Michaela Gack

Research Summary
Understanding host-virus interactions is an essential step in developing safe and effective antimicrobials against existing and newly emerging pathogens. The early detection of invading viruses by the host depends on a limited number of specific receptors that detect viral patterns and activate signaling cascades, thereby triggering interferon (IFN)-mediated antiviral defense mechanisms. Intracellular innate immune receptors, such as RIG-I-like receptors (RLRs) and the intracellular viral DNA sensors cGAS and IFI16, detect a variety of RNA and DNA viruses including influenza virus, measles virus, dengue virus and herpesviruses. In addition, members of the tripartite motif (TRIM) protein family play a major role in the antiviral host response. Research in the Gack laboratory seeks a better understanding of the cell-intrinsic mechanisms underlying the host innate immune response against viral infections. Another area of our research focuses on the detailed mechanisms by which viral pathogens – influenza viruses, measles virus, dengue virus and herpesviruses – suppress the innate immune system. The Gack laboratory uses an integrative approach that combines RNAi screens and proteomics with molecular, biochemical, and cell-biological approaches as well as viral infection studies including reverse genetics systems for the generation of recombinant mutant viruses.
Keywords
Virology, Immunology, Infectious Diseases
Education
  • FAU Erlangen-Nuremberg, Germany, German Diplom (BS and MSc equivalent) Molecular Medicine 2005
  • Harvard Medical School and FAU Erlangen-Nuremberg, PhD Virology 2008
Biosciences Graduate Program Association
Awards & Honors
  • 1998 - Karl von Frisch Prize German Biology Society
  • 2007 - Millipore Young Cell Signaler Award Millipore
  • 2009 - GE & Science Prize for Young Life Scientists GE & Science
  • 2009 - Otto Westphal Prize German Society for Immunology
  • 2009 - Robert Koch Postdoctoral Prize Robert Koch Foundation, Germany
  • 2011 - Fast Track Fellowship Robert Bosch Foundation
  • 2011 - Selected as one of “100 Women of Tomorrow” President of Germany
  • 2012 - William F. Milton Fund Award Milton Foundation
  • 2013 - 2015 ‘Top 40 under 40’ Scientist, Germany
  • 2013 - Ann Palmenberg Junior Investigator Award American Society for Virology
  • 2013 - Junior Investigator Award European Society for Virology
  • 2013 - Stewart Trust Fellow The Alexander & Margaret Stewart Trust Foundation
  • 2013 - The Christina Fleischmann Award to Young Women Investigators International Cytokine and Interferon Society
  • 2014 - Merck Irving S. Sigal Memorial Award American Society for Microbiology
  • 2015 - John and Virginia Kaneb Award
  • 2017 - Vilcek Prize for Creative Promise in Biomedical Science Vilcek Foundation
  • 2017 - ‘Top 10 under 40’ list in Biopharma and Business, US
Publications
  1. Lee JH, Chiang C, Gack MU. Endogenous Nucleic Acid Recognition by RIG-I-Like Receptors and cGAS. J Interferon Cytokine Res. 2019 May 07. View in: PubMed

  2. Serman TM, Gack MU. FBXO38 Drives PD-1 to Destruction. Trends Immunol. 2019 Feb; 40(2):81-83. View in: PubMed

  3. Full F, van Gent M, Sparrer KMJ, Chiang C, Zurenski MA, Scherer M, Brockmeyer NH, Heinzerling L, Stürzl M, Korn K, Stamminger T, Ensser A, Gack MU. Centrosomal protein TRIM43 restricts herpesvirus infection by regulating nuclear lamina integrity. Nat Microbiol. 2019 01; 4(1):164-176. View in: PubMed

  4. Riedl W, Gack MU. Dusting for flu's fingerprints. Nat Microbiol. 2018 11; 3(11):1196-1197. View in: PubMed

  5. Sanchez JG, Sparrer KMJ, Chiang C, Reis RA, Chiang JJ, Zurenski MA, Wan Y, Gack MU, Pornillos O. TRIM25 Binds RNA to Modulate Cellular Anti-viral Defense. J Mol Biol. 2018 Dec 07; 430(24):5280-5293. View in: PubMed

  6. van Gent M, Gack MU. Viral Anti-CRISPR Tactics: No Success without Sacrifice. Immunity. 2018 09 18; 49(3):391-393. View in: PubMed

  7. van Gent M, Sparrer KMJ, Gack MU. TRIM Proteins and Their Roles in Antiviral Host Defenses. Annu Rev Virol. 2018 09 29; 5(1):385-405. View in: PubMed

  8. Sparrer KMJ, Gack MU. TRIM proteins: New players in virus-induced autophagy. PLoS Pathog. 2018 02; 14(2):e1006787. View in: PubMed

  9. Chiang C, Pauli EK, Biryukov J, Feister KF, Meng M, White EA, Münger K, Howley PM, Meyers C, Gack MU. The Human Papillomavirus E6 Oncoprotein Targets USP15 and TRIM25 To Suppress RIG-I-Mediated Innate Immune Signaling. J Virol. 2018 03 15; 92(6). View in: PubMed

  10. D'Cruz AA, Kershaw NJ, Hayman TJ, Linossi EM, Chiang JJ, Wang MK, Dagley LF, Kolesnik TB, Zhang JG, Masters SL, Griffin MDW, Gack MU, Murphy JM, Nicola NA, Babon JJ, Nicholson SE. Identification of a second binding site on the TRIM25 B30.2 domain. Biochem J. 2018 01 23; 475(2):429-440. View in: PubMed

  11. Chiang JJ, Sparrer KMJ, van Gent M, Lässig C, Huang T, Osterrieder N, Hopfner KP, Gack MU. Viral unmasking of cellular 5S rRNA pseudogene transcripts induces RIG-I-mediated immunity. Nat Immunol. 2018 Jan; 19(1):53-62. View in: PubMed

  12. Ma Q, Ruan H, Peng L, Zhang M, Gack MU, Yao WD. Proteasome-independent polyubiquitin linkage regulates synapse scaffolding, efficacy, and plasticity. Proc Natl Acad Sci U S A. 2017 10 10; 114(41):E8760-E8769. View in: PubMed

  13. Sparrer KMJ, Gableske S, Zurenski MA, Parker ZM, Full F, Baumgart GJ, Kato J, Pacheco-Rodriguez G, Liang C, Pornillos O, Moss J, Vaughan M, Gack MU. TRIM23 mediates virus-induced autophagy via activation of TBK1. Nat Microbiol. 2017 Nov; 2(11):1543-1557. View in: PubMed

  14. Gack MU. What viruses can teach us about the human immune system. PLoS Pathog. 2017 07; 13(7):e1006364. View in: PubMed

  15. van Gent M, Gack MU. Viral pathogenesis: Dengue virus takes on cGAS. Nat Microbiol. 2017 03 27; 2:17050. View in: PubMed

  16. Chiang C, Gack MU. Post-translational Control of Intracellular Pathogen Sensing Pathways. Trends Immunol. 2017 01; 38(1):39-52. View in: PubMed

  17. Gack MU, Diamond MS. Innate immune escape by Dengue and West Nile viruses. Curr Opin Virol. 2016 10; 20:119-128. View in: PubMed

  18. Sanchez JG, Chiang JJ, Sparrer KMJ, Alam SL, Chi M, Roganowicz MD, Sankaran B, Gack MU, Pornillos O. Mechanism of TRIM25 Catalytic Activation in the Antiviral RIG-I Pathway. Cell Rep. 2016 08 02; 16(5):1315-1325. View in: PubMed

  19. Chan YK, Gack MU. Viral evasion of intracellular DNA and RNA sensing. Nat Rev Microbiol. 2016 06; 14(6):360-73. View in: PubMed

  20. Chan YK, Gack MU. A phosphomimetic-based mechanism of dengue virus to antagonize innate immunity. Nat Immunol. 2016 May; 17(5):523-30. View in: PubMed

  21. Chiang JJ, Gack MU. Reading the fine print: sequence-specific activation of cGAS. Nat Immunol. 2015 Oct; 16(10):1009-10. View in: PubMed

  22. Full F, Gack MU. Delicate coordination of TRIM21's dual activity in virus neutralization and signaling. Proc Natl Acad Sci U S A. 2015 Aug 11; 112(32):9797-8. View in: PubMed

  23. Sparrer KM, Gack MU. Intracellular detection of viral nucleic acids. Curr Opin Microbiol. 2015 Aug; 26:1-9. View in: PubMed

  24. Chan YK, Gack MU. RIG-I works double duty. Cell Host Microbe. 2015 Mar 11; 17(3):285-287. View in: PubMed

  25. Davis ME, Gack MU. Ubiquitination in the antiviral immune response. Virology. 2015 May; 479-480:52-65. View in: PubMed

  26. Chan YK, Gack MU. RIG-I-like receptor regulation in virus infection and immunity. Curr Opin Virol. 2015 Jun; 12:7-14. View in: PubMed

  27. Carocci M, Hinshaw SM, Rodgers MA, Villareal VA, Burri DJ, Pilankatta R, Maharaj NP, Gack MU, Stavale EJ, Warfield KL, Yang PL. The bioactive lipid 4-hydroxyphenyl retinamide inhibits flavivirus replication. Antimicrob Agents Chemother. 2015 Jan; 59(1):85-95. View in: PubMed

  28. Chiang JJ, Davis ME, Gack MU. Regulation of RIG-I-like receptor signaling by host and viral proteins. Cytokine Growth Factor Rev. 2014 Oct; 25(5):491-505. View in: PubMed

  29. Mesman AW, Zijlstra-Willems EM, Kaptein TM, de Swart RL, Davis ME, Ludlow M, Duprex WP, Gack MU, Gringhuis SI, Geijtenbeek TB. Measles virus suppresses RIG-I-like receptor activation in dendritic cells via DC-SIGN-mediated inhibition of PP1 phosphatases. Cell Host Microbe. 2014 Jul 09; 16(1):31-42. View in: PubMed

  30. Davis ME, Wang MK, Rennick LJ, Full F, Gableske S, Mesman AW, Gringhuis SI, Geijtenbeek TB, Duprex WP, Gack MU. Antagonism of the phosphatase PP1 by the measles virus V protein is required for innate immune escape of MDA5. Cell Host Microbe. 2014 Jul 09; 16(1):19-30. View in: PubMed

  31. Verrier ER, Gack MU, Baumert TF. Cyclic guanosine monophosphate/adenosine monophosphate synthase (cGAS), innate immune responses, and viral hepatitis. Hepatology. 2014 Sep; 60(3):1098-100. View in: PubMed

  32. Full F, Gack MU. Prostaglandin E2: the villain in the host response to influenza virus. Immunity. 2014 Apr 17; 40(4):453-4. View in: PubMed

  33. Gack MU. Mechanisms of RIG-I-like receptor activation and manipulation by viral pathogens. J Virol. 2014 May; 88(10):5213-6. View in: PubMed

  34. Pauli EK, Chan YK, Davis ME, Gableske S, Wang MK, Feister KF, Gack MU. The ubiquitin-specific protease USP15 promotes RIG-I-mediated antiviral signaling by deubiquitylating TRIM25. Sci Signal. 2014 Jan 07; 7(307):ra3. View in: PubMed

  35. D'Cruz AA, Kershaw NJ, Chiang JJ, Wang MK, Nicola NA, Babon JJ, Gack MU, Nicholson SE. Crystal structure of the TRIM25 B30.2 (PRYSPRY) domain: a key component of antiviral signalling. Biochem J. 2013 Dec 01; 456(2):231-40. View in: PubMed

  36. Wies E, Wang MK, Maharaj NP, Chen K, Zhou S, Finberg RW, Gack MU. Dephosphorylation of the RNA sensors RIG-I and MDA5 by the phosphatase PP1 is essential for innate immune signaling. Immunity. 2013 Mar 21; 38(3):437-49. View in: PubMed

  37. Rajsbaum R, Albrecht RA, Wang MK, Maharaj NP, Versteeg GA, Nistal-Villán E, García-Sastre A, Gack MU. Species-specific inhibition of RIG-I ubiquitination and IFN induction by the influenza A virus NS1 protein. PLoS Pathog. 2012; 8(11):e1003059. View in: PubMed

  38. Maharaj NP, Wies E, Stoll A, Gack MU. Conventional protein kinase C-a (PKC-a) and PKC-ß negatively regulate RIG-I antiviral signal transduction. J Virol. 2012 Feb; 86(3):1358-71. View in: PubMed

  39. Gack MU. TRIMming Flavivirus infection. Cell Host Microbe. 2011 Sep 15; 10(3):175-7. View in: PubMed

  40. Inn KS, Gack MU, Tokunaga F, Shi M, Wong LY, Iwai K, Jung JU. Linear ubiquitin assembly complex negatively regulates RIG-I- and TRIM25-mediated type I interferon induction. Mol Cell. 2011 Feb 04; 41(3):354-65. View in: PubMed

  41. Nistal-Villán E, Gack MU, Martínez-Delgado G, Maharaj NP, Inn KS, Yang H, Wang R, Aggarwal AK, Jung JU, García-Sastre A. Negative role of RIG-I serine 8 phosphorylation in the regulation of interferon-beta production. J Biol Chem. 2010 Jun 25; 285(26):20252-61. View in: PubMed

  42. Gack MU, Nistal-Villán E, Inn KS, García-Sastre A, Jung JU. Phosphorylation-mediated negative regulation of RIG-I antiviral activity. J Virol. 2010 Apr; 84(7):3220-9. View in: PubMed

  43. Gack MU, Albrecht RA, Urano T, Inn KS, Huang IC, Carnero E, Farzan M, Inoue S, Jung JU, García-Sastre A. Influenza A virus NS1 targets the ubiquitin ligase TRIM25 to evade recognition by the host viral RNA sensor RIG-I. Cell Host Microbe. 2009 May 08; 5(5):439-49. View in: PubMed

  44. Myong S, Cui S, Cornish PV, Kirchhofer A, Gack MU, Jung JU, Hopfner KP, Ha T. Cytosolic viral sensor RIG-I is a 5'-triphosphate-dependent translocase on double-stranded RNA. Science. 2009 Feb 20; 323(5917):1070-4. View in: PubMed

  45. Gack MU, Kirchhofer A, Shin YC, Inn KS, Liang C, Cui S, Myong S, Ha T, Hopfner KP, Jung JU. Roles of RIG-I N-terminal tandem CARD and splice variant in TRIM25-mediated antiviral signal transduction. Proc Natl Acad Sci U S A. 2008 Oct 28; 105(43):16743-8. View in: PubMed

  46. Liang C, Lee JS, Inn KS, Gack MU, Li Q, Roberts EA, Vergne I, Deretic V, Feng P, Akazawa C, Jung JU. Beclin1-binding UVRAG targets the class C Vps complex to coordinate autophagosome maturation and endocytic trafficking. Nat Cell Biol. 2008 Jul; 10(7):776-87. View in: PubMed

  47. Shin YC, Joo CH, Gack MU, Lee HR, Jung JU. Kaposi's sarcoma-associated herpesvirus viral IFN regulatory factor 3 stabilizes hypoxia-inducible factor-1 alpha to induce vascular endothelial growth factor expression. Cancer Res. 2008 Mar 15; 68(6):1751-9. View in: PubMed

  48. Joo CH, Shin YC, Gack M, Wu L, Levy D, Jung JU. Inhibition of interferon regulatory factor 7 (IRF7)-mediated interferon signal transduction by the Kaposi's sarcoma-associated herpesvirus viral IRF homolog vIRF3. J Virol. 2007 Aug; 81(15):8282-92. View in: PubMed

  49. Gack MU, Shin YC, Joo CH, Urano T, Liang C, Sun L, Takeuchi O, Akira S, Chen Z, Inoue S, Jung JU. TRIM25 RING-finger E3 ubiquitin ligase is essential for RIG-I-mediated antiviral activity. Nature. 2007 Apr 19; 446(7138):916-920. View in: PubMed

  50. Heck E, Friedrich U, Gack MU, Lengenfelder D, Schmidt M, Müller-Fleckenstein I, Fleckenstein B, Ensser A, Biesinger B. Growth transformation of human T cells by herpesvirus saimiri requires multiple Tip-Lck interaction motifs. J Virol. 2006 Oct; 80(20):9934-42. View in: PubMed

  51. Deichen JT, Prante O, Gack M, Schmiedehausen K, Kuwert T. Uptake of [18F]fluorodeoxyglucose in human monocyte-macrophages in vitro. Eur J Nucl Med Mol Imaging. 2003 Feb; 30(2):267-73. View in: PubMed