Alexander Sobolevsky, PhD

Alexander Sobolevsky, MD

Overview

Academic Appointments

  • Assistant Professor of Biochemistry and Molecular Biophysics

Alexander Sobolevsky (Columbia University) earned his PhD in biophysics in 1999 from the Moscow Institute of Physics and Technology, working under guidance of Prof. Boris Khodorov. He held his first postdoctoral position in 2000, studying physiology and neuroscience with Dr. Lonnie Wollmuth at the State University of New York, Stony Brook. He continued his training in biochemistry and biophysics with Dr. Eric Gouaux, first at Columbia University and then at the Oregon Health and Science University. He joined Columbia University’s faculty in 2010 as an assistant professor of biochemistry and molecular biophysics, focusing on structure and function of ion channels. In 2017, he became an associate professor.

Languages

  • Russian

Gender

  • Male

Credentials & Experience

Honors & Awards

1998             International Soros Science Education Program Grant (No. a98-2018)

1998             International Brain Research Organization Travel Grant for participation in the 29th Annual Meeting of the Society for Neuroscience (Miami, Florida, October 1999)

1999             International Soros Science Education Program Grant (No. a99-1650)

2000             International Brain Research Organization Travel Grant for participation in the 31st Annual Meeting of the Society for Neuroscience (San Diego, California, November 2001)

2002             Burroughs Wellcome Fund Postdoctoral Travel Award for participation in the 32nd Annual Meeting of the Society for Neuroscience (Orlando, Florida, November 2002)

2011             Klingenstein Award in the Neurosciences

2012             Schaefer Research Scholar Award

2013             Pew Scholar Award

2015             Irma T. Hirschl Career Scientist Award

Research

Grants

STRUCTURE AND FUNCTION OF AMPA SUBTYPE IONOTROPIC GLUTAMATE RECEPTORS (Federal Gov)

Jul 1 2018 - Jun 30 2023

SINGLE-PARTICLE CRYO-EM CHARACTERIZATION OF AMPA RECEPTOR FUNCTIONAL STATES (Federal Gov)

Aug 1 2018 - May 31 2023

TOWARDS DEVELOPMENT OF THE STRUCTURAL DETERMINANTS OF THE GLUTAMATE RECEPTOR GATING REGULATION BY AUXILIARY MEMBRANE ANCHORED PROTEINS (Federal Gov)

Aug 1 2018 - Jul 31 2022

STRUCTURE AND FUNCTION OF TRANSIENT RECEPTOR POTENTIAL CHANNELS (Federal Gov)

Jan 1 2017 - Dec 31 2021

STRUCTURAL AND FUNCTIONAL CHARACTERIZATION OF THE EPITHELIAL CALCIUM CHANNEL TRPV6 (Federal Gov)

Sep 1 2018 - Aug 31 2021

MOLECULAR MECHANISMS OF IONTROPIC GLUTAMATE RECEPTOR GATING, ASSEMBLY AND REGULATION (Private)

Jan 1 2015 - Dec 31 2019

STRUCTURAL ELUCIDATION OF IONOTROPIC GLUTAMATE RECEPTOR STATES WITH CRYOELECTRON MICROSCOPY (Federal Gov)

Sep 1 2016 - Aug 31 2019

STRUCTURE AND FUNCTION OF TRP CHANNELS (Private)

Aug 1 2013 - Jul 31 2017

NYSBC STRUCTURAL GENOMICS OF MEMBRANE PROTEINS (Federal Gov)

Jul 1 2010 - Dec 31 2015

NYSBC STRUCTURAL GENOMICS OF MEMBRANE PROTEINS (Federal Gov)

Jul 1 2010 - Jun 30 2015

STRUCTURAL AND FUNCTIONAL STUDIES OF IONOTROPIC GLUTAMATE RECEPTORS (Private)

Jul 1 2011 - Jun 30 2013

Selected Publications

Papers

  1. Storozhevikh T. P., Sorokina E. G., Vinskaya N. P., Pinelis V. G., Vergun O. V., Fayuk D. A., Sobolevskiy A. I. and Khodorov B. I. (1996) Bepridil exacerbates glutamate-induced deterioration of calcium homeostasis and cultured nerve cell injury. Int. J. Neurosci. 88: 199-214.
  2. Sobolevsky A., Koshelev S. and Khodorov B. I. (1997) Bepridil-induced blockade of NMDA channels in rat hippocampal neurones. Neuropharmacology 36: 319-324.
  3. Sobolevsky A. and Koshelev S. (1998) Two blocking sites of amino-adamantane derivatives in open N-methyl-d-aspartate channels. Biophys. J. 74: 1305-1319.
  4. Sobolevsky A. I., Koshelev S. G. and Khodorov B. I. (1998) Interaction of memantine and amantadine with agonist-unbound NMDA-receptor channels in acutely isolated rat hippocampal neurons. J. Physiol. 512: 47-60.
  5. Sobolevsky A. I., Koshelev S. G. and Khodorov B. I. (1999) Molecular size and hydrophobicity as factors which determine the efficacy of the blocking action of amino-adamantane derivatives on NMDA channels. Membr. Cell Biology 13: 79-93.
  6. Sobolevsky A. I. (1999) Two-component blocking kinetics of open NMDA channels by organic cations. Biochim. Biophys. Acta 1416: 69-91.
  7. Sobolevsky A. I. and Khodorov B. I. (1999) Blockade of NMDA channels in acutely isolated rat hippocampal neurons by the Na+/Ca2+ exchange inhibitor KB-R7943. Neuropharmacology 38: 1235-1242.
  8. Sobolevsky A. I., Koshelev S. G. and Khodorov B. I. (1999) Probing of NMDA channels with fast blockers. J. Neurosci. 19: 10611-10626.
  9. Sobolevsky A. I., Yelshansky M. V. and Khodorov B. I. (2000) Eosine-induced blockade of N-methyl-d-aspartate channels in acutely isolated rat hippocampal neurons. Mol. Pharmacol. 57: 334-341.
  10.  Sobolevsky A. I. and Yelshansky M. V. (2000) The trapping block of NMDA-receptor channels in acutely isolated rat hippocampal neurones. J. Physiol. 526: 493-506.
  11.  Sobolevsky A. I. (2000) Quantitative analysis of tetrapentylammonium-induced blockade of open N-methyl-d-aspartate channels. Biophys. J. 79: 1324-1335.
  12.  Elshanskaia M. V.,Val'dman E. A. and Khodorov B. I. (2000) Effect of the potential antiparkinsonian agent adamantane derivative on ion channels of NMDA glutamate receptors. Eksp. Klin. Farmakol. (in Russian) 64: 18-21.
  13.  Vergun O., Sobolevsky A. I., Yelshansky M. V., Keelan J., Khodorov B. I. and Duchen M. R. (2001) Exploration of the role of reactive oxygen species in glutamate neurotoxicity in rat hippocampal neurones in culture. J. Physiol. 531: 147-163.
  14. Yelshansky M. V., Sobolevsky A. I. and KhodorovB. I. (2002) Study of the Effect of Arachidonic Acid on NMDA Channels in Acutely Isolated Rat Hippocampal Neurons. Membr. Cell Biology 19: 93-108.
  15.  Sobolevskii A. I. and Khodorov B. I. (2002) Blocker studies of the functional architecture of the NMDA receptor channel. Neurosci. Behav. Physiol. 32: 157-171.
  16.  Sobolevsky A. I., Beck C. and Wollmuth L. P. (2002) Molecular Rearrangements of the Extracellular Vestibule in NMDAR Channels During Gating. Neuron 33: 75-85.
  17.  Sobolevsky A. I., Rooney L. and Wollmuth L. P. (2002) Staggering of Subunits in NMDAR Channels. Biophys. J. 83: 3304-3314.
  18.  Sobolevsky A. I., Yelshansky M. V. and Wollmuth L. P. (2003) Different Gating Mechanisms in Glutamate Receptor and K+ Channels. J. Neurosci. 23: 7559-7568.
  19.  Sobolevsky A. I., Yelshansky M. V. and Wollmuth L. P. (2004) The Outer Pore of the Glutamate Receptor Channel has Two-fold Rotational Symmetry. Neuron 41: 367-378 (Cover; Preview by Stern-Bach Y. AMPA Receptor Activation: Not a Square Dance. Neuron 41: 309-311).
  20.  Yelshansky M. V., Sobolevsky A. I., Jatzke C. and Wollmuth L. P. (2004) Block of AMPA Receptor Desensitization by a Point Mutation outside the Ligand-Binding Domain. J. Neurosci. 24: 4728-4736.
  21.  Sobolevsky A. I., Yelshansky M.V. and Wollmuth L. P. (2005) State-dependent Changes in the Electrostatic Potential in the Pore of a GluR Channel. Biophys. J. 88: 235-242.
  22.  Sobolevsky A. I., Prodromou M. L., Yelshansky M. V. and Wollmuth L. P. (2007) Subunit-specific Contribution of Pore-Forming Domains to NMDA Receptor Channel Structure and Gating. J. Gen. Physiol. 129: 509-525.
  23. Jin R., Singh S. K., Gu S., Furukawa H., Sobolevsky A. I., Zhou J., Jin Y. and Gouaux E. (2009) EMBO Journal 28: 1812–1823.
  24.  Sobolevsky A. I., Rosconi M. P. and Gouaux E. (2009) X-ray structure, symmetry and mechanism of an AMPA-subtype glutamate receptor. Nature 462: 745–756 (Cover; News&Views by Wollmuth L. P. and Traynelis S. F. Neuroscience: Excitatory view of a receptor. Nature 462: 729-731).
  25. Giannone G., Hosy E., Levet F., Constals A., Schulze K., Sobolevsky A. I., Rosconi M. P., Gouaux E., Tampé R., Choquet D. and Cognet L. (2010) Biophys J. 99: 1303-1310.
  26. Yelshanskaya M.V., Li M. and Sobolevsky A. I. (2014) Structure of an agonist-bound ionotropic glutamate receptor. Science 345: 1070-1074.
  27. Yelshanskaya M. V., Saotome K., Singh A. K. and Sobolevsky A. I. (2016) Probing Intersubunit Interfaces in AMPA-subtype Ionotropic Glutamate Receptors. Scientific Reports : 19082.
  28. Saotome K., Singh A. K., Yelshanskaya M. V., Sobolevsky A. I. (2016) Crystal structure of the epithelial calcium channel TRPV6. Nature 534: 506–511.
  29. Twomey E. C., Yelshanskaya M. V., Grassucci R. A., Frank J., Sobolevsky A. I. (2016) Elucidation of AMPA receptor-stargazin complexes by cryo-electron microscopy. Science 353: 83-86.
  30. Yelshanskaya M. V., Singh A. K., Sampson J. M., Narangoda C., Kurnikova M., Sobolevsky A. I. (2016) Structural Bases of Noncompetitive Inhibition of AMPA-Subtype Ionotropic Glutamate Receptors by Antiepileptic Drugs. Neuron 91: 1305-1315 (Preview by Regan M. C. and Furukawa H. Deeper Insights into the allosteric modulation of ionotropic glutamate receptors. Neuron 91: 1187-1189).
  31.  Yelshanskaya M. V., Mesbahi-Vasey S., Kurnikova M., Sobolevsky A. I. (2016) Role of the Ion Channel Extracellular Collar in AMPA Receptor Gating. Scientific Reports 7: 1050.
  32. Twomey E. C., Yelshanskaya M. V., Grassucci R. A., Frank J., Sobolevsky A. I. (2017) Structural Bases of Desensitization in AMPA Receptor-Auxiliary Subunit Complexes. Neuron 94: 569-580.
  33.  Twomey E. C., Yelshanskaya M. V., Grassucci R. A., Frank J., Sobolevsky A. I. (2017) Structural Bases of Desensitization in AMPA Receptor-Auxiliary Subunit Complexes. Nature doi: 10.1038/nature23479.
  34.  Singh A. K., Saotome K., Sobolevsky A. I. (2016) Swapping of transmembrane domains in the epithelial calcium channel TRPV6. Scientific Reports Accepted for publication.

Reviews

  1. Sobolevsky A. I. (2003) Channel Block of Glutamate Receptors. In Recent Research Developments in Physiology 1 (Pandalai S.G. Ed.) pp 1-38. Kerala, India: Research Signpost.
  2. Wollmuth L. P. and (2004) Structure and gating of the glutamate receptor ion channel. Trends Neurosci. 27: 321-328.
  3. Sobolevsky A. I. (2007) Insights into Structure and Function of Ionotropic Glutamate Receptor Channels: Starting from Channel Block. Biochemistry (Moscow) Supplement Series A: Membrane and Cell Biology 1: 45–56 and Biologicheskie Membrany 24 (1): 50–61.
  4. Sobolevsky A. I. (2015) Structure and Gating of Tetrameric Glutamate Receptors. J. Physiol. 593: 29-38 (Cover).
  5. Yelshanskaya M.V., Saotome K., Li M. and Sobolevsky A. I. (2016) Expression, Purification and Crystallization of Full Length Ionotropic Glutamate Receptors. Neuromethods 106: 83-100.
  6. Saotome K., Singh A. K., Sobolevsky A. I. (2016) Determining the Crystal Structure of TRPV6. In Calcium Entry Channels in Non-Excitable Cells (Kozak J.A. and Putney J.W. Eds.), chapter 14. CRC Press, Taylor & Francis Group, LLC.