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UF scientist studies unique receptor’s relationship to immune system disease

By Sarah Carey

Dr. Liang Zhou studies the role of a unique protein molecule and its relationship to immune system disease. (Photo by Paul Privette)

As a researcher seeking to understand more about how the body regulates immune responses, Dr. Liang Zhou focuses on a receptor that is best known for detecting environmental contaminants inside the body, such as the dioxin that poisoned former Ukrainian president Victor Yushchenko in 2004.

Yushchenko survived the incident, which drew international attention after he fell mysteriously ill and developed disfiguring lesions on his face, as well as other symptoms.

“This receptor was originally only known for its effects in mediating environmental toxins and is commonly referred to as ‘dioxin receptor,’” said Zhou, an associate professor in the University of Florida College of Veterinary Medicine’s department of infectious diseases and immunology who joined the faculty in 2015 through the university’s preeminence initiative. “It has been studied for a long time in the toxicology and pharmacology fields.”

The receptor, an intracellular protein molecule officially known as aryl hydrocarbon receptor, or AHR, has some unique aspects that have not been widely explored scientifically. For example, it is well-conserved over time across many different species, including nematodes, or worms, Zhou said.

“This means it should not have evolved to only detect man-made pollutants, as it appeared even before man appeared on the planet,” he said. “We are interested in the receptor’s physiological function and how it responds to other stimuli, such as dietary compounds.”

Over the years, Zhou has investigated AHR from many angles, including its effects on immune cell genes. Previously published reports note the molecule that stimulates AHR activity can be found in vegetables such as broccoli, cauliflower and cabbage.

“AHR expression can be found not only in humans, but also in other organisms, including farm or pet animals, so understanding its role in humans and in animal models of disease will benefit veterinary medicine,” he said. “Animals are exposed to environmental stimuli such as pollutants just like we are, and suffer from similar diseases.”

His most recent paper, which was published in Cell Reports in November, reports that AHR preferentially marks and promotes regulatory T-cells — a subtype of white blood cell that plays a key role in regulating cell-mediated immunity — in the gut. Zhou and his colleagues say their findings show that AHR is important for the suppression of gut inflammation in a mouse model of colitis.

“This work has implications for understanding how to modulate intestinal immune responses in different disease settings, and may ultimately lead to the identification of new therapeutic targets for human inflammatory bowel disease or colon cancer,” Zhou said, adding that he hoped one day therapies might be developed for animals with similar diseases as well.

Zhou was lead author on the paper, which also included contributions from researchers at the University of California, San Francisco and Northwestern University, as well as from scientists working in his lab at UF and collaboratively within his department.

Like much of basic science, investigating the body’s response to disease at the intracellular, molecular level is complex. But the work is especially rewarding when relationships between disease types and cell function can be identified, said Zhou, who prior to joining UF’s faculty was an associate professor with tenure at Northwestern.

In addition to holding a Ph.D. from the University of California, Los Angeles, Zhou holds an M.D. degree from Nanjing Medical University in China. In 2011, Zhou was named a Pew Scholar in the Biomedical Sciences, a national, intensely competitive program that provides several years of continuous funding to young investigators of outstanding promise in science relevant to the advancement of human health.

He also has received funding for investigating the pathogenesis of infectious disease from the Burroughs Wellcome Fund and served as an investigator with the Cancer Research Institute. Zhou’s research has been continuously funded by the National Institutes of Health and other agencies.

Zhou said he enjoys being at UF and especially appreciates the College of Veterinary Medicine’s culture and atmosphere, which he says supports good science in various biomedical areas to achieve preeminence.

“I believe our research fits the One Health mission that our college advocates for,” he said. “I also hope our research will eventually benefit both animal and human patient health.”