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Linda Columbus

Linda Columbus

Professor, Chemistry

Primary Location
PO Box 400319
Charlottesville, VA 22904
Primary Phone Number
321.23.
Email
[email protected]
Website
http://www.columbuslabs.org/

Bio & Overview

Membrane proteins facilitate the transfer of information across lipid bilayers, comprise approximately 25% of a typical proteome, and represent over half of all drug targets. The membrane proteins that mediate interactions between bacterial pathogens and hosts are of particular interest to our laboratory. Invasive bacterial pathogens are responsible for many lethal diseases and epidemics, including plague and meningitis. Although these bacteria have diverse mechanisms of cellular invasion, all of the pathways rely upon interactions between host and bacterial membrane proteins. Our lab seeks to determine the structure and dynamics of membrane proteins involved in bacterial pathogenesis and to develop tools to accelerate membrane protein structure determination using a combination of site-directed spin labeling (SDSL), nuclear magnetic resonance (NMR) spectroscopy, and X-ray crystallography.

Academic Information

Department
Chemistry
Academic Title
Associate Professor

Primary Education

  • BA, Chemistry, Smith College, 1996
  • PhD, Biochemistry and Molecular Biology, University of California Los Angeles, 2001

Other Appointments

  • Associate Professor, Molecular Physiology and Biological Physics
  • Pharmacology
  • Assistant Professor, SCBB

Other Affiliations

  • Assistant Professor, Arts & Sciences
  • Member, Chemical and Structural Biology Program
  • MSTP
  • Assistant Professor, BIMS

Research Interests

Biophysical Chemistry: Membrane protein structure, function, and dynamics

Research Disciplines

  • Biochemistry
  • Biophysics
  • Biophysics & Structural Biology
  • Biotechnology
  • Chemistry
  • Infectious Diseases/Biodefense
  • Microbiology
  • Structural Biology

Research Opportunities

  • Biochemistry
  • Biophysics & Structural Biology
  • Chemistry and Physics of Living Systems
  • Infectious Diseases
  • Microbiology

PhD Programs

  • Biophysics

Selected Publications

2024

Wolpe, A. G., Luse, M. A., Baryiames, C., Schug, W. J., Wolpe, J. B., Johnstone, S. R., . . . Isakson, B. E. (2024). Pannexin-3 stabilizes the transcription factor Bcl6 in a channel-independent manner to protect against vascular oxidative stress. SCIENCE SIGNALING, 17(821). doi:10.1126/scisignal.adg2622

2023

Nygaard, R., Graham, C. L. B., Dufrisne, M. B., Colburn, J. D., Pepe, J., Hydorn, M. A., . . . Mancia, F. (2023). Structural basis of peptidoglycan synthesis by E. coli RodA-PBP2 complex. NATURE COMMUNICATIONS, 14(1). doi:10.1038/s41467-023-40483-8

Necelis, M., Mcdermott, C., Dufrisne, M. B., Baryiames, C., & Columbus, L. (2023). Solution NMR investigations of integral membrane proteins: Challenges and innovations. CURRENT OPINION IN STRUCTURAL BIOLOGY, 82. doi:10.1016/j.sbi.2023.102654

2022

Williams, R. V., Huang, C., McDermott, C., Ahmed, T., Columbus, L., Moremen, K. W., . . . Amster, I. J. (2022). Site-to-site cross-talk in OST-B glycosylation of hCEACAM1-IgV. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 119(43). doi:10.1073/pnas.2202992119

Wolpe, A. G., Luse, M. A., Johnstone, S. R., Xue, J., Sabapathy, V., Wakefield, B., . . . Isakson, B. E. (2022). Endothelial Pannexin 3-B Cell Lymphoma-6 Interactions Protect Against Oxidative Stress. FASEB JOURNAL, 36. doi:10.1096/fasebj.2022.36.S1.R5405

2020

Werner, L. M., Palmer, A., Smirnov, A., Dufrisne, M. B., Columbus, L., & Criss, A. K. (2020). Imaging Flow Cytometry Analysis of CEACAM Binding to Opa-Expressing Neisseria gonorrhoeae. CYTOMETRY PART A, 97(10), 1081-1089. doi:10.1002/cyto.a.24037

2019

Kieber, M., Ono, T., Oliver, R. C., Nyenhuis, S. B., Tieleman, D. P., & Columbus, L. (2019). The Fluidity of Phosphocholine and Maltoside Micelles and the Effect of CHAPS (vol 116, pg 1682, 2019). BIOPHYSICAL JOURNAL, 117(11), 2240. doi:10.1016/j.bpj.2019.11.001

Kuhn, J., Smirnov, A., Criss, A. K., & Columbus, L. (2019). Quantifying Carcinoembryonic Antigen-like Cell Adhesion Molecule-Targeted Liposome Delivery Using Imaging Flow Cytometry. MOLECULAR PHARMACEUTICS, 16(6), 2354-2363. doi:10.1021/acs.molpharmaceut.8b01274

Shu, X., Ruddiman, C. A., Keller, T. C. S., Keller, A. S., Yang, Y., Good, M. E., . . . Isakson, B. E. (2019). Heterocellular Contact Can Dictate Arterial Function. CIRCULATION RESEARCH, 124(10), 1473-1481. doi:10.1161/CIRCRESAHA.118.313926

Kieber, M., Ono, T., Oliver, R. C., Nyenhuis, S. B., Tieleman, D. P., & Columbus, L. (2019). The Fluidity of Phosphocholine and Maltoside Micelles and the Effect of CHAPS. BIOPHYSICAL JOURNAL, 116(9), 1682-1691. doi:10.1016/j.bpj.2019.03.019

2018

Hays, J. M., Kieber, M. K., Li, J. Z., Han, J. I., Columbus, L., & Kasson, P. M. (2018). Refinement of Highly Flexible Protein Structures using Simulation‐Guided Spectroscopy. Angewandte Chemie, 130(52), 17356-17360. doi:10.1002/ange.201810462

Hays, J. M., Kieber, M. K., Li, J. Z., Han, J. I., Columbus, L., & Kasson, P. M. (2018). Refinement of Highly Flexible Protein Structures using Simulation-Guided Spectroscopy. ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 57(52), 17110-17114. doi:10.1002/anie.201810462

Caldwell, T. A., Baoukina, S., Brock, A. T., Oliver, R. C., Root, K. T., Krueger, J. K., . . . Columbus, L. (2018). Low-q Bicelles Are Mixed Micelles. JOURNAL OF PHYSICAL CHEMISTRY LETTERS, 9(15), 4469-4473. doi:10.1021/acs.jpclett.8b02079

Hays, J., Kieber, M., Li, J., Han, J. I., Columbus, L., & Kasson, P. (2018). Refinement of highly flexible protein structures using simulation-guided spectroscopy. doi:10.1101/319335

2017

Yang, J., Zong, Y., Su, J., Li, H., Zhu, H., Columbus, L., . . . Liu, Q. (2017). Conformation transitions of the polypeptide-binding pocket support an active substrate release from Hsp70s. NATURE COMMUNICATIONS, 8. doi:10.1038/s41467-017-01310-z

2016

Keller, T. C. S., Butcher, J. T., Broseghini-Filho, G. B., Marziano, C., DeLalio, L. J., Rogers, S., . . . Isakson, B. E. (2016). Modulating Vascular Hemodynamics With an Alpha Globin Mimetic Peptide (HbX). HYPERTENSION, 68(6), 1494-1503. doi:10.1161/HYPERTENSIONAHA.116.08171

Martin, J. N., Ball, L. M., Solomon, T. L., Dewald, A. H., Criss, A. K., & Columbus, L. (2016). Neisserial Opa Protein-CEACAM Interactions: Competition for Receptors as a Means of Bacterial Invasion and Pathogenesis. BIOCHEMISTRY, 55(31), 4286-4294. doi:10.1021/acs.biochem.6b00124

2015

Shu, X., Keller, T. C. S., Begandt, D., Butcher, J. T., Biwer, L., Keller, A. S., . . . Isakson, B. E. (2015). Endothelial nitric oxide synthase in the microcirculation. CELLULAR AND MOLECULAR LIFE SCIENCES, 72(23), 4561-4575. doi:10.1007/s00018-015-2021-0

Columbus, L. (2015). Post-expression strategies for structural investigations of membrane proteins. CURRENT OPINION IN STRUCTURAL BIOLOGY, 32, 131-138. doi:10.1016/j.sbi.2015.04.005

Gray, C., Price, C. W., Lee, C. T., Dewald, A. H., Cline, M. A., McAnany, C. E., . . . Mura, C. (2015). Known structure, unknown function: An inquiry-based undergraduate biochemistry laboratory course. BIOCHEMISTRY AND MOLECULAR BIOLOGY EDUCATION, 43(4), 245-262. doi:10.1002/bmb.20873

Columbus, L., & Kroncke, B. (2015). Solution NMR Structure Determination of Polytopic α-Helical Membrane Proteins: A Guide to Spin Label Paramagnetic Relaxation Enhancement Restraints. MEMBRANE PROTEINS - ENGINEERING, PURIFICATION AND CRYSTALLIZATION, 557, 329-348. doi:10.1016/bs.mie.2014.12.005

2014

Johnson, M. B., Ball, L. M., Daily, K. P., Martin, J. N., Columbus, L., & Criss, A. K. (2015). Opa plus Neisseria gonorrhoeae exhibits reduced survival in human neutrophils via Src family kinase-mediated bacterial trafficking into mature phagolysosomes. CELLULAR MICROBIOLOGY, 17(5), 648-665. doi:10.1111/cmi.12389

Oliver, R. C., Lipfert, J., Fox, D. A., Lo, R. H., Kim, J. J., Doniach, S., & Columbus, L. (2014). Tuning Micelle Dimensions and Properties with Binary Surfactant Mixtures. LANGMUIR, 30(44), 13353-13361. doi:10.1021/la503458n

Lo, R. H., Kroncke, B. M., Solomon, T. L., & Columbus, L. (2014). Mapping Membrane Protein Backbone Dynamics: A Comparison of Site-Directed Spin Labeling with NMR 15N-Relaxation Measurements. BIOPHYSICAL JOURNAL, 107(7), 1697-1702. doi:10.1016/j.bpj.2014.08.018

Straub, A. C., Butcher, J. T., Billaud, M., Mutchler, S. M., Artamonov, M. V., Nguyen, A. T., . . . Isakson, B. E. (2014). Hemoglobin α/eNOS Coupling at Myoendothelial Junctions Is Required for Nitric Oxide Scavenging During Vasoconstriction. ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 34(12), 2594-2600. doi:10.1161/ATVBAHA.114.303974

Fox, D. A., Larsson, P., Lo, R. H., Kroncke, B. M., Kasson, P. M., & Columbus, L. (2014). Structure of the Neisserial Outer Membrane Protein Opa60: Loop Flexibility Essential to Receptor Recognition and Bacterial Engulfment. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 136(28), 9938-9946. doi:10.1021/ja503093y

Butcher, J. T., Johnson, T., Beers, J., Columbus, L., & Isakson, B. E. (2014). Hemoglobin α in the blood vessel wall. FREE RADICAL BIOLOGY AND MEDICINE, 73, 136-142. doi:10.1016/j.freeradbiomed.2014.04.019

Lo, R. H., Fox, D. A., & Columbus, L. (2014). Structure, Dynamics, and Receptor Binding of Opa Proteins. Biophysical Journal, 106(2), 266a-267a. doi:10.1016/j.bpj.2013.11.1561

Baker, L. A., Chakraverty, D., Columbus, L., Feig, A. L., Jenks, W. S., Pilarz, M., . . . Wesemann, J. L. (2014). Cottrell Scholars Collaborative New Faculty Workshop: Professional Development for New Chemistry Faculty and Initial Assessment of Its Efficacy. JOURNAL OF CHEMICAL EDUCATION, 91(11), 1874-1881. doi:10.1021/ed500547n

2013

Kenwood, B. M., Weaver, J. L., Bajwa, A., Poon, I. K., Byrne, F. L., Murrow, B. A., . . . Hoehn, K. L. (2014). Identification of a novel mitochondria! uncoupler that does not depolarize the plasma membrane. MOLECULAR METABOLISM, 3(2), 114-123. doi:10.1016/j.molmet.2013.11.005

Li, J., Liu, Q., Xiao, L., Haverstick, D. M., Dewald, A., Columbus, L., . . . Landers, J. P. (2013). Label-Free Method for Cell Counting in Crude Biological Samples via Paramagnetic Bead Aggregation. ANALYTICAL CHEMISTRY, 85(23), 11233-11239. doi:10.1021/ac401402h

Fox, D. A., & Columbus, L. (2013). Solution NMR resonance assignment strategies for -barrel membrane proteins. PROTEIN SCIENCE, 22(8), 1133-1140. doi:10.1002/pro.2291

Elkin, S. R., Kumar, A., Price, C. W., & Columbus, L. (2013). A broad specificity nucleoside kinase from Thermoplasma acidophilum. PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS, 81(4), 568-582. doi:10.1002/prot.24212

Anton, B. P., Chang, Y. -C., Brown, P., Choi, H. -P., Faller, L. L., Guleria, J., . . . Kasif, S. (2013). The COMBREX Project: Design, Methodology, and Initial Results. PLOS BIOLOGY, 11(8). doi:10.1371/journal.pbio.1001638

Oliver, R. C., Lipfert, J., Fox, D. A., Lo, R. H., Doniach, S., & Columbus, L. (2013). Dependence of Micelle Size and Shape on Detergent Alkyl Chain Length and Head Group. PLOS ONE, 8(5). doi:10.1371/journal.pone.0062488

2012

Straub, A. C., Lohman, A. W., Billaud, M., Johnstone, S. R., Dwyer, S. T., Lee, M. Y., . . . Isakson, B. E. (2012). Endothelial cell expression of haemoglobin α regulates nitric oxide signalling. NATURE, 491(7424), 473-477. doi:10.1038/nature11626

Kroncke, B. M., & Columbus, L. (2013). Backbone 1H, 13C and 15N resonance assignments of the α-helical membrane protein TM0026 from Thermotoga maritima. BIOMOLECULAR NMR ASSIGNMENTS, 7(2), 203-206. doi:10.1007/s12104-012-9410-1

Johnstone, S. R., Kroncke, B. M., Straub, A. C., Best, A. K., Dunn, C. A., Mitchell, L. A., . . . Isakson, B. E. (2012). MAPK Phosphorylation of Connexin 43 Promotes Binding of Cyclin E and Smooth Muscle Cell Proliferation. CIRCULATION RESEARCH, 111(2), 201-U205. doi:10.1161/CIRCRESAHA.112.272302

Kroncke, B. M., & Columbus, L. (2012). Identification and removal of nitroxide spin label contaminant: Impact on PRE studies of a-helical membrane proteins in detergent. PROTEIN SCIENCE, 21(4), 589-595. doi:10.1002/pro.2038

Johnstone, S. R., Kroncke, B. M., Straub, A. C., Best, A. K., Dunn, C. A., Koval, M., . . . Isakson, B. E. (2012). MAPK phosphorylation of connexin 43 promotes binding of cyclin E and smooth muscle cell proliferation. FASEB JOURNAL, 26. Retrieved from https://www.webofscience.com/

2011

Dewald, A. H., Hodges, J. C., & Columbus, L. (2011). Physical Determinants of β-Barrel Membrane Protein Folding in Lipid Vesicles. BIOPHYSICAL JOURNAL, 100(9), 2131-2140. doi:10.1016/j.bpj.2011.03.025

2010

Kroncke, B. M., Horanyi, P. S., & Columbus, L. (2010). Structural Origins of Nitroxide Side Chain Dynamics on Membrane Protein α-Helical Sites. BIOCHEMISTRY, 49(47), 10045-10060. doi:10.1021/bi101148w

Beuck, C., Szymczyna, B. R., Kerkow, D. E., Carmel, A. B., Columbus, L., Stanfield, R. L., & Williamson, J. R. (2010). Structure of the GLD-1 Homodimerization Domain: Insights into STAR Protein-Mediated Translational Regulation. STRUCTURE, 18(3), 377-389. doi:10.1016/j.str.2009.12.016