Jonathan Abraham, M.D., Ph.D.
Department of Microbiology and Immunobiology, Harvard Medical School
Our laboratory seeks to understand at the molecular level how the human body tackles infections by agents that cause highly lethal human diseases that have limited treatment or vaccine options.
For example, while several enveloped RNA viruses cause human viral hemorrhagic fevers high case fatality rates, only infection by the New World arenavirus Junin is reliably treated with immune plasma transfusions (‘passive immunity’). Using passive immunity 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 mediated by Fc receptor-engagement) that can explain how to best adapt passive immunity to treat emerging viral infections. The pathogens we study include arena-, filo-, flavi-, and hantaviruses. Methods we use include molecular biology, X-crystallography, electron microscopy, and in vivo studies with 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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