College of Medicine Gut Researcher Gets $1.7 Million Federal Grant to Study IBD

June 13, 2023 | News, Research, UToday, Alumni, Medicine and Life Sciences
By Tyrel Linkhorn

A University of Toledo biochemist has received a major grant from the National Institutes of Health to advance his studies of inflammatory bowel disease.

The latest research by Dr. Matam Vijay-Kumar, a professor in the Department of Physiology and Pharmacology, focuses on neutrophil extracellular traps, a powerful but not well-understood function of the body’s immune response.

Feature photo of Dr. Matam Vijay-Kumar, a professor in the Department of Physiology and Pharmacology.

Dr. Matam Vijay-Kumar, a professor in the Department of Physiology and Pharmacology, received a four-year, $1.7 million grant to advance his studies of inflammatory bowel disease.

Discovered less than 20 years ago, neutrophil extracellular traps — or NETs — are formed by interwoven webs of DNA from white blood cells called neutrophils and can trap and kill bacteria, fungi and other microorganisms.

But they also can damage the body, having been implicated in the slow healing of diabetic wounds, the pathogenesis of lupus and the progression of heart disease if not cleared in a timely manner.

However, studies done by Vijay-Kumar suggest NETs also play an important role in limiting intestinal inflammation and may be protective against inflammatory bowel diseases like Crohn’s disease and ulcerative colitis.

He will build on that evidence with a four-year, $1.7 million grant from the National Institute of Diabetes and Digestive and Kidney Diseases.

Inflammatory bowel disease is a chronic and often debilitating condition that affects more than 1.5 million Americans. Though some cases are relatively mild, at its worst, the condition can cause life-threatening complications.

“Living with any chronic condition is difficult, and managing inflammatory bowel disease can be very challenging,” Vijay-Kumar said. “It also can bring with it serious consequences. For example, individuals with IBD have a higher risk of severe anemia and colorectal cancer.”

Working in animal models, UToledo researchers will seek to develop a more complete understanding of the role of neutrophil extracellular traps in inflammatory bowel disease and their significance in preventing bacteria from breaching the intestinal wall and infiltrating the inner lining of the intestinal tract.

Researchers also will look at gut health in mice that have a deficiency of PAD4, a protein that’s essential for the formation of neutrophil extracellular traps.

Previous findings from Vijay-Kumar’s lab, which have yet to be published, suggest mice deficient in PAD4 are highly susceptible to inflammatory bowel disease and prone to intestinal bacterial pathogens.

With pharmaceutical companies looking to develop PAD4 inhibitors to help treat conditions ranging from rheumatoid arthritis to cancer, it’s important that scientists understand the potential link between inflammatory bowel disease and NETs.

“PAD4 inhibitors are an attractive target for many conditions, but we have to be careful we aren’t also inadvertently promoting inflammatory bowel disease,” Vijay-Kumar said. “While NETs may not have a beneficial role in some parts of the body, in the intestine they represent an appropriate immune response. It’s important we understand the full scope of their role within various organ systems.”

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