFAS exposure and develop culturally tailored, scalable interventions. The project is organized into four interconnected research areas: Area 1 (Investigating PFAS-Health Effects) will analyze data from over 50,000 participants across 18 diverse cohorts to examine PFAS associations with omics biomarkers and metabolic health outcomes, creating a comprehensive dataset that links environmental exposures to disease risk across the lifespan. Area 2 (Uncovering Biological Mechanisms) will elucidate the mechanisms by which PFAS disrupt metabolic function, using innovative in vitro models, including 3D liver tissue cultures and single-cell RNA sequencing. Area 3 (Applying Data Science and Integrating Multi-Omics) will apply cutting-edge data science techniques to integrate in vitro and epidemiological data to identify "omics signatures" associated with PFAS exposure and enhance precision in risk assessment and targeted interventions. Area 4 (Engaging Communities in Translation) will co-create prevention and intervention strategies with affected communities, ensuring research findings are translated into actionable health outcomes. Supported by the PI’s sustained leadership and track record in PFAS and environmental health research, this RIVER program will provide the flexibility needed to integrate large-scale epidemiological discovery, translational mechanistic research, and data-driven analytic innovation to address emerging PFAS exposures and evolving public health priorities. The anticipated outcomes include innovative tools to mitigate PFAS-related health risks and support long-term progress in precision environmental health research. Project Number: 1R35ES035051-01A1 | Fiscal Year: 2026 | NIH Institute/Center: National Institute of Environmental Health Sciences (NIEHS) | Principal Investigator: VAIA LIDA CHATZI | Institution: UNIVERSITY OF SOUTHERN CALIFORNIA, Los Angeles, CA | Award Amount: $1,256,897 | Activity Code: R35 | Study Section: Special Emphasis Panel[ZRG1 KUDS-N (57)] View on NIH RePORTER: https://reporter.nih.gov/project-details/11222269