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. Wang R, Simoneau CR, Kulsuptrakul J, Bouhaddou M, Travisano KA, Hayashi JM, Carlson-Stevermer J, Zengel JR, Richards CM, Fozouni P, Oki J, Rodriguez L, Joehnk B, Walcott K, Holden K, Sil A, Carette JE, Krogan NJ, Ott M, Puschnik AS. Genetic Screens Identify Host Factors for SARS-CoV-2 and Common Cold Coronaviruses. Cell. 2021 01 07; 184(1):106-119.e14.
  2. Fozouni P, Son S, Díaz de León Derby M, Knott GJ, Gray CN, D'Ambrosio MV, Zhao C, Switz NA, Kumar GR, Stephens SI, Boehm D, Tsou CL, Shu J, Bhuiya A, Armstrong M, Harris AR, Chen PY, Osterloh JM, Meyer-Franke A, Joehnk B, Walcott K, Sil A, Langelier C, Pollard KS, Crawford ED, Puschnik AS, Phelps M, Kistler A, DeRisi JL, Doudna JA, Fletcher DA, Ott M. Amplification-free detection of SARS-CoV-2 with CRISPR-Cas13a and mobile phone microscopy. Cell. 2021 01 21; 184(2):323-333.e9.
  3. Simoneau CR, Ott M. Modeling Multi-organ Infection by SARS-CoV-2 Using Stem Cell Technology. Cell Stem Cell. 2020 12 03; 27(6):859-868.
  4. Samuel RM, Majd H, Richter MN, Ghazizadeh Z, Zekavat SM, Navickas A, Ramirez JT, Asgharian H, Simoneau CR, Bonser LR, Koh KD, Garcia-Knight M, Tassetto M, Sunshine S, Farahvashi S, Kalantari A, Liu W, Andino R, Zhao H, Natarajan P, Erle DJ, Ott M, Goodarzi H, Fattahi F. Androgen Signaling Regulates SARS-CoV-2 Receptor Levels and Is Associated with Severe COVID-19 Symptoms in Men. Cell Stem Cell. 2020 12 03; 27(6):876-889.e12.
  5. Covarrubias AJ, Kale A, Perrone R, Lopez-Dominguez JA, Pisco AO, Kasler HG, Schmidt MS, Heckenbach I, Kwok R, Wiley CD, Wong HS, Gibbs E, Iyer SS, Basisty N, Wu Q, Kim IJ, Silva E, Vitangcol K, Shin KO, Lee YM, Riley R, Ben-Sahra I, Ott M, Schilling B, Scheibye-Knudsen M, Ishihara K, Quake SR, Newman J, Brenner C, Campisi J, Verdin E. Senescent cells promote tissue NAD+ decline during ageing via the activation of CD38+ macrophages. Nat Metab. 2020 11; 2(11):1265-1283.
  6. Schoof M, Faust B, Saunders RA, Sangwan S, Rezelj V, Hoppe N, Boone M, Billesbølle CB, Puchades C, Azumaya CM, Kratochvil HT, Zimanyi M, Deshpande I, Liang J, Dickinson S, Nguyen HC, Chio CM, Merz GE, Thompson MC, Diwanji D, Schaefer K, Anand AA, Dobzinski N, Zha BS, Simoneau CR, Leon K, White KM, Chio US, Gupta M, Jin M, Li F, Liu Y, Zhang K, Bulkley D, Sun M, Smith AM, Rizo AN, Moss F, Brilot AF, Pourmal S, Trenker R, Pospiech T, Gupta S, Barsi-Rhyne B, Belyy V, Barile-Hill AW, Nock S, Liu Y, Krogan NJ, Ralston CY, Swaney DL, García-Sastre A, Ott M, Vignuzzi M, QCRG Structural Biology Consortium , Walter P, Manglik A. An ultrapotent synthetic nanobody neutralizes SARS-CoV-2 by stabilizing inactive Spike. Science. 2020 12 18; 370(6523):1473-1479.
  7. Gordon DE, Hiatt J, Bouhaddou M, Rezelj VV, Ulferts S, Braberg H, Jureka AS, Obernier K, Guo JZ, Batra J, Kaake RM, Weckstein AR, Owens TW, Gupta M, Pourmal S, Titus EW, Cakir M, Soucheray M, McGregor M, Cakir Z, Jang G, O'Meara MJ, Tummino TA, Zhang Z, Foussard H, Rojc A, Zhou Y, Kuchenov D, Hüttenhain R, Xu J, Eckhardt M, Swaney DL, Fabius JM, Ummadi M, Tutuncuoglu B, Rathore U, Modak M, Haas P, Haas KM, Naing ZZC, Pulido EH, Shi Y, Barrio-Hernandez I, Memon D, Petsalaki E, Dunham A, Marrero MC, Burke D, Koh C, Vallet T, Silvas JA, Azumaya CM, Billesbølle C, Brilot AF, Campbell MG, Diallo A, Dickinson MS, Diwanji D, Herrera N, Hoppe N, Kratochvil HT, Liu Y, Merz GE, Moritz M, Nguyen HC, Nowotny C, Puchades C, Rizo AN, Schulze-Gahmen U, Smith AM, Sun M, Young ID, Zhao J, Asarnow D, Biel J, Bowen A, Braxton JR, Chen J, Chio CM, Chio US, Deshpande I, Doan L, Faust B, Flores S, Jin M, Kim K, Lam VL, Li F, Li J, Li YL, Li Y, Liu X, Lo M, Lopez KE, Melo AA, Moss FR, Nguyen P, Paulino J, Pawar KI, Peters JK, Pospiech TH, Safari M, Sangwan S, Schaefer K, Thomas PV, Thwin AC, Trenker R, Tse E, Tsui TKM, Wang F, Whitis N, Yu Z, Zhang K, Zhang Y, Zhou F, Saltzberg D, QCRG Structural Biology Consortium , Hodder AJ, Shun-Shion AS, Williams DM, White KM, Rosales R, Kehrer T, Miorin L, Moreno E, Patel AH, Rihn S, Khalid MM, Vallejo-Gracia A, Fozouni P, Simoneau CR, Roth TL, Wu D, Karim MA, Ghoussaini M, Dunham I, Berardi F, Weigang S, Chazal M, Park J, Logue J, McGrath M, Weston S, Haupt R, Hastie CJ, Elliott M, Brown F, Burness KA, Reid E, Dorward M, Johnson C, Wilkinson SG, Geyer A, Giesel DM, Baillie C, Raggett S, Leech H, Toth R, Goodman N, Keough KC, Lind AL, Zoonomia Consortium , Klesh RJ, Hemphill KR, Carlson-Stevermer J, Oki J, Holden K, Maures T, Pollard KS, Sali A, Agard DA, Cheng Y, Fraser JS, Frost A, Jura N, Kortemme T, Manglik A, Southworth DR, Stroud RM, Alessi DR, Davies P, Frieman MB, Ideker T, Abate C, Jouvenet N, Kochs G, Shoichet B, Ott M, Palmarini M, Shokat KM, García-Sastre A, Rassen JA, Grosse R, Rosenberg OS, Verba KA, Basler CF, Vignuzzi M, Peden AA, Beltrao P, Krogan NJ. Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms. Science. 2020 12 04; 370(6521).
  8. Xu C, Wang L, Fozouni P, Evjen G, Chandra V, Jiang J, Lu C, Nicastri M, Bretz C, Winkler JD, Amaravadi R, Garcia BA, Adams PD, Ott M, Tong W, Johansen T, Dou Z, Berger SL. SIRT1 is downregulated by autophagy in senescence and ageing. Nat Cell Biol. 2020 10; 22(10):1170-1179.
  9. Wang R, Simoneau CR, Kulsuptrakul J, Bouhaddou M, Travisano K, Hayashi JM, Carlson-Stevermer J, Oki J, Holden K, Krogan NJ, Ott M, Puschnik AS. Functional genomic screens identify human host factors for SARS-CoV-2 and common cold coronaviruses. bioRxiv. 2020 Sep 24.
  10. Pérez-Bermejo JA, Kang S, Rockwood SJ, Simoneau CR, Joy DA, Ramadoss GN, Silva AC, Flanigan WR, Li H, Nakamura K, Whitman JD, Ott M, Conklin BR, McDevitt TC. SARS-CoV-2 infection of human iPSC-derived cardiac cells predicts novel cytopathic features in hearts of COVID-19 patients. bioRxiv. 2020 Sep 12.
  11. Miao Y, Ha A, de Lau W, Yuki K, Santos AJM, You C, Geurts MH, Puschhof J, Pleguezuelos-Manzano C, Peng WC, Senlice R, Piani C, Buikema JW, Gbenedio OM, Vallon M, Yuan J, de Haan S, Hemrika W, Rösch K, Dang LT, Baker D, Ott M, Depeille P, Wu SM, Drost J, Nusse R, Roose JP, Piehler J, Boj SF, Janda CY, Clevers H, Kuo CJ, Garcia KC. Next-Generation Surrogate Wnts Support Organoid Growth and Deconvolute Frizzled Pleiotropy In Vivo. Cell Stem Cell. 2020 11 05; 27(5):840-851.e6.
  12. Schoof M, Faust B, Saunders RA, Sangwan S, Rezelj V, Hoppe N, Boone M, Billesbølle CB, Puchades C, Azumaya CM, Kratochvil HT, Zimanyi M, Deshpande I, Liang J, Dickinson S, Nguyen HC, Chio CM, Merz GE, Thompson MC, Diwanji D, Schaefer K, Anand AA, Dobzinski N, Zha BS, Simoneau CR, Leon K, White KM, Chio US, Gupta M, Jin M, Li F, Liu Y, Zhang K, Bulkley D, Sun M, Smith AM, Rizo AN, Moss F, Brilot AF, Pourmal S, Trenker R, Pospiech T, Gupta S, Barsi-Rhyne B, Belyy V, Barile-Hill AW, Nock S, Liu Y, Krogan NJ, Ralston CY, Swaney DL, García-Sastre A, Ott M, Vignuzzi M, QCRG Structural Biology Consortium , Walter P, Manglik A. An ultra-potent synthetic nanobody neutralizes SARS-CoV-2 by locking Spike into an inactive conformation. bioRxiv. 2020 Aug 17.
  13. Chen IP, Ott M. Turning up the heat on HIV-1. Proc Natl Acad Sci U S A. 2020 07 14; 117(28):16109-16111.
  14. Bouhaddou M, Memon D, Meyer B, White KM, Rezelj VV, Correa Marrero M, Polacco BJ, Melnyk JE, Ulferts S, Kaake RM, Batra J, Richards AL, Stevenson E, Gordon DE, Rojc A, Obernier K, Fabius JM, Soucheray M, Miorin L, Moreno E, Koh C, Tran QD, Hardy A, Robinot R, Vallet T, Nilsson-Payant BE, Hernandez-Armenta C, Dunham A, Weigang S, Knerr J, Modak M, Quintero D, Zhou Y, Dugourd A, Valdeolivas A, Patil T, Li Q, Hüttenhain R, Cakir M, Muralidharan M, Kim M, Jang G, Tutuncuoglu B, Hiatt J, Guo JZ, Xu J, Bouhaddou S, Mathy CJP, Gaulton A, Manners EJ, Félix E, Shi Y, Goff M, Lim JK, McBride T, O'Neal MC, Cai Y, Chang JCJ, Broadhurst DJ, Klippsten S, De Wit E, Leach AR, Kortemme T, Shoichet B, Ott M, Saez-Rodriguez J, tenOever BR, Mullins RD, Fischer ER, Kochs G, Grosse R, García-Sastre A, Vignuzzi M, Johnson JR, Shokat KM, Swaney DL, Beltrao P, Krogan NJ. The Global Phosphorylation Landscape of SARS-CoV-2 Infection. Cell. 2020 08 06; 182(3):685-712.e19.
  15. Leon K, Ott M. An 'Arms Race' between the Nonsense-mediated mRNA Decay Pathway and Viral Infections. Semin Cell Dev Biol. 2021 03; 111:101-107.
  16. Vallejo-Gracia A, Chen IP, Perrone R, Besnard E, Boehm D, Battivelli E, Tezil T, Krey K, Raymond KA, Hull PA, Walter M, Habrylo I, Cruz A, Deeks S, Pillai S, Verdin E, Ott M. FOXO1 promotes HIV latency by suppressing ER stress in T cells. Nat Microbiol. 2020 09; 5(9):1144-1157.
  17. Lyons DE, McMahon S, Ott M. A combinatorial view of old and new RNA polymerase II modifications. Transcription. 2020 04; 11(2):66-82.
  18. Gordon DE, Jang GM, Bouhaddou M, Xu J, Obernier K, White KM, O'Meara MJ, Rezelj VV, Guo JZ, Swaney DL, Tummino TA, Hüttenhain R, Kaake RM, Richards AL, Tutuncuoglu B, Foussard H, Batra J, Haas K, Modak M, Kim M, Haas P, Polacco BJ, Braberg H, Fabius JM, Eckhardt M, Soucheray M, Bennett MJ, Cakir M, McGregor MJ, Li Q, Meyer B, Roesch F, Vallet T, Mac Kain A, Miorin L, Moreno E, Naing ZZC, Zhou Y, Peng S, Shi Y, Zhang Z, Shen W, Kirby IT, Melnyk JE, Chorba JS, Lou K, Dai SA, Barrio-Hernandez I, Memon D, Hernandez-Armenta C, Lyu J, Mathy CJP, Perica T, Pilla KB, Ganesan SJ, Saltzberg DJ, Rakesh R, Liu X, Rosenthal SB, Calviello L, Venkataramanan S, Liboy-Lugo J, Lin Y, Huang XP, Liu Y, Wankowicz SA, Bohn M, Safari M, Ugur FS, Koh C, Savar NS, Tran QD, Shengjuler D, Fletcher SJ, O'Neal MC, Cai Y, Chang JCJ, Broadhurst DJ, Klippsten S, Sharp PP, Wenzell NA, Kuzuoglu-Ozturk D, Wang HY, Trenker R, Young JM, Cavero DA, Hiatt J, Roth TL, Rathore U, Subramanian A, Noack J, Hubert M, Stroud RM, Frankel AD, Rosenberg OS, Verba KA, Agard DA, Ott M, Emerman M, Jura N, von Zastrow M, Verdin E, Ashworth A, Schwartz O, d'Enfert C, Mukherjee S, Jacobson M, Malik HS, Fujimori DG, Ideker T, Craik CS, Floor SN, Fraser JS, Gross JD, Sali A, Roth BL, Ruggero D, Taunton J, Kortemme T, Beltrao P, Vignuzzi M, García-Sastre A, Shokat KM, Shoichet BK, Krogan NJ. A SARS-CoV-2 protein interaction map reveals targets for drug repurposing. Nature. 2020 07; 583(7816):459-468.
  19. Khan S, Lew I, Wu F, Fritts L, Fontaine KA, Tomar S, Trapecar M, Shehata HM, Ott M, Miller CJ, Sanjabi S. Low expression of RNA sensors impacts Zika virus infection in the lower female reproductive tract. Nat Commun. 2019 09 25; 10(1):4344.
  20. Ali I, Ruiz DG, Ni Z, Johnson JR, Zhang H, Li PC, Khalid MM, Conrad RJ, Guo X, Min J, Greenblatt J, Jacobson M, Krogan NJ, Ott M. Crosstalk between RNA Pol II C-Terminal Domain Acetylation and Phosphorylation via RPRD Proteins. Mol Cell. 2019 06 20; 74(6):1164-1174.e4.
  21. Schilling B, Meyer JG, Wei L, Ott M, Verdin E. High-Resolution Mass Spectrometry to Identify and Quantify Acetylation Protein Targets. Methods Mol Biol. 2019; 1983:3-16.
  22. Tomar S, Ali I, Ott M. A BAF'ling Approach to Curing HIV. Cell Chem Biol. 2018 12 20; 25(12):1441-1442.
  23. Fozouni P, Ott M. How cells hush a viral invader. Nature. 2018 12; 564(7735):193-194.
  24. Fontaine KA, Leon KE, Khalid MM, Tomar S, Jimenez-Morales D, Dunlap M, Kaye JA, Shah PS, Finkbeiner S, Krogan NJ, Ott M. The Cellular NMD Pathway Restricts Zika Virus Infection and Is Targeted by the Viral Capsid Protein. mBio. 2018 11 06; 9(6).
  25. Ali I, Conrad RJ, Verdin E, Ott M. Lysine Acetylation Goes Global: From Epigenetics to Metabolism and Therapeutics. Chem Rev. 2018 02 14; 118(3):1216-1252.