Institute of Biological Chemistry, Academia Sinica

Research

Danny’s research focuses on the atomic and molecular insights into the structure-function relationships of biomolecules. Danny coined the term, pyrophosphate cage, to describe how the potent antimicrobial peptide, Nisin, recognizes bacterial cell wall precursor, Lipid II, to achieve the novel targeted pore-forming bactericidal activity. He reported the first demonstration of direct structural investigation of the dynamic co-translational folding events of a nascent polypeptide chain as it emerges from the ribosome by using NMR, which has paved the way towards fundamental understanding of protein folding and misfolding. He also unravelled unique structural and dynamic features of several oncogenic DNA/RNA G-quadruplex forming motifs to help drug designs. After starting his independent career in Taiwan, Danny continues to deepen our basic understanding of protein folding while collaborating with several research teams to study novel lectins and glyco/membrane proteins, and designs of better lectin inhibitors. His recent research focuses on how mutations impact on host recognition and immunity escape of coronaviruses, and how cancer-associated mutations allosterically impair the deubiquitinase activity and increase aggregation propensity of an important oncogene suppressor BAP1. Danny also establishes industrial collaborations to characterize the physicochemical and structural attributes protein drug targets.

Degrees and Positions Held

• 2000 – 2004   Ph.D., cum laude (with honour), Chemistry, Utrecht University, The Netherlands
• 1998 – 2000   M.Sc., Life Sciences (first place), National Tsing Hua University, Taiwan
• 1994 – 1998   B.Sc., Physics and Life Sciences (Double Major), National Tsing Hua University, Taiwan

• 2022 – present   Deputy Director, Institute of Biological Chemistry, Academia Sinica, Taiwan
• 2022 – present   Research Fellow, Institute of Biological Chemistry, Academia Sinica, Taiwan
• 2017 – 2022   Associate Research Fellow, Institute of Biological Chemistry, Academia Sinica, Taiwan
• 2011 – 2017   Assistant Research Fellow, Institute of Biological Chemistry, Academia Sinica, Taiwan
• 2010 – 2011   Assistant Professor, Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Taiwan
• 2009 – 2010   Research Associate, Department of Chemistry, University of Cambridge, UK
• 2007 – 2010   Research Fellow, Wolfson College, University of Cambridge, UK
• 2006 – 2008   Human Frontier Science Program (HFSP) Long-term Fellow, Department of Chemistry, University of Cambridge, UK
• 2005 – 2006   Netherlands Ramsay Fellow of the Royal Netherlands Academy of Arts and Sciences, Department of Chemistry, University of Cambridge, UK
• 2004 – 2005   Junior Researcher, Department of Chemistry, Utrecht University, the Netherlands

Selected Publications

Folding and functions of knotted proteins.   
Hsu STD*   
Current Opinion in Structural Biologys (2023)

In situ structure and dynamics of an alphacoronavirus spike protein by cryo-ET and cryo-EM.   
Huang CY, Draczkowski P, Wang YS, Chang CY, Chien YC, Cheng YH, Wu YM, Wang CH, Chang YC, Chang YC, Yang TJ, Tsai YX, Khoo KH, Chang HW, Hsu STD*   
Nature Communications (2022)

Tumor suppressor BAP1 nuclear import is governed by transportin-1.   
Yang TJ, Li TN, Huang RS, Pan MY, Lin SY, Lin S, Wu KP, Wang LH, Hsu STD*   
Journal of Cell Biology (2022)

Impacts of cancer-associated mutations on the structure-activity relationship of BAP1.   
Puri S, Chen SN, Chiu YH, Draczkowski P, Ko KT, Yang TJ, Wang YS, Uchiyama S, Hsu STD*   
Journal of Molecular Biology (2022)

D614G mutation in the SARS-CoV-2 spike protein enhances viral fitness by desensitizing it to temperature-dependent denaturation.   
Yang TJ, Yu PY, Chang YC, Hsu STD*   
Journal of Biological Chemistry (2021)

Effect of SARS-CoV-2 B.1.1.7 mutations on spike protein structure and function.   
Yang TJ, Yu PY, Chang YC, Liang KH, Tso HC, Ho MR, Chen WY, Lin HT, Wu HC, Hsu STD*   
Nature Structural & Molecular Biology (2021)

Cryo-EM analysis of a feline coronavirus spike protein reveals a unique structure and camouflaging glycans.   
Yang TJ, Chang YC, Ko TP, Draczkowski P, Chien YC, Chang YC, Wu KP, Khoo KH, Chang HW*, Hsu STD*   
Proceedings of the National Academy of Sciences of the United States of America (2020)

Untying a knotted SPOUT RNA methyltransferase by circular permutation results in a domain-swapped dimer.   
Ko KT, Hu IC, Huang KF, Lyu PC, Hsu STD*   
Structure (2019)

Untying a protein knot by circular permutation.   
Chuang YC, Hu IC, Lyu PC, Hsu STD*   
Journal of Molecular Biology (2019)

Topologically knotted deubiquitinases exhibit unprecedented mechanostability to withstand the proteolysis by an AAA+ protease.   
Sriramoju MS, Chen Y, Lee YC, Hsu STD*   
Scientific Reports (2018)

Publication List