Scholars@Duke

• Background
• 

  Education, Training, & Certifications

  • Ph.D., University of Texas at Dallas 1997
• 

  Previous Appointments & Affiliations

  • Assistant Professor in Medicine, Medicine, Endocrinology, Metabolism, and Nutrition, Medicine 2006 - 2020
  • Assistant Research Professor in Medicine, Medicine, Endocrinology, Metabolism, and Nutrition, Medicine 2002 - 2006
  • Instructor, Temporary in the Department of Medicine, Medicine, Endocrinology, Metabolism, and Nutrition, Medicine 2002
• Research
• 

  Selected Grants

  • Mechanisms connecting dysregulated BCAA, glucose & lipid metabolism in the pathogenesis of metabolic disease awarded by National Institutes of Health 2019 - 2023
  • The role of gastrin in esophageal submucosal gland acinar ductal metaplasia awarded by National Institutes of Health 2018 - 2023
  • Role of CAV3 Mutation in the Pathogenesis of Barrett's Esophagus awarded by Case Western Reserve University 2019 - 2021
  • Reversible Mitochondrial Protein Acetylation and Metabolic Regulation awarded by Buck Institute for Research on Aging 2017 - 2020
  • Manipulation of BCAA Metabolism for Therapy of Diabetes and its Co-morbidities awarded by Eli Lilly and Company 2017 - 2018
  • Reversible Mitochondrial Protein Acetylation and Metabolic Regulation awarded by Gladstone 2010 - 2017
• Publications & Artistic Works
• 

  Selected Publications

  • Academic Articles

    • Zhang, Guo-Fang, Mette V. Jensen, Sarah M. Gray, Kimberley El, You Wang, Danhong Lu, Thomas C. Becker, Jonathan E. Campbell, and Christopher B. Newgard. “Reductive TCA cycle metabolism fuels glutamine- and glucose-stimulated insulin secretion.” Cell Metab 33, no. 4 (April 6, 2021): 804-817.e5. https://doi.org/10.1016/j.cmet.2020.11.020.
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    • Khan, Md Wasim, Medha Priyadarshini, Jose Cordoba-Chacon, Thomas C. Becker, and Brian T. Layden. “Hepatic hexokinase domain containing 1 (HKDC1) improves whole body glucose tolerance and insulin sensitivity in pregnant mice.” Biochim Biophys Acta Mol Basis Dis 1865, no. 3 (March 1, 2019): 678–87. https://doi.org/10.1016/j.bbadis.2018.11.022.
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    • Haldeman, Jonathan M., Amanda E. Conway, Michelle E. Arlotto, Dorothy H. Slentz, Deborah M. Muoio, Thomas C. Becker, and Christopher B. Newgard. “Creation of versatile cloning platforms for transgene expression and dCas9-based epigenome editing.” Nucleic Acids Res 47, no. 4 (February 28, 2019): e23. https://doi.org/10.1093/nar/gky1286.
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    • Pusec, Carolina M., Adam De Jesus, Md Wasim Khan, Alexander R. Terry, Anton E. Ludvik, Kai Xu, Nicholas Giancola, et al. “Hepatic HKDC1 Expression Contributes to Liver Metabolism.” Endocrinology 160, no. 2 (February 1, 2019): 313–30. https://doi.org/10.1210/en.2018-00887.
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    • Oh, Eunjin, Miwon Ahn, Solomon Afelik, Thomas C. Becker, Bart O. Roep, and Debbie C. Thurmond. “Syntaxin 4 Expression in Pancreatic β-Cells Promotes Islet Function and Protects Functional β-Cell Mass.” Diabetes 67, no. 12 (December 2018): 2626–39. https://doi.org/10.2337/db18-0259.
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    • Wang, Huan, Aaron Bender, Peng Wang, Esra Karakose, William B. Inabnet, Steven K. Libutti, Andrew Arnold, et al. “Insights into beta cell regeneration for diabetes via integration of molecular landscapes in human insulinomas.” Nat Commun 8, no. 1 (October 3, 2017): 767. https://doi.org/10.1038/s41467-017-00992-9.
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    • Hayes, Heather L., Lu Zhang, Thomas C. Becker, Jonathan M. Haldeman, Samuel B. Stephens, Michelle Arlotto, Larry G. Moss, Christopher B. Newgard, and Hans E. Hohmeier. “A Pdx-1-Regulated Soluble Factor Activates Rat and Human Islet Cell Proliferation.” Mol Cell Biol 36, no. 23 (December 1, 2016): 2918–30. https://doi.org/10.1128/MCB.00103-16.
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    • Rosario, Wilfredo, Inderroop Singh, Arnaud Wautlet, Christa Patterson, Jonathan Flak, Thomas C. Becker, Almas Ali, et al. “The Brain-to-Pancreatic Islet Neuronal Map Reveals Differential Glucose Regulation From Distinct Hypothalamic Regions.” Diabetes 65, no. 9 (September 2016): 2711–23. https://doi.org/10.2337/db15-0629.
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    • Marzban, L., A. Tomas, T. C. Becker, L. Rosenberg, J. Oberholzer, P. E. Fraser, P. A. Halban, and C. B. Verchere. “Erratum: Small interfering RNA-mediated suppression of proislet amyloid polypeptide expression inhibits islet amyloid formation and enhances survival of human islets in culture (Diabetes (2008) 57 (3045-3055)).” Diabetes 65, no. 3 (March 1, 2016): 818. https://doi.org/10.2337/db16-er03.
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    • Guo, Cong, Anton E. Ludvik, Michelle E. Arlotto, M Geoffrey Hayes, Loren L. Armstrong, Denise M. Scholtens, Christopher D. Brown, et al. “Coordinated regulatory variation associated with gestational hyperglycaemia regulates expression of the novel hexokinase HKDC1.” Nat Commun 6 (February 4, 2015): 6069. https://doi.org/10.1038/ncomms7069.
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    • Hobson, Amanda, Carrie Draney, Andrew Stratford, Thomas C. Becker, Danhong Lu, Michelle Arlotto, and Jeffery S. Tessem. “Aurora Kinase A is critical for the Nkx6.1 mediated β-cell proliferation pathway.” Islets 7, no. 1 (2015): e1027854. https://doi.org/10.1080/19382014.2015.1027854.
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    • Odegaard, Matthew L., Jamie W. Joseph, Mette V. Jensen, Danhong Lu, Olga Ilkayeva, Sarah M. Ronnebaum, Thomas C. Becker, and Christopher B. Newgard. “The mitochondrial 2-oxoglutarate carrier is part of a metabolic pathway that mediates glucose- and glutamine-stimulated insulin secretion.” J Biol Chem 285, no. 22 (May 28, 2010): 16530–37. https://doi.org/10.1074/jbc.M109.092593.
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    • Civitarese, Anthony E., Paul S. MacLean, Stacy Carling, Lyndal Kerr-Bayles, Ryan P. McMillan, Anson Pierce, Thomas C. Becker, et al. “Regulation of skeletal muscle oxidative capacity and insulin signaling by the mitochondrial rhomboid protease PARL.” Cell Metab 11, no. 5 (May 5, 2010): 412–26. https://doi.org/10.1016/j.cmet.2010.04.004.
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    • Anderson, Keith R., Ciara A. Torres, Keely Solomon, Thomas C. Becker, Christopher B. Newgard, Christopher V. Wright, James Hagman, and Lori Sussel. “Cooperative transcriptional regulation of the essential pancreatic islet gene NeuroD1 (beta2) by Nkx2.2 and neurogenin 3.” J Biol Chem 284, no. 45 (November 6, 2009): 31236–48. https://doi.org/10.1074/jbc.M109.048694.
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    • Dunn-Meynell, Ambrose A., Nicole M. Sanders, Douglas Compton, Thomas C. Becker, Jun-ichi Eiki, Bei B. Zhang, and Barry E. Levin. “Relationship among brain and blood glucose levels and spontaneous and glucoprivic feeding.” J Neurosci 29, no. 21 (May 27, 2009): 7015–22. https://doi.org/10.1523/JNEUROSCI.0334-09.2009.
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    • Marzban, Lucy, Alejandra Tomas, Thomas C. Becker, Lawrence Rosenberg, Jose Oberholzer, Paul E. Fraser, Philippe A. Halban, and C Bruce Verchere. “Small interfering RNA-mediated suppression of proislet amyloid polypeptide expression inhibits islet amyloid formation and enhances survival of human islets in culture.” Diabetes 57, no. 11 (November 2008): 3045–55. https://doi.org/10.2337/db08-0485.
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    • Ronnebaum, Sarah M., Jamie W. Joseph, Olga Ilkayeva, Shawn C. Burgess, Danhong Lu, Thomas C. Becker, A Dean Sherry, and Christopher B. Newgard. “Chronic suppression of acetyl-CoA carboxylase 1 in beta-cells impairs insulin secretion via inhibition of glucose rather than lipid metabolism.” J Biol Chem 283, no. 21 (May 23, 2008): 14248–56. https://doi.org/10.1074/jbc.M800119200.
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    • Levin, Barry E., Thomas C. Becker, Jun-ichi Eiki, Bei B. Zhang, and Ambrose A. Dunn-Meynell. “Ventromedial hypothalamic glucokinase is an important mediator of the counterregulatory response to insulin-induced hypoglycemia.” Diabetes 57, no. 5 (May 2008): 1371–79. https://doi.org/10.2337/db07-1755.
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    • Schisler, Jonathan C., Patrick T. Fueger, Daniella A. Babu, Hans E. Hohmeier, Jeffery S. Tessem, Danhong Lu, Thomas C. Becker, et al. “Stimulation of human and rat islet beta-cell proliferation with retention of function by the homeodomain transcription factor Nkx6.1.” Mol Cell Biol 28, no. 10 (May 2008): 3465–76. https://doi.org/10.1128/MCB.01791-07.
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    • Schroeder-Gloeckler, Jill M., Shaikh Mizanoor Rahman, Rachel C. Janssen, Liping Qiao, Jianhua Shao, Michael Roper, Stephanie J. Fischer, et al. “CCAAT/enhancer-binding protein beta deletion reduces adiposity, hepatic steatosis, and diabetes in Lepr(db/db) mice.” J Biol Chem 282, no. 21 (May 25, 2007): 15717–29. https://doi.org/10.1074/jbc.M701329200.
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    • Hardy, Olga T., Hans E. Hohmeier, Thomas C. Becker, Elisabetta Manduchi, Nicolai M. Doliba, Rana K. Gupta, Peter White, et al. “Functional genomics of the beta-cell: short-chain 3-hydroxyacyl-coenzyme A dehydrogenase regulates insulin secretion independent of K+ currents.” Mol Endocrinol 21, no. 3 (March 2007): 765–73. https://doi.org/10.1210/me.2006-0411.
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    • Ronnebaum, Sarah M., Olga Ilkayeva, Shawn C. Burgess, Jamie W. Joseph, Danhong Lu, Robert D. Stevens, Thomas C. Becker, A Dean Sherry, Christopher B. Newgard, and Mette V. Jensen. “A pyruvate cycling pathway involving cytosolic NADP-dependent isocitrate dehydrogenase regulates glucose-stimulated insulin secretion.” J Biol Chem 281, no. 41 (October 13, 2006): 30593–602. https://doi.org/10.1074/jbc.M511908200.
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    • Jensen, Mette V., Jamie W. Joseph, Olga Ilkayeva, Shawn Burgess, Danhong Lu, Sarah M. Ronnebaum, Matthew Odegaard, Thomas C. Becker, A Dean Sherry, and Christopher B. Newgard. “Compensatory responses to pyruvate carboxylase suppression in islet beta-cells. Preservation of glucose-stimulated insulin secretion.” J Biol Chem 281, no. 31 (August 4, 2006): 22342–51. https://doi.org/10.1074/jbc.M604350200.
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    • Cao, Wenhong, Qu Fan Collins, Thomas C. Becker, Jacques Robidoux, Edgar G. Lupo, Yan Xiong, Kiefer W. Daniel, Lisa Floering, and Sheila Collins. “p38 Mitogen-activated protein kinase plays a stimulatory role in hepatic gluconeogenesis.” J Biol Chem 280, no. 52 (December 30, 2005): 42731–37. https://doi.org/10.1074/jbc.M506223200.
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    • Schisler, Jonathan C., Per Bo Jensen, David G. Taylor, Thomas C. Becker, Filip Krag Knop, Shiro Takekawa, Michael German, et al. “The Nkx6.1 homeodomain transcription factor suppresses glucagon expression and regulates glucose-stimulated insulin secretion in islet beta cells.” Proc Natl Acad Sci U S A 102, no. 20 (May 17, 2005): 7297–7302. https://doi.org/10.1073/pnas.0502168102.
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    • Iype, Tessy, Joshua Francis, James C. Garmey, Jonathan C. Schisler, Rafael Nesher, Gordon C. Weir, Thomas C. Becker, Christopher B. Newgard, Steven C. Griffen, and Raghavendra G. Mirmira. “Mechanism of insulin gene regulation by the pancreatic transcription factor Pdx-1: application of pre-mRNA analysis and chromatin immunoprecipitation to assess formation of functional transcriptional complexes.” J Biol Chem 280, no. 17 (April 29, 2005): 16798–807. https://doi.org/10.1074/jbc.M414381200.
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    • Bain, James R., Jonathan C. Schisler, Koji Takeuchi, Christopher B. Newgard, and Thomas C. Becker. “An adenovirus vector for efficient RNA interference-mediated suppression of target genes in insulinoma cells and pancreatic islets of langerhans.” Diabetes 53, no. 9 (September 2004): 2190–94. https://doi.org/10.2337/diabetes.53.9.2190.
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    • Newgard, C. B., T. C. Becker, H. K. Berman, and R. M. O’Doherty. “Regulation of overexpressed hexokinases in liver and islet cells.” Biochem Soc Trans 25, no. 1 (February 1997): 118–22. https://doi.org/10.1042/bst0250118.
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    • Becker, T. C., R. J. Noel, J. H. Johnson, R. M. Lynch, H. Hirose, Y. Tokuyama, G. I. Bell, and C. B. Newgard. “Differential effects of overexpressed glucokinase and hexokinase I in isolated islets. Evidence for functional segregation of the high and low Km enzymes.” J Biol Chem 271, no. 1 (January 5, 1996): 390–94. https://doi.org/10.1074/jbc.271.1.390.
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    • Argaud, D., A. J. Lange, T. C. Becker, D. A. Okar, M. R. el-Maghrabi, C. B. Newgard, and S. J. Pilkis. “Adenovirus-mediated overexpression of liver 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase in gluconeogenic rat hepatoma cells. Paradoxical effect on Fru-2,6-P2 levels.” J Biol Chem 270, no. 41 (October 13, 1995): 24229–36. https://doi.org/10.1074/jbc.270.41.24229.
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    • Becker, T. C., H. BeltrandelRio, R. J. Noel, J. H. Johnson, and C. B. Newgard. “Overexpression of hexokinase I in isolated islets of Langerhans via recombinant adenovirus. Enhancement of glucose metabolism and insulin secretion at basal but not stimulatory glucose levels.” J Biol Chem 269, no. 33 (August 19, 1994): 21234–38.
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    • Ferber, S., H. BeltrandelRio, J. H. Johnson, R. J. Noel, L. E. Cassidy, S. Clark, T. C. Becker, S. D. Hughes, and C. B. Newgard. “GLUT-2 gene transfer into insulinoma cells confers both low and high affinity glucose-stimulated insulin release. Relationship to glucokinase activity.” J Biol Chem 269, no. 15 (April 15, 1994): 11523–29.
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    • Thomas, C. B., J. C. Meade, and E. W. Holmes. “Aminoimidazole carboxamide ribonucleoside toxicity: a model for study of pyrimidine starvation.” J Cell Physiol 107, no. 3 (June 1981): 335–44. https://doi.org/10.1002/jcp.1041070305.
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