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Deborah Muoio

Associate Professor
Pharmacology and Cancer Biology
(919) 479-2328
Research Summary: 
Mechanisms of metabolic regulation and metabolic disease; impact of diet and exercise on skeletal muscle physiology; interplay between mitochondrial bioenergetics and insulin action.
Research Description: 

My expertise lies in the areas of intermediary metabolism, lipid biochemistry, metabolic disease, exercise physiology and mitochondrial bioenergetics. The work in my laboratory focuses on metabolic networks that control skeletal muscle fuel homeostasis, with emphasis on mechanisms linking obesity, inactivity and lipid dysregulation to the development of whole-body and muscle insulin resistance. Our research program features a translational approach that combines work in animal and cell-based models with human studies, using functional genomics, molecular physiology and mass spectrometry-based metabolomics as tools to understand the interplay between mitochondrial energetics, redox signaling and insulin action. My group works closely with the Metabolomics and Biomarkers Core Laboratory in the Stedman Center and in recent years we have been applying metabolomics approaches to gain insights into the metabolic basis of nutrient-induced mitochondrial stress and insulin resistance in skeletal muscle. Our recent work has uncovered a novel link between mitochondrial-derived acylcarnitine metabolites, incomplete fat oxidation and glucose intolerance. We are now keenly interested in understanding the molecular nature and pathophysiological relevance of this connection.

Muscle-specific deletion of carnitine acetyltransferase compromises glucose tolerance and metabolic flexibility.
Muoio DM, Noland RC, Kovalik JP, Seiler SE, Davies MN, DeBalsi KL, Ilkayeva OR, Stevens RD, Kheterpal I, Zhang J, Covington JD, Bajpeyi S, Ravussin E, Kraus W, Koves TR, Mynatt RL.
Cell Metab. 2012. 15:764-77.

Lipid-induced mitochondrial stress and insulin action in muscle.
Muoio DM, Neufer PD.
Cell Metab. 2012. 15:595-605.

Metabolic remodeling of human skeletal myocytes by cocultured adipocytes depends on the lipolytic state of the system.
Kovalik JP, Slentz D, Stevens RD, Kraus WE, Houmard JA, Nicoll JB, Lea-Currie YR, Everingham K, Kien CL, Buehrer BM, Muoio DM.
Diabetes. 2011. 60:1882-93.

Carnitine insufficiency caused by aging and overnutrition compromises mitochondrial performance and metabolic control.
Noland RC, Koves TR, Seiler SE, Lum H, Lust RM, Ilkayeva O, Stevens RD, Hegardt FG, Muoio DM.
J Biol Chem. 2009. 284:22840-52.

Mitochondrial overload and incomplete fatty acid oxidation contribute to skeletal muscle insulin resistance.
Koves TR, Ussher JR, Noland RC, Slentz D, Mosedale M, Ilkayeva O, Bain J, Stevens R, Dyck JR, Newgard CB, Lopaschuk GD, Muoio DM.
Cell Metab. 2008. 7:45-56.