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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 School of Medicine
47-201 Carmichael Building
Durham, NC 27701
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.
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.
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.
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*. 2008. Genetic networks of liver metabolism revealed by integration of metabolic and transcriptomic profiling. PLoS Genetics 4: e1000034. *Co-senior authors
Schisler J, Fueger, P. T., Babu, D. A., Hohmeier, H.E., Tessem, J. S., Lu, D., Becker, T.C., Naziruddin, B., Levy, M., Mirmira R.G., and Newgard CB. 2008. Stimulation of human and rat islet-bell proliferation with retention of function by the homeodomain transcription factor Nkx6.1. 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 beta-cell replication in human and rodent pancreatic islets. Molecular Endocrinology 22: 1251-1259.
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 283: 28909-28917
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.
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. American Journal of Physiology 295: E1287-E1297.
Moss, L.G., Newgard, C.B. 2009. The liver—a potential new player in islet regeneration? Cell Metabolism 9: 5-6.
Turer, A.T., Stevens, R. D., Bain, J.R., Muehlbauer, M.J., van der Westhuizen J., Mathew, J. P., Schwinn, D.A., Glower, D.D., Newgard, C.B.*, Podgoreanu, M.V.*2009. Metabolomic profiling reveals distinct patterns of metabolic substrate utilization in humans with coronary artery disease or left ventricular dysfunction during surgical ischemia-reperfusion. Circulation 119: 1736-1746. * Co-senior authors.
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 contributes to insulin resistance. Cell Metabolism 9: 311-326.
Shah, S.H., Hauser, E.R., Bain, J.R., Muehlbauer, M.J., Haynes, C., Stevens, R.D., Wenner, B.R., Dowdy, Z.E., Granger, C.B., Ginsburg, G.S., Newgard, C.B., Kraus, W.E. 2009. High heritability of metabolomic profiles in families burdened with premature cardiovascular disease. Molecular Systems Biology 5: 258-266.
Rathmell, J.C., Newgard, C.B. 2009. A glucose-to-gene link. Science 324: 1021-22.
Bain, J.R., Stevens, R.D., Wenner B.R., Ilkayeva, O., Muoio, D.M., Newgard, C.B. 2009. Metabolomics applied to diabetes research: Moving from information to knowledge. Diabetes, in press.