Bei Yang, PhDAssistant Professor

Our recent research are briefed below.

1. Though structure-guided protein engineering, we contributed to the development of several high-precision gene editing tools (Cell Res., 2017; Nat. Biotechnol., 2018a; Nat. Biotechnol., 2018b; Cell Rep., 2020; Nat. Cell Biol., 2021; Nat. Commun., 2022). We are now actively exploring the application potential of these gene editing tools in genetic diseases and high-risk infectious diseases. Recently, we and our collaborators used transformer base editor (tBE) to disrupt transcription factor binding motifs in hematopoietic stem cells, thereby reactivating the silenced γ-globin expression for β-thalassemia treatment (Cell Stem Cell, 2023). 

Figure 1. tBE-mediated editing of the HBG promoter induces potent fetal hemoglobin expression in HSPCs.

2. Env proteins are the focus of HIV-1 vaccine development. We investigated the structures and immune recognition of the Envs from Asia prevalent HIV-1 subtypes (i.e., CRF01_AE and CRF07_BC), revealed the unique features of their V1 regions and associated them with certain bNAbs resistance, and unraveled the epitope and unique working mechanism of a bNAb from CRF01_AE infected individuals (Nat. Commun., 2023). These findings broaden our understanding of Asia prevalent HIV-1 subtypes and shed lights on future immunofocusing HIV-1 vaccine design.

Figure 2. Structural and immunogenic understanding of Envs from CRF subtypes.

3. By performing detailed and comparative analysis on the fusion core structures of α-and β-human coronaviruses (HCoVs), we revealed the commons and differences among the HR1s from different HCoVs. Built upon the knowledge gained and collaborating with a team of virologists from Fudan University, we then successfully developed a pan-coronavirus (pan-CoV) inhibitor EK1, which blocks the host entry process of multiple HCoVs in vitro & in vivo by functioning as a HR2 mimicry targeting their HR1s (Sci. Adv., 2019). Most recently, we further unraveled the antigenic landscape of α-HCoV spike protein to provide clues for the development of broadly effective CoV vaccines (Commun. Biol., 2022) and explored using high-precision genome editing tool, PE, to accurately ablate the virus-related roles of host factors while preserving their physiological functions to provide long-lasting, broad-spectrum antiviral effects (Medcomm, 2023). 

4. 3C protein is one of the drug development focuses of Enterovirus, yet its hydrophilic protease active center has frustrated previous drug discovery efforts. Using an integrative approach which combines mass spectrometry and x-ray crystallography, we identified unique sites of therapeutic vulnerability on 3C and demonstrated that 3C plays an important regulatory role in enteroviruses genome replication and that this unexplored role could serve as a novel antiviral intervention opportunity against enterovirus infections (Proc. Natl. Acad. Sci. U.S.A., 2020). We are now screening for lead compounds against this newly discovered target site.