Joe Lim was enrolled in a Master of Science program at the University of Washington (UW) when a class on environmental health changed his life.
The class was called the Microbiome and Environmental Health and was being taught for the first time by Julia Cui, now Affiliate Professor in the UW Department of Environmental and Occupational Health Sciences (DEOHS) and Head of the Department of Environmental and Molecular Toxicology at Oregon State University; Scott Meschke, Professor in DEOHS; and Jerry Cangelosi, Professor Emeritus in DEOHS. During Cui’s portion of the course, she taught about applications of the microbiome and presented computational methods. Lim, who was working at the time in a computational biology lab in the UW Department of Computer Science and Engineering, asked Cui for advice on his project. They scheduled a couple meetings and soon Lim was working in her lab. “I never saw it coming,” said Lim.
Previously Lim had been studying the ecology of mosquitos who act as pollinators for native North American orchids with Jeff Riffell in the Department of Biology.
Lim finished his master’s degree with Cui and then started on a Ph.D., focusing on how early life exposures to environmental toxicants influence health in adulthood using a mouse model. Specifically, he focused on the influence of early exposure to flame retardants known as polybrominated diphenyl ethers (PBDEs) on liver function in later life. “My main organ of interest was the liver because the liver is a really important organ for metabolizing drugs, food, wine, beer, soda, and so many other things,” said Lim. “It also has multiple cell types. Each cell type performs their own specialized task.”
PBDEs can cross the placenta, and female mice concentrate PBDEs in breast milk, suggesting that early life development is a critical time window for PBDE exposure. Lim and colleagues exposed newborn mice to PBDEs to mimic PBDE exposure through breast milk consumption. They found that early life PBDE exposure altered key liver processes by decreasing signatures of drug metabolism and increasing signatures of inflammation, in both young and old mice. Inflammation is often an early indication of disease. Early life PBDE exposure also altered the gut microbiome composition. Because the liver is fed by a portal vein from the gut, the gut microbiome has an important role in influencing metabolism in the liver.
In order to examine the role of the gut microbiome in mediating the effect of PBDE on the development of metabolic disease, Lim and his colleagues used special “germ free” mice who were bred not to have a microbiome. They transplanted microbiomes into these germ free mice from either mice who had been exposed to PBDE in early development or unexposed mice.
They found that mice with the unexposed microbes developed what is known as “immune tolerance” in their livers—a reduced reactivity that supports healthier liver function. In contrast, mice with PBDE-exposed microbes had a heightened inflammatory response and impaired ability to regenerate, similar to the mice who had been directly exposed to PBDE. This suggests that not all the effects of PBDE exposure on adult liver function are direct—at least some are mediated by effects of PBDE on the gut microbiome.
PBDE is considered a “legacy” flame retardant, having been phased out of regular use. Lim also ran his experiments using tetrabromobisphenol A (TBBPA), currently one of the most commonly used flame retardants in the world. “Both flame retardants have been shown to activate important drug and lipid-sensing receptors expressed in the liver. Both have been linked to altered lipid and carbohydrate metabolism and xenobiotic metabolism [the metabolism of compounds from outside the body],” Lim said. As predicted, early TBBPA exposure was also associated with liver dysfunction in adult mice.
Lim and his colleagues also explored the interaction of TBBPA exposure with another known risk factor for metabolic disease—a fatty diet. After exposed and unexposed mice were weaned, they were placed on either a normal diet or a fatty “Western” diet. While all mice on the fatty diet showed signs of liver dysfunction in adulthood, the ones who had had exposure to TBBPAs in early development had the worst signs of disease. “Overall, this suggests that TBBPA exposure is a secondary risk factor” for metabolic disease, said Lim.
“I think it’s fascinating that environmental exposures can have short and long-term impacts depending on our health status,” said Lim about his work. “I think the most important takeaway is that not all determinants of health are as fixed as our genetics. Some, like the microbiome, are not fixed and can be changed through interventions like altered diet.”
Until September of 2025, Cui directed the Genomics, Bioinformatics & Biostatistics, Microphysiological Systems Facility Core for the UW Interdisciplinary Center for Exposures, Diseases, Genomics & Environment (EDGE). Over the years Lim had extensive support from the core, getting help from Theo Bammler, manager of the core, and Jim MacDonald, core staff, with various aspects of his projects from molecular biology applications like checking the integrity of his RNA samples to statistical analysis.
Lim successfully defended his thesis on July 25, 2025. In the future he hopes to continue his work with the microbiome. “I would love to learn more about the contribution of the gut microbial ecosystem to modulation of the metabolic or immunological landscapes of metabolically active organs,” said Lim. “I’d like to understand more about drugs and therapeutic strategies that are currently used as interventions to mitigate disease development.” We at the EDGE Center wish him luck in his next chapter and look forward to following his progress!
- Metabolomics
- Microbiome
- Gene Environment Interactions
