ZiZhang Sheng, PhD

Profile Headshot

Overview

Academic Appointments

  • Assistant Professor of Medical Sciences (in Medicine) at CUMC

Languages

  • Chinese

Gender

  • Male

Credentials & Experience

Education & Training

  • BA, 2006 Biotechnology, Department of Life Science, Shandong Normal University
  • PhD, 2011 Cell Biology, Kunming Institute of Zoology, Chinese Academy of Science
  • Fellowship: 2013 Department of Chemistry and Biochemistry, South Dakota State University
  • Fellowship: 2014 Department of Biochemistry and Molecular Biophysics, Columbia University
  • Fellowship: 2020 Zuckerman Mind Brain Behavior Institute, Columbia University

Research

The Sheng lab uses interdisciplinary approaches to elucidate the mechanisms of humoral immune response to infection and to understand the role of B cells in autoimmunity.

 

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

 

  • Immune response to infection and vaccination: We develop computational methods to study immune responses of humans and animal models. In collaboration with labs at ADARC, we sequence viral antigen-specific B cell receptors (BCRs) to identify immune signatures of infections including HIV-1, SARS-CoV-2, and influenza. Our research reveals a class of IGHV1-2 derived neutralizing antibodies that are potent and prevalent in human response to SARS-CoV-2. In collaboration with the Vaccine Research Center at NIH, we study the longitudinal maturation trajectories of broadly HIV-1 neutralization antibodies (bnAbs) following sequential or/and cocktail immunizations. Our studies reveal distinct roles of different immunogens for bnAb potency and breadth development, which provide information for optimizing HIV-1 vaccine strategy.
  • Learning how nature designs antibody: Accumulation of somatic hypermutation is critical for antibody affinity maturation, but our current understanding on structural and functional roles of somatic hypermutation is still limited. We have been developing a platform to incorporate bioinformatics (BCR repertoire, molecular dynamics simulation, molecular evolution, etc.) and biochemical approaches to elucidate structural basis of modulation of antibody affinity by somatic hypermutation. The findings will be used to develop knowledge-based methods to engineer therapeutic antibodies.
  • B cells in autoimmune diseases and cancers: Self-reactive B cells appear in many autoimmune 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 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 Systemic Lupus Erythematosus, Myelin oligodendrocyte glycoprotein antibody disease, and IgA Nephropathy. We also apply similar approaches to study functional roles of B cells in liver tumor micro-environment.

Selected Publications

  • 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 AntibodyCell 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)