Sheng Lab

Principal Investigator

The Sheng lab uses interdisciplinary approaches to elucidate the mechanisms of humoral immune response to infection and vaccine and to understand the role of autoantibodies in autoimmunity. Since joining ADARC, Dr. Sheng has co-authored 53 papers in high-impact journals (Nature, Cell, Immunity, Arthritis Rheumatology, Cell Reports, etc.) with over 9,000 citations (Google Scholar) and 13 funding awards from NIH and private foundations.

Currently, the Sheng lab focuses on three areas of research: 

Immune response to infection and vaccination. 

We sequence antigen-specific antibody repertoire and develop antibodyomics methods to study immune responses of humans and animal models. The goals are to identify signatures and epitopes of antibody responses to infectious diseases and vaccines, elucidate the mechanisms of antibody affinity maturation and neutralization, and determine immune features associated with protection. The knowledge we obtained from these studies will guide vaccine design and protection efficacy evaluation. The pathogens we currently study include HIV-1, malaria, influenza, and SARS-CoV-2.

Origin of autoreactive B cells.

Self-reactive B cells appear in many autoimmune and infectious diseases and play an important role in disease progression. But how auto-reactive B cells escape immune surveillance and develop is still poorly characterized. To address this question, we apply single cell BCR sequencing technology to isolate and characterize genetic features of auto-reactive BCRs and to investigate their longitudinal development trajectories. We also perform single cell transcriptome sequencing to identify disease associated B cell populations and cellular factors. Currently, we are studying autoantibodies in HIV infection, Systemic Lupus Erythematosus, and IgA Nephropathy. For example, the Dong et al. study identified early B cell developmental aberrations that modulate the emergence of autoreactive B cells in systemic lupus erythematosus (SLE), offering new clues to disease pathogenesis and pointing to potential targets for therapeutic intervention.

Antibody-antigen interaction. 

Mechanisms like V(D)J recombination, heavy-light chain pairing, and somatic hypermutation generate vast antibody diversity, but predicting antibody binding affinity and specificity remains a major challenging. We have been developing algorithms to incorporate bioinformatics (BCR repertoire, molecular dynamics simulation, molecular evolution, nanopore sequencing, deep learning, etc.) and biochemical approaches to study the principles underlying antibody and antigen interaction, predict antibody neutralization potency, design immunogens, and optimize therapeutic antibodies. Our characterization of SARS-CoV-2 neutralizing antibodies and their co-evolution with the virus uncovered key mechanisms of viral escape from antibody recognition, provided critical mechanistic insight into the durability and breadth of immunity, helping to guide timely surveillance strategies during a rapidly evolving global pandemic.

Join Our Team

A bioinformatics Postdoctoral Research Fellow position is open in the Sheng lab.

Lab Members

Select Publications

  • Zizhang Sheng*, Qin Xiao, Yujie Qiao, Hong Lu, Joseph McWhirter, Manish Sagar, Xueling Wu. NanoHIVSeq: A Long-Read Bioinformatics Pipeline for High-Throughput Processing of HIV Env Sequences. bioRxiv. 2026.02. 17.706429

  • Yicheng Guo, Eric Waltari , Hong Lu, Zizhang Sheng* and Xueling Wu*. Novel rhesus macaque immunoglobulin germline genes identified by three sequencing approaches. Front. Immunol. 15:1506348. doi: 10.3389/fimmu.2024.1506348.

  • Chen Dong, Yicheng Guo, Zechuan Chen, Teng Li, Juan Ji, Chi Sun, Jing Li, Haixia Cao, Yunfei Xia, Zhonghui Xue, Xixi Gu, Qian Liang, Rui Zhao, Ting Fu, Jiaqiang Ma, Shan Jiang, Chunmei Wu, Qiong Fu, Genkai Guo, Yanfeng Bao, Hua Guo, Junling Yang, Min Xu, Xiaoming Zhang*, Zizhang Sheng*, Zhifeng Gu*. Single-Cell Profiling of Bone Marrow B Cells and Early B Cell Developmental Disorders Associated With Systemic Lupus Erythematosus. Arthritis Rheumatol. 2024 Apr;76(4):599-613. doi: 10.1002/art.42750. PubMed PMID: 37946666.

  • Zizhang Sheng*, Jude S Bimela, Maple Wang, Zhiteng Li, Yicheng Guo, David D Ho. An optimized thermodynamics integration protocol for identifying beneficial mutations in antibody design. Frontiers in Immunology. 14: 1190416, 2023.

  • Gabriele Cerutti, Yicheng Guo, Lihong Liu, Liyuan Liu, Zhening Zhang, Yang Luo, Yiming Huang, Harris H Wang, David D Ho, Zizhang Sheng*, Lawrence Shapiro. Cryo-EM structure of the SARS-CoV-2 omicron spike. Cell Reports. 38 (9), 110428 2022. 

  • Zizhang Sheng, Jude S Bimela, Phinikoula S Katsamba, Saurabh D Patel, Yicheng Guo, Haiqing Zhao, Youzhong Guo, Peter D Kwong, Lawrence Shapiro. Structural basis of antibody conformation and stability modulation by framework somatic hypermutation. Front. Immunol. 5573, 2022. 

  • Gabriele Cerutti, Yicheng Guo, Pengfei Wang, Manoj S Nair, Maple Wang, Yaoxing Huang, Jian Yu, Lihong Liu, Phinikoula S Katsamba, Fabiana Bahna, Eswar R Reddem, Peter D Kwong, David D Ho, Zizhang Sheng*, Lawrence Shapiro. Neutralizing antibody 5-7 defines a distinct site of vulnerability in SARS-CoV-2 spike N-terminal domain. Cell Reports. 37 (5). 2021. 

  • Micah Rapp, Yicheng Guo, Eswar R Reddem, Jian Yu, Lihong Liu, Pengfei Wang, Gabriele Cerutti, Phinikoula Katsamba, Jude S Bimela, Fabiana A Bahna, Seetha M Mannepalli, Baoshan Zhang, Peter D Kwong, Yaoxing Huang, David D Ho, Lawrence Shapiro, Zizhang Sheng. Modular basis for potent SARS-CoV-2 neutralization by a prevalent VH1-2-derived antibody class. Cell Reports. 35 (1), 108950. (2021) 

  • Yicheng Guo, Peter D. Kwong, Lawrence Shapiro, Zizhang Sheng. cAb-Rep: a database of curated antibody repertoires for exploring B cell response and predicting antibody prevalence. Frontiers in Immunology 2356 (2019)

  • Rui Kong*, Hongying Duan*, Zizhang Sheng*, Kai Xu*, Priyamvada Acharya*, Xuejun Chen*, Cheng Cheng*, Gwo-Yu Chuang*, Adam S. Dingens*, Jason Gorman*, Mallika Sastry*, Chen-Hsiang Shen*, Baoshan Zhang*, Tongqing Zhou*, Alexander J. Jafari, Mark K. Louder, Sijy O’Dell1, Ariana P. Rowshan, Elise G. Viox, Cara W. Chao, Chang W. Choi, Martin M. Corcoran, Angela R. Corrigan, Venkata P. Dandey, Edward T. Eng, Hui Geng, Kathryn E. Foulds, Ying Gu, Yicheng Guo, Young D. Kwon, Bob Lin, Kevin Liu, Rosemarie D. Mason, Martha C. Nason, Tiffany Y. Ohr, Li Ou, Reda Rawi, Edward K. Sarfo, Arne Schön, John P. Todd, Shuishu Wang, Yiran Wang, Hui Wei, Winston Wu, NISC Comparative Sequencing Program, James C. Mullikin, Robert T. Bailer, Nicole A. Doria-Rose, Gunilla B. Karlsson Hedestam, Diana G. Scorpio, Julie Overbaugh, Jesse D. Bloom, Bridget Carragher, Clint S. Potter, Lawrence Shapiro, Peter D. Kwong, and John R. Mascola. Antibody Lineages with Vaccine-Induced Antigen- Binding Hotspots Develop Broad HIV Neutralization. Cell, 178:1-18, 2019 

  • Zizhang Sheng*, Chaim A. Schramm*, Rui Kong, NISC Comparative Sequencing Program, James C. Mullikin, John R. Mascola, Peter D. Kwong, and Lawrence Shapiro. Gene-specific substitution profiles describe the types and frequencies of amino acid changes during antibody somatic hypermutation. Front. Immunol. 8:537. doi: 10.3389/mmu.2017.00537 (2017). 

  • Chaim A. Schramm*, Zizhang Sheng*, Zhenhai Zhang*, John R. Mascola, Peter D. Kwong, and Lawrence Shapiro. SONAR: A high-throughput pipeline for detecting antibody ontogenies in longitudinal deep-sequencing data. Front. Immunol., 7-372, (2016)

  • Zizhang Sheng, Chaim Schramm, Mark Connors, Lynn Morris, John R. Mascola, Peter D. Kwong, and Lawrence Shapiro. Effects of Darwinian selection and mutability on rate of broadly neutralizing antibody evolution during HIV-1 infection. PLoS Comp Bio 12 (5), e1004940, (2016)

  • Mattia Bonsignori*, Tongqing Zhou*, Zizhang Sheng*, Lei Chen*, Feng Gao, M. Gordon Joyce, Gabriel Ozorowski, Gwo-Yu Chuang, Chaim A. Schramm, Kevin Wiehe, S. Munir Alam, Todd Bradley, Morgan Gladden, Kwan-Ki Hwang, Sheelah Iyengar, Amit Kumar, Xiaozhi Lu, Kan Luo, Michael Mangiapani, Robert J. Parks, Hongshuo Song, Priyamvada Acharya, Robert T. Bailer, Allen Cao, Aliaksandr Druz, Ivelin S. Georgiev, Young D. Kwon, Mark K. Louder, Xueling Wu, Baoshan Zhang, Anqi Zheng, Brenna J. Hill, Rui Kong, Cinque Soto, NISC Comparative Sequencing Program, James C. Mullikin, Daniel C. Douek, David C. Montefiori, Michael A. Moody, George M. Shaw, Beatrice H. Hahn, Garnett Kelsoe, Peter T. Hraber, Bette T. Korber, Scott D. Boyd, Andrew Z. Fire, Thomas B. Kepler, Lawrence Shapiro, Andrew B. Ward, John R. Mascola, Hua-Xin Liao, Peter D. Kwong and Barton F. Haynes. Maturation Pathway from Germline to Broad HIV-1 Neutralizer of a CD4-Mimicking Antibody. Cell 165(2):449-63. (2016). 

  • Xueling Wu*, Zhenhai Zhang*, Chaim A. Schramm*, M. Gordon Joyce*, Young Do Kwon*, Tongqing Zhou*, Zizhang Sheng*, Baoshan Zhang, Sijy O’Dell, Krisha McKee, Ivelin S. Georgiev, Gwo-Yu Chuang, Nancy S. Longo, Rebecca M. Lynch, Kevin O. Saunders, Cinque Soto, Sanjay Srivatsan, Yongping Yang, Robert T. Bailer, Mark K. Louder, NISC Comparative Sequencing Program, James C. Mullikin, Mark Connors, Peter D. Kwong, John R. Mascola, and Lawrence Shapiro. Maturation and diversity of the VRC01-antibody lineage over 15 years of chronic HIV-1 infection. Cell, 161(3), 470-85. (2015).

  • Joseph R. Francica*, Zizhang Sheng*, Zhenhai Zhang, Yoshiaki Nishimura, Masashi Shingai, Akshaya Ramesh, Brandon F. Keele, Stephen D. Schmidt, Barbara J. Flynn, Sam Darko, Rebecca M. Lynch, Takuya Yamamoto, Rodrigo Matus-Nicodemos, David Wolinsky, NISC Comparative Sequencing Program, Martha Nason, Nicholas M. Valiante, Padma Malyala, Ennio De Gregorio, Susan W. Barnett, Manmohan Singh, Derek T. O’Hagan, Richard A. Koup, John R. Mascola, Malcolm A. Martin, Thomas B. Kepler, Daniel C. Douek, Lawrence Shapiro,  Robert A. Seder. Analysis of immunoglobulin transcripts and hypermutation following SHIV(AD8) infection and protein-plus-adjuvant immunization. Nature Communications, 6, 6565. (2015)

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