The Johnson Laboratory: From Atoms to Hearts to Health (AH₂)

We study atoms to understand hearts and improve human health.

Dr. Johnson is a structural biologist that utilizes a multi-disciplinary approach to understand how calcium sensitive proteins and enzymes modify or tune the function of ion channels. Working at the interface of science and medicine, his research combines structural biology, biophysics, and electrophysiology to understand how the intracellular calcium sensing protein “calmodulin” senses changes in calcium concentration and modifies protein-protein interactions. Their team is actively investigating how ion channel - accessory protein interactions, post-tranlational modification and local environment help or hinder an ion to pass through a channel pore.   By developing a detailed understanding of structure (NMR), function (whole cell patch clamp), and timing (stopped-flow), they seek to: (i) understand mechanisms that govern physiology, and genetically driven channelopathies, (ii) develop small molecule probes that test their models, and (iii) explore novel strategies for treating excitable cell disease.

A newly renovated fishbowl style office allows Dr. Johnson to stay in the lab and work with his team at the bench.

An open floor concept arrangement allows team members to routinely interact with other aspects of each project. This encourages integration of technique and interdisciplinary data awareness.

Specialized microscopes allow for investigation of ion channel function and calcium signaling.

A new 800MHz NMR joins the fleet (600MHz, 500 MHz and 300 MHz), and opens up new opportunities for advanced structural and biophysical characterization.

Select Publications from past 7 years:

An Interdisciplinary Approach to Science: Editorial   

Szulcek, R., Johnson, C. N., Pearson, J. T. & Sequeira, V. Editorial: Bridging Techniques: Basic Science of Molecules, Cellular Systems, and Whole-Organ Physiology. Frontiers in Physiology (2022). PMID: 35399270, PMCID: PMC8987352 DOI.org/10.3389/fphys.2022.879396

Enzymes 

Xu et al. Hypercontractility and Oxidative Stress Drive Creatine Kinase Dysfunction in Hypertrophic Cardiomyopathy. Circulation, manuscript accepted Sept 29^th 2025 - link coming soon

Williams, R. B. et al. Human disease-associated calmodulin mutations alter calcineurin function through multiple mechanisms. Cell Calcium (2023). PMID: 37245392, PMCID: PMC10330910

Williams, R. B. & Johnson, C. N. A review of calcineurin biophysics with implications for cardiac physiology. Int J Mol Sci (2021). PMID: 34768996, PMCID: PMC8583826

Sun, B. et al. Non-Canonical Interaction between Calmodulin and Calcineurin Contributes to the Differential Regulation of Plant-Derived Calmodulins on Calcineurin. J Chem Inf Model (2021). PMID: 34615359, PMCID: PMC8867402

Ligand Gated Channels (RyR2 and MCU)

M. N. Afsar. et al. Quantification of Sarcoplasmic Reticulum Ca²⁺ Release in Primary Ventricular Cardiomyocytes. Curr Protoc Pharmacol (2024). PMID: 39475381,  DOI: 10.1002/cpz1.70048

Garcia et al. Calmodulin Enhancement of Mitochondrial Calcium Uniporter Function in Isolated Mitochondria. Cell Calcium (2025) PMID: 40768860  DOI: 10.1016/j.ceca.2025.103056

Voltage Gated Channels (Na_Vs and Ca_V) 

Rita F. Gyawu et al. Molecular interactions of the NaV1.5 C-terminal domain: CaM sequestered the IQ motif from the CTD, Journal of Biological Chemistry (2025) manuscript accepted -link coming soon

Plumereau et al. Characterization of the SCN4A/E452K variant in myotonia and paramyotonia congenita: Biophysical properties and structural implications. Scientific Reports (2025)  manuscript accepted, DOI.org/10.1038/s41598-025-17816-2 

Lile, S. K. et al. Potential C-terminal domain interactions of the cardiac voltage gated sodium channel. Scientific Reports (2025). PMID: 40269094, PMCID: PMC12019241         

Knotts, G. M. et al. An all-atom model of the human cardiac sodium channel in a lipid bilayer. Scientific Reports (2024). PMID: 39500978, PMCID: PMC11538489

Christopher N. Johnson et al. A Mechanism of Calmodulin Modulation of the Human Cardiac Sodium Channel. Structure (2018). PMID: 29606593  PMCID: PMC5932218 DOI: 10.1016/j.str.2018.03.005

Christopher N. Johnson Calcium modulation of cardiac sodium channels. Journal of Physiology (2019) PMID: 30707447  DOI: 10.1113/JP277553    

Induced Pluripotent Stem Cell derived Cardiomyocytes (iPSC-CMs)

O’Neill, M. J. et al. Multiplexed Assays of Variant Effect and Automated Patch Clamping Improve KCNH2-LQTS Variant Classification and Cardiac Event Risk Stratification. Circulation (2024). PMID: 39315434, PMCID: PMC11611689 (available on 2025-12-03)

Mitchell, D. et al. Generation of human induced pluripotent stem cell (hiPSC) lines from patients with extreme high and low polygenic scores for QT interval. Stem Cell Research (2025). PMID: 40043554, DOI: 10.1016/j.scr.2025.103691       

Small Molecule Interactions 

CN Johnson et al. The CaMKII inhibitor KN93-calmodulin interaction and implications for calmodulin tuning of Na_V1.5 and RyR2 function. Cell Calcium (2019) PMID: 31401388 PMCID: PMC6708471 DOI.org/10.1016/j.ceca.2019.102063 

Johnson laboratory graduate student team (blue)  undergraduate students (blue)

2025

Gordon Conference: Excitation Contraction Coupling: All-Atom Ion Channel Models Explore Allosteric Communication Between Cytosol and Transmembrane Helices.  Spencer Lile, Garrett Knots, Vineeth Vanga, Caden McGarity, Randy Kubi, Jarrod Smith and Christopher N. Johnson, Barcelona Spain.

Gordon Conference: Excitation Contraction Coupling: Quantification of SR Ca²⁺ release at multiple free [Ca²⁺] interrogated the effects of RyR2 phosphorylation on Ca²⁺ induced Ca²⁺ release (CICR). Md Nure Alam Afsar, Mahmuda Akter, and Christopher N. Johnson Barcelona Spain.

International Society for Heart Research - World Congress: Alterations to SR Ca²⁺ Release and Potential Rescue by Kavalactones. Md Nure Alam Afsar, Mahmuda Akter, Deb Arpita, Barbara Kaplan, Tengfei Bian, Xing Chengguo, and Christopher N. Johnson, Nara Japan.

International Society for Heart Research - World Congress: Structural Differences Between Full Sequence Models of Na_Vs. Spencer K. Lile, Randy K. Appiah, Emily M. Campbell, Steven R. Gwaltney, and Christopher N. Johnson, Nara Japan.

International Biophysical Society Conference: Improved Descriptions of Voltage Gated Sodium Channel C Terminal Domain Interactions. Spencer K. Lile, Garrett M. Knotts, Emily M. Campbell, Rita F. Gyawu, Jarrod A. Smith, Steven R. Gwaltney, and Christopher N. Johnson. Los Angeles CA.

International Biophysical Society Conference: Quantifying the Effects of Kavalactones on Sarcoplasmic Reticulum Ca²⁺ Release in Permeabilized Cardiomyocytes Mahmuda Akter, Md Nure Alam Afsar, Bian Tengfei, Vasco Sequeira, Chengguo Xing, and Christopher N. Johnson Los Angeles CA.

2024

International Biophysical Society Conference: Insight into the Biophysical Nature of Calmodulin through the Lens of Disease Associated Mutations. Sara A. Garcia, Justin R. Lovett, Emily M. Campbell, and Christopher N. Johnson, Philadelphia PA.

International Biophysical Society Conference: An All Atom Model of a Voltage Gated Calcium Channel with Explicit Salt and Water. Emily M. Campbell , Steven R. Gwaltney ¹, and Christopher N. Johnson. Philadelphia PA.

International Biophysical Society Conference. Engineering point mutations in Calmodulin to fine-tune calcium release properties of Ryanodine Receptor Type II (RyR2). Md Nure Alam Afsar, Vladimir Bogdanov, Svetlana Tikunova, Mahmuda Akter, Jonathan P. Davis and Christopher N. Johnson, Philadelphia PA.

International Biophysical Society Conference: An All Atom Model of a Voltage Gated Calcium Channel with Explicit Salt and Water. Garrett M. Knotts, Spencer K. Lile, Emily M. Campbell, Steven R. Gwaltney, and Christopher N. Johnson, Philadelphia PA.

Gordon Conference: Cardiac Regulatory Mechanisms: Differences in Sodium Channel Inactivation Gate Sequences Provide Insight into Channel Tuning. Rita F. Gyawu, Justin R. Lovett, Taylor A. Agee, Emily M. Campbell, Spencer K. Lile, Garrett M. Knotts,  Johnathan P. Davis and Christopher N. Johnson, New London NH.

Gordon Conference: Cardiac Regulatory Mechanisms: A multidisciplinary approach for investigating communication between cytosolic components and ion channel conduction. Emily M. Campbell, Rita F. Gyawu, Sara A. Garcia, Taylor A. Agee, Garrett M. Knotts and Christopher N. Johnson. New London NH.

Gordon Conference: Cardiac Regulatory Mechanisms: A His Button on Na_V1.5 Modifies Ion Channel Accessory Protein Interaction and Gating in Response to Changes in Intracellular pH. Taylor Agee, Sara Garcia, Garrett Knotts, Christopher N. Johnson, New London NH.

South Eastern Meeting of American Chemical Society: Exploring Calcium-mediated phosphorylation status of RyR2 and potential contribution to cardiac disease. Md Nure Alam Afsar, Mahmuda Akter, and Christopher N. Johnson, Atlanta GA

South Eastern Meeting of American Chemical Society: Defining the calmodulin-sodium channel interactions and evaluating potential for harnessing as a means of therapeutic intervention. Rita F. Gyawu, Justin R. Lovett, Taylor A. Agee, Johnathan P. Davis and Christopher N. Johnson, Atlanta GA

European Muscle Conference: Calmodulin enhanced myofilament function; potential for a novel interaction with cardiac myofillament protein(s)? Maicon L. Vieria, Jose R. Pinto, Weikang Ma, Jolanda van der Velden, Thomas Irving, Vasco Sequeira, and Christopher N. Johnson, Ljubljana Slovenia.

International Society for Heart Research: All Atom Models of Voltage-Gated Ion Channels (Na_V1.5 and Ca_V1.2) in Lipid Bilayers. Emily M. Campbell, Spencer K. Lile, Garrett M. Knotts, Steven R. Gwaltney, and Christopher N. Johnson, Toulouse France.

2023

International Biophysical Society Conference: Human Disease Associated Calmodulin Mutations Alter Calcineurin Function Through Multiple Mechanisms. MD Nure Alam Afsar, Ryan B. Williams, Svetlana Tikunova, Yongjun Kou, Xuan Fang, Radha P. Somarathne, Rita F. Gyawu, Garrett M. Knotts, Taylor A. Agee, Sara A. Garcia, Nicholas C. Fitzkee, Peter M. Kekenes-Huskey, Jonathan P. Davis, and Christopher N. Johnson, San Diego, CA

International Biophysical Society Conference: Insight into sodium channel calcium sensing and mechanisms of gating modification. Rita F. Gyawu, Garrett M. Knotts, Bailey S. Herring, Torien M. Beard, MNA Afsar, Taylor A. Agee, Jarrod A. Smith, Brett Kroncke, and Christopher N. Johnson San Diego, CA.

Gordon Conference: Cardiac Regulatory Mechanisms: An Atomistic Description of the Human Cardiac Sodium Channel in a Lipid Membrane with insights into B-subunit modification. Bailey S. Herring, Kelsei Elmore, Garrett Knotts, Jarrod Smith, Steven R. Gwaltney, Christopher N. Johnson, New Haven NH.

Gordon Conference: Cardiac Regulatory Mechanisms: Insight into the assemble of the cardiac sodium channel calcium sensing apparatus and mechanisms of gating modification. Rita F. Gyawu, Torien M. Beard, MNA Afsar, Taylor A. Agee, Jarrod A. Smith, Brett Kroncke, and Christopher N. Johnson, New Haven NH.

Gordon Conference: Cardiac Regulatory Mechanisms: Insight into Calmodulin signal transduction and "potential" contributions to the cardiac Calmodulinopathy phenotype. Taylor A. Agee, Ryan B. Williams, Md. Nure Alam Afsar, Yongjun Kou, Svetlana Tikunova, Jonathan P. Davis, and Christopher N. Johnson, New Haven NH.

International Society for Heart Research World Congress: Solution NMR reveals a pH influence for sodium channel calcium mediated interactions, Rita F. Gyawu, Garett Knotts, MNA Afsar, Taylor A. Agee, Jarrod A. Smith, Brett Kroncke, and Christopher N. Johnson. Berlin Germany

International Society for Heart Research World Congress: Disease-Associated Calmodulin Mutations Impair Calcineurin Function Through Multiple Mechanisms. Ryan B. Williams, Md. Nure Alam Afsar, Yongjun Kou, Taylor A. Agee, Svetlana Tikunova, Jonathan P. Davis, and Christopher N. Johnson, Berlin Germany.

Vanderbilt University Integrated Application of Structural Biology Symposium: An Atomistic Description of the Human Cardiac Sodium Channel in a Lipid Membrane Bailey S. Herring, Jarrod Smith, Steven R. Gwaltney, and Christopher N. Johnson, Nashville TN.

Vanderbilt University Integrated Application of Structural Biology Symposium: A Creative Use of NMR Spectroscopy to Interrogate Protein-Protein Interactions in a Multicomponent System Rita F. Gyawu, Torien M. Beard, MNA Afsar, Taylor A. Agee, Jarrod A. Smith, Brett Kroncke, and Christopher N. Johnson, Nashville TN.

Lester Andrews Graduate Research Symposium: Electricity to Localization: Enhancing Understanding of a Heartbeat. Garrett Knotts, Kelsei Elmore, MNA Afsar, Rita Gyawu, Bailey Herring, Ryan B. Williams, Taylor Agee, and Christopher N. Johnson, Starkville MS.

Lester Andrews Graduate Research Symposium: Potential Sodium Channel Modifying Proteins: Who are They and What Do They Do in the Heart ? *Kelsei Elmore, Garrett Knotts, MNA Afsar, Rita Gyawu, Ryan Williams, Bailey Herring, Taylor Agee, and Christopher N. Johnson, Starkville MS.                                   *Undergraduate poster presenter award

2022

International Biophysical Society Conference: Altered calcineurin function has potential to contribute to Calmodulinopathy. Ryan B. Williams, Taylor A. Agee, Svetlana Tikunova, Jonathan P. Davis, and Christopher N. Johnson, San Francisco, CA.

International Biophysical Society Conference: NMR Competition Experiments Interrogate Mechanistic Details of Sodium Channel Calcium Sensitivity. Torien Beard, Rita F. Gyawu, MNA Afsar, TaylorA.Agee, JarrodA.Smith, BrettKroncke, and Christopher N. Johnson, San Francisco, CA.

2021

      Mississippi State University Pitt Festival Conference: A Clever Twist of NMR to Unmask Ligand Binding Preference. Torien M. Beard, Rita F. Gyawu, MNA Afsar, Taylor A. Agee, Jarrod A. Smith, Brett Kroncke, and Christopher N. Johnson, Starkville MS.

Current Team Members:

Afsar Alam - 5^th year graduate student

Rita Gyawu - 5^th year graduate student

Taylor Agee - 5^th year graduate student

Sara Garcia - 3^rd year graduate student 

Randy Kubi Appiah - 2^nd year graduate student

Spencer Lile - 3^rd year undergraduate student 

Katie Robinson - 1^st year undergraduate student

Elice Richardson - 1^st year graduate student

Godfred Sunyele - 1^st year graduate student

Dilmini Abayawardana - 1^st year graduate student 

Laboratory Alumni

Garrett Knotts

Emily Campbell

Luke Lossardo

Nolan Binion

Kelsie Elmoore

Torien Beard

Ryan Williams