Pharmacology & Cancer Biology | Duke University Medical Center

Dr. Christopher B. Newgard

Christopher B.Newgard, Ph.D.
Professor of Pharmacology and Cancer Biology
Professor of Internal Medicine
W. David and Sarah W. Stedman Distinguished Professor
Director, Sarah W. Stedman Nutrition and Metabolism Center

Duke University Medical Center
Duke Independence Park Facility
4321 Medical Park Drive
Durham, NC 27704

Phone: 919-668-6059
E-mail: newga002@mc.duke.edu

Research Interests

Our laboratory focuses on understanding of metabolic regulatory mechanisms, and the application of this knowledge for gaining insights into chronic conditions and diseases such as obesity and diabetes. Key projects in the lab include: 1) Molecular and biochemical mechanisms of fuel-mediated insulin secretion and their impairment in obesity and diabetes; 2) Mechanisms of pancreatic beta-cell growth and survival; 3) Regulation of glucose and lipid metabolism in liver; 4) Mechanisms by which metabolic alterations in liver affect peripheral (e.g muscle) fuel metabolism. The laboratory employs a highly interdisciplinary approach to each of these projects, including gene discovery (microarray analysis), genetic engineering, enzymology and biochemistry, and state-of-the-art tools for metabolic analysis including flux measurements by stable isotope NMR and metabolic profiling by mass spectrometry. In his role as Director of the Sarah W. Stedman Nutrition and Metabolism Center, Dr. Newgard has also formed a clinical research team that is applying comprehensive metabolic and biomarker profiling to obese humans as they lose weight by eight different interventions that are available on the Duke campus or in the surrounding community.

Publications

Yang, R. and Newgard, C.B. 2003. Hepatic expression of a targeting subunit of protein phosphatase-1 in STZ-diabetic rats reverses hyperglycemia and hyperphagia despite depressed glucokinase expression. Journal of Biological Chemistry 278: 23418-23425.

An, J., Muoio, D.M., Shiota, M., Fujimoto, Y., Cline, G.W., Shulman, G.I.,, Stevens, R., Millington, D., and Newgard, C.B. 2004. Hepatic Expression of Malonyl CoA Decarboxylase Reverses Muscle, Liver, and Whole-Animal Insulin Resistance. Nature Medicine 10: 268-274

Boucher, A., Lu, D., Burgess, S., Telemaque-Potts, S., Jensen, M., Mulder, H., Wang, M-Y., Unger, R.H., Sherry, A.D., and Newgard, C.B. 2004. Mechanism of lipid-induced impairment of glucose-stimulated insulin secretion and its reversal by an analogue of malate. Journal of Biological Chemistry 279: 27263-27271.

Lin J, Yang R, Tarr PT, Wu, P-H, Yang W, Uldry M, Newgard C.B., Spielgeman BM. 2005. Hyperlipidemic Effects of Dietary Saturated Fatty Acids Mediated Through PGC-1b Coactivation of SREBP. Cell 120:261-273.

Schisler J, Jensen PB, Taylor, DG, Becker TC, Knop F, Lu, D., German M, Weir G, Mirmira R, and Newgard C.B. 2005. The Nkx 6.1 homeodomain transcription factor suppresses glucagon expression and regulates glucose-stimulated insulin secretion in islet b-cells. Proceedings of the National Academy of Sciences USA 102: 7297-7302

Hohmeier, H.E. and Newgard, C.B. 2005. Islets for all? Nature Biotechnology 10: 1231-1232.

Jensen, M.V., Joseph, J., Ilkayeva, O., Burgess, S., Lu, D., Ronnebaum, S., Odegaard, M., Becker, T.C., Sherry, A.D., Newgard, C.B. 2006. Compensatory responses to pyruvate carboxylase suppression in islet beta-cells: Preservation of glucose-stimulated insulin secretion. Journal of Biological Chemistry 281: 22342-22351.

Ronnebaum, S., Joseph, J.W., Burgess, S.C., Lu, D., Ilkayeva, O., Stevens, R., Becker, T.C., Muehlbauer, J., Sherry, A.D., Newgard, C.B., Jensen, M.V. 2006. A pyruvate cycling pathway involving cytosolic NAPD-dependent isocitrate dehydrogenase regulates glucose-stimulated insulin secretion. Journal of Biological Chemistry 281: 31041-31049.

Joseph, J.W., Jensen, M.V., Ilkayeva, O., Palmieri, F., Alarcon, C., Rhodes, C.J., Newgard, C.B. 2006. The mitochondrial citrate carrier plays a regulatory role in glucose-stimulated insulin secretion. Journal of Biological Chemistry 281: 35624-35632.

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.

Hardy, O.T., Hohmeier, H.E., Becker, T.C., Manduchi E., Doliba, N.M, Gupta, R.K., White, P., Stoeckert C.J., Matschinsky F.M., Newgard, C.B., Kaestner, K.H. 2007. Functional genomics of the beta-cell: SCHAD regulates insulin secretion independent of K+ currents. Molecular Endocrinology 21: 765-773.

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

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.

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

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, in press.

Muoio D.M., Newgard C.B. 2008. Molecular and metabolic mechanisms of insulin resistance and b-cell failure in type 2 diabetes. Nature Reviews Molecular Cell Biology, in press.

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