Schmidt

Aaron Schmidt, PhD

Lab Info:

Principal Investigator: Aaron Schmidt, PhD

Office/Location: 400TS 954

Email: aschmidt@crystal.harvard.edu

Category: Group Leaders, Members

Click here to visit the Schmidt Lab Website.

 

Dr. Aaron G. Schmidt is an Assistant Professor in Microbiology at Harvard Medical School and a Group Leader of the Ragon Institute of MGH, MIT and Harvard.

 

As a structural biologist, Dr. Schmidt applies biophysical and biochemical approaches to address fundamental problems in virology and immunology. Their group primarily studies orthomyxoviruses (e.g., influenza) and flaviviruses (e.g., dengue, West Nile virus), but is also interested in emerging viruses (e.g., arena-, bunya- and filoviruses) and other pathogens.

 

Dr. Schmidt’s work focuses on immunogen engineering and therapeutics discovery. Using a structure-guided approach, the group uses protein engineering to design and ultimately test immunogens in vivo aimed at directing and re-directing immune responses. This work aims to understand the molecular ‘rules’ underlying the development of immune responses and may contribute to the design of vaccines against pathogens such as influenza. In the absence of effective vaccines against viruses such as influenza and dengue, antibodies and small-molecule inhibitors represent possible therapeutic interventions. Dr. Schmidt uses directed evolution to understand broadly neutralizing antibody (bnAb) development and engineer antibodies with increased antigen specificity and breadth. In the area of chemical therapeutic approaches, Dr. Schmidt is developing assays to identify small-molecule inhibitors of viral entry and strategies to deliver these inhibitors to the appropriate subcellular compartment to block viral entry and fusion.

 

Dr. Schmidt’s work has led to patents on broadly neutralizing influenza antibodies and immunogen design strategies. Many of the emerging or re-emerging viruses studied in the Schmidt lab lack effective vaccines or therapeutics; Dr. Schmidt’s work may help fill these unmet needs.

 

Dr. Schmidt received undergraduate degrees in biology and chemistry from Emmanuel College and a PhD in virology from Harvard University with Stephen C. Harrison. Postdoctoral training was done at Harvard Medical School and Boston Children’s Hospital, also with Stephen C. Harrison.

 

Selected Publications

McCarthy KR, Watanabe A, Kuraoka M, Do KT, McGee CE, Sempowski GD, Schmidt AG, Kelsoe G, Harrison SC (2017) Human Memory B cells The Cross-React with Group 1 and Group 2 Influenza A Viruses. Immunity. 48: 174-184

 

Raymond DD, Bajic G, Ferdman J, Suphaphiphat P, Settembre E, Moody MA, Schmidt AG, Harrison SC. (2018) Conserved epitope on influenza-virus hemagglutinin head defined by a vaccine-induced antibody. PNAS 17154711: 1-6.

 

Raymond DD, Stewart S, Lee J, Ferdman J, Bajic G, Do KT, Ernandes MJ, Suphaphiphat P, Settembre EC, Dormitzer PR, Del Giudice G, Finco O, Kang TH, Ippolito GC, Georgiou G, Kepler TB, Haynes BF, Moody MA, Liao H-X, Schmidt AG, Harrison SC (2016) Influenza immunization elicits hemagglutinin receptor-site antibodies specific for an egg-adapted vaccine strain. Nature Medicine. 10.1038: 1-7.

 

Kuraoka M, Schmidt AG, Nojima, T, Feng F, Watanabe A, Kitamura D, Harrison SC, Kepler TB and Kelsoe G (2016) B-cell selection in germinal centers elicited by complex antigens. Immunity, 44 1-11.

 

Schmidt AG, Khoi KT, McCarthy KR, Kepler TB, Liao HX, Moody MA, Haynes BF and Harrison SC (2015) Immunogenic stimulus for germline precursors of influenza-specific antibodies Cell Reports, 13 2842-50.

 

Schmidt AG, Therkelsen MD, Stewart S, Kepler TB, Liao HX, Moody MA, Haynes BF and Harrison SC (2015) Viral receptor-binding site antibodies with diverse germline origins. Cell 161 1026-34.

 

Schmidt AG*, Xu H*, Khan AR, O’Donnell T, Khurana S, King LR, Manischewitz J, Golding H, P. Suphaphiphat P, Carfi, A, Settembre EC, Dormitzer PR, Kepler TB, Zhang R-J, Moody MA, Haynes BF, Liao HX, Shaw DE and Harrison SC (2013) Preconfiguration of the antigen-binding site during affinity maturation of a broadly neutralizing influenza antibody PNAS 110 (1) 264-269.

 

Schmidt AG, Lee K, Yang PL and Harrison SC (2012) Small-molecule inhibitors of dengue-virus entry. PLoS Pathogens 8 (4): 1-10.

 

Schmidt AG, Yang PL and Harrison SC (2010) Peptide inhibitors of flavivirus entry derived from the E protein stem. J Virol. 2010 Dec; 84 (24):12549-54.

 

Schmidt AG, Yang PL, and Harrison SC (2010). Peptide Inhibitors of Dengue-Virus Entry Target a Late Stage Fusion Intermediate. PLoS Pathogens (6 ) 4.


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