Introduction
Research in this lab is biological question driven. This means that we would not be limited by technique hurdles, instead we use an array of different methods, such as x-ray crystallography, mass spectrometry, cryo-EM, SAXS, biochemical reconstitution, high-throughput screening, deep sequencing, in vitro & in vivo evaluation etc., to tackle biological questions with clinical significance. Training in this lab entails scientific curiosity and persistence, encourages critical thinking and cooperation, while it also offers a free climate of interdisciplinary research and a chance to master difference techniques.
We study the molecular basis of a range of high-risk infectious diseases and genetic diseases, so as to identify novel therapeutic vulnerabilities in organisms. On top of these basic research, we seek to translate gained knowledge into the development of preventive opportunities like vaccine immunogens, and therapeutic interventions such as small-molecule or peptidic inhibitors, protective antibodies and gene therapies through collaborative efforts. Examples of our recent research are briefed below.
3C protein is one of the drug development focus 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).
By performing detailed and comparative analysis on the fusion core structures of alpha- and beta-human coronaviruses (HCoVs), we generalized the commons and differences among the HR1s from different HCoVs (Acta Cryst. D., 2018). Built upon the knowledge gained and collaborating with a team of virologists from Fudan University, we 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).
We contributed in the development of several precision gene editing technologies (Cell Res., 2017; Nat. Biotechnol., 2018a; Nat. Biotechnol., 2018b) and are actively applying these genome editing tools to combat several genetic and infectious diseases.
