An Oklahoma Medical Research Foundation scientist has received $3.4 million grant from the National Institutes of Health to investigate genetic changes believed to be catalysts for the autoimmune disease lupus.
With the four-year federal grant, scientist Swapan Nath, Ph.D., hopes to identify DNA errors that disrupt a routine biological clean-up process called autophagy. In this continual process, cells recycle old parts and discard faulty parts.
“Problems with autophagy in immune cells and kidney cells seem to be closely linked to lupus,” said Nath, who holds the William H. & Rita Bell Chair in Biomedical Research at OMRF. “Our lab and others have found that when autophagy goes wrong, immune cells release too many inflammatory signals, and kidney cells become damaged and leak protein, which ultimately can lead to kidney failure.”
Nath has spent his career trying to identify specific genetic changes, or variants, associated with lupus – a challenging task since the body has more than 3 million genetic variants spread across about 20,000 different genes.
Lupus is a chronic illness that can cause widespread inflammation and organ damage. It affects more than 200,000 Americans, about 90% of whom are female. Existing treatments mainly focus on managing symptoms and preventing flares of the disease. There is no cure.
Scientists have long known lupus has a strong genetic component, but environmental triggers like sunlight, cigarette smoke, stress and viruses are also necessary to activate the disease.
Through previous work, Nath’s lab analyzed large genetic datasets to identify regions of the genome associated with lupus risk. The data came from samples housed at OMRF and donated by thousands of lupus patients and healthy controls through the Lupus Family Registry and Repository and the Oklahoma Cohort of Rheumatic Diseases.
“The challenge is narrowing down which specific genetic variants are causing the problem and which gene they affect,” Nath said. “We do this through statistical analysis and then testing in the lab.”
With this grant, Nath’s lab hopes to further narrow the list of potential genes associated with lupus by looking specifically for variants in genes of kidney cells. Ultimately, his work could help lupus scientists and physicians better understand the biological mechanism that links genetic disease risk to cell dysfunction and organ damage.
“This could lead to new drug targets, better risk prediction, and perhaps even cell-based therapies in the future,” said OMRF Executive Vice President and Chief Medical Officer Judith James, M.D., Ph.D. “That would be a huge advancement, as it could mean earlier intervention and the prevention of organ damage for our patients.”
Nath’s grant, No. R01AI191517-01A1, was awarded by the National Institute of Allergy and Infectious Diseases, part of the NIH. He previously received funding from the Presbyterian Health Foundation and from the Oklahoma Center for Adult Stem Cell Research, part of the Tobacco Settlement Endowment Trust, for preliminary research.
