Emma Winkler

  • Bloomington, Indiana

  • Indiana U. Bloomington (2015)

  • Immunology

  • Michael S. Diamond, M.D., Ph.D.

  • Immunity to Emerging RNA Viruses

  • eswinkler@wustl.edu

Research

In the past decade, newly emerged and re-emerged pathogenic RNA viruses such as Ebola, H1N1, and Zika virus have become substantial threats to global health. Two notable examples include the explosive re-appearance of chikungunya virus in the 2000s in Asia and the Western Hemisphere and, more recently, the global COVID-19 pandemic. Therefore, an improved understanding of immunity to emerging RNA viruses is critical for defining host susceptibility and restriction factors to viral infection as well as appropriate vaccine and antiviral therapeutic design.


My thesis work initially focused on understanding how the intestinal microbiome modulates systemic immune responses to virus infection, specifically mosquito-born alphaviruses such as Chikungunya virus. My work focused on how specific microbiome-derived metabolites such as secondary bile acids support type I interferon responses needed to restrict systemic alphavirus infection. With the emergence of SARS-CoV-2, I also worked on the development of mouse models of SARS-CoV-2 pathogenesis and the evaluation of monoclonal antibody therapies against SARS-CoV-2 in these mouse models.

Graduate Publications:

Chen RE, Zhang X, Case JB, Winkler ES, Liu Y, VanBlargan LA, Liu J, Errico JM, Xie X, Suryadevara N, Gilchuk P, Zost SJ, Tahan S, Droit L, Turner JS, Kim W, Schmitz AJ, Thapa M, Wang D, Boon ACM, Presti RM, O'Halloran JA, Kim AHJ, Deepak P, Pinto D, Fremont DH, Crowe JE Jr, Corti D, Virgin HW, Ellebedy AH, Shi PY, Diamond MS. 2021 Resistance of SARS-CoV-2 variants to neutralization by monoclonal and serum-derived polyclonal antibodies. Nat Med, 27(4):717-726.

Case JB, Winkler ES, Errico JM, Diamond MS.. 2021 On the road to ending the COVID-19 pandemic: Are we there yet?. Virology, 557():70-85.

Dugan HL, Stamper CT, Li L, Changrob S, Asby NW, Halfmann PJ, Zheng NY, Huang M, Shaw DG, Cobb MS, Erickson SA, Guthmiller JJ, Stovicek O, Wang J, Winkler ES, Madariaga ML, Shanmugarajah K, Jansen MO, Amanat F, Stewart I, Utset HA, Huang J, Nelson CA, Dai YN, Hall PD, Jedrzejczak RP, Joachimiak A, Krammer F, Diamond MS, Fremont DH, Kawaoka Y, Wilson PC. 2021 Profiling B cell immunodominance after SARS-CoV-2 infection reveals antibody evolution to non-neutralizing viral targets. Immunity, 54(6):1290-1303.e7.

Chen RE, Winkler ES, Case JB, Aziati ID, Bricker TL, Joshi A, Darling TL, Ying B, Errico JM, Shrihari S, VanBlargan LA, Xie X, Gilchuk P, Zost SJ, Droit L, Liu Z, Stumpf S, Wang D, Handley SA, Stine WB Jr, Shi PY, Davis-Gardner ME, Suthar MS, Knight MG, Andino R, Chiu CY, Ellebedy AH, Fremont DH, Whelan SPJ, Crowe JE Jr, Purcell L, Corti D, Boon ACM, Diamond M. 2021 In vivo monoclonal antibody efficacy against SARS-CoV-2 variant strains. Nature, 596(7870):103-108.

Williamson LE, Reeder KM, Bailey K, Tran MH, Roy V, Fouch ME, Kose N, Trivette A, Nargi RS, Winkler ES, Kim AS, Gainza C, Rodriguez J, Armstrong E, Sutton RE, Reidy J, Carnahan RH, McDonald WH, Schoeder CT, Klimstra WB, Davidson E, Doranz BJ, Alter G, Meiler J, Schey KL, Julander JG, Diamond MS, Crowe JE Jr. 2021 Therapeutic alphavirus cross-reactive E1 human antibodies inhibit viral egress. Cell, 184(17):4430-4446.e22.

Kim AS, Kafai NM, Winkler ES, Gilliland TC Jr, Cottle EL, Earnest JT, Jethva PN, Kaplonek P, Shah AP, Fong RH, Davidson E, Malonis RJ, Quiroz JA, Williamson LE, Vang L, Mack M, Crowe JE Jr, Doranz BJ, Lai JR, Alter G, Gross ML, Klimstra WB, Fremont DH, Diamond MS. 2021 Pan-protective anti-alphavirus human antibodies target a conserved E1 protein epitope. Cell, 184(17):4414-4429.e19.

VanBlargan LA*, Adams LJ*, Liu Z*, Chen RE, Gilchuk P, Raju S, Smith BK, Zhao H, Case JB, Winkler ES, Whitener BM, Droit L, Aziati ID, Bricker TL, Joshi A, Shi PY, Creanga A, Pegu A, Handley SA, Wang D, Boon ACM, Crowe JE Jr, Whelan SPJ, Fremont DH, Diamond MS. 2021 A potently neutralizing SARS-CoV-2 antibody inhibits variants of concern by utilizing unique binding residues in a highly conserved epitope.. Immunity, ():S1074-7613(21)00348-4.

Chen RE, Smith BK, Errico JM, Gordon DN, Winkler ES, VanBlargan LA, Desai C, Handley SA, Dowd KA, Amaro-Carambot E, Cardosa MJ, Sariol CA, Kallas EG, Sékaly RP, Vasilakis N, Fremont DH, Whitehead SS, Pierson TC, Diamond MS. 2021 Implications of a highly divergent dengue virus strain for cross-neutralization, protection, and vaccine immunity. Cell Host Microbe, (Sept. 29):S1931-3128(21)00422-4.

Winkler ES, Gilchuk P, Yu J, Bailey AL, Chen RE, Chong Z, Zost SJ, Jang H, Huang Y, Allen JD, Case JB, Sutton RE, Carnahan RH, Darling TL, Boon ACM, Mack M, Head RD, Ross TM, Crowe JE Jr, Diamond MS. 2021 Human neutralizing antibodies against SARS-CoV-2 require intact Fc effector functions for optimal therapeutic protection. Cell, 184(7):1804-1820.e16.

Suryadevara N, Shrihari S, Gilchuk P, VanBlargan LA, Binshtein E, Zost SJ, Nargi RS, Sutton RE, Winkler ES, Chen EC, Fouch ME, Davidson E, Doranz BJ, Chen RE, Shi PY, Carnahan RH, Thackray LB, Diamond MS, Crowe JE Jr. 2021 Neutralizing and protective human monoclonal antibodies recognizing the N-terminal domain of the SARS-CoV-2 spike protein. Cell, 184(9):2316-2331.e15.

Case JB, Chen RE, Cao L, Ying B, Winkler ES, Johnson M, Goreshnik I, Pham MN, Shrihari S, Kafai NM, Bailey AL, Xie X, Shi PY, Ravichandran R, Carter L, Stewart L, Baker D, Diamond MS. 2021 Ultrapotent miniproteins targeting the SARS-CoV-2 receptor-binding domain protect against infection and disease. Cell Host Microbe, 29(7):1151-1161.e5.

Winkler ES, Bailey AL, Kafai NM, Nair S, McCune BT, Yu J, Fox JM, Chen RE, Earnest JT, Keeler SP, Ritter JH, Kang LI, Dort S, Robichaud A, Head R, Holtzman MJ, Diamond MS. 2020 SARS-CoV-2 infection of human ACE2-transgenic mice causes severe lung inflammation and impaired function. Nat Immunol, 21(11):1327-1335.

Zost SJ, Gilchuk P, Case JB, Binshtein E, Chen RE, Nkolola JP, Schäfer A, Reidy JX, Trivette A, Nargi RS, Sutton RE, Suryadevara N, Martinez DR, Williamson LE, Chen EC, Jones T, Day S, Myers L, Hassan AO, Kafai NM, Winkler ES, Fox JM, Shrihari S, Mueller BK, Meiler J, Chandrashekar A, Mercado NB, Steinhardt JJ, Ren K, Loo YM, Kallewaard NL, McCune BT, Keeler SP, Holtzman MJ, Barouch DH, Gralinski LE, Baric RS, Thackray LB, Diamond MS, Carnahan RH, Crowe JE Jr. 2020 Potently neutralizing and protective human antibodies against SARS-CoV-2. Nature, 584(7821):443-449.

Hassan AO, Case JB, Winkler ES, Thackray LB, Kafai NM, Bailey AL, McCune BT, Fox JM, Chen RE, Alsoussi WB, Turner JS, Schmitz AJ, Lei T, Shrihari S, Keeler SP, Fremont DH, Greco S, McCray PB Jr, Perlman S, Holtzman MJ, Ellebedy AH, Diamond MS. 2020 A SARS-CoV-2 Infection Model in Mice Demonstrates Protection by Neutralizing Antibodies. Cell, 182(3):744-453.e4.

Case JB, Rothlauf PW, Chen RE, Kafai NM, Fox JM, Smith BK, Shrihari S, McCune BT, Harvey IB, Keeler SP, Bloyet LM, Zhao H, Ma M, Adams LJ, Winkler ES, Holtzman MJ, Fremont DH, Whelan SPJ, Diamond MS. 2020 Replication-Competent Vesicular Stomatitis Virus Vaccine Vector Protects against SARS-CoV-2-Mediated Pathogenesis in Mice. Cell Host Microbe, 28(3):465-474.e4.

Alsoussi WB, Turner JS, Case JB, Zhao H, Schmitz AJ, Zhou JQ, Chen RE, Lei T, Rizk AA, McIntire KM, Winkler ES, Fox JM, Kafai NM, Thackray LB, Hassan AO, Amanat F, Krammer F, Watson CT, Kleinstein SH, Fremont DH, Diamond MS, Ellebedy AH. 2020 A Potently Neutralizing Antibody Protects Mice against SARS-CoV-2 Infection. J Immunol, 205(4):915-22.

Hassan AO, Kafai NM, Dmitriev IP, Fox JM, Smith BK, Harvey IB, Chen RE, Winkler ES, Wessel AW, Case JB, Kashentseva E, McCune BT, Bailey AL, Zhao H, VanBlargan LA, Dai YN, Ma M, Adams LJ, Shrihari S, Danis JE, Gralinski LE, Hou YJ, Schäfer A, Kim AS, Keeler SP, Weiskopf D, Baric RS, Holtzman MJ, Fremont DH, Curiel DT, Diamond MS. 2020 A Single-Dose Intranasal ChAd Vaccine Protects Upper and Lower Respiratory Tracts against SARS-CoV-2. Cell, 183(1):169-184.e13.

Zhang R, Earnest JT, Kim AS, Winkler ES, Desai P, Adams LJ, Hu G, Bullock C, Gold B, Cherry S, Diamond MS. 2019 Expression of the Mxra8 Receptor Promotes Alphavirus Infection and Pathogenesis in Mice and Drosophila. Cell Rep, 28(10):2647-2658.e5.

Slon-Campos JL, Dejnirattisai W, Jagger BW, López-Camacho C, Wongwiwat W, Durnell LA, Winkler ES, Chen RE, Reyes-Sandoval A, Rey FA, Diamond MS, Mongkolsapaya J, Screaton GR. 2019 A protective Zika virus E-dimer-based subunit vaccine engineered to abrogate antibody-dependent enhancement of dengue infection. Nat Immunol, 20(10):1291-1298.

Last Updated: 8/21/2017 4:53:10 PM

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