A leading physician-scientist at the Keck School of Medicine of USC has been awarded the prestigious Revolutionizing Innovative, Visionary Environmental health Research (RIVER) grant from the National Institute of Environmental Health Sciences (NIEHS), a division of the National Institutes of Health (NIH). This $10 million funding will empower groundbreaking research into the pervasive health impacts of per- and polyfluoroalkyl substances, commonly known as PFAS. The project will be spearheaded by Dr. Vaia Lida Chatzi, a distinguished professor of population and public health science and pediatrics. The grant aims to unravel complex biological mechanisms that link PFAS exposure to metabolic diseases, while also developing actionable solutions to mitigate their health burden.
PFAS are synthetic chemicals widely used in industrial applications and consumer products owing to their resistance to heat, water, and oil. Often referred to as “forever chemicals” due to their environmental persistence and bioaccumulation, PFAS have contaminated ecosystems and are detectable in the bloodstream of nearly all individuals across the United States. Despite their ubiquity, scientific understanding of how these substances disrupt human biology remains incomplete. Chatzi and her collaborators have previously identified associations between PFAS exposure and an array of health issues, yet the underlying pathways and effective intervention strategies remain elusive.
Unraveling the metabolism-disrupting role of PFAS represents one of the most urgent research frontiers in environmental health. Initial studies suggest that PFAS may interfere with hormonal signaling, lipid metabolism, and inflammatory responses, potentially exacerbating conditions such as obesity, type 2 diabetes, and metabolic-associated steatotic liver disease (MASLD). These conditions carry immense public health implications, given their rising prevalence and association with significant morbidity. The RIVER-funded initiative intends to close critical gaps in mechanistic insights and high-risk population identification.
Dr. Chatzi’s research methodology embodies a multifaceted, translational approach, combining epidemiological analyses with cutting-edge laboratory experiments and community-engaged science. Large-scale cohort studies encompassing over 50,000 participants will be leveraged to detect subtle yet significant metabolic perturbations associated with PFAS exposure. Data integration across 18 separate research projects will facilitate comprehensive lifespan analyses, evaluating gene-environment interactions, proteomic alterations, and other biological markers indicative of early disease processes.
Furthermore, meticulous investigation of human tissue samples using advanced three-dimensional organotypic models will shed light on cellular-level disruptions induced by PFAS. These models, simulating liver and pancreatic tissues, allow detailed interrogation of biochemical pathways implicated in metabolic regulation. Understanding how PFAS perturb intracellular signaling networks and cellular homeostasis is critical to deciphering their pathogenic potential and identifying molecular targets for intervention.
The research team will also apply state-of-the-art multi-omics analytical techniques to identify unique biological signatures of PFAS exposure. Integrating genomics, transcriptomics, proteomics, and metabolomics datasets, this approach aims to pinpoint specific biomarkers predictive of increased susceptibility to metabolic disorders. Such signatures could revolutionize personalized health surveillance and facilitate early detection strategies, enabling targeted preventive measures for high-risk populations.
A distinctive element of the project is its commitment to community-based participatory research in collaboration with the Silent Spring Institute. This paradigm fosters bidirectional engagement, where scientific inquiry is informed by and responsive to the lived experiences of communities disproportionately burdened by PFAS contamination. Through partnerships with affected neighborhoods, including areas in Southern California with elevated PFAS levels in drinking water systems, the team seeks to develop culturally tailored interventions that are both effective and implementable within these contexts.
The RIVER award’s provision of flexible, long-term funding liberates investigators from conventional grant constraints, promoting innovative and high-risk research avenues. This autonomy supports exploratory studies with transformative potential, aligning with the urgent need to address emergent environmental health crises like the PFAS epidemic. According to Carolyn C. Meltzer, dean of the Keck School of Medicine, Dr. Chatzi’s visionary leadership is pivotal in bridging gap between chemical exposure science and real-world health outcomes.
Over the coming years, the project aspires to produce robust evidence to guide science-based public health policies and regulatory frameworks. By elucidating the earliest biological effects of PFAS and developing scalable risk reduction strategies, this research stands to influence guidelines for exposure limits, remediation efforts, and clinical management of affected individuals. The interdisciplinary collaboration spans multiple institutions and specialties, enhancing the breadth and impact of findings.
Dr. Chatzi is also principal investigator of the Southern California Superfund Research Program for PFAS Assessment, Remediation, and Prevention (ShARP) Center and the USC Center for Translational Exposomics Research (CTER), both NIEHS-funded initiatives. These programs complement the RIVER research by focusing on environmental sampling, exposure assessment, and translation of scientific knowledge into preventative technologies and policies.
Previous investigations led or co-led by Chatzi have revealed that adolescent PFAS exposure substantially increases the risk of liver disease by as much as threefold. Additional work has demonstrated that these chemicals may negatively influence outcomes following bariatric surgery and are associated with liver cancer and other metabolic disorders. These compelling findings underscore the urgency of advancing mechanistic research and intervention development supported by the RIVER grant.
In summary, the award to Dr. Vaia Lida Chatzi marks a significant milestone in environmental health sciences, catalyzing a multidisciplinary initiative to decode the metabolic repercussions of PFAS exposure. This comprehensive and innovative research program aims to translate scientific discoveries into tangible public health solutions, ultimately mitigating the pervasive threat posed by these persistent environmental contaminants and improving health outcomes at the population level.
Subject of Research: Health effects of per- and polyfluoroalkyl substances (PFAS) and their link to metabolic disorders including obesity, type 2 diabetes, and metabolic-associated steatotic liver disease.
Article Title: NIH Awards $10 Million RIVER Grant to Keck School Researcher to Combat ‘Forever Chemicals’ Impact on Metabolic Health
News Publication Date: Not provided
Web References:
– https://keck.usc.edu/
– https://www.niehs.nih.gov/research/supported/training/river
– https://keck.usc.edu/faculty-search/vaia-lida-chatzi/
– https://silent-spring.org/
– https://sharpcenter.usc.edu/
– https://keck.usc.edu/cter/
References: Supported by National Institute of Environmental Health Sciences [1R35ES035051]
Image Credits: Photo by Gus Ruelas, USC
