Structural Biology Section
Tongqing Zhou, Ph.D.
Chief, Structural Virology and Vaccinology Section
Chief, Structural Bioinformatics Core
Chief, Structural Biology Section
Earl-Stadtman Tenure-Track Investigator
Contact: tzhou@mail.nih.gov
Major Areas of Research
- Cryo-EM and X-ray crystallographic structural analysis of proteins
- Analysis of immune responses by EM polyclonal epitope mapping (EMPEM)
- Expression and purification of viral proteins and antibodies
- Biochemical and biophysical characterization of protein interactions
- Development and production of novel protein probes for B cell analysis
Program Description
The Structural Biology Section is dedicated to meeting the structural biology needs of the Vaccine Research Center. Its mission is to provide comprehensive support for understanding the atomic-level details underlying viral entry, viral-host interaction and immune responses, contributing directly to the design and development of vaccines and therapeutics.
A primary focus of the core is conducting detailed structural analyses of proteins using advanced techniques such as cryo-electron microscopy (cryo-EM) and X-ray crystallography. These methods allow for the visualization of proteins at near-atomic resolution, offering critical insights into their structure and function. Such structural information is instrumental in guiding vaccine design, particularly in identifying and stabilizing key viral targets.
The core also plays a crucial role in the analysis of immune responses. Through the use of electron microscopy polyclonal epitope mapping (EMPEM), the core examines how antibody responses develop and where they target on viral proteins. This approach provides a deeper understanding of the specificity and breadth of immune responses, which is essential for evaluating the efficacy of vaccine candidates and designing immunogens capable of eliciting broadly neutralizing antibodies.
In addition to structural analysis, the core specializes in the expression and purification of viral proteins and antibodies. These high-quality materials are essential for both structural studies and functional assays, ensuring the accuracy and reproducibility of experiments. The core also conducts biochemical and biophysical characterizations of protein interactions and is equipped with advanced instruments, such as Biacore 8K, Carterra, and Nicoya Alto for Surface Plasmon Resonance and Octet for Biolayer Interferometry.
A distinctive strength of the core is its ability to develop and produce novel protein probes for B cell analysis. These innovative biotinylated proteins are designed to identify and characterize B cells that produce specific antibodies, providing critical data for vaccine development, antibody discovery and the study of immune responses.
Through its multifaceted expertise, the Structural Biology Section is dedicated to advancing the field of structural biology in service of vaccine research. By combining cutting-edge technology with a deep understanding of structural biology, the core aims to play an integral role in the fight against infectious diseases, contributing to the development of life-saving vaccines and therapeutics.
Biography
Education
Ph.D., 1994, Chinese Academy of Sciences, Beijing, China
M.S., 1999, Wayne State University, Detroit, MI
B.S., 1989, Wuhan University, Wuhan, China
Dr. Tongqing Zhou earned his Ph.D. in cell biology from the Chinese Academy of Sciences in 1994 and an M.Sc. in electronic and computer controlled systems from Wayne State University School of Engineering in 1999. From 1995 to 2001, he completed postdoctoral training at Wayne State University School of Medicine, specializing in structural biology. In 2001, Dr. Zhou joined the Dale and Betty Bumpers Vaccine Research Center, and in 2024, he was appointed as an NIH Earl Stadtman Tenure-Track Investigator.
Dr. Zhou has led pioneering research in applying structural biology to uncover the mechanisms of viral-host interactions, immune evasion, antibody neutralization, and antibody-guided, structure-based immunogen design. His work has significantly advanced our understanding of viral envelope conformations and sites of vulnerability across a range of viral pathogens, including HIV-1, RSV, influenza, HMPV, HPIV, and SARS-CoV-2. Dr. Zhou’s contributions have earned him multiple NIH Director’s Awards, NIAID Merit Awards, and recognition as a Clarivate Analytics Highly Cited Researcher in Microbiology since 2014.
Selected Publications
Abu-Shmais AA, Freeman G, Creanga A, Vukovich MJ, Malla T, Mantus GE, Shimberg GD, Gillespie RA, Guerra Canedo V, Dadonaite B, Rodgers MD, Chopde AJ, Bardwil-Lugones E, Bylund T, Henry AR, Roberts-Torres J, Johnston TS, Smith S, Yang ES, Cheng C, Walker EL, Ravichandran M, Gordon IJ, Dittakavi TS, Reed DS, Pierson TC, Dropulic L, Bloom JD, Tsybovsky Y, Boritz EA, Douek DC, Zhou T, Kanekiyo M, Andrews SF. Cross-neutralizing and potent human monoclonal antibodies against historical and emerging H5Nx influenza viruses. Nat Microbiol. 2025 Nov;10(11):2903-2918.
Madel Alfajaro M, Keeler EL, Li N, Catanzaro NJ, Teng IT, Zhao Z, Grunst MW, Yount B, Schäfer A, Wang D, Kim AS, Synowiec A, Peña-Hernández MA, Zepeda S, Arinola R, Kaur R, Menasche BL, Wei J, Russell GA, Huck J, Song J, Ring A, Iwasaki A, Jangra RK, Lee S, Martinez DR, Mothes W, Uchil PD, Doench JG, Spaulding AB, Baric RS, Serebryannyy L, Tsybovsky Y, Zhou T, Douek DC, Wilen CB. HKU5 bat merbecoviruses engage bat and mink ACE2 as entry receptors. Nat Commun. 2025 Jul 24;16(1):6822.
Cheng J, Krug PW, Lei H, Moss DL, Lang ZC, Morton AJ, Shen CH, Pletnev S, Huang RK, Pierson TC, Zhou T, Ruckwardt TJ, Kwong PD. Structural insights from vaccine candidates for EV-D68. Commun Biol. 2025 Jun 4;8(1):860.
Wang H, Cheng C, Dal Santo JL, Shen CH, Bylund T, Henry AR, Howe CA, Hwang J, Morano NC, Morris DJ, Pletnev S, Roark RS, Zhou T, Hansen BT, Hoyt FH, Johnston TS, Wang S, Zhang B, Ambrozak DR, Becker JE, Bender MF, Changela A, Chaudhary R, Corcoran M, Corrigan AR, Foulds KE, Guo Y, Lee M, Li Y, Lin BC, Liu T, Louder MK, Mandolesi M, Mason RD, McKee K, Nair V, O'Dell S, Olia AS, Ou L, Pegu A, Raju N, Rawi R, Roberts-Torres J, Sarfo EK, Sastry M, Schaub AJ, Schmidt SD, Schramm CA, Schwartz CL, Smith SC, Stephens T, Stuckey J, Teng IT, Todd JP, Tsybovsky Y, Van Wazer DJ, Wang S, Doria-Rose NA, Fischer ER, Georgiev IS, Karlsson Hedestam GB, Sheng Z, Woodward RA, Douek DC, Koup RA, Pierson TC, Shapiro L, Shaw GM, Mascola JR, Kwong PD. Potent and broad HIV-1 neutralization in fusion peptide-primed SHIV-infected macaques. Cell. 2024 Dec 12;187(25):7214-7231.e23.
Zhou T, Wang L, Misasi J, Pegu A, Zhang Y, Harris DR, Olia AS, Talana CA, Yang ES, Chen M, Choe M, Shi W, Teng IT, Creanga A, Jenkins C, Leung K, Liu T, Stancofski ED, Stephens T, Zhang B, Tsybovsky Y, Graham BS, Mascola JR, Sullivan NJ, Kwong PD. Structural basis for potent antibody neutralization of SARS-CoV-2 variants including B.1.1.529. Science. 2022 Apr 22;376(6591):eabn8897.
Zhou T, Teng IT, Olia AS, Cerutti G, Gorman J, Nazzari A, Shi W, Tsybovsky Y, Wang L, Wang S, Zhang B, Zhang Y, Katsamba PS, Petrova Y, Banach BB, Fahad AS, Liu L, Lopez Acevedo SN, Madan B, Oliveira de Souza M, Pan X, Wang P, Wolfe JR, Yin M, Ho DD, Phung E, DiPiazza A, Chang LA, Abiona OM, Corbett KS, DeKosky BJ, Graham BS, Mascola JR, Misasi J, Ruckwardt T, Sullivan NJ, Shapiro L, Kwong PD. Structure-Based Design with Tag-Based Purification and In-Process Biotinylation Enable Streamlined Development of SARS-CoV-2 Spike Molecular Probes. Cell Rep. 2020 Oct 27;33(4):108322.