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/
Mass spectrometry captures biased signalling and allosteric modulation of a G-protein-coupled receptor.
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
Nature Chemistry (2022)
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
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
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)