Timothy Robert Koves | Scholars@Duke

Timothy Robert Koves
Associate Professor in Medicine

My research is focused on 1) understanding metabolic perturbations that occur in subpopulations of skeletal muscle mitochondria in response to a chronic high lipid environment, 2) identifying specific metabolites of lipid-induced mitochondrial stress that contribute to skeletal muscle insulin resistance and type II diabetes, and 3) understanding how mitochondrial adaptations in response to exercise confer protection against lipid-induced mitochondrial dysfunction.

Current Appointments & Affiliations

Associate Professor in Medicine, Medicine, Geriatrics, Medicine 2017
Member of Sarah W. Stedman Nutrition & Metabolism Center, Sarah Stedman Nutrition & Metabolism Center, Duke Molecular Physiology Institute 2002

Contact Information

300 North Duke Street, 50-202 / Carmichael Bldg, Durham, NC 27701
Duke Box 104775, Durham, NC 27704
tim.koves@duke.edu (919) 479-2324

Background
Education, Training, & Certifications
- M.B.A., East Carolina University 2006
- Ph.D., East Carolina University 2002
Duke Appointment History
- Assistant Professor in Medicine, Medicine, Geriatrics, Medicine 2008 - 2017
- Assistant Research Professor in Medicine, Medicine, Geriatrics, Medicine 2007 - 2008
- Instructor, Temporary in the Department of Medicine, Medicine, Geriatrics, Medicine 2006 - 2007
Research
Selected Grants
- Mechanisms of lipid-induced bioenergetic stress in muscle awarded by National Institutes of Health 2010 - 2023
- Systemic Inflammation in Microphysiological Models of Muscle and Vascular Disease awarded by National Institutes of Health 2017 - 2022
- STIM1 and mitochondrial quality control awarded by National Institutes of Health 2017 - 2022
- Metabolic inflexibility is related to elevated muscle anaerobic glycolysis awarded by East Carolina University 2020 - 2021
- Probing the Role of Mitochondrial Short-Chain Carbon Homeostasis in the Hypertrophied and Failing Heart awarded by University of Pennsylvania 2017 - 2021
- Role of cardiac and skeletal muscle ketone oxidation in permitting adaptive mitochondrial remodeling in response to lipid stress awarded by Eli Lilly and Company 2019 - 2021
- Pilot Study: Testing of Comprehensive Mitochondrial Profiling Platform in Islet cells awarded by Eli Lilly and Company 2020
- Microbial regulation of host nutrient metabolism awarded by National Institutes of Health 2013 - 2020
- Circulatory system and integrated muscle tissue for drug and tissue toxicity awarded by National Institutes of Health 2012 - 2018
- Probing the role of Mitochondrial Short-Chain Carbon Homeostasis in the Hypertrophied and Failing Heart awarded by Sanford-Burnham Medical Research Institute 2017
- Mechanisms linking the adipogenic phenotype of aging muscle to insulin resistance awarded by National Institutes of Health 2006 - 2012
- Molecular Genetics of Muscle Specialization awarded by National Institutes of Health 2001 - 2009
Publications & Artistic Works
Selected Publications
- Academic Articles
  - Davidson, Michael T., Paul A. Grimsrud, Ling Lai, James A. Draper, Kelsey H. Fisher-Wellman, Tara M. Narowski, Dennis M. Abraham, Timothy R. Koves, Daniel P. Kelly, and Deborah M. Muoio. “Extreme Acetylation of the Cardiac Mitochondrial Proteome Does Not Promote Heart Failure.” Circ Res 127, no. 8 (September 25, 2020): 1094–1108. https://doi.org/10.1161/CIRCRESAHA.120.317293.
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  - Williams, Ashley S., Timothy R. Koves, Michael T. Davidson, Scott B. Crown, Kelsey H. Fisher-Wellman, Maria J. Torres, James A. Draper, et al. “Disruption of Acetyl-Lysine Turnover in Muscle Mitochondria Promotes Insulin Resistance and Redox Stress without Overt Respiratory Dysfunction.” Cell Metab 31, no. 1 (January 7, 2020): 131-147.e11. https://doi.org/10.1016/j.cmet.2019.11.003.
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  - Bartlett, David B., Cris A. Slentz, Leslie H. Willis, Andrew Hoselton, Janet L. Huebner, Virginia B. Kraus, Jennifer Moss, et al. “Rejuvenation of Neutrophil Functions in Association With Reduced Diabetes Risk Following Ten Weeks of Low-Volume High Intensity Interval Walking in Older Adults With Prediabetes - A Pilot Study.” Front Immunol 11 (2020): 729. https://doi.org/10.3389/fimmu.2020.00729.
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  - Lin, Kevin H., Abigail Xie, Justine C. Rutter, Yeong-Ran Ahn, Julia M. Lloyd-Cowden, Amanda G. Nichols, Ryan S. Soderquist, et al. “Systematic Dissection of the Metabolic-Apoptotic Interface in AML Reveals Heme Biosynthesis to Be a Regulator of Drug Sensitivity.” Cell Metab 29, no. 5 (May 7, 2019): 1217-1231.e7. https://doi.org/10.1016/j.cmet.2019.01.011.
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  - Khodabukus, Alastair, Lauran Madden, Neel K. Prabhu, Timothy R. Koves, Christopher P. Jackman, Deborah M. Muoio, and Nenad Bursac. “Electrical stimulation increases hypertrophy and metabolic flux in tissue-engineered human skeletal muscle.” Biomaterials 198 (April 2019): 259–69. https://doi.org/10.1016/j.biomaterials.2018.08.058.
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  - Fisher-Wellman, Kelsey H., James A. Draper, Michael T. Davidson, Ashley S. Williams, Tara M. Narowski, Dorothy H. Slentz, Olga R. Ilkayeva, et al. “Respiratory Phenomics across Multiple Models of Protein Hyperacylation in Cardiac Mitochondria Reveals a Marginal Impact on Bioenergetics.” Cell Rep 26, no. 6 (February 5, 2019): 1557-1572.e8. https://doi.org/10.1016/j.celrep.2019.01.057.
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  - Dai, Qunsheng, Creighton E. Likes, Anthony L. Luz, Lan Mao, Jason S. Yeh, Zhengzheng Wei, Maragatha Kuchibhatla, Olga R. Ilkayeva, Timothy R. Koves, and Thomas M. Price. “A Mitochondrial Progesterone Receptor Increases Cardiac Beta-Oxidation and Remodeling.” J Endocr Soc 3, no. 2 (February 1, 2019): 446–67. https://doi.org/10.1210/js.2018-00219.
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  - Andonian, Brian J., Ching-Heng Chou, Olga R. Ilkayeva, Timothy R. Koves, Margery A. Connelly, William E. Kraus, Virginia B. Kraus, and Kim M. Huffman. “Plasma MicroRNAs in Established Rheumatoid Arthritis Relate to Adiposity and Altered Plasma and Skeletal Muscle Cytokine and Metabolic Profiles.” Front Immunol 10 (2019): 1475. https://doi.org/10.3389/fimmu.2019.01475.
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  - Davis, Brittany N. J., Jeffrey W. Santoso, Michaela J. Walker, Cindy S. Cheng, Timothy R. Koves, William E. Kraus, and George A. Truskey. “Human, Tissue-Engineered, Skeletal Muscle Myobundles to Measure Oxygen Uptake and Assess Mitochondrial Toxicity.” Tissue Eng Part C Methods 23, no. 4 (April 2017): 189–99. https://doi.org/10.1089/ten.tec.2016.0264.
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  - Schmidt, Elyse A., Brian E. Fee, Stanley C. Henry, Amanda G. Nichols, Mari L. Shinohara, Jeffrey C. Rathmell, Nancie J. MacIver, et al. “Metabolic Alterations Contribute to Enhanced Inflammatory Cytokine Production in Irgm1-deficient Macrophages.” J Biol Chem 292, no. 11 (March 17, 2017): 4651–62. https://doi.org/10.1074/jbc.M116.770735.
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  - Huffman, Kim M., Ryan Jessee, Brian Andonian, Brittany N. Davis, Rachel Narowski, Janet L. Huebner, Virginia B. Kraus, et al. “Molecular alterations in skeletal muscle in rheumatoid arthritis are related to disease activity, physical inactivity, and disability.” Arthritis Res Ther 19, no. 1 (January 23, 2017): 12. https://doi.org/10.1186/s13075-016-1215-7.
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  - Consitt, Leslie A., Timothy R. Koves, Deborah M. Muoio, Masato Nakazawa, Christopher A. Newton, and Joseph A. Houmard. “Plasma acylcarnitines during insulin stimulation in humans are reflective of age-related metabolic dysfunction.” Biochem Biophys Res Commun 479, no. 4 (October 28, 2016): 868–74. https://doi.org/10.1016/j.bbrc.2016.09.116.
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  - Aubert, Gregory, Ola J. Martin, Julie L. Horton, Ling Lai, Rick B. Vega, Teresa C. Leone, Timothy Koves, et al. “The Failing Heart Relies on Ketone Bodies as a Fuel.” Circulation 133, no. 8 (February 23, 2016): 698–705. https://doi.org/10.1161/CIRCULATIONAHA.115.017355.
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  - Barrientos, Tomasa, Indira Laothamatas, Timothy R. Koves, Erik J. Soderblom, Miles Bryan, M Arthur Moseley, Deborah M. Muoio, and Nancy C. Andrews. “Metabolic Catastrophe in Mice Lacking Transferrin Receptor in Muscle.” Ebiomedicine 2, no. 11 (November 2015): 1705–17. https://doi.org/10.1016/j.ebiom.2015.09.041.
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  - Kien, C Lawrence, Dwight E. Matthews, Matthew E. Poynter, Janice Y. Bunn, Naomi K. Fukagawa, Karen I. Crain, David B. Ebenstein, et al. “Increased palmitate intake: higher acylcarnitine concentrations without impaired progression of β-oxidation.” J Lipid Res 56, no. 9 (September 2015): 1795–1807. https://doi.org/10.1194/jlr.M060137.
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  - Seiler, Sarah E., Timothy R. Koves, Jessica R. Gooding, Kari E. Wong, Robert D. Stevens, Olga R. Ilkayeva, April H. Wittmann, et al. “Carnitine Acetyltransferase Mitigates Metabolic Inertia and Muscle Fatigue during Exercise.” Cell Metab 22, no. 1 (July 7, 2015): 65–76. https://doi.org/10.1016/j.cmet.2015.06.003.
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  - Baker, Peter R., Kristen E. Boyle, Timothy R. Koves, Olga R. Ilkayeva, Deborah M. Muoio, Joseph A. Houmard, and Jacob E. Friedman. “Metabolomic analysis reveals altered skeletal muscle amino acid and fatty acid handling in obese humans.” Obesity (Silver Spring) 23, no. 5 (May 2015): 981–88. https://doi.org/10.1002/oby.21046.
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  - Baker, P. R., K. E. Boyle, T. R. Koves, O. R. Ilkayeva, D. M. Muoio, J. A. Houmard, and J. E. Friedman. “Metabolomic analysis reveals altered skeletal muscle amino acid and fatty acid handling in obese humans.” Obesity 23, no. 5 (January 1, 2015): 981–88. https://doi.org/10.1002/oby.21046.
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  - Li, Lei O., Trisha J. Grevengoed, David S. Paul, Olga Ilkayeva, Timothy R. Koves, Florencia Pascual, Christopher B. Newgard, Deborah M. Muoio, and Rosalind A. Coleman. “Compartmentalized acyl-CoA metabolism in skeletal muscle regulates systemic glucose homeostasis.” Diabetes 64, no. 1 (January 2015): 23–35. https://doi.org/10.2337/db13-1070.
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  - Huffman, Kim M., Timothy R. Koves, Monica J. Hubal, Hiba Abouassi, Nina Beri, Lori A. Bateman, Robert D. Stevens, et al. “Metabolite signatures of exercise training in human skeletal muscle relate to mitochondrial remodelling and cardiometabolic fitness.” Diabetologia 57, no. 11 (November 2014): 2282–95. https://doi.org/10.1007/s00125-014-3343-4.
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  - Lai, Ling, Teresa C. Leone, Mark P. Keller, Ola J. Martin, Aimee T. Broman, Jessica Nigro, Kapil Kapoor, et al. “Energy metabolic reprogramming in the hypertrophied and early stage failing heart: a multisystems approach.” Circ Heart Fail 7, no. 6 (November 2014): 1022–31. https://doi.org/10.1161/CIRCHEARTFAILURE.114.001469.
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  - Lindeboom, Lucas, Christine I. Nabuurs, Joris Hoeks, Bram Brouwers, Esther Phielix, M Eline Kooi, Matthijs K. C. Hesselink, et al. “Long-echo time MR spectroscopy for skeletal muscle acetylcarnitine detection.” J Clin Invest 124, no. 11 (November 2014): 4915–25. https://doi.org/10.1172/JCI74830.
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  - Tio, Maria Clarissa Yasmin Ong, Timothy R. Koves, Catherine Mikus, C Lawrence Kien, and Deborah M. Muoio. “A Transcriptomic Analysis of Responses to Overnight Fasting and Refeeding in the Human Skeletal Muscle.” Endocrine Reviews 35, no. 3 (June 1, 2014).
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  - Ussher, John R., Wendy Keung, Natasha Fillmore, Timothy R. Koves, Jun Mori, Liyan Zhang, David G. Lopaschuk, et al. “Treatment with the 3-ketoacyl-CoA thiolase inhibitor trimetazidine does not exacerbate whole-body insulin resistance in obese mice.” J Pharmacol Exp Ther 349, no. 3 (June 2014): 487–96. https://doi.org/10.1124/jpet.114.214197.
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  - Seiler, Sarah E., Ola J. Martin, Robert C. Noland, Dorothy H. Slentz, Karen L. DeBalsi, Olga R. Ilkayeva, Jie An, Christopher B. Newgard, Timothy R. Koves, and Deborah M. Muoio. “Obesity and lipid stress inhibit carnitine acetyltransferase activity.” J Lipid Res 55, no. 4 (April 2014): 635–44. https://doi.org/10.1194/jlr.M043448.
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  - DeBalsi, Karen L., Kari E. Wong, Timothy R. Koves, Dorothy H. Slentz, Sarah E. Seiler, April H. Wittmann, Olga R. Ilkayeva, et al. “Targeted metabolomics connects thioredoxin-interacting protein (TXNIP) to mitochondrial fuel selection and regulation of specific oxidoreductase enzymes in skeletal muscle.” J Biol Chem 289, no. 12 (March 21, 2014): 8106–20. https://doi.org/10.1074/jbc.M113.511535.
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  - Kien, C Lawrence, Janice Y. Bunn, Robert Stevens, James Bain, Olga Ikayeva, Karen Crain, Timothy R. Koves, and Deborah M. Muoio. “Dietary intake of palmitate and oleate has broad impact on systemic and tissue lipid profiles in humans.” Am J Clin Nutr 99, no. 3 (March 2014): 436–45. https://doi.org/10.3945/ajcn.113.070557.
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  - Huynh, Frank K., Michelle F. Green, Timothy R. Koves, and Matthew D. Hirschey. “Measurement of fatty acid oxidation rates in animal tissues and cell lines.” Methods Enzymol 542 (2014): 391–405. https://doi.org/10.1016/B978-0-12-416618-9.00020-0.
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  - Kien, C. L., J. Y. Bunn, C. L. Tompkins, J. A. Dumas, K. I. Crain, D. B. Ebenstein, T. R. Koves, and D. M. Muoio. “Erratum: Substituting dietary monounsaturated fat for saturated fat is associated with increased daily physical activity and resting energy expenditure and with changes in mood (American Journal of Clinical Nutrition (2013) 97 (689-697)).” American Journal of Clinical Nutrition 98, no. 2 (August 1, 2013): 511. https://doi.org/10.3945/ajcn.113.066282.
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  - Wong, Kari E., Timothy R. Koves, Robert D. Stevens, Olga Ikayeva, Dorothy Slentz, and Deborah M. Muoio. “Increased Muscle Mitochondrial Mass in MCK-PGC1 alpha Transgenic Mice Alters Metabolic Responses to Diet and Exercise Intervention But Does Not Improve Clinically Relevant Outcomes.” Diabetes 62 (July 1, 2013): A15–A15.
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  - Laurent, Gaëlle, Natalie J. German, Asish K. Saha, Vincent C. J. de Boer, Michael Davies, Timothy R. Koves, Noah Dephoure, et al. “SIRT4 coordinates the balance between lipid synthesis and catabolism by repressing malonyl CoA decarboxylase.” Mol Cell 50, no. 5 (June 6, 2013): 686–98. https://doi.org/10.1016/j.molcel.2013.05.012.
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  - Kien, C Lawrence, Janice Y. Bunn, Connie L. Tompkins, Julie A. Dumas, Karen I. Crain, David B. Ebenstein, Timothy R. Koves, and Deborah M. Muoio. “Substituting dietary monounsaturated fat for saturated fat is associated with increased daily physical activity and resting energy expenditure and with changes in mood.” Am J Clin Nutr 97, no. 4 (April 2013): 689–97. https://doi.org/10.3945/ajcn.112.051730.
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  - Kien, C Lawrence, Janice Y. Bunn, Matthew E. Poynter, Robert Stevens, James Bain, Olga Ikayeva, Naomi K. Fukagawa, et al. “A lipidomics analysis of the relationship between dietary fatty acid composition and insulin sensitivity in young adults.” Diabetes 62, no. 4 (April 2013): 1054–63. https://doi.org/10.2337/db12-0363.
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  - Jackson, Kathryn C., Lindsay M. Wohlers, Richard M. Lovering, Rosemary A. Schuh, Amy C. Maher, Arend Bonen, Timothy R. Koves, et al. “Ectopic lipid deposition and the metabolic profile of skeletal muscle in ovariectomized mice.” Am J Physiol Regul Integr Comp Physiol 304, no. 3 (February 2013): R206–17. https://doi.org/10.1152/ajpregu.00428.2012.
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  - Koves, Timothy R., Lauren M. Sparks, J. P. Kovalik, Merrie Mosedale, Ramamani Arumugam, Karen L. DeBalsi, Karen Everingham, et al. “PPARγ coactivator-1α contributes to exercise-induced regulation of intramuscular lipid droplet programming in mice and humans.” J Lipid Res 54, no. 2 (February 2013): 522–34. https://doi.org/10.1194/jlr.P028910.
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  - Truskey, George A., Hardean E. Achneck, Nenad Bursac, Hon Chan, Cindy S. Cheng, Cristina Fernandez, Sungmin Hong, et al. “Design considerations for an integrated microphysiological muscle tissue for drug and tissue toxicity testing.” Stem Cell Res Ther 4 Suppl 1 (2013): S10. https://doi.org/10.1186/scrt371.
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  - Smith, Brennan K., Christopher G. R. Perry, Timothy R. Koves, David C. Wright, Jeffrey C. Smith, P Darrell Neufer, Deborah M. Muoio, and Graham P. Holloway. “Identification of a novel malonyl-CoA IC(50) for CPT-I: implications for predicting in vivo fatty acid oxidation rates.” Biochem J 448, no. 1 (November 15, 2012): 13–20. https://doi.org/10.1042/BJ20121110.
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  - Kien, C. L., Janice Y. Bunn, Matthew E. Poynter, Robert Stevens, James Bain, Olga Ikayeva, Naomi K. Fukagawa, et al. “Diet Oleic Acid (OA) Improves Metabolic Risk Factors in Young Adults: Lipidomic Analysis of Sexually Dimorphic Responsiveness.” Diabetes 61 (June 1, 2012).
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  - Muoio, Deborah M., Robert C. Noland, Jean-Paul Kovalik, Sarah E. Seiler, Michael N. Davies, Karen L. DeBalsi, Olga R. Ilkayeva, et al. “Muscle-specific deletion of carnitine acetyltransferase compromises glucose tolerance and metabolic flexibility.” Cell Metab 15, no. 5 (May 2, 2012): 764–77. https://doi.org/10.1016/j.cmet.2012.04.005.
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  - Glynn, Erin L., Jie An, Li-Ping Wang, Olga R. Ilkayeva, Robert D. Stevens, James R. Bain, Michael J. Muehlbauer, et al. “Caloric restriction, aerobic exercise or a combination improves metabolic profiles following diet-induced obesity.” Faseb Journal 26 (April 1, 2012).
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  - Miranda, Diego A., Timothy R. Koves, David A. Gross, Alexandra Chadt, Hadi Al-Hasani, Gary W. Cline, Gary J. Schwartz, Deborah M. Muoio, and David L. Silver. “Re-patterning of skeletal muscle energy metabolism by fat storage-inducing transmembrane protein 2.” J Biol Chem 286, no. 49 (December 9, 2011): 42188–99. https://doi.org/10.1074/jbc.M111.297127.
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  - Boyle, K. E., J. P. Canham, L. A. Consitt, D. Zheng, T. R. Koves, T. P. Gavin, D. Holbert, et al. “A high-fat diet elicits differential responses in genes coordinating oxidative metabolism in skeletal muscle of lean and obese individuals.” J Clin Endocrinol Metab 96, no. 3 (March 2011): 775–81. https://doi.org/10.1210/jc.2010-2253.
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  - Ellis, Jessica M., Shannon M. Mentock, Michael A. Depetrillo, Timothy R. Koves, Shiraj Sen, Steven M. Watkins, Deborah M. Muoio, et al. “Mouse cardiac acyl coenzyme a synthetase 1 deficiency impairs Fatty Acid oxidation and induces cardiac hypertrophy.” Mol Cell Biol 31, no. 6 (March 2011): 1252–62. https://doi.org/10.1128/MCB.01085-10.
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  - Ussher, John R., Timothy R. Koves, Virgilio J. J. Cadete, Liyan Zhang, Jagdip S. Jaswal, Suzanne J. Swyrd, David G. Lopaschuk, et al. “Inhibition of de novo ceramide synthesis reverses diet-induced insulin resistance and enhances whole-body oxygen consumption.” Diabetes 59, no. 10 (October 2010): 2453–64. https://doi.org/10.2337/db09-1293.
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  - Thyfault, John P., Melanie G. Cree, Edward B. Tapscott, Jill A. Bell, Timothy R. Koves, Olga Ilkayeva, Robert R. Wolfe, G Lynis Dohm, and Deborah M. Muoio. “Metabolic profiling of muscle contraction in lean compared with obese rodents.” Am J Physiol Regul Integr Comp Physiol 299, no. 3 (September 2010): R926–34. https://doi.org/10.1152/ajpregu.00093.2010.
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  - Ellis, Jessica M., Lei O. Li, Pei-Chi Wu, Timothy R. Koves, Olga Ilkayeva, Robert D. Stevens, Steven M. Watkins, Deborah M. Muoio, and Rosalind A. Coleman. “Adipose acyl-CoA synthetase-1 directs fatty acids toward beta-oxidation and is required for cold thermogenesis.” Cell Metab 12, no. 1 (July 7, 2010): 53–64. https://doi.org/10.1016/j.cmet.2010.05.012.
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  - Consitt, Leslie A., Jill A. Bell, Timothy R. Koves, Deborah M. Muoio, Matthew W. Hulver, Kimberly R. Haynie, G Lynis Dohm, and Joseph A. Houmard. “Peroxisome proliferator-activated receptor-gamma coactivator-1alpha overexpression increases lipid oxidation in myocytes from extremely obese individuals.” Diabetes 59, no. 6 (June 2010): 1407–15. https://doi.org/10.2337/db09-1704.
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  - Koonen, Debby P. Y., Miranda M. Y. Sung, Cindy K. C. Kao, Vernon W. Dolinsky, Timothy R. Koves, Olga Ilkayeva, René L. Jacobs, et al. “Alterations in skeletal muscle fatty acid handling predisposes middle-aged mice to diet-induced insulin resistance.” Diabetes 59, no. 6 (June 2010): 1366–75. https://doi.org/10.2337/db09-1142.
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  - Li, Lei O., Jessica M. Ellis, Heather A. Paich, Shuli Wang, Nan Gong, George Altshuller, Randy J. Thresher, et al. “Liver-specific loss of long chain acyl-CoA synthetase-1 decreases triacylglycerol synthesis and beta-oxidation and alters phospholipid fatty acid composition.” J Biol Chem 284, no. 41 (October 9, 2009): 27816–26. https://doi.org/10.1074/jbc.M109.022467.
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  - Lum, H., T. R. Koves, K. L. DeBalsi, O. Ilkayeva, H. Van Remmen, and D. M. Muoio. “ALTERATIONS IN MITOCHONDRIAL FUEL METABOLISM AND SURVIVAL WITH REDUCED MANGANESE SUPEROXIDE DISMUTASE (SOD2).” Gerontologist 49 (October 1, 2009): 25–25.
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  - Noland, Robert C., Timothy R. Koves, Sarah E. Seiler, Helen Lum, Robert M. Lust, Olga Ilkayeva, Robert D. Stevens, Fausto G. Hegardt, and Deborah M. Muoio. “Carnitine insufficiency caused by aging and overnutrition compromises mitochondrial performance and metabolic control.” J Biol Chem 284, no. 34 (August 21, 2009): 22840–52. https://doi.org/10.1074/jbc.M109.032888.
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  - Ussher, John R., 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.” Diabetes 58, no. 8 (August 2009): 1766–75. https://doi.org/10.2337/db09-0011.
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  - Malakauskas, Sandra M., Wissam M. Kourany, Xiao Yin Zhang, Danhong Lu, Robert D. Stevens, Timothy R. Koves, Hans E. Hohmeier, Deborah M. Muoio, Christopher B. Newgard, and Thu H. Le. “Increased insulin sensitivity in mice lacking collectrin, a downstream target of HNF-1alpha.” Mol Endocrinol 23, no. 6 (June 2009): 881–92. https://doi.org/10.1210/me.2008-0274.
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  - Makowski, Liza, Robert C. Noland, Timothy R. Koves, Weibing Xing, Olga R. Ilkayeva, Michael J. Muehlbauer, Robert D. Stevens, and Deborah M. Muoio. “Metabolic profiling of PPARalpha-/- mice reveals defects in carnitine and amino acid homeostasis that are partially reversed by oral carnitine supplementation.” Faseb J 23, no. 2 (February 2009): 586–604. https://doi.org/10.1096/fj.08-119420.
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  - Ussher, J. R., T. R. Koves, J. S. Jaswal, L. Zhang, O. Ilkayeva, J. R. B. Dyck, D. M. Muoio, and G. D. Lopaschuk. “Insulin-stimulated cardiac glucose oxidation is increased in high-fat diet-induced obese mice lacking malonyl CoA decarboxylase (Diabetes (2009) 58, (1766-1775)).” Diabetes 58, no. 10 (2009): 2425-.
  - Ussher, John Edward R., Timothy R. Koves, Jagdip S. Jaswal, Christopher B. Newgard, Jason R. Dyck, Deborah M. Muoio, and Gary D. Lopaschuk. “Insulin-Stimulated Glucose Oxidation is Increased in Hearts from High Fat Diet-Induced Obese Mice Lacking Malonyl CoA Decarboxylase.” Circulation 118, no. 18 (October 28, 2008): S539–S539.
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  - Koves, Timothy R., John R. Ussher, Robert C. Noland, Dorothy Slentz, Merrie Mosedale, Olga Ilkayeva, James Bain, et al. “Mitochondrial overload and incomplete fatty acid oxidation contribute to skeletal muscle insulin resistance.” Cell Metab 7, no. 1 (January 2008): 45–56. https://doi.org/10.1016/j.cmet.2007.10.013.
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  - Muoio, Deborah M., and Timothy R. Koves. “Skeletal muscle adaptation to fatty acid depends on coordinated actions of the PPARs and PGC1 alpha: implications for metabolic disease.” Appl Physiol Nutr Metab 32, no. 5 (October 2007): 874–83. https://doi.org/10.1139/H07-083.
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  - Thyfault, John P., Melanie G. Cree, Donghai Zheng, Jennifer J. Zwetsloot, Edward B. Tapscott, Timothy R. Koves, Olga Ilkayeva, Robert R. Wolfe, Deborah M. Muoio, and G Lynis Dohm. “Contraction of insulin-resistant muscle normalizes insulin action in association with increased mitochondrial activity and fatty acid catabolism.” Am J Physiol Cell Physiol 292, no. 2 (February 2007): C729–39. https://doi.org/10.1152/ajpcell.00311.2006.
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  - Muoio, Deborah M., and Timothy R. Koves. “Lipid-induced metabolic dysfunction in skeletal muscle.” Novartis Found Symp 286 (2007): 24–38. https://doi.org/10.1002/9780470985571.ch4.
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  - Gaillard, Stéphanie, Linda L. Grasfeder, Christiane L. Haeffele, Edward K. Lobenhofer, Tzu-Ming Chu, Russ Wolfinger, Dmitri Kazmin, et al. “Receptor-selective coactivators as tools to define the biology of specific receptor-coactivator pairs.” Mol Cell 24, no. 5 (December 8, 2006): 797–803. https://doi.org/10.1016/j.molcel.2006.10.012.
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  - Koves, Timothy R., Ping Li, Jie An, Takayuki Akimoto, Dorothy Slentz, Olga Ilkayeva, G Lynis Dohm, Zhen Yan, Christopher B. Newgard, and Deborah M. Muoio. “Peroxisome proliferator-activated receptor-gamma co-activator 1alpha-mediated metabolic remodeling of skeletal myocytes mimics exercise training and reverses lipid-induced mitochondrial inefficiency.” J Biol Chem 280, no. 39 (September 30, 2005): 33588–98. https://doi.org/10.1074/jbc.M507621200.
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  - Koves, Timothy R., Robert C. Noland, Andrew L. Bates, Sarah T. Henes, Deborah M. Muoio, and Ronald N. Cortright. “Subsarcolemmal and intermyofibrillar mitochondria play distinct roles in regulating skeletal muscle fatty acid metabolism.” Am J Physiol Cell Physiol 288, no. 5 (May 2005): C1074–82. https://doi.org/10.1152/ajpcell.00391.2004.
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  - Berggren, Jason R., Charles J. Tanner, Timothy R. Koves, Deborah M. Muoio, and Joseph A. Houmard. “Glucose uptake in muscle cell cultures from endurance-trained men.” Med Sci Sports Exerc 37, no. 4 (April 2005): 579–84. https://doi.org/10.1249/01.mss.0000158180.11224.e8.
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  - Fluckey, James D., Ronald N. Cortright, Edward Tapscott, Timothy Koves, Latasha Smith, Steven Pohnert, and G Lynis Dohm. “Active involvement of PKC for insulin-mediated rates of muscle protein synthesis in Zucker rats.” Am J Physiol Endocrinol Metab 286, no. 5 (May 2004): E753–58. https://doi.org/10.1152/ajpendo.00155.2003.
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  - An, Jie, Deborah M. Muoio, Masakazu Shiota, Yuka Fujimoto, Gary W. Cline, Gerald I. Shulman, Timothy R. Koves, Robert Stevens, David Millington, and Christopher B. Newgard. “Hepatic expression of malonyl-CoA decarboxylase reverses muscle, liver and whole-animal insulin resistance.” Nat Med 10, no. 3 (March 2004): 268–74. https://doi.org/10.1038/nm995.
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  - Sizemore, Glen M., Conchita Co, Timothy R. Koves, Thomas J. Martin, and James E. Smith. “Time-dependent recovery from the effects of 6-hydroxydopamine lesions of the rat nucleus accumbens on cocaine self-administration and the levels of dopamine in microdialysates.” Psychopharmacology (Berl) 171, no. 4 (February 2004): 413–20. https://doi.org/10.1007/s00213-003-1596-6.
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  - Smith, J. E., T. R. Koves, and C. Co. “Brain neurotransmitter turnover rates during rat intravenous cocaine self-administration.” Neuroscience 117, no. 2 (2003): 461–75. https://doi.org/10.1016/s0306-4522(02)00819-9.
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  - Kim, Jong-Yeon, Timothy R. Koves, Geng-Sheng Yu, Tod Gulick, Ronald N. Cortright, G Lynis Dohm, and Deborah M. Muoio. “Evidence of a malonyl-CoA-insensitive carnitine palmitoyltransferase I activity in red skeletal muscle.” Am J Physiol Endocrinol Metab 282, no. 5 (May 2002): E1014–22. https://doi.org/10.1152/ajpendo.00233.2001.
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  - Koves, T. R., R. C. Noland, J. M. Bennett, and R. N. Cortright. “Increased sensitivity to malonyl-CoA in intermyofibrillar but not subsarcolemmal skeletal muscle mitochondria after exercise training.” Faseb Journal 16, no. 4 (March 20, 2002): A31–A31.
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  - Noland, R. C., T. R. Koves, J. M. Bennett, R. N. Cortright, and R. M. Lust. “Mitochondrial fatty acid oxidative capacity is not significantly altered following exercise training in rat heart.” Faseb Journal 16, no. 4 (March 20, 2002): A34–A34.
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  - Cameron, Vicky A., Dominic J. Autelitano, John J. Evans, Leigh J. Ellmers, Eric A. Espiner, M Gary Nicholls, and A Mark Richards. “Adrenomedullin expression in rat uterus is correlated with plasma estradiol.” Am J Physiol Endocrinol Metab 282, no. 1 (January 2002): E139–46. https://doi.org/10.1152/ajpendo.2002.282.1.E139.
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  - Tanner, Charles J., Timothy R. Koves, Ronald L. Cortright, Walter J. Pories, Young-Bum Kim, Barbara B. Kahn, G Lynis Dohm, and Joseph A. Houmard. “Effect of short-term exercise training on insulin-stimulated PI 3-kinase activity in middle-aged men.” Am J Physiol Endocrinol Metab 282, no. 1 (January 2002): E147–53. https://doi.org/10.1152/ajpendo.2002.282.1.E147.
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  - Hickner, R. C., P. M. Mehta, D. Dyck, P. Devita, J. A. Houmard, T. Koves, and P. Byrd. “Relationship between fat-to-fat-free mass ratio and decrements in leg strength after downhill running.” J Appl Physiol (1985) 90, no. 4 (April 2001): 1334–41. https://doi.org/10.1152/jappl.2001.90.4.1334.
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  - Koves, T. R., and R. N. Cortright. “Comparison of palmitate oxidative capacities of isolated mitochondrial subpopulations from rat skeletal muscle by CO2 and acid soluble metabolite production.” Faseb Journal 15, no. 5 (March 8, 2001): A815–A815.
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  - Noland, R. C., W. R. Fannon, T. R. Koves, R. N. Conright, and R. M. Lust. “Myocardial palmitate oxidation in spontaneously hypertensive corpulent rats.” Faseb Journal 15, no. 5 (March 8, 2001): A1142–A1142.
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  - Fannon, W. R., R. C. Noland, T. R. Koves, J. M. Bennett, R. C. Hickner, and R. N. Cortright. “Reduced insulin action and elevated fatty acid oxidation in obese-hypertensive rats.” Faseb Journal 15, no. 4 (March 7, 2001): A77–A77.
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  - Berry, M. J., T. R. Koves, and J. J. Benedetto. “The influence of speed, grade and mass during simulated off road bicycling.” Appl Ergon 31, no. 5 (October 2000): 531–36. https://doi.org/10.1016/s0003-6870(00)00022-3.
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  - Cortright, R. N., and T. R. Koves. “Sex differences in substrate metabolism and energy homeostasis.” Can J Appl Physiol 25, no. 4 (August 2000): 288–311. https://doi.org/10.1139/h00-023.
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  - Houmard, J. A., M. L. Weidner, T. R. Koves, R. C. Hickner, and R. L. Cortright. “Association between muscle fiber composition and blood pressure levels during exercise in men.” Am J Hypertens 13, no. 6 Pt 1 (June 2000): 586–92. https://doi.org/10.1016/s0895-7061(99)00259-9.
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  - Hemby, S. E., C. Co, T. R. Koves, J. E. Smith, and S. I. Dworkin. “Differences in extracellular dopamine concentrations in the nucleus accumbens during response-dependent and response-independent cocaine administration in the rat.” Psychopharmacology (Berl) 133, no. 1 (September 1997): 7–16. https://doi.org/10.1007/s002130050365.
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  - Dworkin, S. I., S. Gleeson, D. Meloni, T. R. Koves, and T. J. Martin. “Effects of ibogaine on responding maintained by food, cocaine and heroin reinforcement in rats.” Psychopharmacology (Berl) 117, no. 3 (February 1995): 257–61. https://doi.org/10.1007/BF02246099.
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  - Vrana, S. L., K. E. Vrana, T. R. Koves, J. E. Smith, and S. I. Dworkin. “Chronic cocaine administration increases CNS tyrosine hydroxylase enzyme activity and mRNA levels and tryptophan hydroxylase enzyme activity levels.” J Neurochem 61, no. 6 (December 1993): 2262–68. https://doi.org/10.1111/j.1471-4159.1993.tb07468.x.
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- Conference Papers
  - Torres Alcalde, Maria J., Xu Zang, Dorothy H. Slentz, Timothy R. Koves, George A. Truskey, and Deborah M. Muoio. “Abstract P284: The Chemotherapeutic Agent Docetaxel Disrupts Mitochondrial Energetics in 3D Human Bioengineered Myobundles.” In Circulation, Vol. 139. Ovid Technologies (Wolters Kluwer Health), 2019. https://doi.org/10.1161/circ.139.suppl_1.p284.
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  - Khodabukus, A., L. Madden, C. Jackman, N. Prabhu, T. Koves, and N. Bursac. “Combined Drug and Electrical Stimulation Synergistically Increase Function of Engineered Human Skeletal Muscle.” In Tissue Engineering Part A, 23:S39–40. MARY ANN LIEBERT, INC, 2017.
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  - McCommis, Kyle S., Carrie M. Gierasch, Attila Kovacs, Carla J. Weinheimer, Timothy R. Koves, Deborah M. Muoio, and Brian N. Finck. “Cardiac Deletion of the Mitochondrial Pyruvate Carrier Results in Dilated Cardiomyopathy with Preservation of Fatty Acid Catabolism.” In Circulation Research, Vol. 121. LIPPINCOTT WILLIAMS & WILKINS, 2017.
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  - Williams, Ashley S., Paul A. Grimsrud, Dorothy H. Slentz, April H. Wittmann, Timothy R. Koves, William E. Kraus, and Deborah M. Muoio. “Regulation of Carnitine Acetyltransferase by Lysine Acetylation.” In Diabetes, 65:A15–A15. AMER DIABETES ASSOC, 2016.
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  - Glynn, Erin L., Jie An, Li-Ping Wang, Olga R. Ilkayeva, Robert D. Stevens, James R. Bain, Michael J. Muehlbauer, et al. “Caloric restriction, aerobic exercise or a combination improves metabolic profiles following diet-induced obesity.” In Faseb Journal, Vol. 26, 2012.
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  - Zhang, Jingying, Robert C. Nolan, Sarah E. Seiler, Timothy R. Koves, Indu Kheterpal, Robert D. Stevens, Olga R. Ilkayeva, Deborah M. Muoio, and Randall L. Mynatt. “Effects of Muscle Specific Deletion of Carnitine Palmitoyltransferase and Carnitine Acetyltransferase on Fuel Selection.” In Diabetes, 60:A466–A466. AMER DIABETES ASSOC, 2011.
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  - Kien, C Lawrence, Janice Y. Bunn, Catherine M. Champagne, Karen I. Everingham, Tim R. Koves, and Deborah M. Muoio. “Effects of High and Low Palmitic Acid Diets on Whole Body, Tissue, and Serum Lipids.” In Obesity, 18:S103–S103. NATURE PUBLISHING GROUP, 2010.
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  - Kien, C. L., J. Y. Bunn, T. Koves, Olga Ilkayeva, and D. M. Muoio. “Effects of High and Low Palmitic Acid Diets on Fatty Acid Metabolism in Non-Obese Human Subjects.” In Obesity, 18:S67–S67. NATURE PUBLISHING GROUP, 2010.
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  - Berggren, J. R., M. W. Hulver, C. L. Tanner, T. Koves, D. M. Muoio, and J. A. Houmard. “Defects in morbidly obese skeletal muscle lipid metabolism are retained in primary cultures.” In Faseb Journal, 18:A689–A689. FEDERATION AMER SOC EXP BIOL, 2004.
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Education, Training, & Certifications

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Conference Papers