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School of Medicine » Sarah W. Stedman Nutrition & Metabolism Center
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Deborah M. Muoio, PhD

Associate Professor
Dept. of Pharmacology and Cancer Biology
Dept. of Medicine
 
 
Dr. Deborah Muoio is an Associate Professor in the Sarah. W. Stedman Nutrition and Metabolism Center, with appointments in the Departments of Medicine and Pharmacology & Cancer Biology.  She earned a Ph.D. in nutritional biochemistry at the University of North Carolina where she studied lipid metabolism in the laboratory of Dr. Rosalind Coleman. Her post-doctoral training centered on metabolic disease and exercise physiology in the laboratories of Dr. Lynis Dohm at East Carolina University, and Drs. William Kraus and Chris Newgard at Duke University.  She was recruited to join the faculty at Duke University in 2004.  Her laboratory investigates mechanisms of metabolic regulation in skeletal muscle, with emphasis on molecular events that link overnutrition and inactivity to the development of insulin resistance. Her program features a multidisciplinary approach that combines integrative physiology and intermediary metabolism with cellular and molecular biochemistry, using model systems that range from primary human myocytes to genetically engineered mice.  Recent studies by her research team have employed mass spectrometry-based metabolomics as a tool to understand the interplay between mitochondrial energetics and insulin action.  Emergent findings from this work suggest that obesity-associated glucose intolerance stems from excessive β-oxidation and lipid-induced mitochondrial stress.  Ongoing studies seek to identify signaling mechanisms that mediate crosstalk between muscle mitochondria and glucose transport.  Three main project areas of her laboratory include: 1) mechanisms that link lipid oversupply to mitochondrial malfunction and insulin resistance in skeletal muscle, 2) mechanisms through which exercise enhances mitochondrial function, lipid tolerance and insulin sensitivity, and 3) translational studies to examine the impact of diet and/or exercise interventions on metabolic regulation and mitochondrial function in human skeletal muscle.  She receives funding from the NIH and the American Diabetes Association.  
 
Publications:
 
1. Koves, T.R., Ping, L, Jie, A., Akimoto, T., Slentz, D., Ilkayeva, O, Dohm, G.L, Yan, Z., Newgard, C.B. and Muoio, D.M.  PGC1a-mediated Metabolic Remodeling of Skeletal Myocytes Mimics Exercise Training and Reverses Lipid-Induced Mitochondrial Inefficiency.  J. Biol. Chem., 2005, 280(39):33588-98.
 
2. Hulver M, Berggren, J.R., Carper, M.J., Miyazaki, M., Ntambi, J.M., Hoffman, E., Thyfault, J.P., Stevens, R., G. Dohm, G.L, Houmard J.A. and Muoio, D.M.  Elevated Stearoyl-CoA Desaturase-1 Expression in Skeletal Muscle Contributes to Abnormal Fatty Acid Partitioning in Obese Humans.  Cell Metabolism, 2005, 2 (10):251-261.
 
3. Muoio, DM and Newgard, CB. Obesity-Related Derangements in Metabolic Regulation. Annual Reviews of Biochemistry, 2006;75:367-401. 
 
4. Gaillard, S. Grasfeder, L, Haeffele, CL, Lobenhofer, EK,Chu, T, Wolfinger, R, Kazmin, D, Koves, TK, Muoio, DM, Chang, C and McDonnell, DP.  Engineering Receptor Selective Coactivators: An approach to define the molecular pathways regulated by receptor-coactivator pairs.  Mol Cell 2006; 24(5):797-803.
 
5. Thyfault, JP, Cree, MG, Zheng, D, Zwetsloot, JJ, Tapscott, EB, Koves,TR, Ilkayeva,O, Wolfe, RR, Muoio, DM and Dohm, GL.P PContraction of Insulin Resistant Muscle Normalizes Insulin Action in Association with Increased Mitochondrial Activity and Fatty Acid Catabolism.  Am J Physiol Cell Physiol. 2007, 292(2):C729-39.
 
6. Power, R A, Hulver, M WP3P, Zhang, J Y, Dubois, J, Marchand, R, Ikayeva, O, Muoio, DM and Mynatt, RL.  Carnitine revisited: potential use as adjunctive treatment in diabetes.  Diabetologia. 2007, 50(4):824-32.
 
7. Muoio, DM.  TXNIP Links Redox Circuitry to Glucose Control.  Cell Metabolism. 2007, 5(6):412-4.
 
8. Muoio, DM* and Koves, TR. Skeletal muscle adaptation to fatty acid depends on coordinated actions of the PPARs and PGC1a: Implications for metabolic disease. Appl Physiol Nutr Metab. 2007, 32(5):874-83.
 
9. Koves TR, Ussher, JR, Slentz, DS, Mosedale, M, Ikayeva, O, J, Stevens R, Dyck, J, Newgard, CB, Lopaschuk, G and Muoio, DM*.   Mitochondrial Overload and Incomplete Fatty Acid Oxidation Contribute to Skeletal Muscle Insulin Resistance. Cell Metabolism. 2008 (7): 45–56.
 
10. Muoio, DM and Newgard, CB. Molecular and Metabolic Mechanisms of Insulin Resistance and β-cell Failure in Type 2 Diabetes.  Nat Rev Mol Cell Biol. 2008 (3):193-205.
 
11. Stoltzman, CA,  Peterson, CW, Kaadige, MR, Breen, KT, Muoio, DM, Billin, AN, and Ayer, DE.  Glucose-sensing by MondoA:Mlx complexes:  A Role for Hexokinases and Direct Regulation of Thioredoxin Interacting Protein.  Proc Natl Acad Sci U S A. 2008;105(19):6912-7.
 
12. Muoio, DM and Newgard, CB.  Fatty Acid Oxidation and Insulin Resistance: When less is more.  Diabetes, 2008;57(6):1455-6.
 
13. Makowski, L, Koves, T, Noland, R, Xing, W., Ilkayeva, O, Muehlbauer, M, Newgard, CB and Muoio, DM. Metabolomics Analysis of PPARa Null Mice Reveals Defects in Carnitine and Amino Acid Homeostasis that are Partially Reversed by Carnitine Supplementation.  FASEB J. 2009;23(2):586-604. 
 
14. John R. Ussher, Timothy R. Koves, Jagdip S. Jaswal, Liyan Zhang, Olga Ilkayeva, Jason R. B. Dyck, Deborah M. Muoio, and Gary D. Lopaschuk.  Insulin-stimulated cardiac glucose oxidation is increased in high fat diet-induced obese mice lacking malonyl CoA decarboxylase. Submitted for publication.
 
15. Timothy R. Koves, Terry E. Jones, Dorothy Slentz, James Way, Ann Louise Olson, G. Lynis Dohm, and Deborah M. Muoio.  Fatty Acid-Induced Repression of Skeletal Muscle GLUT4 Involves PPAR Activation and is not Prevented by Overexpression of PGC1a. Submitted for publication.
 
16.  Bell, J., Reed, M.A., Consitt, L, Martin, O, Bonen, A. Hulver, M.W., Muoio, D.M. and Dohm, G.L. Lipid partitioning, incomplete fatty acid oxidation, and insulin signal transduction in primary human muscle cells: effects of obesity, fatty acid incubation, and FAT/CD36 overexpression.  Submitted for publication.
 
17.  Noland, R., Koves, Lum H., T.R., Slentz, D.S., Ilkayeva, O, Stevens, R and Muoio DM.  Carnitine Insufficiency Caused by Aging and Overnutrition Compromises Mitochondrial Performance and Metabolic Control. Submitted for publication.
 
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