About the Harris Research Program

 

Professor Eva Harris has developed a multidisciplinary approach to study the molecular virology, pathogenesis, immunology, epidemiology, clinical aspects, and control of dengue, Zika, and chikungunya—the most prevalent mosquito-borne diseases in humans.

Our program investigates viral and host factors that modulate disease severity and immune correlates of protection and pathogenesis, using in vitro approaches, animal models, and research involving human populations.

 

Projects

One major focus of the Harris Research Program is on studies of arboviral disease in humans, including:

  1. Antibody and B cell responses and correlates of protection

  2. Systems immunology profiling of the innate response

  3. Viral evolution, fitness, and intra-host diversity

  4. Viral pathogenesis: the role of non-structural 1 (NS1) protein in vascular leak

Professor Harris’ international work focuses on laboratory-based and epidemiological studies of dengue, Zika, chikungunya, and influenza in endemic Latin American countries, particularly in Nicaragua, where she has been working closely with the Ministry of Health for over 30 years. Long-term collaborations include clinical, biological, and immunological studies of severe disease through a 20-year pediatric hospital-based study; a 15-year ongoing pediatric cohort study of dengue, Zika, chikungunya, and influenza transmission in Managua; and a cluster randomized controlled trial of evidence-based community-derived interventions to prevent and control arboviral diseases.

Recent Publications

Increased serum sialic acid is associated with morbidity and mortality in a murine model of dengue disease.
Espinosa DA, Beatty PR, Puerta-Guardo H, Islam MN, Belisle JT, Perera R, Harris E. (2019)
J Gen Virol. 2019 Sep 17. doi: 10.1099/jgv.0.001319

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Endocytosis of flavivirus NS1 is required for NS1-mediated endothelial hyperpermeability and is abolished by a single N-glycosylation site mutation.
Wang C, Puerta-Guardo H, Biering SB, Glasner DR, Tran EB, Patana M1 Gomberg TA, Malvar C, Lo NTN, Espinosa DA, Harris E. (2019)
PLoS Pathog. 2019 Jul 19. doi: 10.1371/journal.ppat.1007938

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Impact of pre-existing dengue immunity on human antibody and memory B cell responses to Zika.

Andrade P, Gimblet-Ochieng C, Modirian F, Collins M, Cárdenas M, Katzelnick LC, Montoya M, Michlmayr D, Kuan G, Balmaseda A, Coloma J, de Silva AM, Harris E. (2019)
Nature Comm. 2019 Feb 26
. doi: 10.1038/s41467-019-08845-3.
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Magnitude and Functionality of the NS1-Specific Antibody Response Elicited by a Live-Attenuated Tetravalent Dengue Vaccine Candidate.
Sharma M, Glasner DR, Watkins H, Puerta-Guardo H, Kassa Y, Egan MA, Dean H, Harris E. (2019)
J. Infect. Dis. 2019 Feb 19. doi:10.1093/infdis/jiz081.

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Flavivirus NS1 triggers tissue-specific vascular endothelial dysfunction reflecting disease tropism.
Puerta-Guardo H, Glasner DR, Espinosa DA, Biering SB, Patana M, Ratnasiri K, Wang C, Beatty PR, Harris E. (2019)
Cell Rep. 2019 Feb 5. doi: 10.1016/j.celrep.2019.01.036

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Epidemiological Evidence for Lineage-Specific Differences in the Risk of Inapparent Chikungunya Virus Infection.
Bustos Carrillo F, Collado D, Sanchez N, Ojeda S, Lopez Mercado B, Burger-Calderon R, Gresh L, Gordon A, Balmaseda A, Kuan G, Harris E. (2019)
J Virology. 2019 Feb 5; 93(4). doi:10.1128/JVI.01622-18

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Prior dengue virus infection and risk of Zika: A pediatric cohort in Nicaragua.
Gordon A, Gresh L, Ojeda S, Katzelnick LC, Sanchez N, Mercado JC, Chowell G, Lopez B, Elizondo D, Coloma J, Burger-Calderon R, Kuan G, Balmaseda A, Harris E. (2019)
PLoS Medicine. 2019 Jan 22; 16(1):e1002726. doi: 10.1371/journal.pmed.1002726

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Cyclic Dinucleotide-Adjuvanted Dengue Virus Nonstructural Protein 1 Induces Protective Antibody and T Cell Responses.
Espinosa DA, Beatty PR, Reiner GL, Sivick KE, Hix Glickman L, Dubensky TW Jr, Harris E. (2019)
J. Immunol. 2019 Jan 18. doi:10.4049/jimmunol.1801323

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Dynamics and determinants of the force of infection of dengue virus from 1994 to 2015 in Managua, Nicaragua.
Katzelnick LC, Ben-Shachar R, Mercado JC, Rodriguez-Barraquer I, Elizondo D, Arguello S, Nuñez A, Ojeda S, Sanchez N, Lopez Mercado B, Gresh L, Burger-Calderon R, Kuan G, Gordon A, Balmaseda A, Harris E. (2018)
PNAS. 2018 Oct 16; 115(42):10762-10767
. doi:10.1073/pnas.1809253115.
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Comprehensive innate immune profiling of chikungunya virus infection in pediatric cases.
Michlmayr D, Pak TR, Rahman AH, Amir ED, Kim EY, Kim-Schulze S, Suprun M, Stewart MG, Thomas GP, Balmaseda A, Wang L, Zhu J, Suaréz-Fariñas M, Wolinsky SM, Kasarskis A, Harris E. (2018)
Molec. Syst. Biol. 2018 Aug 27; 14(8):e7862. doi:10.15252/msb.20177862.

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Recent advances in understanding the adaptive immune response to Zika virus and the effect of previous flavivirus exposure.
Andrade DV, Harris E. (2018)
Virus Res. 2018 Aug 2; 254:27-33. doi:10.1016/j.virusres.2017.06.019.

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Longitudinal Analysis of Antibody Cross-neutralization Following Zika Virus and Dengue Virus Infection in Asia and the Americas.
Montoya M, Collins M, Dejnirattisai W, Katzelnick LC, Puerta-Guardo H, Jadi R, Schildhauer S, Supasa P, Vasanawathana S, Malasit P, Mongkolsapaya J, de Silva AD, Tissera H, Balmaseda A, Screaton G, de Silva AM, Harris E. (2018)
J. Infect. Dis. 2018 Jul 13; 218(4):536-545. doi:10.1093/infdis/jiy164.

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Featured Publications

Seroprevalence, risk factor, and spatial analysis of Zika virus infection after the 2016 epidemic in Managua, Nicaragua. 
Zambrana JV, Bustos F, Burger-Calderon R, Collado D, Jairo Sanchez N, Ojeda S, Plazaola M, Lopez B, Arguello S, Elizondo D, Aviles W, Kuan G, Balmaseda A, Gordon A, Harris E. (2018)
Proc. Natl. Acad. Sci. USA. 2018 Sep 11;115(37):9294-9299. doi: 10.1073/pnas.1804672115. Epub 2018 Aug 27.

Comprehensive innate immune profiling of chikungunya virus infection in pediatric cases.
Michlmayr D., Pak T.R., Rahman A.H., Amir E.D., Kim E.Y., Kim-Schulze S., Suprun M., Stewart M.G., Thomas G.P., Balmaseda A., Wang L., Zhu J., Suaréz-Fariñas M., Wolinsky S.M., Kasarskis A., Harris E. (2018)
Mol. Syst. Biol. 2018 Aug 27;14(8):e7862. doi: 10.15252/msb.20177862.

Differences in transmission and disease severity between two successive waves of chikungunya.
Gordon, A., Gresh, L., Ojeda, S., Chowell-Puente, G., Gonzalez, K., Sanchez, N., Saborio, S., Mercado, J.C., Kuan, G., Balmaseda, A., and Harris, E. (2018)
Clin. Infect. Dis. 2018 Apr 25. doi: 10.1093/cid/ciy356. [Epub ahead of print].

Antibody-dependent enhancement of severe dengue disease in humans.
Katzelnick., L. Gresh, L, Halloran, M.E., Mercado, J.C., Kuan, G., Gordon, A., Balmaseda, A., and Harris, E. (2017)
Science. 358(6365):929-932.

Longitudinal analysis of antibody cross-neutralization following Zika and dengue virus infection in Asia and the Americas
Montoya, M., Collins, M., Dejnirattisai, W., Katzelnick, L.C., Puerta-Guardo, H., Jadi, R., Schildhauer, S., Supasa, P., Vasanawathana, S., Malasit, P., Mongkolsapaya, J., de Silva, A.D., Tissera, H., Balmaseda, A., Screaton, G., de Silva, A.M., Harris, E. (2018)
J. Infect. Dis. 218(4):536-545.

CD14+ CD16+ monocytes are the main targets of Zika virus infection in peripheral blood mononuclear cells in a paediatric study in Nicaragua.
Michlmayr, D., Andrade, P., Gonzalez, K., Balmaseda, A., and Harris E. (2017)
Nat Microbiol. 2(11):1462-1470. 2017.

Dengue virus NS1 cytokine-independent vascular leak is dependent on endothelial glycocalyx integrity. 
Glasner, D.R., Ratnasiri, K., Puerta-Guardo, H., Beatty, P.R., and Harris, E. (2017)
PLoS Pathog. 13(11):e1006673.

Analysis of individuals from a dengue-endemic region helps define the footprint and repertoire of antibodies targeting dengue virus 3 type-specific epitopes.
Andrade, D.V., Katzelnick, L.C., Widman, D.G., Balmaseda, A., de Silva A.M., Baric, R.S., and Harris, E. (2017)
mBio. 8(5):e01205-17.

Intrahost selection pressures drive rapid dengue virus microevolution in acute human infections.
Parameswaran, P., Wang, C., Trivedi, S.B., Eswarappa, M., Montoya, M., Balmaseda, A., and Harris, E. (2017)  
Cell Host Microbe. 22(3):400-410.e5.

Zika virus targets different primary human placental cells, suggesting two routes for vertical transmission. 
Tabata, T., Petitt, M., Puerta-Guardo, H., Michlmayr, D., Wang, C., Fang-Hoover, J., Harris, E.* and Pereira, L.* (2016)
Cell Host Microbe. In press (Epub July 18, 2016) S1931-3128(16)30300-6. doi: 10.1016/j.chom.2016.07.002. *Co-corresponding authors. 

Dengue virus NS1 disrupts the endothelial glycocalyx, leading to hyperpermeability. 
Puerta-Guardo, H., Glasner, D.R., and Harris, E. (2016)
PLoS Pathog.12(7):e1005738.

Dengue virus non-structural protein 1 (NS1) triggers vascular leak that can be inhibited by anti-NS1 antibodies. 
Beatty, P.R., Puerta Guardo, H., Killingbeck, S., Glasner, D., Hopkins, K., and Harris, E. (2015)
Sci Transl Med. 7:304ra141.

Evidence based community mobilization for dengue prevention in Nicaragua and Mexico (Camino Verde, the Green Way): cluster randomized controlled trial.
Andersson, N., Nava-Aguilera, E., Arostegui, J., Morales-Perez, A., Suazo-Laguna, H., Legorreta-Soberanis, J., Hernandez-Alvarez, C., Fernandez-Salas, I., Balmaseda, A., Cortés-Guzmán, A.J., Coloma, J., Ledogar, R.J., and Harris, E. (2015)  
BMJ. 351:h3267.

Contact Us

To reach the Harris Research Program, email Dr. Eva Harris at eharris (at) berkeley (dot) edu

 

Address:
510D Li Ka Shing Center
University of California
1951 Oxford Street
Berkeley, CA 94720-3370