Alexander Sobolevsky, PhD

  • Professor of Biochemistry and Molecular Biophysics

On the web

Profile Headshot

Profile Navigation

Overview

Alexander Sobolevsky earned his PhD in biophysics in 1999 from the Moscow Institute of Physics and Technology, where he studied the mechanisms of gating and ion channel block of NMDA receptor channels using kinetic modeling and patch-clamp recordings from freshly isolated rat hippocampal neurons under the guidance of Prof. Boris Khodorov. He held his first postdoctoral position in the lab of Dr. Lonnie Wollmuth at Stony Brook University, where he studied the functional architecture of ionotropic glutamate receptors (iGluRs) using the substituted cysteine accessibility method (SCAM). He continued his postdoctoral training with Dr. Eric Gouaux, first at Columbia University and then at Oregon Health and Science University, where he solved the first structure of iGluR. He joined Columbia University’s faculty in 2010 as an Assistant Professor of biochemistry and molecular biophysics, focusing on the structure and function of ion channels, particularly iGluRs and transient receptor potential (TRP) channels. He was promoted to Associate Professor in 2017 and Professor in 2024.

Academic Appointments

  • Professor of Biochemistry and Molecular Biophysics

Languages

  • Russian

Gender

  • Male

Credentials & Experience

Education & Training

  • PhD, 1999 Biophysics, Moscow Institute of Physics and Technology, Dolgoprudny, Russia
  • Fellowship: 2000 Wollmuth Lab, SUNY at Stony Brook
  • Fellowship: 2004 Gouaux Lab, Oregon Health and Science University

Committees, Societies, Councils

  • American Heart Association
  • Biophysical Society
  • American Chemical Society
  • Society for Neuroscience

Honors & Awards

  • 2024: Javits Neuroscience Investigator Award, NINDS/NIH
  • 2024: HFSP grant award from the Human Frontier Science Program
  • 2024: Keynote speaker at 9th German Pharm-Tox Summit, Munich, Germany
  • 2023: Keynote speaker at XXIX Symposium on Bioinformatics and Computer-Aided Drug Discovery, Moscow, Russia
  • 2023: Keynote speaker at Three-Dimensional Electron Microscopy GRS, Newry, ME
  • 2017: Amgen Young Investigator Award
  • 2017: Keynote speaker at Cryo-Electron Microscopy Conference RICCEM2017, MSU, Moscow
  • 2015: Future of Biophysics Symposium Speaker, Biophysical Society 59th Annual Meeting, Baltimore
  • 2015: Irma T. Hirschl Career Scientist Award
  • 2013: Pew Scholar Award
  • 2012: Schaefer Research Scholar Award
  • 2011: Klingenstein Award in the Neurosciences

Research

We study structure and function of ion channels, particularly ionotropic glutamate receptors (iGluRs) and transient receptor potential (TRP) channels.
The Sobolevsky lab studies structure and function of ion channels using a combination of biochemical and biophysical methods, including structural (cryo-EM and X-ray crystallography), functional (patch-clamp and single-channel recordings, Fura-2-based ratiometric fluorescent measurements of intracellular calcium), molecular biological (protein engineering and mutagenesis) and computational (MD simulations) approaches. The lab solved numerous structures of full-length iGluRs, including the first agonist-bound, open and desensitized state structures and proposed the first complete structural model of iGluR gating. We also solved the first crystal structure of a TRP channel (TRPV6). Using cryo-EM, Sobolevsky lab determined structures of several TRP channels (e.g., TRPV1, TRPV3, TRPV4, TRPV6, TRPM7 and TRP1) in different conformations and proposed their gating mechanisms. We solved the first structure of an ion channel opened exclusively by heat (TRPV3) and the first time uncovered the structural basis of TRP channel activation by temperature. For many TRP channels and iGluRs, we solved structures in complex with different agonists and antagonists, proposed the mechanisms of activation and inhibition, which lay the foundations of structure-based drug design.

Research Interests

  • Channel Gating
  • Cryo-Electron Microscopy (cryo-EM)
  • Disease Mutations
  • Ion Channels
  • Neurotransmission
  • Protein-Ligand Interactions
  • Protein-Protein Interaction
  • Protein Engineering
  • Structural Biology
  • Temperature Sensitivity

Grants

  • HFSP Research Grant Award from Human Frontier Science Program
  • R37 NS083660 - Javits Neuroscience Investigator Award
  • R01 CA206573 from National Cancer Institute (NCI)
  • R01 NS107253 from National Institute of Neurological Disorders and Stroke (NINDS)
  • R01 AR078814 from National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Selected Publications

  1. Gangwar S. P., Yelshanskaya M. V., Nadezhdin K. D., Yen L. Y., Newton T. P., Aktolun M., Kurnikova M. G., and Sobolevsky A. I. (2024) Kainate receptor channel opening and gating mechanism. Nature 630: 762-768.
  2. Yelshanskaya M. V., Patel D. S., Kottke C. M., Kurnikova M. G. and Sobolevsky A. I. (2022) Opening of glutamate receptor channel to subconductance levels. Nature 605: 172-178.
  3. Nadezhdin K. D., Neuberger A., Trofimov Y. A., Krylov N. A., Sinica V., Kupko N., Vlachova V., Zakharian E., Efremov R. G. and Sobolevsky A. I. (2021) Structural mechanism of heat-induced opening of a temperature-sensitive TRP channel. Nature Structural and Molecular Biology 28: 564-572 .
  4. McGoldrick L. L., Singh A. K., Saotome K., Yelshanskaya M. V., Twomey E. C., Grassucci R. A. and Sobolevsky A. I. (2018) Opening of the Human Epithelial Calcium Channel TRPV6. Nature 553: 233-237.
  5. Twomey E. C., Yelshanskaya M. V., Grassucci R. A., Frank J. and Sobolevsky A. I. (2017) Channel opening and gating mechanism in AMPA-subtype glutamate receptors. Nature 549: 60-65.
  6. Twomey E. C., Yelshanskaya M. V., Grassucci R. A., Frank J. and Sobolevsky A. I. (2016) Elucidation of AMPA receptor-stargazin complexes by cryo-electron microscopy. Science 353: 83-86.
  7. Saotome K., Singh A. K., Yelshanskaya M. V. and Sobolevsky A. I. (2016) Crystal structure of the epithelial calcium channel TRPV6. Nature 534: 506–511.
  8. Yelshanskaya M. V., Li M. and Sobolevsky A. I. (2014) Structure of an agonist-bound ionotropic glutamate receptor. Science 345: 1070-1074.
  9. 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.

For a complete list of publications, please visit PubMed.gov