Melanie Ott, MD, PhD

Senior Investigator, Gladstone Institute of Virology and Immunology
Professor
Department of Medicine
Primary Thematic Area
Secondary Thematic Area
Research Summary
Molecular Pathogenesis of HIV and Hepatitis C Virus Infections
+1 415 734-4807

We study viruses of today to be prepared for the viruses of tomorrow. Currently, we focus on multiple human pathogens—the human immunodeficiency virus (HIV-1), Zika virus, the hepatitis B and C viruses (HBV and HCV), influenza A and B , SARS-CoV-2 and multiple common cold coronaviruses. We use four main technologies—human organoids, rapid quantitative diagnostics, a viral protein expression library, and transcriptomics. We deliberately apply lessons learned from one virus to others; specifically, we search for common host and viral factors that can be targeted by panviral therapeutics against respiratory viruses, define new ways to silence and cure chronic viral infections such as HIV and HBV and develop versatile, easy to reprogram CRISPR diagnostics that use mobile phones as readers. We welcome graduate students into our diverse and friendly research teams as equal partners and nurture their scientific success and personal growth.

Publications

Structure-based discovery of highly bioavailable, covalent, broad-spectrum coronavirus MPro inhibitors with potent in vivo efficacy.

Science advances

Detomasi TC, Degotte G, Huang S, Suryawanshi RK, Diallo A, Lizzadro L, Zaptero-Belinchón FJ, Taha TY, Li J, Richards AL, Hantz ER, Alam Z, Montano M, McCavitt-Malvido M, Gumpena R, Partridge JR, Correy GJ, Matsui Y, Charvat AF, Glenn IS, Rosecrans J, Revalde JL, Anderson D, Hultquist JF, Arkin MR, Neitz RJ, Swaney DL, Krogan NJ, Shoichet BK, Verba KA, Ott M, Renslo AR, Craik CS

The Mac1 ADP-ribosylhydrolase is a Therapeutic Target for SARS-CoV-2.

bioRxiv : the preprint server for biology

Suryawanshi RK, Jaishankar P, Correy GJ, Rachman MM, O'Leary PC, Taha TY, Zapatero-Belinchón FJ, McCavitt-Malvido M, Doruk YU, Stevens MGV, Diolati ME, Jogalekar MP, Richards AL, Montano M, Rosecrans J, Matthay M, Togo T, Gonciarz RL, Gopalkrishnan S, Neitz RJ, Krogan NJ, Swaney DL, Shoichet BK, Ott M, Renslo AR, Ashworth A, Fraser JS

Fibrin drives thromboinflammation and neuropathology in COVID-19.

Nature

Ryu JK, Yan Z, Montano M, Sozmen EG, Dixit K, Suryawanshi RK, Matsui Y, Helmy E, Kaushal P, Makanani SK, Deerinck TJ, Meyer-Franke A, Rios Coronado PE, Trevino TN, Shin MG, Tognatta R, Liu Y, Schuck R, Le L, Miyajima H, Mendiola AS, Arun N, Guo B, Taha TY, Agrawal A, MacDonald E, Aries O, Yan A, Weaver O, Petersen MA, Meza Acevedo R, Alzamora MDPS, Thomas R, Traglia M, Kouznetsova VL, Tsigelny IF, Pico AR, Red-Horse K, Ellisman MH, Krogan NJ, Bouhaddou M, Ott M, Greene WC, Akassoglou K

Immediate myeloid depot for SARS-CoV-2 in the human lung.

Science advances

Magnen M, You R, Rao AA, Davis RT, Rodriguez L, Bernard O, Simoneau CR, Hysenaj L, Hu KH, Maishan M, Conrad C, Gbenedio OM, Samad B, Consortium TUC, Love C, Woodruff PG, Erle DJ, Hendrickson CM, Calfee CS, Matthay MA, Roose JP, Sil A, Ott M, Langelier CR, Krummel MF, Looney MR

Hepatitis C virus infects and perturbs liver stem cells.

mBio

Meyers NL, Ashuach T, Lyons DE, Khalid MM, Simoneau CR, Erickson AL, Bouhaddou M, Nguyen TT, Kumar GR, Taha TY, Natarajan V, Baron JL, Neff N, Zanini F, Mahmoudi T, Quake SR, Krogan NJ, Cooper S, McDevitt TC, Yosef N, Ott M

Previous exposure to Spike-providing parental strains confers neutralizing immunity to XBB lineage and other SARS-CoV-2 recombinants in the context of vaccination.

Emerging microbes & infections

Suryawanshi RK, Taha TY, McCavitt-Malvido M, Silva I, Khalid MM, Syed AM, Chen IP, Saldhi P, Sreekumar B, Montano M, Foresythe K, Tabata T, Kumar GR, Sotomayor-Gonzalez A, Servellita V, Gliwa A, Nguyen J, Kojima N, Arellanor T, Bussanich A, Hess V, Shacreaw M, Lopez L, Brobeck M, Turner F, Wang Y, Ghazarian S, Davis G, Rodriguez D, Doudna J, Spraggon L, Chiu CY, Ott M

SARS-CoV-2 infection of airway organoids reveals conserved use of Tetraspanin-8 by Ancestral, Delta, and Omicron variants.

Stem cell reports

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

Catching BETs by viruses.

Biochimica et biophysica acta. Gene regulatory mechanisms

Zandian M, Chen IP, Byrareddy SN, Fujimori DG, Ott M, Kutateladze TG

Tropism of SARS-CoV-2 for human cortical astrocytes.

Proceedings of the National Academy of Sciences of the United States of America

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

Neutralizing antibody activity against SARS-CoV-2 variants in gestational age-matched mother-infant dyads after infection or vaccination.

JCI insight

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 JM, Rincon M, Myatt L, Asiodu IV, Flaherman VJ, Afshar Y, Jacoby VL, Murtha AP, Robinson JF, Ott M, Greene WC, Gaw SL

Limited cross-variant immunity from SARS-CoV-2 Omicron without vaccination.

Nature

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

Immediate myeloid depot for SARS-CoV-2 in the human lung.

bioRxiv : the preprint server for biology

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

Limited cross-variant immunity after infection with the SARS-CoV-2 Omicron variant without vaccination.

medRxiv : the preprint server for health sciences

Suryawanshi RK, Chen IP, Ma T, Syed AM, Simoneau CR, Ciling A, Khalid MM, Sreekumar B, Chen PY, George AF, Kumar GR, Montano M, Garcia-Knight MA, Brazer N, Saldhi P, 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, Fang X, Maishan M, Matthay M, Morris MK, Wadford D, Hanson C, Greene WC, Andino R, Spraggon L, Roan NR, Chiu CY, Doudna J, Ott M

Publisher Correction: Accelerated RNA detection using tandem CRISPR nucleases.

Nature chemical biology

Liu TY, Knott GJ, Smock DCJ, Desmarais JJ, Son S, Bhuiya A, Jakhanwal S, Prywes N, Agrawal S, Díaz de León Derby M, Switz NA, Armstrong M, Harris AR, Charles EJ, Thornton BW, Fozouni P, Shu J, Stephens SI, Kumar GR, Zhao C, Mok A, Iavarone AT, Escajeda AM, McIntosh R, Kim S, Dugan EJ, IGI Testing Consortium, Pollard KS, Tan MX, Ott M, Fletcher DA, Lareau LF, Hsu PD, Savage DF, Doudna JA

Accelerated RNA detection using tandem CRISPR nucleases.

Nature chemical biology

Liu TY, Knott GJ, Smock DCJ, Desmarais JJ, Son S, Bhuiya A, Jakhanwal S, Prywes N, Agrawal S, Díaz de León Derby M, Switz NA, Armstrong M, Harris AR, Charles EJ, Thornton BW, Fozouni P, Shu J, Stephens SI, Kumar GR, Zhao C, Mok A, Iavarone AT, Escajeda AM, McIntosh R, Kim S, Dugan EJ, IGI Testing Consortium , Pollard KS, Tan MX, Ott M, Fletcher DA, Lareau LF, Hsu PD, Savage DF, Doudna JA

SARS-CoV-2 infection studies in lung organoids identify TSPAN8 as novel mediator.

bioRxiv : the preprint server for biology

Hysenaj L, Little S, Kulhanek K, Gbenedio OM, Rodriguez L, Shen A, Lone JC, Lupin-Jimenez LC, Bonser LR, Serwas NK, Bahl K, Mick E, Li JZ, Ding VW, Matsumoto S, Maishan M, Simoneau C, Fragiadakis G, Jablons DM, Langelier CR, Matthay M, Ott M, Krummel M, Combes AJ, Sil A, Erle DJ, Kratz JR, Roose JP

Transmission, infectivity, and neutralization of a spike L452R SARS-CoV-2 variant.

Cell

Deng X, Garcia-Knight MA, Khalid MM, Servellita V, Wang C, Morris MK, Sotomayor-González A, Glasner DR, Reyes KR, Gliwa AS, Reddy NP, Sanchez San Martin C, Federman S, Cheng J, Balcerek J, Taylor J, Streithorst JA, Miller S, Sreekumar B, Chen PY, Schulze-Gahmen U, Taha TY, Hayashi JM, Simoneau CR, Kumar GR, McMahon S, Lidsky PV, Xiao Y, Hemarajata P, Green NM, Espinosa A, Kath C, Haw M, Bell J, Hacker JK, Hanson C, Wadford DA, Anaya C, Ferguson D, Frankino PA, Shivram H, Lareau LF, Wyman SK, Ott M, Andino R, Chiu CY

Transmission, infectivity, and antibody neutralization of an emerging SARS-CoV-2 variant in California carrying a L452R spike protein mutation.

medRxiv : the preprint server for health sciences

Deng X, Garcia-Knight MA, Khalid MM, Servellita V, Wang C, Morris MK, Sotomayor-González A, Glasner DR, Reyes KR, Gliwa AS, Reddy NP, Sanchez San Martin C, Federman S, Cheng J, Balcerek J, Taylor J, Streithorst JA, Miller S, Kumar GR, Sreekumar B, Chen PY, Schulze-Gahmen U, Taha TY, Hayashi J, Simoneau CR, McMahon S, Lidsky PV, Xiao Y, Hemarajata P, Green NM, Espinosa A, Kath C, Haw M, Bell J, Hacker JK, Hanson C, Wadford DA, Anaya C, Ferguson D, Lareau LF, Frankino PA, Shivram H, Wyman SK, Ott M, Andino R, Chiu CY

An ultrapotent synthetic nanobody neutralizes SARS-CoV-2 by stabilizing inactive Spike.

Science (New York, N.Y.)

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

Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms.

Science (New York, N.Y.)

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

The Global Phosphorylation Landscape of SARS-CoV-2 Infection.

Cell

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

A SARS-CoV-2 protein interaction map reveals targets for drug repurposing.

Nature

Gordon DE, Jang GM, Bouhaddou M, Xu J, Obernier K, White KM, O'Meara MJ, Rezelj VV, Guo JZ, Swaney DL, Tummino TA, Huettenhain 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 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-Human Protein-Protein Interaction Map Reveals Drug Targets and Potential Drug-Repurposing.

bioRxiv : the preprint server for biology

Gordon DE, Jang GM, Bouhaddou M, Xu J, Obernier K, O'Meara MJ, 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, Naing ZZC, Zhou Y, Peng S, Kirby IT, Melnyk JE, Chorba JS, Lou K, Dai SA, Shen W, Shi Y, Zhang Z, Barrio-Hernandez I, Memon D, Hernandez-Armenta C, Mathy CJP, Perica T, Pilla KB, Ganesan SJ, Saltzberg DJ, Ramachandran R, Liu X, Rosenthal SB, Calviello L, Venkataramanan S, Lin Y, Wankowicz SA, Bohn M, Trenker R, Young JM, Cavero D, Hiatt J, Roth T, Rathore U, Subramanian A, Noack J, Hubert M, Roesch F, Vallet T, Meyer B, White KM, Miorin L, Agard D, Emerman M, Ruggero D, García-Sastre A, Jura N, von Zastrow M, Taunton J, Schwartz O, Vignuzzi M, d'Enfert C, Mukherjee S, Jacobson M, Malik HS, Fujimori DG, Ideker T, Craik CS, Floor S, Fraser JS, Gross J, Sali A, Kortemme T, Beltrao P, Shokat K, Shoichet BK, Krogan NJ

The mTOR Complex Controls HIV Latency.

Cell host & microbe

Besnard E, Hakre S, Kampmann M, Lim HW, Hosmane NN, Martin A, Bassik MC, Verschueren E, Battivelli E, Chan J, Svensson JP, Gramatica A, Conrad RJ, Ott M, Greene WC, Krogan NJ, Siliciano RF, Weissman JS, Verdin E