BIOGRAPHICAL SKETCH
Provide the following information for the key personnel and other significant contributors in the order listed on Form Page 2.
Follow this format for each person. DO NOT EXCEED FOUR PAGES.
NAME
POSITION TITLE
Deborah M. Muoio
Associate Professor
eRA COMMONS USER NAME
MUOIO001
EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, and include postdoctoral training.)
INSTITUTION AND LOCATION
DEGREE
(if applicable)
YEAR(s)
FIELD OF STUDY
University of Florida, Gainesville, Fla
B.S.
1983-1987
SUNY Buffalo, Buffalo, New York
M.S.
1990-1992
University of North Carolina, Chapel Hill
Ph.D.
Postdoctoral
Postdoctoral
1994-1999
Nutrition, Food Science
Nutrition, Exercise
Physiology
Nutritional Biochemistry
Muscle Metabolism,
Metabolic Disease
Muscle Metabolism,
Metabolic Disease
East Carolina University, Greenville, NC
Duke University, Durham, NC
1999-2001
2001-2002
A. Positions and Honors.
U
PROFESSIONAL POSITIONS
U
6/87-4/92
9/92-3/94
Food Technologist Dept. of Research and Development, Rich Products Corporation. Buffalo, NY.
Clinical Instructor, University at Buffalo Sports Medicine Institute, School of Medicine and
Biomedical Sciences, SUNY, Buffalo, NY
9/93-2/94 Clinical Research Project Coordinator Department of Behavioral Medicine, SUNY, Buffalo, NY.
9/02-7/04 Research Assistant Professor, Department of Medicine, Duke University, Durham, NC
8/04-11/08 Assistant Professor (Tenure Track), Departments of Medicine and Pharmacology & Cancer
Biology, Sarah W. Stedman Nutrition and Metabolism Center, Duke University, Durham, NC
12/08Associate Professor, Department of Medicine, Sarah W. Stedman Nutrition and Metabolism Center,
Duke University, Durham, NC
Honors, Fellowships and Awards
1994-97 NIH National Research Service Award, Pre-doctoral Traineeship
1996
North Carolina Institute of Nutrition Pre-doctoral Fellowship
1996
American Institute of Nutrition Kraft Pre-doctoral Fellowship
1997
Sigma Xi Grants-in-aid Research Award
1997
North Carolina American Heart Association Pre-doctoral Fellowship
1997
American Society for Clinical Nutrition Young Investigator Award
1998
University of North Carolina Dissertation Fellowship
1999
A. Hughes Bryan Outstanding Doctoral Student Award
1999
Dannon Institute of Nutrition Leadership Recipient
1999-02 NIH National Research Service Award, Post-doctoral Fellowship
2008
David L. Williams Lectureship & Award, Kern Aspen Lipid Conference
U
B. Selected peer-reviewed publications
1. Muoio DM, Awad AB, Horvath P, Leddy J and Pendergast DR. Effect of dietary fat on metabolic
adjustments to maximal Vo 2 and endurance in trained runners. Medicine and Science in Sports Exercise.
1994 26;81-88.
B
B
2. Muoio DM, Dohm GL, Fiedorek FT, Tapscott EB and Coleman RA.
partitioning in skeletal muscle. Diabetes. 1997 46;1360-63 .
Leptin directly alters lipid
3. Meyer WK, Muoio DM, and Hackney AC. The effect of sex steroids on beta-endorphin levels at rest
and during submaximal treadmill exercise in anovulatory and ovulatory runners. Fertility and Sterility. 1998
71; 1085-91.
4. Cortright, R, Muoio, DM, and Dohm, GL. Skeletal muscle lipid metabolism: a frontier for new insights
into the regulation of energy homeostasis. Journal of Nutritional Biochemistry. 1997 8:228-245.
5. Muoio DM, Dohm GL, Tapscott EB and Coleman RA. Counter-regulatory effects of leptin and insulin in
muscles from lean and obese ob/ob mice. American Journal of Physiology. 1999 276; E913-E921.
6. Muoio DM, Seefeld K, Witters LA and Coleman RA. AMP-activated kinase reciprocally regulates
triacylglycerol synthesis and fatty acid oxidation in liver and muscle: Evidence that sn-glycerol-3-phoshate
acyltransferase is a novel target of AMP-kinase. Biochemical Journal. 1999 338; 783-791.
7. Muoio DM, Lewin TM, Wiedmer P. and Coleman RA. Acyl-CoAs are functionally channeled in liver:
potential role of acyl-CoA synthetase. American Journal of Physiology 279, 2000 E1366-73.
8. Vidal-Puig, A, Grujic D, Zhang C, Hagen T, Boss O, Ido Y, Huppertz C, Szczepanik A, Wade J, Mootha
V, Cortright R, Muoio DM, and Lowell BB. Energy Metabolism in uncoupling protein 3 knock-out mice.
Journal of Biological Chemistry. 275, 2000, 16258-16266.
9. Coleman, RA, Lewin T, and Muoio, DM. Nutritional and physiological regulation of the enzymes of
triacylglycerol synthesis. Annual Reviews of Nutrition, 2000 20;77-103.
10. Kim, J, Koves, TR, Yu, GS, Gulick, T., Cortright, RN, Dohm, GL and Muoio, DM. Evidence of a
malonyl CoA insensitive carnitine palmitoyltransferase activity in red skeletal muscle. American Journal of
Physiology. 282, 2002 E1014-E1022.
11. Muoio DM, Way JM, Winegar DA, Kliewer SA, Houmard J, Kraus WE, and Dohm GL. Peroxisome
proliferator activated receptor alpha regulates fatty acid utilization in primary human skeletal muscle cells.
Diabetes. 51, 2002, 901-909.
12. Muoio, DM, MacLean, PS, Lang, D, Li, S, Houmard, J, Way, J, Winegar, DA, Corton C, Dohm, GL and
Kraus, WE. Fatty acid homeostasis and induction of lipid regulatory genes in skeletal muscles of PPARknockout mice: Evidence for compensatory regulation by PPAR. Journal of Biological Chemistry, 277,
2002, 26089-26097.
13. Muoio, DM and Dohm GL. Peripheral Metabolic Actions of Leptin. Best Pract Res Clin Endocrinol
Metab. 2002 Dec;16(4):653-66.
14. An, J., Muoio DM, Shiota, M., Fujimota, Y., Cline, GW, Shulman, GI, Koves, T.R., Stevens R.,
Millington, D. and Newgard, C.B. Hepatic expression of malonyl CoA decarboxylase reverses muscle, liver
and whole-animal insulin resistance. Nature Medicine, 2004 Mar;10(3):268-74.
P
P
15. Muoio, DM and Newgard, CB. Insulin resistance takes a trip through the ER. Science. 2004 Oct
15;306(5695):425-6.
16. Berggren, JR, Tanner, CJ, Koves, TR, Muoio, DM and Houmard, JA. Glucose uptake in muscle cell
cultures from endurance-trained men. Med Sci Sports Exerc. 2005 Apr;37(4):579-584.
17. Koves, T.R., Noland, R.C., Bates, A.L. Muoio, D.M. and Cortright, R.N. Subsarcolemmal and
intermyofibrillar mitochondria play distinct roles in regulating skeletal muscle fatty acid metabolism. Am J
Physiol Cell Physiol. 2005 May;288(5):C1074-82.
18. Hammond, LE, Neschen, S, Cline, GW, Ilkayeva, O, Shulman, G, Muoio, DM and Coleman, RA.
Mitochondrial glycerol-3-phosphate acyltransferase1 is essential for the handling of excess acyl-CoA. J.
Biol. Chem. 2005, 280(27):25629-36.
19. Muoio DM and Newgard CB. Metabolism: A is for adipokine. Nature 436: 337-338, 2005.
20. 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. PGC1-mediated Metabolic Remodeling of Skeletal Myocytes Mimics Exercise Training
and Reverses Lipid-Induced Mitochondrial Inefficiency. J. Biol. Chem., 2005, 280(39):33588-98.
21. 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.
22. Muoio, DM and Newgard, CB. Obesity-Related Derangements in Metabolic Regulation. Annual
Reviews of Biochemistry, 2006;75:367-401.
23. 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.
24. Thyfault, JP, Cree, MG, Zheng, D, Zwetsloot, JJ, Tapscott, EB, Koves,TR, Ilkayeva,O, Wolfe, RR,
Muoio, DM and Dohm, GL. Contraction 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.
P
P
25. Power, R A, Hulver, M W 3 , 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):82432.
P
P
26. Muoio, DM. TXNIP Links Redox Circuitry to Glucose Control. Cell Metabolism. 2007, 5(6):412-4.
27. Muoio, DM* and Koves, TR. Skeletal muscle adaptation to fatty acid depends on coordinated actions of
the PPARs and PGC1: Implications for metabolic disease. Appl Physiol Nutr Metab. 2007, 32(5):874-83.
28. 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.
29. 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.
30. 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.
31. Muoio, DM and Newgard, CB.
Diabetes, 2008;57(6):1455-6.
Fatty Acid Oxidation and Insulin Resistance: When less is more.
32. Muoio, DM, Koves, TR, An, J and Newgard, CB. Metabolic Mechanisms of Muscle Insulin Resistance
in Type 2 Diabetes Mellitus: An Evidence-Based Approach to Practical Management M. Feinglos, Editor,
Humana Press Inc. In Press
U
U
33. Makowski, L, Koves, T, Noland, R, Xing, W., Ilkayeva, O, Muehlbauer, M, Newgard, CB and Muoio,
DM. Metabolomics Analysis of PPAR Null Mice Reveals Defects in Carnitine and Amino Acid
Homeostasis that are Partially Reversed by Carnitine Supplementation. FASEB J. 2009;23(2):586-604
34. Lillian F Lien, Andrea M Haqq, Michelle Arlotto, Cris A Slentz, Michael J, Muehlbauer, Ross L
McMahon, James Rochon, Dianne Gallup, James R Bain, Olga Ilkayeva, Brett R Wenner, Robert D
Stevens, David S Millington, Deborah M Muoio, Mark D Butler, Christopher B Newgard, and Laura P
Svetkey. The STEDMAN Project: Biophysical, Biochemical and Metabolic Effects of a Behavioral Weight
Loss Intervention during Weight Loss, Maintenance and Regain. OMICS: A Journal of Integrative Biology.
In Press.
35. Malakauskas SM, Kourany WM, Zhang XY, Lu D, Stevens RD, Koves TR, Hohmeier HE, Muoio DM,
Newgard CB, Le TH. Increased Insulin Sensitivity in Mice Lacking Collectrin, a Downstream Target of HNF1a. Mol Endocrinol. In Press.
36. 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. In revision.
37. 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 PGC1. Submitted..
38. 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.
39. 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.
Manuscripts in Preparation
Makowski, L, Koves, T.R., Noland, R., Slentz, D, Ikayeva, O, An, J, Newgard, CB and Muoio, DM. Ectopic
Overexpression of the Ketogenic Enzyme HMG-CoA Synthase 2 in Skeletal Myocytes Increases Glucose
Uptake and Metabolism.
Thyfault, JP, Koves, TR, Cree, MG, Zheng, D, Zwetsloot, JJ, Tapscott, EB, Ilkayeva,O, Wolfe, RR, Dohm, GL
and Muoio, DM. Metabolic Profiling of Contracted Skeletal Muscle in Lean Compared to Obese Rodents.
Jean-Paul Kovalik, Robert Noland, Olga Ilkayeva and Deborah M. Muoio. Metabolic Reprogramming of
Primary Human Skeletal Myocytes by Co-cultured Adipocytes.
C. Research Support
Active Support
2 R01 DK046121-13 (Dohm)
08/8/05 – 05/31/2010
(Subcontract with East Carolina University)
Fatty Acid Transports and Insulin Resistance in Humans
This project studies role of three distinct fatty acid transporters in regulating lipid balance and insulin sensitivity
in human skeletal myocytes from obese compared to lean subjects.
Role: PI
U
2 R01 DK056112-06A1 (Houmard)
02/15/05 – 1/3/2011
(Subcontract with East Carolina University)
Obesity and Muscle Fatty Acid Oxidation in Humans
This project studies role of the muscle PPAR nuclear hormone receptors in regulating lipid balance and insulin
sensitivity in human skeletal myocytes from obese compared to lean subjects.
Role: PI
R01 AG028930-01(Muoio)
07/01/06 – 06/30/11
Mechanisms Linking the Adipogenic Phenotype of Aging Muscle to Insulin Resistance
This grant explores the role of lipid infiltration of the musculoskeletal system to the etiology of age-related
mitochondrial dysfunction and insulin resistance in humans. We will use a newly developed co-culture system
to examine the impact of local adipocytes on mitochondrial function and insulin action in neighboring myocytes.
We also seek to understand how exercise combats age-related metabolic decline. To this end, we are
collaborating with Dr. William Kraus to perform metabolic and transcriptional profiling analyses of human
skeletal muscle samples from the STRRIDE I and STRRIDE II exercise intervention studies.
Role: PI
U
American Diabetes Association (Muoio)
07/01/07 – 12/31/11
Mitochondrial Stress and Insulin Resistance in Skeletal Muscle
This grant proposes to test the hypothesis that muscle insulin resistance results from mitochondrial energy
overload and oxidative stress. In both rodent and cell culture models, we will examine the metabolic
consequences of deficient or enhanced antioxidant defense via pharmacologic, nutritional and genetic
maneuvers.
Role: PI
NIH NIDDK (Kien/Muoio)
05/01/07 – 03/31/11
(Subcontract with University of Vermont)
Mechanisms for Differential Effects of Dietary Fatty Acid on Metabolism
This grant proposes to explore the distinct effects of diets enriched in saturated (palmitate) and monuunsaturated (oleate) fatty acids on whole body and skeletal muscle fuel homeostasis in humans.
Role: Co-PI
Completed Support
K01 DK67200-02 (Muoio)
7/1/2004 – 6/30/2007
Ketone Dysregulation and Muscle Insulin Resistance
The major goal of this project is to determine whether hepatic and/or intramuscular ketogenesis plays a role in
mediating lipid-induced insulin resistance in skeletal muscle using rodent and muscle cell culture models.
Role: PI
American Diabetes Association (Muoio)
1/1/2004 – 12/31/2007
1-04-JF-38
Ketone Dysregulation and Muscle Insulin Resistance
The project studies lipid-induced intramuscular ketogenesis in rodent models of obesity and diabetes, and
proposed to determine whether intramuscular ketone accumulation contributes to insulin resistance.
Role: PI
NIH (DP2)
07/01/06 – 06/30/08
Claude D. Pepper Older Americans Independence Centers (OIACs)
The goal of this project is to apply targeted metabolic profiling to examine age-related perturbations in
metabolic control and insulin resistance. Dr. Muoio was awarded pilot project funding to develop a conditional
knockout mouse model targeted against skeletal muscle carnitine acetyltransferase.
Role: Project Leader
U