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. He remained at Harvard for a year as a postdoctoral fellow and then continued his postdoctoral studies at the Massachusetts Institute of Technology. He was then 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 2014 Gouaux received an honorary PhD from the University of Copenhagen and in 2015 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 Gouaux lab seeks to understand the molecular basis for signal transduction at chemical synapses in the central nervous system and at sites of mechanical-electrical transduction (MET) in hair cells of the inner ear. We strive to not only elucidate molecular structures of the neurotransmitter receptors and transporters at synapses, but we also aim to elucidate the composition and molecular organization of the MET complex. We apply a host of structural and biophysical approaches, including single particle and tomographic cryo-EM, together with fluorescence microscopy methods, biochemical methods, patch clamp electrophysiology and molecular biological manipulations.

We are also keenly interested in leveraging our expertise in synaptic structure and physiology to unravel the molecular basis of NMDA receptor encephalitis, and related glutamate receptor neuroinflammatory diseases, and to decipher the subunit composition of AMPA receptors over-expressed in human glioblastoma, aiming to work with collaborators to ultimately develop new therapeutic strategies. To bolster our research, we create tools to facilitate cryo-EM studies, at both the single particle and tomographic levels, by developing cryo-EM grids and electron dense fiducial markers.

Matsui A*, Spangler CJ*, 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. (*contributed equally)

Srivastava DK, Navratna V, Tosh DK, Chinn A, Sk MF, Tajkhorshid E, Jacobson KA, Gouaux E. (2024) Structure of the human dopamine transporter and mechanisms of inhibition. Nature. 632(8025):672-677.

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. 

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.

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

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.

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.

Srivastava DK, Navratna V, Tosh DK, Chinn A, Sk MF, Tajkhorshid E, Jacobson KA, Gouaux E. (2024) Structure of the human dopamine transporter and mechanisms of inhibition. Nature. 632(8025):672-677.

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.