Antibody Biology Unit
Joshua Tan, Ph.D.
Chief, Antibody Biology Unit
Earl Stadtman Tenure-Track Investigator
Major Areas of Research
- Characterization of human monoclonal antibodies to infectious pathogens
- Biology of antibody response to Plasmodium falciparum, SARS-CoV-2, and Mycobacterium tuberculosis
Human monoclonal antibodies are emerging as powerful tools to combat infectious disease. At the Antibody Biology Unit (ABU), we aim to use cutting-edge technology to study B cells at the single cell level and to identify and characterize human monoclonal antibodies against a range of pathogens. The Unit currently focuses on three diseases with substantial global burden: malaria, COVID-19, and tuberculosis (TB). We have two major aims:
- To study basic antibody biology. The sequences of monoclonal antibodies isolated from a vaccinated or naturally infected individual provide a high-resolution portrait of the antibody response to a given pathogen. Information revealed includes the predominant antibody isotype that is generated, the degree of somatic mutation and affinity maturation required for the development of a potent neutralizing response, and the preferential usage of specific VH genes to mount a response against a given antigen.
- To investigate the use of monoclonal antibodies for prevention of infection and as tools for vaccine design. An array of tools including the Berkeley Lights Beacon and Carterra LSA will be used for high-throughput antibody identification and characterization. Monoclonal antibodies that are isolated will be screened in in vitro and in vivo assays to determine their potency in preventing infection. Their affinity for their targets will be measured using biophysical assays. In collaboration with structural biologists, we will identify the specific epitopes targeted by the most potent antibodies and develop these sites as novel vaccine candidates. The most potent antibodies will also be considered as candidates to prevent infection in early-phase clinical trials.
Ph.D., University of Oxford, England
Joshua Tan, Ph.D., is a Stadtman Tenure-track Investigator and an NIH Distinguished Scholar in the Division of Intramural Research of the National Institute of Allergy and Infectious Diseases. He received his Ph.D. from the University of Oxford, England. Prior to joining the NIH, he was awarded the Pfizer Research Prize for his malaria work and the Sir Henry Wellcome Postdoctoral Fellowship to investigate human monoclonal antibodies that target the malaria-causing parasite P. falcipar
Dacon C, Tucker C, Peng L, Lee CD, Lin TH, Yuan M, Cong Y, Wang L, Purser L, Williams JK, Pyo CW, Kosik I, Hu Z, Zhao M, Mohan D, Cooper AJR, Peterson M, Skinner J, Dixit S, Kollins E, Huzella L, Perry D, Byrum R, Lembirik S, Drawbaugh D, Eaton B, Zhang Y, Yang ES, Chen M, Leung K, Weinberg RS, Pegu A, Geraghty DE, Davidson E, Douagi I, Moir S, Yewdell JW, Schmaljohn C, Crompton PD, Holbrook MR, Nemazee D, Mascola JR, Wilson IA, Tan J. Broadly neutralizing antibodies target the coronavirus fusion peptide. Science. 2022 Jul 12:eabq3773.
Cho H, Gonzales-Wartz KK, Huang D, Yuan M, Peterson M, Liang J, Beutler N, Torres JL, Cong Y, Postnikova E, Bangaru S, Talana CA, Shi W, Yang ES, Zhang Y, Leung K, Wang L, Peng L, Skinner J, Li S, Wu NC, Liu H, Dacon C, Moyer T, Cohen M, Zhao M, Lee FE, Weinberg RS, Douagi I, Gross R, Schmaljohn C, Pegu A, Mascola JR, Holbrook M, Nemazee D, Rogers TF, Ward AB, Wilson IA, Crompton PD, Tan J. Bispecific antibodies targeting distinct regions of the spike protein potently neutralize SARS-CoV-2 variants of concern. Sci Transl Med. 2021 Oct 20;13(616):eabj5413.
Tan J, Cho H, Pholcharee T, Pereira LS, Doumbo S, Doumtabe D, Flynn BJ, Schön A, Kanatani S, Aylor SO, Oyen D, Vistein R, Wang L, Dillon M, Skinner J, Peterson M, Li S, Idris AH, Molina-Cruz A, Zhao M, Olano LR, Lee PJ, Roth A, Sinnis P, Barillas-Mury C, Kayentao K, Ongoiba A, Francica JR, Traore B, Wilson IA, Seder RA, Crompton PD. Functional human IgA targets a conserved site on malaria sporozoites. Sci Transl Med. 2021 Jun 23;13(599):eabg2344.
Tan J, Sack BK, Oyen D, Zenklusen I, Piccoli L, Barbieri S, Foglierini M, Fregni CS, Marcandalli J, Jongo S, Abdulla S, Perez L, Corradin G, Varani L, Sallusto F, Sim BKL, Hoffman SL, Kappe SHI, Daubenberger C, Wilson IA, Lanzavecchia A. A public antibody lineage that potently inhibits malaria infection through dual binding to the circumsporozoite protein. Nat Med. 2018 May;24(4):401-407.
Pieper K, Tan J, Piccoli L, Foglierini M, Barbieri S, Chen Y, Silacci-Fregni C, Wolf T, Jarrossay D, Anderle M, Abdi A, Ndungu FM, Doumbo OK, Traore B, Tran TM, Jongo S, Zenklusen I, Crompton PD, Daubenberger C, Bull PC, Sallusto F, Lanzavecchia A. Public antibodies to malaria antigens generated by two LAIR1 insertion modalities. Nature. 2017 Aug 31;548(7669):597-601.
Tan J, Pieper K, Piccoli L, Abdi A, Perez MF, Geiger R, Tully CM, Jarrossay D, Maina Ndungu F, Wambua J, Bejon P, Fregni CS, Fernandez-Rodriguez B, Barbieri S, Bianchi S, Marsh K, Thathy V, Corti D, Sallusto F, Bull P, Lanzavecchia A. A LAIR1 insertion generates broadly reactive antibodies against malaria variant antigens. Nature. 2016 Jan 7;529(7584):105-109.
The Antibody Biology Unit aims to study antibody responses to infectious pathogens at the monoclonal level. Our two major goals are to study the antibody responses to vaccination and infection at high resolution, and to investigate the use of monoclonal antibodies for prevention of infection or as tools for vaccine design.