Project Grant R16DK149033

The National Institute of Diabetes and Digestive and Kidney Diseases, part of the Department of Health and Human Services National Institutes of Health, awarded Mercer University $178,400 on August 1, 2026, under the Diabetes, Digestive, and Kidney Diseases Extramural Research program (CFDA 93.847) to evaluate renal complications in Cockayne syndrome.

The research will identify the molecular basis of kidney dysfunction in Cockayne syndrome, a multi-system premature-aging disorder caused by DNA repair gene mutations, and develop novel therapeutic strategies targeting NAD metabolism. Cockayne syndrome patients exhibit shortened life expectancy, neurodegeneration, vision and hearing impairments, and kidney abnormalities; kidney dysfunction is a significant cause of mortality in this population. The study will pursue two specific aims: defining cellular and molecular mechanisms of kidney injury in Cockayne syndrome, including mitochondrial dysfunction and cell death pathways across nephron compartments through in vivo phenotyping of Cockayne syndrome mouse kidneys and in vitro studies in renal cells; and investigating transcriptional and epigenetic regulation of NAD metabolic genes while evaluating the therapeutic potential of NAD replenishment. The research builds on preliminary findings demonstrating that kidney damage in Cockayne syndrome is driven by transcriptional repression of QPRT, a rate-limiting enzyme in NAD biosynthesis, resulting in NAD depletion, mitochondrial dysfunction, and tubular cell death.

The award runs from August 1, 2026, through June 30, 2030, with place of performance in Savannah, Georgia.