Joshua Tan, Ph.D.

Senior Investigator

Antibody Biology Unit

NIAID/DIR

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5625 Fishers Lane
Room 4N-07
Rockville, MD 20852

301-761-5330

joshuahoongyu.tan@nih.gov

Research Topics

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 diseases with substantial burden globally or in the United States.

ABU has two main objectives:

  1. Investigate the use of monoclonal antibodies for the prevention of infection and as tools for immunogen 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 immunogens. The most potent antibodies will also be considered as candidates to prevent infection in early-phase clinical trials.
  2. Study basic antibody biology: The sequences of monoclonal antibodies isolated from an immunized 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.

Biography

Dr. Tan received his Ph.D. from the University of Oxford, England. His Ph.D. work focused on the identification of unusual LAIR1-containing human monoclonal antibodies targeting antigens on Plasmodium falciparum-infected erythrocytes. After his Ph.D., he was awarded a Sir Henry Wellcome Postdoctoral Fellowship to continue his work on human monoclonal antibodies against human-infecting pathogens. He joined the Laboratory of Immunogenetics as an investigator in 2020.

Selected Publications

  1. Wang LT, Cooper AJR, Farrell B, Miura K, Diouf A, Müller-Sienerth N, Crosnier C, Purser L, Kirtley PJ, Maciuszek M, Barrett JR, McHugh K, Ogwang R, Tucker C, Li S, Doumbo S, Doumtabe D, Pyo CW, Skinner J, Nielsen CM, Silk SE, Kayentao K, Ongoiba A, Zhao M, Nguyen DC, Lee FE, Minassian AM, Geraghty DE, Traore B, Seder RA, Wilder BK, Crompton PD, Wright GJ, Long CA, Draper SJ, Higgins MK, Tan J. Natural malaria infection elicits rare but potent neutralizing antibodies to the blood-stage antigen RH5. Cell. 2024.
  2. 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;377(6607):728-735.
  3. Dacon C, Peng L, Lin TH, Tucker C, Lee CD, Cong Y, Wang L, Purser L, Cooper AJR, Williams JK, Pyo CW, Yuan M, Kosik I, Hu Z, Zhao M, Mohan D, Peterson M, Skinner J, Dixit S, Kollins E, Huzella L, Perry D, Byrum R, Lembirik S, Murphy M, Zhang Y, Yang ES, Chen M, Leung K, Weinberg RS, Pegu A, Geraghty DE, Davidson E, Doranz BJ, Douagi I, Moir S, Yewdell JW, Schmaljohn C, Crompton PD, Mascola JR, Holbrook MR, Nemazee D, Wilson IA, Tan J. Rare, convergent antibodies targeting the stem helix broadly neutralize diverse betacoronaviruses. Cell Host Microbe. 2023;31(1):97-111.e12.
  4. 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;13(616):eabj5413.
  5. 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;13(599).

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This page was last updated on Tuesday, February 25, 2025