Mishra and Singh receive $381,500 for oral health research

GRAND FORKS, N.D.— The National Institutes of Health has awarded a $381,500 two-year grant to biomedical scientists Assistant Professor Bibhuti Mishra, PhD, and Professor Brij Singh, PhD, at the University of North Dakota School of Medicine and Health Sciences to fund their research on the role played by proteins called “galectins” in salivary gland inflammation. Mishra’s recent studies suggest that galectins, specifically galectin-3 and galectin-9, act as novel alarmins, which are essentially self-molecules, bits of cells that present no harm to the body as long as they are safely clothed within the membranes of cells. However, during an infection or injury, these cells burst open and release self-molecules or alarmins into the medium outside of cells where they are not supposed to be. The body’s immune system sees the release of these self-molecules as a danger; the self-molecules or alarmins sound the alarm to mobilize the immune system to attack the cells and tissue where the alarmins are present—an autoimmune response—leading to inflammation that causes fever, swelling, and mouth or facial pain. Sjögren’s syndrome is an autoimmune disease of the oral system that leads to salivary gland destruction. Almost 3 percent of the U.S. population is affected by salivary gland hypofunction, a complex disorder resulting from diseases as well as being a common side effect of drug therapy. However, the etiology as to why salivary glands are destroyed in diseases such as Sjögren’s syndrome is still not known. Recent findings have provided strong evidence that, like many inflammatory disorders, Sjögren’s syndrome has its origin in an overactive immune response against salivary tissue, thus causing glandular destruction. However, the mechanisms underlying infiltration of immune cells and development of an inflammatory response in salivary glands remain ill-understood. In the current grant, Mishra and Singh propose that both galectin-3 and galectin-9 function as alarmins in and contribute to the pathophysiology of autoimmune or inflammatory disorders like Sjögren’s syndrome. The role of alarmins during salivary gland inflammation, injury or disease has never been studied. These are highly interdisciplinary studies because of the unique collaboration between Mishra and Singh. “The overall impact of these studies is that it will identify novel alarmins contributing to exacerbation of salivary gland inflammation and destruction,” Mishra said. “These alarmins may be targeted for treatment of Sjögren’s syndrome and possibly other inflammatory conditions.” A part of the U.S. Department of Health and Human Services, the NIH is the nation\u27s medical research agency. The NIH is the largest source of funding for medical research in the world. The mission of the NIH is to seek fundamental knowledge about the nature and behavior of living systems and the application of that knowledge to enhance health, lengthen life, and reduce illness and disability