Melanie Ott, PhD

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Melanie Ott, PhD

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Senior Investigator, The Ott Lab, Gladstone Institute of Virology and Immunology
Professor, School of Medicine
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Biography

My laboratory is interested in the molecular mechanisms of viral pathogenesis. We focus on a variety of viruses including HIV-1, Hepatitis B and C Virus (HBV and HCV), Zika and SARS-CoV-2. We believe that identifying common host pathways involved in different viruses can lead to the discovery of panviral therapeutics. All are important public health problems and with HCV and HIV sharing common traits including high propensities to establish chronic infections and a lack of efficient vaccines, and Zika and SARS-CoV-2 causing global pandemics leading to death and disability. In recent years, we have established four main technologies to study these viruses—rapid quantitative tests, human organoids, a viral protein library and transcriptomics and chromatin biology. We recently applied these technologies to the studies of SARS-CoV-2, leading to the development of a new direct detection CRISPR diagnostic and the identification of shared host factors necessary for the replication of SARS-CoV-2 and common cold coronaviruses. SARS-CoV-2, HCV and HIV research in my laboratory includes replication studies with infectious viral clones, which are performed in the BSL3 laboratory. Recent rotation projects in the lab: • characterizing influenza B infection in human airway organoids • developing a new hepatitis B clone to screen for host factors regulating cccDNA formation
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  1. Taha TY, Chen IP, Hayashi JM, Tabata T, Walcott K, Kimmerly GR, Syed AM, Ciling A, Suryawanshi RK, Martin HS, Bach BH, Tsou CL, Montano M, Khalid MM, Sreekumar BK, Kumar GR, Wyman S, Doudna JA, Ott M. Rapid assembly of SARS-CoV-2 genomes reveals attenuation of the Omicron BA.1 variant through NSP6. bioRxiv. 2023 Feb 09.
  2. Hysenaj L, Little S, Kulhanek K, Magnen M, Bahl K, Gbenedio OM, Prinz M, Rodriguez L, Andersen C, Rao AA, Shen A, Lone JC, Lupin-Jimenez LC, Bonser LR, Serwas NK, Mick E, Khalid MM, Taha TY, Kumar R, Li JZ, Ding VW, Matsumoto S, Maishan M, Sreekumar B, Simoneau C, Nazarenko I, Tomlinson MG, Khan K, von Gottberg A, Sigal A, Looney MR, Fragiadakis GK, Jablons DM, Langelier CR, Matthay M, Krummel M, Erle DJ, Combes AJ, Sil A, Ott M, Kratz JR, Roose JP. SARS-CoV-2 infection of airway organoids reveals conserved use of Tetraspanin-8 by Ancestral, Delta, and Omicron variants. Stem Cell Reports. 2023 Feb 08.
  3. Leon KE, Khalid MM, Flynn RA, Fontaine KA, Nguyen TT, Kumar GR, Simoneau CR, Tomar S, Jimenez-Morales D, Dunlap M, Kaye J, Shah PS, Finkbeiner S, Krogan NJ, Bertozzi C, Carette JE, Ott M. Nuclear accumulation of host transcripts during Zika Virus Infection. PLoS Pathog. 2023 Jan; 19(1):e1011070.
  4. Upadhyay V, Suryawanshi R, Tasoff P, McCavitt-Malvido M, Kumar GR, Murray VW, Noecker C, Bisanz JE, Hswen Y, Ha C, Sreekumar B, Chen IP, Lynch SV, Ott M, Lee S, Turnbaugh PJ. Mild SARS-CoV-2 infection results in long-lasting microbiota instability. bioRxiv. 2022 Dec 08.
  5. Brazer N, Morris MK, Servellita V, Anglin K, Saldhi P, Garcia-Knight M, Bethancourt S, Sotomayor-Gonzalez A, Wang B, Foresythe A, Nguyen J, Gliwa AS, Pineda-Ramirez J, Sanchez RD, Zhang Y, Ott M, Wadford DA, Andino R, Kelly JD, Hanson C, Chiu CY. Neutralizing Immunity Induced Against the Omicron BA.1 and BA.2 Variants in Vaccine Breakthrough Infections. J Infect Dis. 2022 11 11; 226(10):1688-1698.
  6. Kong W, Montano M, Corley MJ, Helmy E, Kobayashi H, Kinisu M, Suryawanshi R, Luo X, Royer LA, Roan NR, Ott M, Ndhlovu LC, Greene WC. Neuropilin-1 Mediates SARS-CoV-2 Infection of Astrocytes in Brain Organoids, Inducing Inflammation Leading to Dysfunction and Death of Neurons. mBio. 2022 Oct 31; e0230822.
  7. Chen IP, Ott M. Viral Hijacking of BET Proteins. Viruses. 2022 10 17; 14(10).
  8. Suryawanshi R, Ott M. SARS-CoV-2 hybrid immunity: silver bullet or silver lining? Nat Rev Immunol. 2022 10; 22(10):591-592.
  9. Walter M, Chen IP, Vallejo-Gracia A, Kim IJ, Bielska O, Lam VL, Hayashi JM, Cruz A, Shah S, Soveg FW, Gross JD, Krogan NJ, Jerome KR, Schilling B, Ott M, Verdin E. SIRT5 is a proviral factor that interacts with SARS-CoV-2 Nsp14 protein. PLoS Pathog. 2022 09; 18(9):e1010811.
  10. Peters CE, Schulze-Gahmen U, Eckhardt M, Jang GM, Xu J, Pulido EH, Bardine C, Craik CS, Ott M, Gozani O, Verba KA, Hüttenhain R, Carette JE, Krogan NJ. Structure-function analysis of enterovirus protease 2A in complex with its essential host factor SETD3. Nat Commun. 2022 09 08; 13(1):5282.
  11. Zandian M, Chen IP, Byrareddy SN, Fujimori DG, Ott M, Kutateladze TG. Catching BETs by viruses. Biochim Biophys Acta Gene Regul Mech. 2022 10; 1865(7):194859.
  12. Simoneau CR, Chen PY, Xing GK, Khalid MM, Meyers NL, Hayashi JM, Taha TY, Leon KE, Ashuach T, Fontaine KA, Rodriguez L, Joehnk B, Walcott K, Vasudevan S, Fang X, Maishan M, Schultz S, Roose J, Matthay MA, Sil A, Arjomandi M, Yosef N, Ott M. NF-κB inhibitor alpha has a cross-variant role during SARS-CoV-2 infection in ACE2-overexpressing human airway organoids. bioRxiv. 2022 Aug 02.
  13. Sreekumar BK, Taha TY, Ott M. Taking cues from convalescence to improve vaccines against hepatitis C virus. J Clin Invest. 2022 08 01; 132(15).
  14. Ravalin M, Roh H, Suryawanshi R, Kumar GR, Pak JE, Ott M, Ting AY. A Single-Component Luminescent Biosensor for the SARS-CoV-2 Spike Protein. J Am Chem Soc. 2022 08 03; 144(30):13663-13672.
  15. Syed AM, Ciling A, Taha TY, Chen IP, Khalid MM, Sreekumar B, Chen PY, Kumar GR, Suryawanshi R, Silva I, Milbes B, Kojima N, Hess V, Shacreaw M, Lopez L, Brobeck M, Turner F, Spraggon L, Tabata T, Ott M, Doudna JA. Omicron mutations enhance infectivity and reduce antibody neutralization of SARS-CoV-2 virus-like particles. Proc Natl Acad Sci U S A. 2022 08 02; 119(31):e2200592119.
  16. Yu B, Li S, Tabata T, Wang N, Cao L, Kumar GR, Sun W, Liu J, Ott M, Wang L. Accelerating PERx reaction enables covalent nanobodies for potent neutralization of SARS-CoV-2 and variants. Chem. 2022 Oct 13; 8(10):2766-2783.
  17. Andrews MG, Mukhtar T, Eze UC, Simoneau CR, Ross J, Parikshak N, Wang S, Zhou L, Koontz M, Velmeshev D, Siebert CV, Gemenes KM, Tabata T, Perez Y, Wang L, Mostajo-Radji MA, de Majo M, Donohue KC, Shin D, Salma J, Pollen AA, Nowakowski TJ, Ullian E, Kumar GR, Winkler EA, Crouch EE, Ott M, Kriegstein AR. Tropism of SARS-CoV-2 for human cortical astrocytes. Proc Natl Acad Sci U S A. 2022 07 26; 119(30):e2122236119.
  18. Chen IP, Longbotham JE, McMahon S, Suryawanshi RK, Khalid MM, Taha TY, Tabata T, Hayashi JM, Soveg FW, Carlson-Stevermer J, Gupta M, Zhang MY, Lam VL, Li Y, Yu Z, Titus EW, Diallo A, Oki J, Holden K, Krogan N, Fujimori DG, Ott M. Viral E protein neutralizes BET protein-mediated post-entry antagonism of SARS-CoV-2. Cell Rep. 2022 07 19; 40(3):111088.
  19. Matsui Y, Li L, Prahl M, Cassidy AG, Ozarslan N, Golan Y, Gonzalez VJ, Lin CY, Jigmeddagva U, Chidboy MA, Montano M, Taha TY, Khalid MM, Sreekumar B, Hayashi JM, Chen PY, Kumar GR, Warrier L, Wu AH, Song D, Jegatheesan P, Rai DS, Govindaswami B, Needens J, Rincon M, Myatt L, Asiodu IV, Flaherman VJ, Afshar Y, Jacoby VL, Murtha AP, Robinson JF, Ott M, Greene WC, Gaw SL. Neutralizing antibody activity against SARS-CoV-2 variants in gestational age-matched mother-infant dyads after infection or vaccination. JCI Insight. 2022 06 22; 7(12).
  20. Ravalin M, Roh H, Suryawanshi R, Kumar GR, Pak J, Ott M, Ting AY. A single-component luminescent biosensor for the SARS-CoV-2 spike protein. bioRxiv. 2022 Jun 15.
  21. Suryawanshi RK, Chen IP, Ma T, Syed AM, Brazer N, Saldhi P, Simoneau CR, Ciling A, Khalid MM, Sreekumar B, Chen PY, Kumar GR, Montano M, Gascon R, Tsou CL, Garcia-Knight MA, Sotomayor-Gonzalez A, Servellita V, Gliwa A, Nguyen J, Silva I, Milbes B, Kojima N, Hess V, Shacreaw M, Lopez L, Brobeck M, Turner F, Soveg FW, George AF, Fang X, Maishan M, Matthay M, Morris MK, Wadford D, Hanson C, Greene WC, Andino R, Spraggon L, Roan NR, Chiu CY, Doudna JA, Ott M. Limited cross-variant immunity from SARS-CoV-2 Omicron without vaccination. Nature. 2022 07; 607(7918):351-355.
  22. Magnen M, You R, Rao AA, Davis RT, Rodriguez L, Simoneau CR, Hysenaj L, Hu KH, UCSF COMET Consortium, Love C, Woodruff PG, Erle DJ, Hendrickson CM, Calfee CS, Matthay MA, Roose JP, Sil A, Ott M, Langelier CR, Krummel MF, Looney MR. Immediate myeloid depot for SARS-CoV-2 in the human lung. Res Sq. 2022 May 17.
  23. Magnen M, You R, Rao AA, Davis RT, Rodriguez L, Simoneau CR, Hysenaj L, Hu KH, UCSF COMET Consortium, Love C, Woodruff PG, Erle DJ, Hendrickson CM, Calfee CS, Matthay MA, Roose JP, Sil A, Ott M, Langelier CR, Krummel MF, Looney MR. Immediate myeloid depot for SARS-CoV-2 in the human lung. bioRxiv. 2022 May 11.
  24. Servellita V, Syed AM, Morris MK, Brazer N, Saldhi P, Garcia-Knight M, Sreekumar B, Khalid MM, Ciling A, Chen PY, Kumar GR, Gliwa AS, Nguyen J, Sotomayor-Gonzalez A, Zhang Y, Frias E, Prostko J, Hackett J, Andino R, Wadford DA, Hanson C, Doudna J, Ott M, Chiu CY. Neutralizing immunity in vaccine breakthrough infections from the SARS-CoV-2 Omicron and Delta variants. Cell. 2022 04 28; 185(9):1539-1548.e5.
  25. Yu B, Li S, Tabata T, Wang N, Kumar GR, Liu J, Ott MM, Wang L. Accelerating PERx Reaction Enables Covalent Nanobodies for Potent Neutralization of SARS-Cov-2 and Variants. bioRxiv. 2022 Mar 14.