The Hirschey Lab in the Duke Molecular Physiology Institute, and the Departments of Medicine and Pharmacology & Cancer Biology at Duke University studies different aspects of metabolic control, mitochondrial signaling, and cellular processes regulating human health and disease.

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“Our research focuses on metabolism, with a particular interest in how cells use metabolites and chemical modifications to proteins in order to control metabolism.”

Changes in cellular nutrient availability or energy status induce global changes in mitochondrial protein acetylation. Mitochondrial protein acetylation levels are primarily regulated by sirtuin 3 (SIRT3), a member of the sirtuin family of NAD(+)-dependent protein deacetylases. We are currently studying acetylated mitochondrial proteins, their regulation by SIRT3, and further defining the role of protein acetylation in mitochondrial function. Read more…
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Our laboratory is exploring the landscape beyond acetylation and identifying new chemical modifications to proteins. We recently discovered a new modification called protein glutarylation and its regulation by the sirtuin SIRT5. We are working to find new modifications, identify metabolic proteins that are modified, their regulation, and further defining nutrient integration and signaling in mitochondrial function. Read more…

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“Phylogenetic analysis of the sirtuins could be key to their enzymology”

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Metabolic regulation is important for several physiological states. Dysregulated metabolism is associated with diabetes and obesity, cardiovascular disease, cancer, inborn errors, and the aging process itself. We are particularly interested in these disease states, and our overall objective is to better understand how altering metabolism could lead to new therapies to treat these human diseases. Read more…
Hirschey Lab News