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Chia-Hsueh Lee, PhD
Chia-Hsueh Lee, PhD

Chia-Hsueh Lee, PhD

Assistant Member, St. Jude Faculty



BS – National Taiwan University, Taipei City Taiwan
MS – National Taiwan University, Taipei City Taiwan
PhD – Oregon Health & Science University, Portland Oregon

Research Interests

  • Structural biology of membrane proteins
  • Functions of ion channels and transporters

We seek to elucidate molecular mechanisms of membrane signaling complexes. We employ biochemical, biophysical, and structural techniques, particularly cryo-electron microscopy, to understand functions and structures of membrane proteins important to human health and disease.

Selected Publications

Pidathala S, Liao S, Dai Y, Li X, Long C, Chang CL, Zhang Z, Lee CH. Mechanisms of neurotransmitter transport and drug inhibition in human VMAT2. Nature Nov 1, 2023. doi: 10.1038/s41586-023-06727-9. PMID: 37914936

Chen H, Ahmed S, Zhao H, Elghobashi-Meinhardt N, Dai Y, Kim JH, McDonald JG, Li X, Lee CH. Structural and functional insights into Spns2-mediated transport of sphingosine-1-phosphate. Cell Jun 8;186(12):2644-2655.e16, 2023. doi: 10.1016/j.cell.2023.04.028. PMID: 37224812

Srivastava S, Shaked HM, Gable K, Gupta SD, Pan X, Somashekarappa N, Han G, Mohassel P, Gotkine M, Doney E, Goldenberg P, Tan QKG, Gong Y, Kleinstiver B, Wishart B, Cope H, Pires CB, Stutzman H, Spillmann RC; Undiagnosed Disease Network; Sadjadi R, Elpeleg O, Lee CH, Bellen HJ, Edvardson S, Eichler F, Dunn TM. SPTSSA variants alter sphingolipid synthesis and cause a complex hereditary spastic paraplegia. Brain Apr 19;146(4):1420-1435, 2023. doi: 10.1093/brain/awac460. PMID: 36718090

Dang Y, Zhou D, Du X, Zhao H, Lee CH, Yang J, Wang Y, Qin C, Guo Z, Zhang Z. Molecular mechanism of substrate recognition by folate transporter SLC19A1. Cell Discov Dec 28;8(1):141, 2022. doi: 10.1038/s41421-022-00508-w. PMID: 36575193

Duan Z, Lin X, Wang L, Zhen Q, Jiang Y, Chen C, Yang J, Lee CH, Qin Y, Li Y, Zhao B, Wang J, Zhang Z. Specificity of TGF-β1 signal designated by LRRC33 and integrin αVβ8. Nat Commun Aug 25;13(1):4988, 2022. doi: 10.1038/s41467-022-32655-9. PMID: 36008481

Ye W, Zhao H, Dai Y, Wang Y, Lo YH, Jan LY, Lee CH. Activation and closed-state inactivation mechanisms of the human voltage-gated KV4 channel complexes. Mol Cell Jul 7;82(13):2427-2442.e4, 2022. doi: 10.1016/j.molcel.2022.04.032. PMID: 35597238

Mohassel P, Donkervoort S, Lone MA, Nalls M, Gable K, Gupta SD, Foley AR, Hu Y, Saute JAM, Moreira AL, Kok F, Introna A, Logroscino G, Grunseich C, Nickolls AR, Pourshafie N, Neuhaus SB, Saade D, Gangfuß A, Kölbel H, Piccus Z, Le Pichon CE, Fiorillo C, Ly CV, Töpf A, Brady L, Specht S, Zidell A, Pedro H, Mittelmann E, Thomas FP, Chao KR, Konersman CG, Cho MT, Brandt T, Straub V, Connolly AM, Schara U, Roos A, Tarnopolsky M, Höke A, Brown RH, Lee CH, Hornemann T, Dunn TM, Bönnemann CG. Childhood amyotrophic lateral sclerosis caused by excess sphingolipid synthesis. Nat Med Jul;27(7):1197-1204, 2021. doi: 10.1038/s41591-021-01346-1. PMID: 34059824

Wang R, Wang J, Hassan A, Lee CH, Xie XS, Li X. Molecular basis of V-ATPase inhibition by bafilomycin A1. Nat Commun Mar 19;12(1):1782, 2021. doi: 10.1038/s41467-021-22111-5. PMID: 33741963

Wang Y, Niu Y, Zhang Z, Gable K, Gupta SD, Somashekarappa N, Han G, Zhao H, Myasnikov AG, Kalathur RC, Dunn TM, Lee CH#. Structural insights into the regulation of human serine palmitoyltransferase complexes. Nat Struct Mol Biol 28:240–248, 2021. (#Corresponding author)

Jiang Y, Liu T, Lee CH, Chang Q, Yang J, Zhang Z. The NAD+-mediated self-inhibition mechanism of pro-neurodegenerative SARM1. Nature 588(7839):658-663, 2020.

Lee CH, MacKinnon R. Voltage Sensor Movements during Hyperpolarization in the HCN Channel. Cell 179:1-8, 2019. 

Lee CH, MacKinnon R. Activation mechanism of a human SK-calmodulin channel complex elucidated by cryo-EM structures. Science 360(6388):508-513, 2018.

Song X, Jensen MØ, Jogini V, Stein RA, Lee CH, Mchaourab HS, Shaw DE, Gouaux E. Mechanism of NMDA receptor channel block by MK-801 and memantine. Nature 556(7702):515-519, 2018. 

Lee CH, MacKinnon R. Structures of the human HCN1 hyperpolarization-activated channel. Cell 168(1-2):111-120.e11, 2017. 

Zhu S, Stein RA, Yoshioka C, Lee CH, Goehring A, Mchaourab HS, Gouaux E. Mechanism of NMDA receptor inhibition and activation. Cell 165(3):704-14. 2016.

Lee CH*, Lü W*, Michel JC, Goehring A, Du J, Song X, Gouaux E. NMDA receptor structures reveal subunit arrangement and pore architecture. Nature 511(7508):191-7, 2014. (* equal contribution)

Goehring A*, Lee CH*, Wang K, Michel JC, Claxton D, Baconguis I, Althoff T, Fischer S, Garcia KC, Gouaux E. Screening and large-scale expression of membrane proteins in mammalian cells for structural studies. Nat Protoc 9(11):2574-85, 2014. 

Last update: November 2023