中央研究院 生物化學研究所

研究領域與專長

The interactions among different biological molecules play a central role in modulating cellular physiology. However, deciphering such complexed and dynamic interactions and their functional impact have turned out to be a challenging task. The merit of native mass spectrometry, which enables proteins and their complexes to survive in the gas phase, offers a unique opportunity in gaining a deeper insight into various biological systems. In our group, we dedicate in understanding the structural mechanisms of GPCRs and their regulations using native mass spectrometry as our central technique. Our research focus is to investigate the regulation of neurological GPCRs, and their physiological and pathological connections with various diseases. The utility of native mass spectrometry can provide unparalleled information on structural dynamics of GPCRs, and their association with native environment in particular. Ultimately, decoding the native interactome of receptors, including lipids, metabolites and partner proteins, will offer a novel perspective in GPCR biology, such as deorphanization, allosteric modulators and lipid-based drug design. Our tenet is to develop state-of-the-art mass spectrometry and apply it to a range of intractable systems.

Researchgate : https://www.researchgate.net/profile/Hsin-Yung-Yen

LinkedIn : https://www.linkedin.com/in/hsin-yung-jason-yen-9393141a3/

OMass Therapeutics : https://www.omass.com/team/

學經歷

• 2007 – 2014   Ph.D., Institute of Biochemical Sciences, National Taiwan University, Taiwan
• 2004 – 2006   M.S., Institute of Biotechnology, National Tsing Hua University, Taiwan
• 2000 – 2004   B.S., National Sun Yat-Sen University, Taiwan

• 2022 – present   Assistant Research Fellow, Institute of Biological Chemistry, Academia Sinica, Taiwan
• 2018 – 2021   Founder and Director of Biology, OMass Therapeutics, Oxford, UK
• 2017 – 2018   Founder and Chief Scientific Officer, OMass Technologies, Oxford, UK
• 2014 – 2017   Postdoctoral Research Fellow, Chemistry Research Laboratory, University of Oxford, UK
• 2007 – 2014   Research Assistant, Genomic Research Center, Academia Sinica, Taiwan

主要著作

Combining native and ‘omics’ mass spectrometry to identify endogenous ligands bound to membrane proteins. 
Gault J, Liko I, Landreh M, Shutin D, Bolla JR, Jefferies D, Agasid M, Yen HY, Ladds MJGW, Lane DP, Khalid S, Mullen C, Remes PM, Huguet R, McAlister G, Goodwin M, Viner R, Syka JEP, Robinson CV 
Nature Methods (2020)

Statedependent Lipid Interactions with the A2a Receptor Revealed by MD Simulations Using In Vivo-Mimetic Membranes. 
Song W, Yen HY, Robinson CV, Sansome MSP 
Structure (2019)

PtdIns(4,5)P2 stabilizes active states of GPCRs and enhances selectivity of G-protein coupling. 
Yen HY, Hoi KK, Liko I, Hedger G, Horrell MR, Song W, Wu D, Heine P, Warne T, Lee Y, Carpenter B, Pluckthun A, Tate CG, Sansome MSP, Robinson CV 
Nature (2018)

Ligand binding to a G protein-coupled receptor captured in a mass spectrometer. 
Yen HY, Hopper JTS, Liko I, Allison TM, Zhu Y, Wang D, Stegmann M, Mohammed S, Wu B, Robinson CV 
Science Advances (2017)

Sialylation and fucosylation of epidermal growth factor receptor suppress its dimerization and activation in lung cancer cells. 
Liu YC, Yen HY, Chen CY, Chen CH, Cheng PF, Juan YH, Chen CH, Khoo KH, Yu CJ, Yang PC, Hsu TL, Wong CH (Co-first author) 
Proceedings of the National Academy of Sciences of the United States of America (2011)

著作列表

1. (Yen HY), Jazayeri A, Robinson CV  (2023-05)  Pharmacological reviews  75(3), 397-415  "G protein-coupled receptor pharmacology - insights from mass spectrometry."
   
2. (Yen HY)*, Liko I, Song W, Kapoor P, Almeida F, Toporowska J, Gherbi K, Hopper JTS, Charlton SJ, Politis A, Sansom MSP, Jazayeri A*, Robinson CV*  (2022-12)  Nature chemistry  14(12), 1375-1382  "Mass spectrometry captures biased signalling and allosteric modulation of a G-protein-coupled receptor."
   
3. (Yen HY)*, Abramsson ML, Agasid MT, Lama D, Gault J, Liko I, Kaldmae M, Saluri M, Qureshi AA, Suades A, Drew D, Degiacomi MT, Marklund EG, Allison TM, Robinson CV, Landreh M*  (2022-04)  RSC advances  12(16), 9671-9680  "Electrospray ionization of native membrane proteins proceeds via a charge equilibration step."
   
4. Gavriilidou AFM, Sokratous K, (Yen HY), De Colibus L  (2022-04)  Frontiers in molecular biosciences  9, 837901  "High-Throughput Native Mass Spectrometry Screening in Drug Discovery."
   
5. Hoi KK, Bada Juarez JF, Judge PJ, (Yen HY), Wu D, Vinals J, Taylor GF, Watts A, Robinson CV  (2021-04)  Nano letters  21(7), 2824-2831  "Detergent-free Lipodisq Nanoparticles Facilitate High-Resolution Mass Spectrometry of Folded Integral Membrane Proteins."
   
6. Xu P, Huang S, Zhang H, Mao C, Zhou XE, Cheng X, Simon IA, Shen DD, (Yen HY), Robinson CV, Harpsoe K, Svensson B, Guo J, Jiang H, Gloriam DE, Melcher K, Jiang Y, Zhang Y, Xu HE  (2021-04)  Nature  592(7854), 469-473  "Structural insights into the lipid and ligand regulation of serotonin receptors."
   
7. Bada Juarez JF, Judge PJ, Adam S, Axford D, Vinals J, Birch J, Kwan TOC, Hoi KK, (Yen HY), Vial A, Milhiet PE, Robinson CV, Schapiro I, Moraes I, Watts A  (2021-01)  Nature communications  12(1), 629  "Structures of the archaerhodopsin-3 transporter reveal that disordering of internal water networks underpins receptor sensitization."
   
8. (Yen HY), Liko I, Gault J, Wu D, Struwe WB, Robinson CV  (2020-09)  Angewandte Chemie - International Edition  59(36), 15560-15564  "Correlating Glycoforms of DC-SIGN with Stability Using a Combination of Enzymatic Digestion and Ion Mobility Mass Spectrometry."
   
9. Gault J, Liko I, Landreh M, Shutin D, Bolla JR, Jefferies D, Agasid M, (Yen HY), Ladds MJGW, Lane DP, Khalid S, Mullen C, Remes PM, Huguet R, McAlister G, Goodwin M, Viner R, Syka JEP, Robinson CV  (2020-05)  Nature methods  17(5), 505-508  "Combining native and \'omics\' mass spectrometry to identify endogenous ligands bound to membrane proteins."
   
10. Urner LH, Liko I, (Yen HY), Hoi KK, Bolla JR, Gault J, Almeida FG, Schweder MP, Shutin D, Ehrmann S, Haag R, Robinson CV, Pagel K  (2020-01)  Nature communications  11(1), 564  "Modular detergents tailor the purification and structural analysis of membrane proteins including G-protein coupled receptors."
    
11. Song W, (Yen HY), Robinson CV, Sansom MSP  (2019-02)  Structure  27(2), 392-403.e3  "State-dependent Lipid Interactions with the A2a Receptor Revealed by MD Simulations Using In Vivo-Mimetic Membranes."
    
12. Gong H, Li J, Xu A, Tang Y, Ji W, Gao R, Wang S, Yu L, Tian C, Li J, (Yen HY), Man Lam S, Shui G, Yang X, Sun Y, Li X, Jia M, Yang C, Jiang B, Lou Z, Robinson CV, Wong LL, Guddat LW, Sun F, Wang Q, Rao Z  (2018-11)  Science  362(6418), eaat8923  "An electron transfer path connects subunits of a mycobacterial respiratory supercomplex."
    
13. (Yen HY), Hoi KK, Liko I, Hedger G, Horrell MR, Song W, Wu D, Heine P, Warne T, Lee Y, Carpenter B, Pluckthun A, Tate CG, Sansom MSP, Robinson CV  (2018-07)  Nature  559(7714), 423-427  "PtdIns(4,5)P2 stabilizes active states of GPCRs and enhances selectivity of G-protein coupling."
    
14. Ambrose S, Housden NG, Gupta K, Fan J, White P, (Yen HY), Marcoux J, Kleanthous C, Hopper JTS, Robinson CV  (2017-11)  Angewandte Chemie - International Edition  56(46), 14463-14468  "Native Desorption Electrospray Ionization Liberates Soluble and Membrane Protein Complexes from Surfaces."
    
15. (Yen HY), Hopper JTS, Liko I, Allison TM, Zhu Y, Wang D, Stegmann M, Mohammed S, Wu B, Robinson CV  (2017-06)  Science advances  3(6), e1701016  "Ligand binding to a G protein-coupled receptor captured in a mass spectrometer."
    
16. Wang YT, Pan SH, Tsai CF, Kuo TC, Hsu YL, (Yen HY), Choong WK, Wu HY, Liao YC, Hong TM, Sung TY, Yang PC, Chen YJ  (2017-03)  Scientific reports  7, 44021  "Phosphoproteomics Reveals HMGA1, a CK2 Substrate, as a Drug-Resistant Target in Non-Small Cell Lung Cancer."
    
17. (Yen HY), Liu YC, Chen NY, Tsai CF, Wang YT, Chen YJ, Hsu TL, Yang PC, Wong CH  (2015-06)  Proceedings of the National Academy of Sciences of the United States of America  112(22), 6955-6960  "Effect of sialylation on EGFR phosphorylation and resistance to tyrosine kinase inhibition."
    
18. Tsai CF, Wang YT, (Yen HY), Tsou CC, Ku WC, Lin PY, Chen HY, Nesvizhskii AI, Ishihama Y, Chen YJ  (2015-03)  Nature communications  6, 6622  "Large-scale determination of absolute phosphorylation stoichiometries in human cells by motif-targeting quantitative proteomics."
    
19. Tsai CS, (Yen HY), Lin MI, Tsai TI, Wang SY, Huang WI, Hsu TL, Cheng YS, Fang JM, Wong CH  (2013-02)  Proceedings of the National Academy of Sciences of the United States of America  110(7), 2466-2471  "Cell-permeable probe for identification and imaging of sialidases."
    
20. Liu YC, (Yen HY), Chen CY, Chen CH, Cheng PF, Juan YH, Chen CH, Khoo KH, Yu CJ, Yang PC, Hsu TL, Wong CH (Co-first author)  (2011-07)  Proceedings of the National Academy of Sciences of the United States of America  108(28), 11332-11337  "Sialylation and fucosylation of epidermal growth factor receptor suppress its dimerization and activation in lung cancer cells."
    
21. Liao HY, Hsu CH, Wang SC, Liang CH, (Yen HY), Su CY, Chen CH, Jan JT, Ren CT, Chen CH, Cheng TJ, Wu CY, Wong CH  (2010-10)  Journal of the American Chemical Society  132(42), 14849-14856  "Differential receptor binding affinities of influenza hemagglutinins on glycan arrays."
    
22. Tsai CS, Liu PY, (Yen HY), Hsu TL, Wong CH  (2010-08)  Chemical Communications  46(30), 5575-5577  "Development of trifunctional probes for glycoproteomic analysis."