Eric Gouaux, Ph.D.

Eric Gouaux, PhD

Senior Scientist, Vollum Institute

Investigator, Howard Hughes Medical Institute

Jennifer and Bernard Lacroute Endowed Chair in Neuroscience Research

Biography

Eric Gouaux completed his B.A. and Ph.D. degrees in Chemistry at Harvard University in 1984 and 1989, respectively. He remained at Harvard for a year as a postdoctoral fellow and then continued his postdoctoral studies at the Massachusetts Institute of Technology. In 1993, he was appointed assistant professor at the University of Chicago Department of Biochemistry and Molecular Biology.

In 1996, Gouaux joined the Department of Biochemistry and Molecular Biology at Columbia University as an assistant professor. In 2000, he was appointed Investigator with the Howard Hughes Medical Institute and associate professor with Columbia, reaching full professor the following year. Gouaux came to Oregon Health & Science University in 2005 as a Senior Scientist at the Vollum Institute and continuing his position with Howard Hughes. He joined the graduate faculty in the Department of Biochemistry and Molecular Biology in 2006. In 2015, Gouaux was appointed the Jennifer and Bernard Lacroute Endowed Chair in Neuroscience Research. He is a member of both the National Academy of Sciences (2010) and the National Academy of Medicine (2020).

Summary of current research

The work in the Gouaux Lab is concentrated on developing molecular mechanisms for the function of receptors and transporters at chemical synapses. At chemical synapses, neurotransmitters released from one neuron diffuse throughout a small space — the synaptic cleft — to receptors on adjacent neurons. At many synapses, the neurotransmitter binds to a receptor that is a ligand-gated ion channel, and this binding event leads to the opening of a transmembrane pore, which in turn results in depolarization of the nerve cell and generation of an electrical signal. Neurotransmitter transporters surrounding the synapse clear the transmitters from the cleft by coupling the thermodynamically unfavorable uptake to the favorable co-transport of one or more sodium ions. Glutamate, glycine and the biogenic amines are neurotransmitters of particular significance and currently we are focusing our efforts on eukaryotic glutamate receptors and on bacterial homologs of the transporters for glutamate, glycine and the biogenic amines. While our primary tool is x-ray crystallography, we also utilize electrophysiology as well as other biophysical and biochemical methods.

Dushyant Kumar Srivastava, Vikas Navratna, Dilip K. Tosh, Audrey Chinn, Md Fulbabu Sk, Emad Tajkhorshid, Kenneth A. Jacobson, Eric Gouaux. (2024) Structure of the human dopamine transporter and mechanisms of inhibition. Nature. doi: 10.1038/s41586-024-07739-9.

Matsui A, Spangler C, Elferich J, Shiozaki M, Jean N, Zhao X, Qin M, Zhong H, Yu Z, Gouaux E. (2024) Cryo-electron tomographic investigation of native hippocampal glutamatergic synapses. eLife. 13:RP98458.

Clark S, Jeong H, Posert R, Goehring A, Gouaux E. (2024) The structure of the Caenorhabditis elegans TMC-2 complex suggests roles of lipid-mediated subunit contacts in mechanosensory transduction. Proc Natl Acad Sci U S A. Feb;121(8):e2314096121.

Sun C, Zhu H, Clark S, Gouaux E. (2023) Cryo-EM structures reveal native GABAA receptor assemblies and pharmacology. Nature. Oct;622(7981):195-201.

Clark S, Jeong H, Goehring A, Kang Y, Gouaux E. (2023) Large-scale growth of C. elegans and isolation of membrane protein complexes. Nat Protoc. Sep;18(9):2699-2716. 

Youn Y, Lau GW, Lee Y, Maity BK, Gouaux E, Chung HJ, Selvin PR. (2023) Quantitative DNA-PAINT imaging of AMPA receptors in live neurons. Cell Rep Methods. 3(2):100408

Rao P, Gouaux E. (2023) Purification and biochemical analysis of native AMPA receptors from three different mammalian species. PLoS One. 18(3):e0275351.

Yang, D., Zhao, Z., Tajkhorshid, E., Gouaux, E. (2023) Structures and membrane interactions of native serotonin transporter in complexes with psychostimulants. Proc Natl Acad Sci. Jul;120(29):e2304602120.

Jeong, H., Clark, S., Goehring, A., Dehghani-Ghahnaviyeh, S., Tajkhorshid, E., Gouaux, E. (2022) Structures of the TMC-1 complex illuminate mechanosensory transduction. Nature Oct;610: 796-803.

Ivica J, Zhu H, Lape R, Gouaux E, Sivilotti LG. (2022) Aminomethanesulfonic acid illuminates the boundary between full and partial agonists of the pentameric glycine receptor. Elife Aug 17;11:e79148.

Gogoi P, Shiozaki M, Gouaux E. (2022) Isolation, cryo-laser scanning confocal microscope imaging and cryo-FIB milling of mouse glutamatergic synaptosomes. PLoS One Aug 12;17(8):e0271799.

Elferich, J., Clark, S., Ge, J., Goehring, A., Matsui, A., Gouaux, E. (2021) Molecular structures and conformations of protocadherin-15 and its complexes on stereocilia elucidated by cryo-electron tomography. Elife Dec 29; 1;10:e74512.

Holt, J.R., Tobin, M., Elferich, J. et al. (2021) Putting the Pieces Together: the Hair Cell Transduction Complex. J Assoc Res Otolaryngol. Dec;22(6):601-608.

Dushyant Kumar Srivastava, Vikas Navratna, Dilip K. Tosh, Audrey Chinn, Md Fulbabu Sk, Emad Tajkhorshid, Kenneth A. Jacobson, Eric Gouaux. (2024) Structure of the human dopamine transporter and mechanisms of inhibition. Nature. doi: 10.1038/s41586-024-07739-9.

Sun C, Zhu H, Clark S, Gouaux E. (2023) Cryo-EM structures reveal native GABAA receptor assemblies and pharmacology. Nature. Oct;622(7981):195-201.

Yu J*, Rao P*, Clark S, Mitra J, Ha T, Gouaux E. (2021) Hippocampal AMPA receptor assemblies and mechanism of allosteric inhibition. Nature 594:448-453. (*contributed equally)

Ge J, Elferich J, Goehring A, Zhao J, Schuck P, Gouaux E. (2018) Structure of mouse protocadherin 15 of the stereocilia tip link in complex with LHFPL5. eLife 7:e38770.

Du J, Lü W, Wu S, Cheng Y, Gouaux E. (2015) Glycine receptor mechanism elucidated by electron cryo-microscopy. Nature 526:224-229.

Wang KH, Penmatsa A, Gouaux E. (2015) Neurotransmitter and psychostimulant recognition by the dopamine transporter. Nature 521:322-327.

Chen L, Dürr KL, Gouaux E. (2014) X-ray structures of AMPA receptor-cone snail toxin complexes illuminate activation mechanism. Science 345:1021-1026.

Lee CH, Lü W, Michel JC, Goehring A, Du J, Song X, Gouaux E. (2014) NMDA receptor structures reveal subunit arrangement and pore architecture. Nature 511:191-197.

Penmatsa A, Wang KH, Gouaux E. (2013) X-ray structure of dopamine transporter elucidates antidepressant mechanism. Nature 503:85-90.

Hattori M, Gouaux E. (2012) Molecular mechanism of ATP binding and ion channel activation in P2X receptors. Nature 485:207-212.

Krishnamurthy H, Gouaux E. (2012) X-ray structures of LeuT in substrate-free outward-open and apo inward-open states. Nature 481:469-474.