Intermediary metabolism is the complex process by which nutrients are transformed into cellular building blocks, redistributed to specific cellular fuels, converted to storage molecules or oxidized to provide energy. Mammalian physiology requires dramatic flexibility in these pathways in order to accommodate inevitable variations in nutrient availability and composition. Normally, this regulation is executed through hormone signaling, enzyme expression/modification and substrate level factors that act in concert to modulate metabolic flux. Complications of metabolic diseases such as obesity, insulin resistance and diabetes are caused by the dysregulation of these processes. The prevention and/or cure of metabolic disease require insight into the connection between altered molecular biology, metabolism and pathophysiology. The Burgess lab investigates intermediary metabolism in liver and other organs in response to molecular/pharmacological interventions and metabolic disease.
We use a combination of Nuclear Magnetic Resonance (NMR) spectroscopy, LC-MS/MS, stable isotope tracer approaches and small animal microsurgery to investigate the effect of molecular and pharmacological interventions in normal and disease models. Administration of stable isotope (non-radioactive) tracers, containing carbon-13 or deuterium, in humans or animals models followed by NMR or LC-MS/MS analysis of tissue or fluid extracts reveals the metabolic flux of a number of biochemical pathways. We study pathways of hepatic lipid and carbohydrate metabolism in mouse models of obesity, insulin resistance and diabetes or in models with specific defects in hepatic energy and glucose metabolism. We also partner with clinicians to translate both the technology and metabolic insight from these studies towards the understanding of human physiology. This powerful cross-disciplinary approach will provide an increasingly integrated picture of the physiology of metabolic diseases.
Our lab has a position available for a PhD student with a background in molecular biology, biochemistry or chemistry. A successful candidate will be hard working, self motivated and capable of integrating concepts in biology, physiology, chemistry and physics.
RESEARCH INTERESTS
Biological NMR methods
Intermediary metabolism: Elucidation of metabolic pathways
In Vivo and Ex Vivo isotope tracer techniques
Metabolism in animal models of diabetes and obesity
RECENT PUBLICATIONS
Shawn C Burgess, Merrill Nuss, Bernard R Landau, A Dean Sherry and Craig R Malloy, "Comparison of 2H2O Measured Gluconeogenesis Determined by Both NMR and MS" Analytical Biochemistry, 318:321-324, 2003
Inagaki T, Dutchak P, Zhao G, Ding X, Gautron L, Parameswara V, Li Y, Goetz R, Mohammad M, Esser V, Elmquist JK, Gerard RD, Burgess SC, Hammer RE, Mangelsdorf DJ, Kliewer SA, "Regulation of the Fasting Response by PPARa-Mediated Induction of Fibroblast Growth Factor 21" Cell Metabolism, IN PRESS 2007
Browning JD, Davis J, Saboorian MH, and Burgess SC, "A low-carbohydrate diet rapidly and dramatically reduces intrahepatic triglyceride content. Hepatology" Hepatology, 44:487-488, 2006
Natasha Hausler, Matthew Merritt, Charles Storey, Angela Milde, A. Dean Sherry Craig R. Malloy and SC Burgess, "Effects of Insulin and Cytosolic Redox State on Glucose Production Pathways in the Isolated Perfused Mouse Liver by Integrated 2H and 13C NMR" Biochemical Journal, 395:663, 2006
S. Satapati, TT. He, T. Inagaki, M. Potthoff, ME. Merritt, V. Esser, DJ. Mangelsdorf, SA Kliewer, JD. Browning and SC. Burgess, "Partial Resistance to PPAR-alpha Agonists in ZDF Rats is Associated with Defective Hepatic Mitochondrial Metabolism" Diabetes, 57:2012-2021, August 2008
SIGNIFICANT PUBLICATIONS
Danhong Lu, Hindrik Mulder, Piyu Zhao, Shawn C Burgess, Mette V Jensen, Svetlana Kamzolova, Christopher B Newgard and A Dean Sherry, "13C NMR Isotopomer Analysis Reveals a Connection Between Pyruvate Cycling and Glucose-Stimulated Insulin Secretion (GSIS)" PNAS, 99:2708-2713, 2002
Pengxiang She, Shawn C. Burgess, Masakazu Shiota, Paul Flakoll, E Patrick Donahue, Craig R Malloy, A Dean Sherry, and Mark A Magnuson, "Mechanisms by which liver-specific PEPCK knockout mice preserve euglycemia during starvation" Diabetes, 52:1649-1654, 2003
Burgess SC, Hausler N, Merritt M, Jeffrey FMH, Storey C, Milde A, Koshy S, Lindner J, Magnuson MA, Malloy CR, and Sherry AD., "Impaired Tricarboxylic Acid Cycle Activity in Mouse Livers Lacking Cytosolic Phosphoenolpyruvate Carboxykinase" Journal of Biological Chemistry, 279:48941-48949, December 2004
Burgess SC, Leone TC, Wende AR, Croce MA, Chen Z, Sherry AD, Malloy CR, and Finck BN, "Diminished hepatic gluconeogenesis via defects in tricarboxylic acid cycle flux in peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha)-deficient mice" Journal of Biological Chemistry, 281:19000-19008, December 2004
34. Burgess SC, He T, Yan Z, Lindner J, Sherry AD, Malloy CR, Browning JD, Magnuson MA, "Cytosolic Phosphoenolpyruvate Carboxykinase Does Not Solely Control the Rate of Hepatic Gluconeogenesis in the Intact Mouse Liver" Cell Metabolism, 5:313-320, April 2007
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