The National Institutes of Health has awarded an Oklahoma Medical Research Foundation scientist a $4.1 million grant to study how tiny genetic changes contribute to lupus.
Swapan Nath, Ph.D., hopes to determine which genetic regions impact a type of immune cell called macrophages, which help protect us from infection. Impairment of normal macrophage function can lead to the immune system mistakenly attacking the body’s own tissues – a hallmark of lupus.
“Macrophages serve as the body’s garbage disposal by consuming dead cells,” said Nath, who holds the William H. and Rita Bell Endowed Chair in Biomedical Research at OMRF. “Just as we depend heavily on the kitchen garbage disposal to clear food debris, our immune system depends on macrophages to clear cellular debris.”
In lupus, the body’s immune system turns against healthy tissue, causing inflammation, organ damage and an increased risk of heart disease. Symptoms can include joint pain, fatigue, fever, sensitivity to sunlight and skin rash.
According to the Centers for Disease Control and Prevention, the most common form of lupus affects about 200,000 Americans, 90 percent of whom are women. Lupus is among the leading causes of death in young women.
Nath focuses on the genetic underpinnings of lupus. His lab uses a DNA-editing tool called CRISPR-Cas9, which has revolutionized genetic research in recent years.
Genetic variants, or deviations from the normal genetic code, aren’t uncommon, nor are they always harmful. However, diseases like lupus can result from the interaction of multiple variants or the interaction of one or more variants with an environmental factor such as diet, smoking, stress or medication.
“The human body has more than 20,000 different genes, and the number of variants within those 20,000 genes is nearly limitless,” Nath said. “That makes pinpointing the specific variants related to lupus very challenging.”
With his new grant, Nath hopes to identify the genetic regions where those variants occur. Using adult stem cells artificially generated in the lab, he’ll then test how genetic differences contribute to the development and progression of lupus.
“While improvements have been made to manage lupus symptoms, the scientific community is still trying to understand the interplay between genetic causes and their therapeutic targets,” said OMRF Executive Vice President & Chief Medical Officer Judith James, M.D., Ph.D. “Dr. Nath’s research could lead to new therapeutic approaches based upon the genetic variants that make some people more susceptible to the disease.”
Nath’s grant, No. 1R01AI183676-01A1, was awarded by the National Institute of Allergies and Infectious Diseases, part of the NIH. Previous support from the Presbyterian Health Foundation and the Oklahoma Center for the Advancement of Science and Technology funded experiments preceding Nath’s new grant.
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