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Joshua C. Munger, Ph.D.

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Joshua C. Munger, Ph.D.

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About Me
Research
Publications

About Me

Faculty Appointments

Professor - Department of Biochemistry and Biophysics (SMD)

Professor - Department of Microbiology and Immunology (SMD) - Joint

Research

A major focus of our laboratory is human cytomegalovirus (HCMV), a herpes virus, which is the leading cause of congenital viral infection, occurring in approximately 1% of all live births. Congenital HCMV infection results in central nervous system damage in the majority of symptomatic newborns. HCMV infection also poses a serious health risk to immunosuppressed individuals, increasing morbidity in the elderly and in patients receiving immunosuppressive chemotherapy, including cancer patients, transplant recipients, and AIDS patients.
The majority of the projects in our lab study the interfaces between viruses and the host cell that determine the outcome of infection. Specifically, we focus on how viruses usurp cellular metabolic controls and subvert cellular anti-viral signaling to support productive infection. The goal of our laboratory is to increase our mechanistic understanding of these processes to identify novel avenues for therapeutic intervention that could prevent virally-associated pathogenesis.

The global SARS-CoV-2 pandemic is responsible for hundreds of thousands of deaths globally. Anti-viral therapeutic strategies are desperately needed to attenuate SARS-CoV-2-associated disease. We have initiated a high-throughput pharmacologic screen of a unique metabolism-focused compound library to identify drugs that limit coronavirus infection in pulmonary human fibroblasts. Our preliminary data has identified several compounds that substantially inhibit coronavirus infection. Our laboratory is in the process of validating the anti-viral activity of these compounds against SARS-CoV-2. In addition, we are elucidating how coronaviruses modulate cellular metabolism to support productive infection in an attempt to identify viral metabolic vulnerabilities that might be targeted for further therapeutic development.

Publications

Journal Articles

FAM210A regulates mitochondrial translation and maintains cardiac mitochondrial homeostasis.

Wu J, Subbaiah KCV, Hedaya O, Chen S, Munger J, Tang WHW, Yan C, Yao P

Cardiovascular research.. 2023 July 31 Epub 07/31/2023.

Raf1 promotes successful Human Cytomegalovirus replication and is regulated by AMPK-mediated phosphorylation during infection.

Dunn DM, Pack LJ, Munger JC

bioRxiv : the preprint server for biology.. 2023 July 26 Epub 07/26/2023.

Proteolytic cleavage and inactivation of the TRMT1 tRNA modification enzyme by SARS-CoV-2 main protease.

Zhang K, Eldin P, Ciesla JH, Briant L, Lentini JM, Ramos J, Cobb J, Munger J, Fu D

bioRxiv : the preprint server for biology.. 2023 July 20 Epub 07/20/2023.

Cytomegalovirus-induced inactivation of TSC2 disrupts the coupling of fatty acid biosynthesis to glucose availability resulting in a vulnerability to glucose limitation.

Raymonda MH, Rodríguez-Sánchez I, Schafer XL, Smorodintsev-Schiller L, Harris IS, Munger J

bioRxiv : the preprint server for biology.. 2023 May 17 Epub 05/17/2023.

Glutathione supports lipid abundance .

Asantewaa G, Tuttle ET, Ward NP, Kang YP, Kim Y, Kavanagh ME, Girnius N, Chen Y, Duncan R, Rodriguez K, Hecht F, Zocchi M, Smorodintsev-Schiller L, Scales TQ, Taylor K, Alimohammadi F, Sechrist ZR, Agostini-Vulaj D, Schafer XL, Chang H, Smith Z, O'Connor TN, Whelan S, Selfors LM, Crowdis J, Gray GK, Bronson RT, Brenner D, Rufini A, Dirksen RT, Hezel AF, Huber AR, Munger J, Cravatt BF, Vasiliou V, Cole CL, DeNicola GM, Harris IS

bioRxiv : the preprint server for biology.. 2023 February 11 Epub 02/11/2023.

Virology under the Microscope-a Call for Rational Discourse.

Goodrum F, Lowen A, Lakdawala S, Alwine J, Casadevall A, Imperiale M, Atwood W, Avgousti D, Baines J, Banfield B, Banks L, Bhaduri-McIntosh S, Bhattacharya D, Blanco-Melo D, Bloom D, Boon A, Boulant S, Brandt C, Broadbent A, Brooke C, Cameron C, Campos S, Caposio P, Chan G, Cliffe A, Coffin J, Collins K, Damania B, Daugherty M, Debbink K, DeCaprio J, Dermody T, Dikeakos J, DiMaio D, Dinglasan R, Duprex WP, Dutch R, Elde N, Emerman M, Enquist L, Fane B, Fernandez-Sesma A, Flenniken M, Frappier L, Frieman M, Frueh K, Gack M, Gaglia M, Gallagher T, Galloway D, García-Sastre A, Geballe A, Glaunsinger B, Goff S, Greninger A, Hancock M, Harris E, Heaton N, Heise M, Heldwein E, Hogue B, Horner S, Hutchinson E, Hyser J, Jackson W, Kalejta R, Kamil J, Karst S, Kirchhoff F, Knipe D, Kowalik T, Lagunoff M, Laimins L, Langlois R, Lauring A, Lee B, Leib D, Liu SL, Longnecker R, Lopez C, Luftig M, Lund J, Manicassamy B, McFadden G, McIntosh M, Mehle A, Miller WA, Mohr I, Moody C, Moorman N, Moscona A, Mounce B, Munger J, Münger K, Murphy E, Naghavi M, Nelson J, Neufeldt C, Nikolich J, O'Connor C, Ono A, Orenstein W, Ornelles D, Ou JH, Parker J, Parrish C, Pekosz A, Pellett P, Pfeiffer J, Plemper R, Polyak S, Purdy J, Pyeon D, Quinones-Mateu M, Renne R, Rice C, Schoggins J, Roller R, Russell C, Sandri-Goldin R, Sapp M, Schang L, Schmid S, Schultz-Cherry S, Semler B, Shenk T, Silvestri G, Simon V, Smith G, Smith J, Spindler K, Stanifer M, Subbarao K, Sundquist W, Suthar M, Sutton T, Tai A, Tarakanova V, tenOever B, Tibbetts S, Tompkins S, Toth Z, van Doorslaer K, Vignuzzi M, Wallace N, Walsh D, Weekes M, Weinberg J, Weitzman M, Weller S, Whelan S, White E, Williams B, Wobus C, Wong S, Yurochko A

mBio.. 2023 January 26 :e0018823. Epub 01/26/2023.

Human cytomegalovirus induces neuronal enolase to support virally mediated metabolic remodeling.

Moreno I, Rodríguez-Sánchez I, Schafer X, Munger J

Proceedings of the National Academy of Sciences of the United States of America.. 2022 December 6119 (49):e2205789119. Epub 12/02/2022.

TNF?-induced metabolic reprogramming drives an intrinsic anti-viral state.

Ciesla J, Moreno I, Munger J

PLoS pathogens.. 2022 July 1418 (7):e1010722. Epub 07/14/2022.

Pharmacologic profiling reveals lapatinib as a novel antiviral against SARS-CoV-2 in vitro.

Raymonda MH, Ciesla JH, Monaghan M, Leach J, Asantewaa G, Smorodintsev-Schiller LA, Lutz MM, Schafer XL, Takimoto T, Dewhurst S, Munger J, Harris IS

Virology.. 2021 November 27566 :60-68. Epub 11/27/2021.

Contributions of the HCMV U30-associated open reading frames to infection.

Monaghan M, Munger J

Journal of virology.. 2021 February 10 Epub 02/10/2021.

Human Cytomegalovirus Induces the Expression of the AMPKa2 Subunit to Drive Glycolytic Activation and Support Productive Viral Infection.

Dunn DM, Rodriguez-Sanchez I, Schafer X, Munger J

Journal of virology.. 2020 December 2 Epub 12/02/2020.

Interplay Between Calcium and AMPK Signaling in Human Cytomegalovirus Infection.

Dunn DM, Munger J

Frontiers in cellular and infection microbiology.. 2020 10 :384. Epub 07/29/2020.

U26 attenuates IKK?-mediated induction of ISG expression and enhanced protein ISGylation during HCMV infection.

Goodwin CM, Schafer X, Munger J

Journal of virology.. 2019 September 18 Epub 09/18/2019.

mTOR dysregulation by vaccinia virus F17 controls multiple processes with varying roles in infection.

Meade N, King M, Munger J, Walsh D

Journal of virology.. 2019 May 22 Epub 05/22/2019.

Meal for Two: Human Cytomegalovirus-Induced Activation of Cellular Metabolism.

Rodríguez-Sánchez I, Munger J

Viruses.. 2019 March 1911 (3)Epub 03/19/2019.

The I?B kinases restrict human cytomegalovirus infection.

Goodwin CM, Munger J

Journal of virology.. 2019 February 13 Epub 02/13/2019.

Editing the human cytomegalovirus genome with the CRISPR/Cas9 system.

King MW, Munger J

Virology.. 2019 January 26529 :186-194. Epub 01/26/2019.

The Human Cytomegalovirus UL38 protein drives mTOR-independent metabolic flux reprogramming by inhibiting TSC2.

Rodríguez-Sánchez I, Schafer XL, Monaghan M, Munger J

PLoS pathogens.. 2019 January 2415 (1):e1007569. Epub 01/24/2019.

Who's Driving? Human Cytomegalovirus, Interferon, and NF?B Signaling.

Goodwin CM, Ciesla JH, Munger J

Viruses.. 2018 August 2110 (9)Epub 08/21/2018.

Cardioprotection by nicotinamide mononucleotide (NMN): Involvement of glycolysis and acidic pH.

Nadtochiy SM, Wang YT, Nehrke K, Munger J, Brookes PS

Journal of molecular and cellular cardiology.. 2018 August 121 :155-162. Epub 06/26/2018.

Accumulation of Succinate in Cardiac Ischemia Primarily Occurs via Canonical Krebs Cycle Activity.

Zhang J, Wang YT, Miller JH, Day MM, Munger JC, Brookes PS

Cell reports.. 2018 May 2923 (9):2617-2628. Epub 1900 01 01.

Potential mechanisms linking SIRT activity and hypoxic 2-hydroxyglutarate generation: no role for direct enzyme (de)acetylation.

Nadtochiy SM, Wang YT, Zhang J, Nehrke K, Schafer X, Welle K, Ghaemmaghami S, Munger J, Brookes PS

The Biochemical journal.. 2017 August 10474 (16):2829-2839. Epub 08/10/2017.

CD73 regulates anti-inflammatory signaling between apoptotic cells and endotoxin-conditioned tissue macrophages.

Murphy PS, Wang J, Bhagwat SP, Munger JC, Janssen WJ, Wright TW, Elliott MR

Cell death and differentiation.. 2017 March 24 (3):559-570. Epub 01/06/2017.

Addiction to Coupling of the Warburg Effect with Glutamine Catabolism in Cancer Cells.

Smith B, Schafer XL, Ambeskovic A, Spencer CM, Land H, Munger J

Cell reports.. 2016 October 1117 (3):821-836. Epub 1900 01 01.

Acidic pH Is a Metabolic Switch for 2-Hydroxyglutarate Generation and Signaling.

Nadtochiy SM, Schafer X, Fu D, Nehrke K, Munger J, Brookes PS

The Journal of biological chemistry.. 2016 September 16291 (38):20188-97. Epub 08/10/2016.

Expression of Oncogenic Alleles Induces Multiple Blocks to Human Cytomegalovirus Infection.

Xu S, Schafer X, Munger J

Journal of virology.. 2016 May 90 (9):4346-4356. Epub 04/14/2016.

Metabolic profiling during HIV-1 and HIV-2 infection of primary human monocyte-derived macrophages.

Hollenbaugh JA, Montero C, Schinazi RF, Munger J, Kim B

Virology.. 2016 April 491 :106-14. Epub 02/16/2016.

Mutation of ataxia-telangiectasia mutated is associated with dysfunctional glutathione homeostasis in cerebellar astroglia.

Campbell A, Bushman J, Munger J, Noble M, Pröschel C, Mayer-Pröschel M

Glia.. 2016 February 64 (2):227-39. Epub 10/15/2015.

Stealing the Keys to the Kitchen: Viral Manipulation of the Host Cell Metabolic Network.

Goodwin CM, Xu S, Munger J

Trends in microbiology.. 2015 December 23 (12):789-798. Epub 10/01/2015.

Metabolomic profiling of the heart during acute ischemic preconditioning reveals a role for SIRT1 in rapid cardioprotective metabolic adaptation.

Nadtochiy SM, Urciuoli W, Zhang J, Schafer X, Munger J, Brookes PS

Journal of molecular and cellular cardiology.. 2015 November 88 :64-72. Epub 09/24/2015.

A roadmap for interpreting (13)C metabolite labeling patterns from cells.

Buescher JM, Antoniewicz MR, Boros LG, Burgess SC, Brunengraber H, Clish CB, DeBerardinis RJ, Feron O, Frezza C, Ghesquiere B, Gottlieb E, Hiller K, Jones RG, Kamphorst JJ, Kibbey RG, Kimmelman AC, Locasale JW, Lunt SY, Maddocks OD, Malloy C, Metallo CM, Meuillet EJ, Munger J, Nöh K, Rabinowitz JD, Ralser M, Sauer U, Stephanopoulos G, St-Pierre J, Tennant DA, Wittmann C, Vander Heiden MG, Vazquez A, Vousden K, Young JD, Zamboni N, Fendt SM

Current opinion in biotechnology.. 2015 August 34 :189-201. Epub 02/28/2015.

Transformation with oncogenic Ras and the simian virus 40 T antigens induces caspase-dependent sensitivity to fatty acid biosynthetic inhibition.

Xu S, Spencer CM, Munger J

Journal of virology.. 2015 June 89 (12):6406-17. Epub 04/08/2015.

Cytomegalovirus-mediated activation of pyrimidine biosynthesis drives UDP-sugar synthesis to support viral protein glycosylation.

DeVito SR, Ortiz-Riaño E, Martínez-Sobrido L, Munger J

Proceedings of the National Academy of Sciences of the United States of America.. 2014 December 16111 (50):18019-24. Epub 12/03/2014.

The human cytomegalovirus UL26 protein antagonizes NF-?B activation.

Mathers C, Schafer X, Martinez-Sobrido L, Munger J

Journal of virology.. 2014 December 88 (24):14289-300. Epub 10/01/2014.

Delayed transplantation of precursor cell-derived astrocytes provides multiple benefits in a rat model of Parkinsons.

Proschel C, Stripay JL, Shih CH, Munger JC, Noble MD

EMBO molecular medicine.. 2014 April 6 (4):504-18. Epub 01/29/2014.

Inhibition of arenavirus by A3, a pyrimidine biosynthesis inhibitor.

Ortiz-Riaño E, Ngo N, Devito S, Eggink D, Munger J, Shaw ML, de la Torre JC, Martínez-Sobrido L

Journal of virology.. 2014 January 88 (2):878-89. Epub 11/06/2013.

Distinct domains within the human cytomegalovirus U(L)26 protein are important for wildtype viral replication and virion stability.

Mathers C, Spencer CM, Munger J

PloS one.. 2014 9 (2):e88101. Epub 02/05/2014.

Targeting aberrant glutathione metabolism to eradicate human acute myelogenous leukemia cells.

Pei S, Minhajuddin M, Callahan KP, Balys M, Ashton JM, Neering SJ, Lagadinou ED, Corbett C, Ye H, Liesveld JL, O'Dwyer KM, Li Z, Shi L, Greninger P, Settleman J, Benes C, Hagen FK, Munger J, Crooks PA, Becker MW, Jordan CT

The Journal of biological chemistry.. 2013 November 22288 (47):33542-58. Epub 10/02/2013.

IDH1(R132H) mutation increases murine haematopoietic progenitors and alters epigenetics.

Sasaki M, Knobbe CB, Munger JC, Lind EF, Brenner D, Brüstle A, Harris IS, Holmes R, Wakeham A, Haight J, You-Ten A, Li WY, Schalm S, Su SM, Virtanen C, Reifenberger G, Ohashi PS, Barber DL, Figueroa ME, Melnick A, Zúñiga-Pflücker JC, Mak TW

Nature.. 2012 August 30488 (7413):656-9. Epub 1900 01 01.

HCMV targets the metabolic stress response through activation of AMPK whose activity is important for viral replication.

McArdle J, Moorman NJ, Munger J

PLoS pathogens.. 2012 January 8 (1):e1002502. Epub 01/26/2012.

The transcription factor Myc controls metabolic reprogramming upon T lymphocyte activation.

Wang R, Dillon CP, Shi LZ, Milasta S, Carter R, Finkelstein D, McCormick LL, Fitzgerald P, Chi H, Munger J, Green DR

Immunity.. 2011 December 2335 (6):871-82. Epub 1900 01 01.

Metabolite profiles of human immunodeficiency virus infected CD4+ T cells and macrophages using LC-MS/MS analysis.

Hollenbaugh JA, Munger J, Kim B

Virology.. 2011 July 5415 (2):153-9. Epub 05/11/2011.

Human cytomegalovirus induces the activity and expression of acetyl-coenzyme A carboxylase, a fatty acid biosynthetic enzyme whose inhibition attenuates viral replication.

Spencer CM, Schafer XL, Moorman NJ, Munger J