9/23/2025 Ben Libman
Bioengineering professor Joseph Irudayaraj has uncovered how PFAS, or “forever chemicals,” damage cells at the epigenetic level and demonstrated a potential way to reverse the harm. His team showed that PFOS, a common PFAS, disrupts gene-regulating methyl groups in kidney cells, impairing survival and function. Using a modified CRISPR system, they were able to restore these epigenetic switches and improve cell health. The findings not only reveal how PFAS contribute to disease but also highlight promising strategies for repairing their toxic effects.
Written by Ben Libman
One of the biggest health concerns for consumers today is the proliferation of per- and polyfluoroalkyl substances (PFAS). PFAS are commonly known as “forever chemicals” because they do not easily break down in the environment or your body. These chemicals are used in products like nonstick cookware, workout clothing and various industrial applications. Though useful for industry, PFAS have been shown to have detrimental effects on human health. PFAS are linked to kidney disease, metabolic issues and even cancer.
Avoiding these chemicals isn’t always possible- not only are PFAS ubiquitous in products today, but they accumulate in the environment around us. For example, a recent study led by bioengineering professor Joseph Irudayaraj tested fish for PFAS from 15 sites around Illinois- each location was contaminated. But major questions remain- how exactly do PFAS impact our cells? And is there any way to reverse the damage?
In a new study, professor Irudayaraj has chosen to examine just that. In a recent paper published in ACS Publications, professor Irudayaraj and his team sought to understand how PFAS disrupts cells at the epigenetic level and to see if there might be a way to repair them. The focus of this study was one of the most well-known PFAS, perfluorooctanesulfonic acid or PFOS.
Professor Irudayaraj focused on epigenetic switches known as methyl groups. These methyl groups act as on/off switches for DNA. “Epigenetic switches regulate gene expression without altering the underlying DNA sequence,” explained professor Irudayaraj. “This is unlike genetic mutations, which involve permanent changes to the DNA sequences. This distinction matters for health because epigenetic changes are often reversible and can be influenced by environmental factors.”
Professor Irudayaraj used kidney cells to test his theory. “The kidney is a critical target organ for PFAS research because it serves as a primary detoxification organ, filtering environmental contaminants from the bloodstream,” said Irudayaraj. “PFAS are known to accumulate more in the kidney among other organs due to their persistence and slow excretion rates. Furthermore, growing epidemiological evidence has linked PFAS exposure to an increased risk of kidney cancer.”
Irudayaraj showed that PFOS disrupts kidney cell function through epigenetics. Exposure to PFOS correlated directly with cell survival- the more PFOS in the system, the greater the likelihood of cell damage or death. PFOS disrupted methylation at particular DNA sites, especially those linked to stress response, inflammation, and cancer.
Once the damage was pinpointed, Irudayaraj’s team attempted to repair it using a version of the gene editing tool CRISPR, modifying it so that it could add or remove methyl groups from DNA and restore normal function. “This approach allows us to precisely control gene expression without altering the underlying genetic code,” explains Irudayaraj.
The results were significant. The team found that they were able to repair methyl groups and restore normal functions across the cells. Treated cells showed higher survival rates and reduced toxic effects. They were able to get these results even while making very small changes to individual CpG sites, which are specific spots in DNA where methyl groups can attach. Irudayaraj explains: “Reversing toxicity by editing a single CpG site is significant because it shows that very precise epigenetic modifications can directly impact cell function and disease-related pathways. This suggests that targeted epigenome editing could be a powerful therapeutic strategy, allowing us to correct harmful gene regulation changes without altering the underlying DNA sequence, potentially reducing off-target effects compared to traditional gene editing. We also expect to utilize our epigenome editors to identify therapeutic targets and to prioritize the efficacy of biomarkers in relation to function.”
Professor Irudayaraj is excited to continue this research and bring it closer to applications in health. “The next steps involve validating our findings in animal models to assess how these epigenetic changes influence kidney cancer development and progression in a whole-organism context. If successful, we can then explore preclinical studies using patient-derived xenograft models, which more closely mimic human disease, before considering early-phase clinical trials. Our team is collaborating with kidney cancer surgeons in Cleveland Clinic to evaluate human samples (blood and tumor tissues) to identify individuals with higher risk for kidney cancer based on PFAS levels.”
Most importantly, the study is significant for clearly demonstrating the ways PFAS can harm our body. “By showing that PFAS can induce specific epigenetic changes, we provide evidence that long-term exposure from drinking water, food and consumer products could have lasting health consequences,” concludes professor Irudayaraj. “This connection underscores the urgency of stricter PFAS regulation, improved water treatment technologies, and public health interventions to reduce exposure in affected communities.”
Professor Joseph Irudayaraj is a professor in the Department of Bioengineering at The Grainger College of Engineering, University of Illinois Urbana-Champaign. He is the Associate Director of Shared Resources at the Cancer Center at Illinois, the Director of the Illinois Superfund Research Center, and affiliated with the Holonyak Micro & Nanotechnology Lab, the Carle Illinois College of Medicine and the Department of Materials Science & Engineering.