Oklahoma Medical Research Foundation scientist Patrick Gaffney, M.D.

Oklahoma Medical Research Foundation scientist Patrick Gaffney, M.D., has received a five-year, $3.1 million grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases to investigate the underlying mechanisms that lead to lupus onset.
Lupus occurs when the immune system becomes unbalanced, leading to the development of antibodies and chronic inflammation that damage the body’s organs and tissues. The disease primarily strikes women and disproportionately affects certain minority groups, including African Americans, American Indians and Latinos.
Risk for lupus is believed to come from changes in the genome, said Gaffney, but researchers don’t actually understand why or how they confer risk. The grant will expand upon information gathered currently through genome-wide association studies, or GWAS.
“In lupus, you have a disease with around 150 associated regions of the genome and maybe thousands of variants related to it,” said Gaffney, who holds the J.G. Puterbaugh Chair in Medical Research at the foundation and is the chair of OMRF’s Genes and Human Disease Research Program. “Each one makes a small contribution to the overall risk of disease, but when we look at them in entirety, the power to predict disease becomes significantly better. All we have now is statistical analysis we’ve gathered from the genome studies. This grant will help us also understand the biology involved in the process.”
GWAS data have been helpful but not particularly useful in getting research into clinics to help lupus patients, because they don’t convey enough about other possible contributing factors, Gaffney said.
To that end, Gaffney will look into the role of “epigenetic” factors, the chemical changes in the genome that affect how DNA is packaged and expressed but do not affect the underlying genetic sequence.
“This is the next step in helping us understand the biology of this data enough to actually generate a real impact for patients,” he said. “We are hopeful this work will lead us to alternative variants in the genome that may not necessarily be associated in a statistical way, but might prove important to the overall disease process.”
The grant, R01 AR073606, is from the NIAMS, a part of the NIH.
“Dr. Gaffney is a recognized expert in the genetics of autoimmune diseases,” said OMRF President Stephen Prescott, M.D. “This novel approach to expanding upon genetic data holds promise for the development of new ways to treat or even prevent diseases like lupus and others.”