Marcel Goldschen

  • Assistant Professor
  • Neuroscience
Profile image of Marcel Goldschen

Biography

Marcel Goldschen-Ohm graduated with a B.S. in Physics from St. Cloud State University, after which he obtained his Ph.D. in Biophysics from the University of Wisconsin - Madison. He did his postdoctoral work at the University of Wisconsin - Madison in the Department of Neuroscience in the lab of Dr. Baron Chanda. During this period, he was also involved in several successful collaborations with Drs. Randall Goldsmith, Robert Pearce, Gail Robertson and Edwin Chapman. Marcel joined the faculty in the Department of Neuroscience at the University of Texas at Austin in 2017. He is a National Merit Scholar, and has received fellowships from the Epilepsy Foundation and American Heart Association, and invitations to speak at international conferences including Gordon Research Conferences and Biophysical Society annual meetings.

Research

Of primary interest in the Goldschen-Ohm lab is uncovering mechanisms of ion channel behavior and drug-modulation. Ion channels are critical for rapid signaling between neurons and other excitable cells necessary for both normal cognition and physiological function. They bind a variety of small molecules that modulate their activity in ways that can be used for therapies that counteract disorders of the nervous system such as epilepsy, or other cellular signaling abnormalities such as cardiac arrhythmias. By uncovering the physical mechanisms by which these molecules drive channel behavior, we will open up a new avenue for developing new therapeutic strategies that impact human health.

Work in the Goldschen-Ohm lab utilizes a variety of approaches such as fluorescence spectroscopy, electrophysiology and biochemistry at both single-molecule and ensemble levels to probe the dynamic motions of proteins that underlie their biological function. Dr. Goldschen-Ohm has recently developed a new high-throughput approach that can resolve binding of a single fluorescently-tagged ligand or drug molecule to its target protein at physiologically relevant concentrations previously inaccessible to single-molecule fluorescence techniques. This advance provides a novel window through which to examine how ligand/drug binding drives molecular function at a single-molecule level. The lab is particularly interested in developing new approaches to resolve the interplay between distinct domains within individual proteins, and uncover the role of these interactions in drug binding and modulation.

Research Areas

  • Biophysics or Structural Biology
  • Neuroscience

Fields of Interest

  • Molecular Biology, Genetics & Genomics
  • Optical Imaging
  • Cellular/Molecular/Structure

Publications

    1. Goldschen-Ohm MP and Chanda B. SnapShot: Channel gating mechanisms. Cell 170: 594, 2017. http://dx.doi.org/10.1016/j.cell.2017.07.019
    2. Goldschen-Ohm MP, White DS, Klenchin VA, Chanda B and Goldsmith RH. Observing single-molecule dynamics at millimolar concentrations. Angewandte Chemie (International Edition) 56: 2399-2402, 2017. https://dx.doi.org/10.1002/anie.201612050
    3. Zhao Y, Goldschen-Ohm MP, Morais Cabral JH, Chanda B and Robertson GA. The Intrinsically-liganded cyclic nucleotide-binding homology domain promotes KCNH channel activation. Journal of General Physiology 149: 249-260, 2017. https://dx.doi.org/1085/jgp.201611701
    4. Goldschen-Ohm MP, Klenchin VA, White DS, Cowgill J, Cui Q, Goldsmith RH and Chanda B. Structure and dynamics underlying elementary ligand binding events in human pacemaking channels. eLife 5, 2016. https://dx.doi.org/10.7554/eLife.20797
    5. Bao H, Goldschen-Ohm MP, Jeggle P, Chanda B, Edwardson JM and Chapman ER. Exocytotic fusion pores are composed of both lipids and proteins. Nature Structural & Molecular Biology 23: 67-73, 2016. https://dx.doi.org/10.1038/nsmb.3141 Also see accompanying News & Views: Sharma S and Lindau M. The mystery of the fusion pore. https://dx.doi.org/10.1038/nsmb.3157
    6. Goldschen-Ohm MP and Chanda B. How to open a proton pore - more than S4? Nature Structural & Molecular Biology 22: 277-278, 2015. https://dx.doi.org/10.1038/nsmb.2997
    7. Goldschen-Ohm MP, Haroldson A, Jones MV, and Pearce RA. A nonequilibrium binary elements-based kinetic model for benzodiazepine regulation of GABAA Journal of General Physiology 144: 27-39, 2014. https://dx.doi.org/10.1085/jgp.201411183
    8. Goldschen-Ohm MP and Chanda B. Probing gating mechanisms of sodium channels using pore blockers. Handbook of Experimental Pharmacology 221: 183-201, 2014. https://dx.doi.org/10.1007/978-3-642-41588-3_9
    9. Oelstrom K, Goldschen-Ohm MP, Holmgren M, and Chanda B. Evolutionarily conserved intracellular gate of voltage-dependent sodium channels. Nature Communications 5: 3420, 2014. https://dx.doi.org/10.1038/ncomms4420
    10. Capes DL*, Goldschen-Ohm MP*, Arcisio-Miranda M*, Bezanilla F, and Chanda B. Domain IV voltage sensor movement is both sufficient and rate-limiting for fast inactivation in sodium channels. Journal of General Physiology 142: 101-112, 2013. https://dx.doi.org/10.1085/jgp.201310998 *Authors contributed equally. Also see accompanying commentary: Ahern C. What activates inactivation. https://dx.doi.org/10.1085/jgp.201311046
    11. Goldschen-Ohm MP, Capes DL, Oelstrom KM, and Chanda B. Multiple pore conformations driven by asynchronous movements of voltage sensors in a eukaryotic sodium channel. Nature Communications 4: 1350, 2013. https://dx.doi.org/10.1038/ncomms2356
    12. Goldschen-Ohm MP, Wagner DA, and Jones MV. Three arginines in the GABAA receptor binding pocket have distinct roles in formation and stability of agonist- versus antagonist-bound complexes. Journal of Molecular Pharmacology 80: 647-656, 2012. https://dx.doi.org/10.1124/mol.111.072033
    13. Goldschen-Ohm MP, Wagner DA, Petrou S, and Jones MV. An epilepsy-related region in the GABAA receptor mediates long-distance effects on GABA and benzodiazepine binding sites. Journal of Molecular Pharmacology 77: 35-45, 2010. https://dx.doi.org/10.1124/mol.109.058289
    14. Wagner DA, Goldschen-Ohm MP, Hales TG, and Jones MV. Kinetics and Spontaneous open probability conferred by the epsilon subunit of the GABAA receptor. Journal of Neuroscience 25: 10462-10468, 2005. https://dx.doi.org/10.1523/JNEUROSCI.1658-05.2005