Jonathan Abraham, M.D., Ph.D.
Department of Microbiology, Harvard Medical School
We use methods in molecular biology, immunology, and structural biology to study host-pathogen interactions, with the goal of informing strategies aimed at treating or preventing infection.
Several enveloped RNA viruses cause human viral hemorrhagic fevers with limited vaccine and treatment options. Infection by the New World arenavirus Junin is reliably treated with neutralizing-antibody containing immune plasma transfusions (‘passive immunity‘). Using this approach to treat Ebola virus infection has yielded mixed results. We are dissecting, at the molecular level, features of both the viruses (e.g. surface glycoprotein architecture and epitope accessibility) and hosts (e.g. antibody neutralizing and non-neutralizing effector functions) that may explain how to best adapt passive immunity to treat emerging viral infections. Pathogens we study include arena-, filo-, flavi-, and hantaviruses.
Methods used in the laboratory span many disciplines and include molecular biology, X-crystallography, electron microscopy, human immunology using primary donor samples, pseudotype viral entry assays, and efficacy studies in relevant animal models (through collaborations).
Mahmutovic S, Clark L, Levis SC, Briggiler AM, Enria DA, Harrison SC, Abraham J. Molecular basis for antibody-mediated neutralization of New World hemorrhagic fever mammarenaviruses. Cell Host & Microbe. 2015; 18(6):705-13. PMID: 26651946
Hood CL, Abraham J, Boyington JC, Leung K, Kwong PD, Nabel GJ. Biochemical and structural characterization of cathepsin L-processed Ebola virus glycoprotein: implications for viral entry and immunogenicity. Journal of Virology. 2010; 84(6):2972-82. PMID: 20053739
Abraham J, Corbett KD, Farzan M, Choe H, Harrison SC. Structural basis for receptor recognition by New World hemorrhagic fever arenaviruses. Nature Structural & Molecular Biology. 2010; 17(4):438-44. PMID: 20208545
Abraham J*, Kwong JA*, Albariño CG, Lu JG, Radoshitzky SR, Salazar-Bravo J, Farzan M, Spiropoulou C, Choe H. (2009) Host-species transferrin receptor 1 orthologs are cellular receptors for nonpathogenic New World clade Barenaviruses. PLoS pathogens. 2009; 5(4):e1000358. PMID: 19343214
Radoshitzky SR*, Abraham J*, Spiropoulou CF, Kuhn JH, Nguyen D, Li W, Nagel J, Schmidt PJ, Nunberg JH, Andrews NC, Farzan M, Choe H. Transferrin receptor 1 is a cellular receptor for New World haemorrhagic fever arenaviruses. Nature. 2007; 446(7131):92-6. PMID: 17287727
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