Laboratory of intermediary metabolism and metabolic imaging
Gaurav Sharma, Ph.D., MBA, is an Assistant Professor in the Department of Cardiovascular and Thoracic Surgery at UT Southwestern Medical Center. He earned a B.Sc. in biological sciences, an M.Sc. in biotechnology, followed by a Ph.D. in biomedical sciences. He also earned an MBA from the Quantic School of Business and Technology.
The Sharma lab is interested in investigating intermediary metabolism utilizing carbon-13 stable isotope tracers in conjunction with magnetic resonance spectroscopy (MRS), magnetic resonance imaging (MRI), and mass spectrometry (MS). The ongoing projects include:
This study demonstrates that biomarkers of mitochondrial and cytosolic redox may be detected simultaneously in functioning tissues using co-polarized [1-13C]pyruvate and [1,3-13C2]AcAc and 13C MRS and that changes in mitochondrial redox may precede changes in cytosolic redox.
Metabolic remodeling precedes most alterations during cardiac hypertrophic growth under hemodynamic stress. The elevation of glucose utilization has been recognized as a hallmark of metabolic remodeling. However, its role in cardiac hypertrophic growth and heart failure in response to pressure overload remains to be fully illustrated. Here, we aimed to dissect the role of cardiac PKM1 (pyruvate kinase muscle isozyme 1) in glucose metabolic regulation and cardiac response under pressure overload.
In this study, we used hyperpolarized (HP) 13C-magnetic resonance spectroscopy to study the impact of a PDK2/PDK4 double knockout (DKO) on pyruvate metabolism in perfused livers from lean and diet-induced obese (DIO) mice and validated the HP observations with high-resolution 13C-nuclear magnetic resonance (NMR) spectroscopy of tissue extracts and steady-state isotopomer analyses.
In this study, we examined the conversion of hyperpolarized (HP) 13C-acetoacetate (AcAc) to 13C-β-hydroxybutyrate (β-HB) as a potential imaging biomarker for mitochondrial redox and dysfunction in perfused rat hearts.
Oxidation of hyperpolarized [1-13 C]pyruvate in isolated rat kidneys.Sharma G, Maptue N, Rahim M, Mijes MLT, Hever T, Wen X, Funk AM, Malloy CR, Young JD, Khemtong C, 2022 Oct NMR Biomed e4857
Co-Polarized [1-13C]Pyruvate and [1,3-13C2]Acetoacetate Provide a Simultaneous View of Cytosolic and Mitochondrial Redox in a Single Experiment.Sharma G, Wen X, Maptue NR, Hever T, Malloy CR, Sherry AD, Khemtong C, 2021 11 ACS Sens 11 6 3967-3977
PKM1 Exerts Critical Roles in Cardiac Remodeling Under Pressure Overload in the Heart.Li Q, Li C, Elnwasany A, Sharma G, An YA, Zhang G, Elhelaly WM, Lin J, Gong Y, Chen G, Wang M, Zhao S, Dai C, Smart CD, Liu J, Luo X, Deng Y, Tan L, Lv SJ, Davidson SM, Locasale JW, Lorenzi PL, Malloy CR, Gillette TG, Vander Heiden MG, Scherer PE, Szweda LI, Fu G, Wang ZV, 2021 08 Circulation 9 144 712-727
Real-time hyperpolarized 13C magnetic resonance detects increased pyruvate oxidation in pyruvate dehydrogenase kinase 2/4-double knockout mouse livers.Sharma G, Wu CY, Wynn RM, Gui W, Malloy CR, Sherry AD, Chuang DT, Khemtong C, 2019 Nov Sci Rep 1 9 16480
Metabolism of hyperpolarized 13 C-acetoacetate to ?-hydroxybutyrate detects real-time mitochondrial redox state and dysfunction in heart tissue.Chen W, Sharma G, Jiang W, Maptue NR, Malloy CR, Sherry AD, Khemtong C, 2019 Apr NMR Biomed e4091
MOXI Is a Mitochondrial Micropeptide That Enhances Fatty Acid ?-Oxidation.Makarewich CA, Baskin KK, Munir AZ, Bezprozvannaya S, Sharma G, Khemtong C, Shah AM, McAnally JR, Malloy CR, Szweda LI, Bassel-Duby R, Olson EN 2018 Jun Cell Rep 13 23 3701-3709
Aflatoxin B1 Toxicity and Protective Effects of Curcumin: Molecular Mechanisms and Clinical Implications.Dai C, Tian E, Hao Z, Tang S, Wang Z, Sharma G, Jiang H, Shen J, 2022 Oct Antioxidants (Basel) 10 11
Quercetin Attenuates Quinocetone-Induced Cell Apoptosis In Vitro by Activating the P38/Nrf2/HO-1 Pathway and Inhibiting the ROS/Mitochondrial Apoptotic Pathway.Dai C, Zhang Q, Shen L, Sharma G, Jiang H, Wang Z, Shen J, 2022 Jul Antioxidants (Basel) 8 11
13C-Labeled Diethyl Ketoglutarate Derivatives as Hyperpolarized Probes of 2-Ketoglutarate Dehydrogenase Activity.Singh J, Suh EH, Sharma G, Chen J, Hackett EP, Wen X, Sherry AD, Khemtong C, Malloy CR, Park JM, Kovacs Z, 2021 Nov Anal Sens 4 1 156-160
Imaging ?-Cell Function Using a Zinc-Responsive MRI Contrast Agent May Identify First Responder Islets.Thapa B, Suh EH, Parrott D, Khalighinejad P, Sharma G, Chirayil S, Sherry AD, 2021 Front Endocrinol (Lausanne) 12 809867
Mitochondrial Substrate Utilization Regulates Cardiomyocyte Cell Cycle Progression.Cardoso AC, Lam NT, Savla JJ, Nakada Y, Pereira AHM, Elnwasany A, Menendez-Montes I, Ensley EL, Petric UB, Sharma G, Sherry AD, Malloy CR, Khemtong C, Kinter MT, Tan WLW, Anene-Nzelu CG, Foo RS, Nguyen NUN, Li S, Ahmed MS, Elhelaly WM, Abdisalaam S, Asaithamby A, Xing C, Kanchwala M, Vale G, Eckert KM, Mitsche MA, McDonald JG, Hill JA, Huang L, Shaul PW, Szweda LI, Sadek HA, 2020 Feb Nat Metab 2 2 167-178
Molecular Insights of Copper Sulfate Exposure-Induced Nephrotoxicity: Involvement of Oxidative and Endoplasmic Reticulum Stress Pathways.Dai C, Liu Q, Li D, Sharma G, Xiong J, Xiao X, 2020 07 Biomolecules 7 10
Probing carbohydrate metabolism using hyperpolarized 13 C-labeled molecules.Singh J, Suh EH, Sharma G, Khemtong C, Sherry AD, Kovacs Z, 2018 Nov NMR Biomed e4018
Targeting hepatic pyruvate dehydrogenase kinases restores insulin signaling and mitigates ChREBP-mediated lipogenesis in diet-induced obese mice.Wu CY, Tso SC, Chuang JL, Gui WJ, Lou M, Sharma G, Khemtong C, Qi X, Wynn RM, Chuang DT 2018 Mar Mol Metab
A novel inhibitor of pyruvate dehydrogenase kinase stimulates myocardial carbohydrate oxidation in diet-induced obesity.Wu CY, Satapati S, Gui W, Wynn RM, Sharma G, Lou M, Qi X, Burgess SC, Malloy C, Khemtong C, Sherry AD, Chuang DT, Merritt ME 2018 Jun J. Biol. Chem. 25 293 9604-9613
Role of Moringa oleifera in regulation of diabetes-induced oxidative stress.Jaiswal D, Rai PK, Mehta S, Chatterji S, Shukla S, Rai DK, Sharma G, Sharma B, Khair S, Watal G, 2013 Jun Asian Pac J Trop Med 6 6 426-32
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UT Southwestern Medical Center
Department of Cardiovascular and Thoracic Surgery
5323 Harry Hines Blvd.
Dallas, TX 75390-8879