A Wayne State University School of Medicine researcher has been awarded a $2.3 million grant by the National Institute of Diabetes and Digestive and Kidney Diseases, part of the National Institutes of Health, to support research in circadian RNA modification in metabolic disease.

Kezhong Zhang, Ph.D., professor of Molecular Medicine and Genetics, and of Biochemistry, Microbiology and Immunology, will use the grant to explore the mechanism by which circadian stress regulates RNA modification associated with the development of non-alcoholic fatty liver disease and hyperlipidemia.

The human body has an internal circadian clock oscillation on the scale of 24 hours that orchestrates behavior and physiology, Dr. Zhang explained. The biological circadian rhythm can be dysregulated by abnormal lifestyle, such as day-night shift work schedules and over-nutrition. Irregular circadian rhythm is closely associated with metabolic disease, such as non-alcoholic fatty liver disease, hyperlipidemia and diabetes. The Zhang lab identified that circadian rhythm controls energy metabolism through modifying RNAs that encode major metabolic factors. That laid the foundation for this latest research project supported by the NIH.

“Irregular circadian rhythm is one of major causes of human metabolic disease, cardiovascular disease and cancer,” Dr. Zhang said. “Due to the modern lifestyle, the problem of irregular circadian rhythm is not only related to shift workers, but also to the public at large in developed counties. Shift workers -- for example nurses -- have higher risk of metabolic syndrome and breast cancer.”

Dr. Zhang will work with Deyu Fang, Ph.D., M.D., professor of Pathology at the Northwestern University Feinberg School of Medicine, who is the multiple-principle investigator on the project.

“Our research discovered a new circadian-regulated pathway that controls lipid levels through modifying RNAs that encode major metabolic enzymes in the liver. We will identify the stress-induced regulators of this new pathway and the therapeutic potential by targeting this pathway,” Dr. Zhang said. “Our work will not only contribute to the understanding of the molecular basis governing energy metabolism, but also shed new light on developing therapeutics for lipid-associated metabolic disease.”

Dr. Zhang is collaborating with School of Medicine colleagues Roger Pique-Regi, Ph.D., associate professor of Molecular Medicine and Genetics, and of Obstetrics and Gynecology, and Hyunbae Kim, research scientist at the Center for Molecular Medicine and Genetics, who are co-investigators for the project.

The project number for this NIH award is R01DK126908.