My translational research program focuses on immunometabolism using IEM as a model system. Patients with inborn errors of metabolism experience life threatening episodes of acute metabolic instability and organ dysfunction brought about by infection termed metabolic decompensation. Our goal is to understand how immune activation during infection contributes to this pathophysiology. This line of research also has implications for organ dysfunction during sepsis, a common problem in the intensive care unit. Since infection is important in patients with IEM, we also wish to understand the role of intermediary metabolism in immune cell function. Many enzymes involved in intermediary metabolism are also expressed in lymphocytes, and have associated IEM. These studies will not only provide insight into immune function in IEM patients, but also help define the role of metabolic enzymes in normal lymphocyte function.

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5
Fiscal Year
2016
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Indirect Cost
Name
Human Genome Research
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Tarasenko, Tatiana N; Cusmano-Ozog, Kristina; McGuire, Peter J (2018) Tissue acylcarnitine status in a mouse model of mitochondrial ?-oxidation deficiency during metabolic decompensation due to influenza virus infection. Mol Genet Metab 125:144-152
Raud, Brenda; Roy, Dominic G; Divakaruni, Ajit S et al. (2018) Etomoxir Actions on Regulatory and Memory T Cells Are Independent of Cpt1a-Mediated Fatty Acid Oxidation. Cell Metab 28:504-515.e7
Kapnick, Senta M; Pacheco, Susan E; McGuire, Peter J (2018) The emerging role of immune dysfunction in mitochondrial diseases as a paradigm for understanding immunometabolism. Metabolism 81:97-112
Raud, Brenda; McGuire, Peter J; Jones, Russell G et al. (2018) Fatty acid metabolism in CD8+ T cell memory: Challenging current concepts. Immunol Rev 283:213-231
Tarasenko, Tatyana N; Pacheco, Susan E; Koenig, Mary Kay et al. (2017) Cytochrome c Oxidase Activity Is a Metabolic Checkpoint that Regulates Cell Fate Decisions During T Cell Activation and Differentiation. Cell Metab 25:1254-1268.e7
Tarasenko, Tatyana N; McGuire, Peter J (2017) The liver is a metabolic and immunologic organ: A reconsideration of metabolic decompensation due to infection in inborn errors of metabolism (IEM). Mol Genet Metab 121:283-288
Larsen, Sasha E; Bilenkin, Abegail; Tarasenko, Tatiana N et al. (2017) Sensitivity to Restimulation-Induced Cell Death Is Linked to Glycolytic Metabolism in Human T Cells. J Immunol 198:147-155
Harrington, Elizabeth A; Sloan, Jennifer L; Manoli, Irini et al. (2016) Neutralizing Antibodies Against Adeno-Associated Viral Capsids in Patients with mut Methylmalonic Acidemia. Hum Gene Ther 27:345-53
MacLeod, Erin L; Hall, Kevin D; McGuire, Peter J (2016) Computational modeling to predict nitrogen balance during acute metabolic decompensation in patients with urea cycle disorders. J Inherit Metab Dis 39:17-24
Gartner, Valerie; McGuire, Peter J; Lee, Paul R (2015) Child Neurology: medium-chain acyl-coenzyme A dehydrogenase deficiency. Neurology 85:e37-40

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