When cells enter mitosis and undergo cell division, they must duplicate their biomass in order to produce two daughter cells. This feat is made possible through the combined activities of numerous metabolic pathways that permit the cell to convert simple nutrients (sugars, amino acids) into macromolecules (proteins, lipids, nucleic acids). We believe that these activities are orchestrated by growth factor-stimulated signal transduction pathways, which compel cells to take up abundant nutrients and allocate them into the proper metabolic pathways. We want to understand how signal transduction impacts metabolism during the physiological proliferation of normal cells and in pathological states like cancer. To do this, we use a combination of techniques in molecular biology, cell biology and biochemistry, coupled with mouse models and metabolic flux analysis using mass spectrometry and NMR spectroscopy.
We are also interested in a class of human diseases called the pediatric inborn errors of metabolism (IEMs). These are genetic diseases caused by mutations impairing such pathways as the tricarboxylic acid cycle, the urea cycle, fatty acid and amino acid oxidation, and the electron transport chain. Although many of these conditions can now be detected on the few drops of blood collected from all babies born in the state of Texas, many questions persist about their pathophysiology and treatment. We are tracking data from affected babies detected through newborn screening programs and using experimental models of metabolic dysfunction to learn more about mechanisms of disease in the IEMs. A long-term goal of the lab is to use in vivo and ex vivo metabolic flux analysis to improve the diagnosis and treatment of these children.
RECENT PUBLICATIONS
DeBerardinis RJ, Sayed N, Ditsworth D and Thompson CB, "Brick by brick: metabolism and tumor cell growth" Curr Opin Genet Devel, 18:54-61, 2008
DeBerardinis RJ , Mancuso A, Daikhin E, Nissim I, Yudkoff M, Wehrli S and Thompson CB., "Beyond Warburg: Transformed cells can engage in glutamine metabolism that exceeds the requirement for protein and nucleotide synthesis" PNAS USA, 104:19345-19350, 2007
Buzzai M, Jones RG, Amaravadi R, Lum JJ, DeBerardinis RJ and Thompson CB, "Systemic treatment with the antidiabetic drug metformin selectively impairs p53-deficient tumor cell growth in vivo." Cancer Research, 67:6745-6752, 2007
Lum JJ, Bui T, Covello KL, DeBerardinis RJ, Simon MC and Thompson CB., "The transcription factor HIF-1alpha plays a critical role in growth factor-dependent regulation of both aerobic and anaerobic glycolysis." Genes Dev, 21:1037-1049, 2007
DeBerardinis RJ, Lum JJ and Thompson CB., "PI3K-dependent modulation of CPT1A expression plays a critical role in regulating lipid metabolism during cell growth." J Biol Chem, 281:37372-37380, 2006
SIGNIFICANT PUBLICATIONS
Deberardinis RJ, Lum JJ, Hatzivassiliou G and Thompson CB., "The biology of cancer: metabolic reporgramming that fuels growth and proliferation" Cell Metab, 7:11-20, 2008
DeBerardins RJ, Mancuso A, Daikhin E, Nissim I, Yudkoff M, Wehrli S and Thompson CB, "Beyond Warburg:Transformed cells can engage in glutamine metabolism that exceeds the requirement for protein and nucleotide synthesis" PNAS USA, 104:19345-19350, 2007
Ostertag EM, DeBerardinis RJ, Goodier JL, Zhang Y, Yang N, Gerton GL and Kazazian HH., "A mouse model of human L1 retrotransposition." Nat Genet, 32:655-660, 2002
Moran JV, DeBerardinis RJ and Kazazian HH., "Exon shuffling by L1 retrotransposition." Science, 283:1530-1534, 1999
DeBerardinis RJ, Goodier JL, Ostertag EM and Kazazian HH., "Rapid amplification of a retrotransposon subfamily is evolving the mouse genome." Nat Genet, 20:288-290, 1998
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