Chanhee Kim, an assistant biology professor at California State University, Northridge, has identified a previously unrecognized gene that influences how human liver cells respond to a common PFAS, or per- and polyfluoroalkyl substances, also known as “forever chemicals.”
His research provides new insight into the biological mechanisms that may contribute to PFAs-associated changes in liver fat metabolism.
“Although the gene has been found during a study on forever chemical toxicity, the potential implication could be bigger than just its association with forever chemicals,” said Kim, who teaches in CSUN’s College of Science and Mathematics. “This gene is very important in making lipids — specialized structures within cells that store fats — accumulate in our liver, its discovery would have therapeutic implications in terms of preventing diabetes and fatty liver diseases.”
Kim’s findings, “A Genome-wide CRISPR screen identifies C18orf32 as a novel modulator of PFOA-induced cytotoxicity and lipid dysregulation,” were published in the journal Environmental Health Perspectives. His co-authors include Abderranhmane Tagmount, Zhaohan Zhu, Frances Wilson, Brad Barbazuk, Rhonda Bacher and Chris D. Vulpe, all with the University of Florida, where Kim did postdoctoral research in the Vulpe’s laboratory at the Center for Environmental and Human Toxicology.
PFAS, or per- and polyfluoroalkyl substances, are a large group of human-made chemicals used in a variety of consumer and industrial products because they resist heat, water, grease, and stains. Due to their extraordinary persistence in the environment, PFAS are often referred to as “forever chemicals.” They have been detected in water, soil, wildlife, and human populations worldwide, raising ongoing concerns about their potential effects on human health.
Kim said one of the most consistently reported biological effects of several PFAS compounds is disruption of lipid metabolism, the cellular processes that regulate how fats are produced, stored, and utilized. In particular, exposure to perfluorooctanoic acid (PFOA), one of the best-studied PFAS compounds, has been associated with alterations in liver function and fat metabolism. However, many of the molecular mechanisms underlying these effects remain poorly understood.
To understand what the molecular mechanisms are that are affecting liver function and fat metabolism, Kim and his colleagues used CRISPR, a gene-editing technology that allows scientists to systematically disable genes and determine how they influence cellular responses to environmental chemicals. By conducting a genome-wide genetic screen in human liver cells, the team identified hundreds of genes that affect how cells respond to PFOA exposure.
Among these genes, one called C18orf32 emerged as a particularly important candidate. The gene produces a protein associated with lipid droplets. When researchers disabled C18orf32, human liver cells became more resistant to the toxic effects of PFOA and accumulated substantially less fat following exposure.
Further analyses showed that the loss of C18orf32 reduced the activity of numerous genes involved in fatty acid metabolism, cholesterol metabolism, and other pathways known to regulate lipid storage.
The researchers also observed similar effects with two additional PFAS compounds, PFOS and GenX, suggesting that the biological role of C18orf32 may extend beyond a single PFAS chemical.
“These findings help identify a previously unrecognized factor involved in how liver cells respond to PFAS exposure,” Kim said. “While additional research is needed, this work advances our understanding of the cellular pathways that may contribute to PFAS-induced changes in lipid metabolism.”
The researchers emphasized that the study was conducted in cultured human liver cells and was designed to uncover biological mechanisms rather than predict health outcomes in people.
“The findings should therefore be viewed as an important step toward understanding how PFAS interact with cellular systems, rather than as evidence of direct health effects,” Kim said.
The research aligns with Kim’s program at CSUN, which focuses on functional toxicogenomics and molecular and cellular toxicology, combining modern genomic technologies with toxicology to understand how environmental exposures affect human health. He aims to improve understanding of the molecular mechanisms underlying environmental exposures and their impacts on human health.
Kim said his work is partly inspired by the film “Dark Waters,” starring Mark Ruffalo. In the film, based on a real incident, Ruffalo plays an attorney who files a lawsuit against the chemical manufacturing company DuPont after it contaminated a town with unregulated chemicals.
“It underscores how important it is for researchers to put an effort into studying forever and other chemicals and the impact they have on human life,” he said.