Eugene Rhee, MD

Institution: Massachusetts General Hospital
Research: Metabolomics of CKD and Diabetes
Grants & Publications: Harvard Catalyst
Categories: MGH

One of my lab’s major interests is the application of LC-MS based metabolomics to epidemiologic and physiologic studies of kidney disease, including diabetic nephropathy. We have spearheaded the first published studies of metabolomics to study the effects of the hemodialysis procedure, identify novel markers of death in end-stage renal disease, identify predictors of new onset CKD, and differentiate individuals with established CKD who do or do not progress. A key feature of these studies has been the integration of physiologic investigation—more specifically, collection of samples from the aorta and renal vein using invasive catheterization—to characterize how the human kidney modulates hundreds of molecules, providing insight on why select metabolites are deranged in renal failure. In parallel, my laboratory is interested in lipid metabolism in the kidney and beyond. In conjunction with Drs. Robert Gerszten (BIDMC) and Clary Clish (Broad Institute), we showed that lipid highly unsaturated fatty acid (HUFA) content can change rapidly, increasing in plasma triglycerides within 2 hours of various glycolytic stimuli, including oral glucose ingestion, sulfonylurea administration, and exercise. In follow up, we recently elucidated the biochemistry that underlies these human observations, identifying HUFA synthesis as a novel mechanism of glycolytic NAD+ recycling, analogous to lactate fermentation. The relevant desaturases are highly expressed in the kidney and liver, where their role in NAD+ recycling is acutely adaptive during acute stress, including acute kidney injury, but may contribute to dyslipidemia over time. In addition, these findings highlight a key biologic role for lipid desaturation independent of the HUFA end products and provide insight into genetic studies linking lipid desaturation with human disease, including diabetes.