DUKE UNIVERSITY
SCHOOL OF MEDICINE
DUKEHEALTH.ORG
| Faculty & Staff |
Christopher B. Newgard, PhD
Director, Sarah W. Stedman Nutrition and Metabolism Center
W. David and Sarah W. Stedman Distinguished Professor
Professor of Pharmacology and Cancer Biology
Professor of Medicine
Christopher Newgard, PhD has served as director of the Sarah W. Stedman Nutrition and Metabolism Center since March 2002. Prior to coming to Duke, Dr. Newgard was the Gifford O. Touchstone and Randolph G. Touchstone Distinguished Professor and co-director of the Touchstone Center for Diabetes Research at UT Southwestern Medical Center in Dallas. Before his appointment as director of the Stedman Center, the Stedman Center was recognized as a clinical research center. Since taking over the leadership of the center, Dr. Newgard has combined a strong basic science research program in metabolism with a new clinical research program focused on nutrition, metabolism, and obesity. To these programs he has added a comprehensive metabolic and biomarker profiling program to put the Stedman Center on an entirely new trajectory for success. A pillar of the basic science research program of the Stedman Center is Dr. Newgard’s own laboratory. His laboratory focuses on understanding metabolic regulatory mechanisms and applying this knowledge to gain insight into chronic conditions and diseases such as obesity and diabetes. Key projects in the lab include the following: 1) mechanisms involved in the regulation of insulin secretion from pancreatic islet β-cells by glucose and other metabolic fuels; 2) mechanisms involved in obesity-related impairment of β -cell function; 3) development of methods for protection of β cells against environmental insults, including elevated lipids and inflammatory mediators; 4) studies on spatial organization and regulation of systems controlling hepatic glucose balance; 5) studies on the mechanisms involved in lipid-induced impairment of insulin action in obesity and diabetes.
Publications:
Shah, S.H., Bain, J., Crosslin, D.R., Muehlbauer, M.J., Stevens, R., Haynes, C., Dungan, J., Newby, K., Hauser, E.R., Ginsburg, G.S, Newgard, C.B., Kraus, W.E. 2009. Association of a peripheral blood metabolic profile with coronary artery disease and risk of subsequent cardiovascular events. Submitted for publication.
Newgard, C.B., An, J., Bain, J.R., Muehlbauer, M.J., Stevens, R.D., Lien, L.F., Haqq, A.M., Shah, S.H., Arolotto, M., Slentz, C.A., Rochon, J., Gallup, D., Ilkayeva, O., Wenner, B.R., Yancy, W.E., Eisenson, H., Musante, G., Surwit, R., Millington, D.S., Butler, M.D., Svetkey, L.P. 2009. A branched-chain amino acid-related metabolic signature that differentiates obese and lean humans and contibutes to insulin resistance. Cell Metabolism, in press.
Shah SH, Freedman NJ, Crosslin DR, Stone DH, Zhang L, Haynes C, Hale AB, Johnson J, Nelson S, Wang L, Muehlbauer M, Crossman DC, Jones CJH, Vance J, Sketch M, Granger CB, Newgard CB, Gregory S, Goldschmidt-Clermont PJ, Hauser ER, Kraus WE. 2008. Neuropeptide Y gene polymorphisms confer risk of early-onset atherosclerosis. PLoS Genetics 5: e1000318.
Turer AT, Stevens RD, Bain JR, Muehlbauer MJ, van der Westhuizen, J, Mathew JP, Schwinn DA, Glower DD, Newgard CB, Podgoreanu MV. 2008. Metabolomic profiling reveals distinct patterns of metabolic substrate utilization in humans with coronary artery disease or left ventricular dysfunction during surgical ischemia-reperfusion. Circulation, in press.
Wardell, S.E., Ilkayeva, O.R., Wieman, H., Rathmell, J.C., Newgard, C.B., McDonnell, D.P. 2007. Histone deacetylase inhibitors affect a quantitative switch from glycolytic to oxidative metabolism in cellular models of multiple myeloma. Molecular Endocrinology, in press.
Chopra, A., Louet, J-F., Saha, P., DMayo, F., Xu, J., York, B., Sarpen, S., Finegold, M., Moore, D., Chan, L., An, J., Newgard, C.B., O’Malley, B.W. 2008. Steroid receptor coactivator SRC-2 governs hepatic glucose production and its absence results in Von Gierke’s disease. Science 322: 1395-1399.
Lien, L.F., Haqq, A. M., Arlotto, M., Slentz, C.A., Muehlbauer, M.J., McMahon, R.L., Rochon, J., Gallup, D., Bain, J.R., Stevens, R., Ilkayeva, O., Millington, D., Butler, M.D., Newgard, C.B., Svetkey, L.P. 2008. The STEDMAN Project: Biophysical, biochemical, and metabolic effects of a behavioral weight loss intervention during weight loss, maintenance, and regain. Omics, in press
Ronnebaum, S.M., Jensen, M. V., Hohmeier, H.E., Burgess, S.C., Zhou, Y-P., Qian, S., MacNeil, D., Howard, A., Thornberry, N., Ilkayeva O., Lu, D., Sherry, A.D., Newgard, C. B. 2008. Silencing of cytosolic or mitochondrial isoforms of malic enzyme has no effect on glucose-stimulated insulin secretion from rodent islets. Journal of Biological Chemistry, in press.
Newgard, C.B., Stevens, R.D., Wenner B. R., Burgess, S.C., Ilkayeva, O., Muehlbauer, M.J., Sherry, A.D., Bain, J.R. 2008. Comprehensive metabolic analysis for understanding of disease mechanisms, in Handbook of Genomic Medicine, Willard, H., Ginsburg, G., editors, Elsevier, in press.
Jensen, M.V., Joseph, J.W., Ronnebaum, S.M., Burgess, S.C., Sherry, A.D., Newgard, C.B. 2008. Metabolic cycling in control of glucose-stimulated insulin secretion. Invited review, American Journal of Physiology 295(6):E1287-97.
Haqq, A., Grambow SC, Muehlbauer M., Newgard CB, Svetkey LP, Carrel AL, Yanovski J, Purnell JQ, Freemark M. 2008. Ghrelin concentrations in Prader-Willi Syndrome (PWS) infants and children: changes during development. Clinical Endocrinology 69(6):911-20.
Muoio DM and Newgard CB. 2008. Fatty acid oxidation and insulin action: when less is more. Diabetes 57: 1455-1456.
Ronnebaum, S.M., Joseph, J.W., Ilkayeva, O., Burgess, S.C., Lu, D., Becker, T.C., Sherry, A.D., Newgard, C.B. 2008. Chronic suppression of acetyl CoA carboxylase-1 in beta-cells impairs insulin secretion via inhibition of glucose rather than lipid metabolism. Journal of Biological Chemistry 283: 14248-14256.
Schisler J, Fueger, P. T., Babu, D. A., Hohmeier, H.E., Tessem, J., Lu, D., Becker, T.C., Naziruddin, B., Levy, M., Mirmira R.G., and Newgard CB. 2008. The homeodomain transcription factor Nkx 6.1 stimulates proliferation and preserves insulin secretion in mature human and rodent pancreatic islet b-cells. Molecular and Cellular Biology 28: 3465-3476.
Fueger, P.T., Schisler, J.S., Lu, D., Babu, D.A., Mirmira, R.G., Newgard, C.B., Hohmeier, H.E. 2008. Trefoil factor-3 stimulates b-cell replication in human and rodent pancreatic islets. Molecular Endocrinology 22: 1251-1259.
Kimple, M.E., Joseph, J.W., Bailey, C.L., Fueger, P.T., Kelly, P., Newgard, C.B., Casey, P.J. 2008. Genetic deletion of Gaz increases insulin secretion and improves glucose homeostasis in mice. Journal of Biological Chemistry 283: 4560-4567.
Ferrara, CT, Wang P, Stevens, RD, Neto EC, Bain JR, Choi Y, Keller MP, Kendziorski CM, Yandell BS, Wenner BR, Oler AT, Basiole DA, Ilkayeva OR, Newgard, CB*, Attie, AD*. 2007. Genetic networks of liver metabolism revealed by integration of metabolic and transcriptomic profiling. PLoS Genetics 4: e1000034. *Co-senior authors
Muoio DM, Newgard CB. 2008. Molecular and metabolic mechanisms of insulin resistance and b-cell failure in type 2 diabetes. Nature Reviews Molecular Cell Biology 9: 193-205.
Haqq AM, Muehlbauer M., Svetkey, L.P., Newgard, C.B., Purnell, O., Grambow, S.C., Freemark M.S. 2007. Altered distribution of adiponectin isoforms in children with PWS: association with insulin sensitivity and circulating satiety peptide hormones. Clinical Endocrinology 67: 944-951.
Joseph, J.W., Odegaard, M. L., Ronnebaum, S.M., Burgess, S.C., Muehlbauer, J., Sherry, A.D., Newgard, C.B. 2007. Normal flux through ATP-citrate lyase or fatty acid synthase is not required for glucose-stimulated insulin secretion. Journal of Biological Chemistry 282: 31592-31600.
Monetti, M., Levin, M.C., Watt, M.J., Sajan, M.P., Marmor, S., Hubbard, B.K., Stevens, R.D., Bain, J.R., Newgard, C.B., Farese, R.V., Sr., Hevener, A., Farese, R. V., Jr. 2007. Dissociation of hepatic steatosis and insulin resistance in mice overexpressing DGAT in the liver. Cell Metabolism 6: 69-78
Qi, L., Heredia, J., Screaton, R., Altarejos, JY, Goebel N., Niessen, S, MaLeod IX, Liew CW, Kulkarni R., Bain J, Newgard, C.B., Nelson, M., Evans, R.M., Yates, J., and Montminy, M. 2006. TRB3 links the E3 ubiquitin ligase COP1 to lipid metabolism. Science 312: 1763-1766.
Collier JJ, Fueger PT, Hohmeier HE, Newgard CB. 2006 Pro- and Anti-apoptotic proteins regulate apoptosis but do not protect against cytokind-mediated cytotoxicity in rat islets and beta-cell lines. Diabetes 55: 1398-1406.
Joseph JW, Jensen MV, Ilkayeva O, Palmieri F, Alarcon C, Rhodes CJ, Newgard CB. The mitochondrial citrate/isocitrate carrier plays a regulatory role in
glucose-stimulated insulin secretion. J Biol Chem. 2006 Sep 25.
glucose-stimulated insulin secretion. J Biol Chem. 2006 Sep 25.
Ronnebaum SM, Ilkayeva O, Burgess SC, Joseph JW, Lu D, Stevens RD, Becker TC, Sherry AD, Newgard CB, Jensen MV. A Pyruvate Cycling Pathway Involving Cytosolic NADP-dependent Isocitrate Dehydrogenase Regulates Glucose-stimulated Insulin Secretion. J Biol Chem. 2006 Oct 13;281(41):30593-30602.
Jensen MV, Joseph JW, Ilkayeva O, Burgess S, Lu D, Ronnebaum SM, Odegaard M, Becker TC, Sherry AD, Newgard CB. Compensatory responses to pyruvate carboxylase suppression in islet beta-cells. Preservation of glucose-stimulated insulin secretion. J Biol Chem. 2006 Aug 4;281(31):22342-51. Epub 2006 Jun 1.
Hohmeier HE, Newgard CB. Islets for all? Nat Biotechnol. 2005 Oct;23(10):1231-2.
Schisler JC, Jensen PB, Taylor DG, Becker TC, Knop FK, Takekawa S, German M, Weir GC, Lu D, Mirmira RG, Newgard CB. The Nkx6.1 homeodomain transcription factor suppresses glucagon expression and regulates glucose-stimulated insulin secretion in islet beta cells. Proc Natl Acad Sci USA. 2005; 102;7297-7302.
Lin J, Yang R, Tarr PT, Wu P-H, Yang W, Uldry M, Newgard CB, Spiegleman BM. Hyperlipedemic effects of dietary saturated fatty acids mediated through PGC-1β coactivation of SREBP. Cell. 2005;120:261-273.
An J, Muoio DM, Shiota M, Fujimoto Y, Cline GW, Shulman GI, Koves T, Stevens R, Millington D, Newgard CB. Hepatic expression of malonyl CoA decarboxylase reverses muscle, liver, and whole animal insulin resistance. Nat Med. 2004;10(3):268-274.
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