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Bei Yang, PhDAssistant Professor

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Email: yangbei@@shanghaitech.edu.cn

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中文信息English
Pathogenic Biology

Principal investigator

Name:

Bei YangAssistant Professor , PhD, Assistant Professor

Position:

Principle Investigator, Tenure-track Assistant Professor

Affiliation:

Honor:

Oriental Talents Program

Education Background:
  • 2000/09-2004/06, National Talents training program, College of Life Science, Wuhan University, B.S.
  • 2004/09-2010/07, Shanghai Institute of Biochemistry and Cell Biology (SIBCB), Chinese Academy of Sciences (CAS), Ph.D.
Working Experience:
  • 2010/08-2013/06, National Institutes of Health (NIH), Postdoctoral Fellow
  • 2013/07-2015/07, University of California at Berkeley, Postdoctoral Fellow
  • 2015/11-2020/09, Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, Research Associate Professor
  • 2020/10-Present, Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, PI
  • 2020/10-Present, School of Life Science and Technology, ShanghaiTech University, Tenure-track Assisitant Professor

Group Introduction

Research Area:
infectious diseases, rare hereditary diseases
Research Interests:

We use an array of different methods, including cryo-EM, mass spectrometry, high-throughput screening, animal models etc., to investigate biological questions with clinical significance. We study the molecular basis of a range of high-risk infectious diseases (e.g. AIDS) and genetic diseases (e.g. β-thalassemia), as well as gene editing tools, so as to identify novel therapeutic and preventive opportunities. On top of the basic research, we also seek to translate gained knowledge into the development of preventive and therapeutic interventions including gene therapies and mRNA vaccines.


Group Website:

Research Achievement

Our representative research achievements are briefed below:

1.  Development and application of gene editing tools: In recent years, nuclear and mitochondrial base editors have been developed by coupling the “locators” like CRISPR/Cas9 or TALE proteins with the “effectors” like APOBEC or DddA to enable base substitutions at defined sites in nuclear and mitochondrial genomes. However, the first-generation of such editors exhibited certain levels of off-target and bystander editing, limiting their broad application in both research and clinical settings. In the past, we have leveraged our expertise in protein engineering to contribute in the development of several high-precision nuclear genome editing tools, including a transformer base editor (tBE) with no detectable off-target effect (Nat Cell Biol, 2021). More recently, we captured the structural snapshots of DdCBE, the mitochondrial base editor, targeting two native mitochondrial gene loci, thus revealing the structural determinants of its editing window. Based on the mechanistic insights, we then developed a “WinPred” model to guide TALE-recognition region and spacer length design and engineered a high-precision variant of DdCBE, i.e., aDdCBE with a 2~3 nt editing window and minimal off-target mutations. Further application of the WinPred model and aDdCBE enabled near single-nucleotide editing at multiple target sites and allowed faithful modelling of Leber hereditary optic neuropathy disease-related mutations (Mol Cell, 2025) (Fig.1). Besides gene editing tools development, we are also actively exploring their application in high-risk infectious disease prevention and hereditary diseases treatment. For instance, we and our collaborators used tBE to disrupt transcription factor binding motifs in the promoter region of γ-globin in hematopoietic stem cells, thereby reactivating the silenced γ-globin expression for β-thalassemia treatment (Cell Stem Cell, 2023). 

Fig.1| Structure-guided development of high-precision mitochondrial base editors

2. Vaccine targets Identification: Revealing conserved immune vulnerabilities in potential immunogens is essential for effective and broad-spectrum vaccine development. The trimeric Env protein on HIV-1 particles has long been the focus of AIDS vaccine design. However, its substantial sequence variability across HIV-1 subtypes and extensive glycosylation together impeded vaccine development for decades. To enable the application of state-of-the-art “epitope-focusing” vaccine strategy on HIV-1, we characterized the structural and immunogenic landscape of Env proteins from Asia prevalent HIV-1 subtypes, CRF01_AE and CRF07_BC. Our work identified CRF01_AE-specific features in the Env V1 region (Fig. 2A–B), uncovered their association with resistance to certain broadly neutralizing antibodies (bNAbs) (Fig. 2C–D), and revealed a novel neutralization mechanism of the first bNAb isolated from a CRF01_AE-infected individual (Fig. 2E) (Nat Commun, 2023). These findings expanded our understanding of Asia-prevalent HIV-1 subtypes and shed lights on future “epitope-focusing” HIV-1 vaccine design. Meanwhile, to better prepare for potential emergent coronaviruses, i.e., “HCoV-X”, we mapped the antigenic landscape of α-coronavirus spike proteins and revealed both conserved and divergent antigenic features across human coronaviruses, thus providing clues for future development of broadly effective coronavirus vaccines (Commun Biol, 2022).

Fig.2| Structural and immunogenic understanding of Envs from CRF subtypes

3.  Drug targets identification and inhibitors screening: Compared to the huge health and economic burden imposed by Enterovirus infections on society, the countermeasures have fallen short. Viral 3C protease is one of the drug development focuses of Enterovirus, yet its protease active center has frustrated previous drug discovery efforts. Using an integrative approach which combines mass spectrometry and X-ray crystallography, we demonstrated that 1) the protease activity of 3C could be modulated allosterically and 2) 3C plays a regulatory role in enteroviruses genome replication by binding to the 5’NCR of viral genome. Notably, both the allosteric site and the 5'NCR-binding site on 3C are highly conserved and locate away from the protease active center, making them attractive broad-spectrum drug targets for enterovirus infection control (PNAS, 2020). In silico screening of 143,621 natural products against the allosteric site further identified dihydromyricetin (DHM), a natural product that can broadly binds and allosterically inhibits the protease activities of 3C proteins from multiple enteroviruses. Notably, DHM shows minimal cytotoxicity and potent antiviral efficacy in different cell models, exhibiting a selective index exceeding 700. These findings establish DHM as a unique, broad-spectrum allosteric inhibitor of Enterovirus 3C proteases and underscore its potential as a promising candidate for the development of pan-enterovirus antivirals (Adv Biol, 2025).



Representative Publications (*First Author, # Corresponding Author)

Monograph

Patent

Funding

  • 1. 2024-General Program, Natural Science Foundation of China, Leader
  • 2. 2023-General Program, Science and Technology Commission of Shanghai Municipality, Leader
  • 3. 2023-Major Program , Ministry of Science and Technology of China, Participator
  • 4. 2021-General Program, Natural Science Foundation of China, Leader
  • 5. 2019-Key Program , Ministry of Science and Technology of China, Participator
  • 6. 2018-Major Program , Ministry of Science and Technology of China, Participator
  • 7. Youth Program, Natural Science Foundation of China, Leader

Awards

  • 1. 2023, Oriental Talents Program
  • 2. 2016, Pujiang Talents Program

Research Achievement

Group Member and Photo

  • Name:Qilian Qi
    Position:Engineer
    Duration:2016/01~present
    Email:qiql@@shanghaitech.edu.cn
  • Name:Xianfang Zhang
    Position:Engineer
    Duration:2016/07~present
    Email:zhangxf1@@shanghaitech.edu.cn
  • Name:Qi Wang
    Position:Doctoral Student
    Duration:2020 ~ present
    Email:wangqi3@@shanghaitech.edu.cn
  • Name:Yanxin Luo
    Position:Doctoral Student
    Duration:2021 ~ present
    Email:luoyx1@@shanghaitech.edu.cn
  • Name:Yaofeng Hou
    Position:Doctoral Student
    Duration:2022 ~ Present
    Email:houyf2022@@shanghaitech.edu.cn
  • Name:Qiang Wang
    Position:Doctoral Student
    Duration:2023 ~ present
    Email:wangqiang2023@@shanghaitech.edu.cn
  • Name:Jiayan Chen
    Position:Doctoral Student
    Duration:2023 ~ present
    Email:chenjy22023@@shanghaitech.edu.cn
  • Name:Xiaomeng He
    Position:Postgraduate Student
    Duration:2024-Now
    Email:hexm2024@@shanghaitech.edu.cn
  • Name:Xiaotian Chen
    Position:Postgraduate Student
    Duration:2024-Now
    Email:chenxt2024@@shanghaitech.edu.cn
  • Name:Xindi Shang
    Position:Postgraduate Student
    Duration:2024-Now
    Email:shangxd2024@@shanghaitech.edu.cn
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