DEPARTMENT OF APPLIED BIOLOGY & CHEMICAL TECHNOLOGY 65 Email yanxiang.zhao@polyu.edu.hk Qualification BSc (Peking University) MA (State University of New York) PhD (The Rockefeller University) ORCID ID 0000-0002-9408-9979 Prof. ZHAO Yanxiang Professor Associate Head of Department Research Overview Our laboratory aims to carry out structural and mechanistic study of cellular metabolism and genome stability, two processes essential for organism viability and development. Specifically, we use modern structural biology tools like cryo-EM, x-ray crystallography and NMR to determine the 3D structures of protein machineries involved in these two processes, followed by structure-guided mechanistic studies to delineate their functional roles. For cellular metabolism, we focus on the evolutionarily conserved autophagy process that is implicated in human diseases including cancer, diabetes and neurodegeneration. We have solved the structures of key autophagy proteins including Beclin 1, Atg14L, UVRAG and p62 (Nat. Comm. 2012, Autophagy 2014, Autophagy 2015, PNAS 2018, Autophagy 2020, Sci. Adv. 2021). We have also developed autophagy-inducing stapled peptides that showed promising anti-proliferative efficacy in cell- and animal-based cancer models (PNAS 2018, J. Med. Chem. 2021, BBRC 2022, BB Reports 2023). For genome stability, we mainly investigate protein complexes involved in telomere maintenance and transcription regulation. We have determined the structures of TbTRF and TbRAP1, two key members of the Shelterin complex to protect the telomere structure and to regulate antigenic variation in the parasite T. brucei (Nucleic Acids Res. 2014, Sci. Adv. 2020, Pathogens 2021). We also study the nuclear import machinery for transcription factors such as NFAT and TFEB that regulate T cell activation and autophagy. Representative Publications • J. Med. Chem. (2021) 64(18): 13475-13486 • Sci. Adv. (2020) 6(38): eabc4065 • Autophagy (2020) 16(5): 917-931 • Proc. Natl. Acad. Sci. U.S.A. (2018) 115(25): E5669-E5678 • PLoS Genet. (2015) 11(2): e1004987 • PLoS Genet. (2014) 10(10): e1004626 • Nucleic Acids Res. (2014) 42(20): 12899-12911 • Autophagy (2012) 8(8): 1258-1260 • Nat. Commun. (2012) 3: 662
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