About

Jonathan Davis, PhD, is a Professor of Physiology and Cell Biology at The Ohio State University College of Medicine. His research focuses on elucidating the biochemical and physiological mechanisms that determine the kinetics and magnitude of cardiac, skeletal, and smooth muscle contraction and relaxation in health and disease through the engineering of proteins. His specific interests include understanding the cellular and molecular basis of muscle contraction and relaxation, and how calcium binding proteins and enzymes are kinetically tuned to respond to calcium transients both in vitro and in vivo. Dr. Davis's laboratory studies the behavior of engineered proteins from isolated systems to complex protein assemblies, muscle cells, and ultimately in vivo models, utilizing advanced virus and protein delivery techniques to study their effects in small and large animal systems.

Research topics

• Medicine
• Biochemistry
• Internal medicine
• Biology
• Chemistry
• Biophysics
• Cardiology
• Anatomy
• Crystallography
• Cell biology

Selected publications

• BPS2026 – Dynamic-structure redesign of calmodulin reduces Ca2+ leak and reveals mechanistic insights into RyR2 regulation

  Biophysical Journal · 2026-02-01

  articleSenior author
  PublisherDOI

• Dynamic-Structure Redesign of Calmodulin Reveals Mechanistic Constraints on Ryr2 Regulation

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-04-17

  articleOpen accessSenior authorCorresponding

  2. ABSTRACT Calmodulin (CaM) is a highly conserved Ca 2+ sensor that regulates hundreds of cellular targets through Ca 2+ -dependent conformational dynamics. Despite its central role in Ca 2+ signaling and disease, its evolutionary conservation and structural flexibility have suggested that CaM is resistant to rational redesign. Here, using the cardiac Ca 2+ release channel Ryanodine receptor 2 (RyR2) as a model system, we tested whether incorporating conformational dynamics into computational protein design enables functional reengineering of CaM. We first applied a static structure–based redesign to increase CaM–RyR2 affinity. Although the resulting variant bound more tightly to both the RyR2 peptide and the intact channel in vitro, it distorted peptide geometry and worsened Ca 2+ leak in cardiomyocytes ex vivo. Guided by molecular dynamics simulations, we then developed a dynamic-structure redesign strategy that preserves conformational integrity while strengthening binding. The resulting CaM variant exhibited increased RyR2 affinity and reduced pathological Ca 2+ leak in a disease-relevant model. These findings show that improved binding affinity alone is insufficient to enhance physiological regulation and that successful CaM redesign requires preservation of conformational dynamics. More broadly, they demonstrate that integrating conformational dynamics into protein redesign can enable functionally predictive engineering of flexible regulatory protein–protein interactions.

  PublisherDOI

• BPS2026 – Troponin enhanceropathies: A novel role for the troponin genes

  Biophysical Journal · 2026-02-01

  articleSenior author
  PublisherDOI

• BPS2026 – The D73N troponin C mouse: A translational model of dilated cardiomyopathy with mitochondrial ROS and novel atrial myxomas

  Biophysical Journal · 2026-02-01

  articleSenior author
  PublisherDOI

• Molecular interactions of the NaV1.5 C-terminal domain: CaM sequestered the IQ motif from the CTD

  Journal of Biological Chemistry · 2025-10-30 · 1 citations

  articleOpen access

  <h2>Abstract</h2> Voltage-gated sodium channels (Na_V) are important for life. Alterations to the synchronized timing of ion conduction can create life-threatening conditions. How Na_V conduction responds to changes in intracellular Ca²⁺ concentration has been the subject of extensive investigation. Crystal structures of the cardiac Na_V (Na_V1.5) cytosolic components were reported as trimeric complexes that are restructured in the presence of Ca²⁺. These results formed the basis for a gating model where two Na_V1.5 molecules interact to alter function in response to Ca²⁺ concentration. Here, we investigated the binding site surface of these trimeric interactions in solution. NMR demonstrated that these trimeric complexes do not form in solution. Analysis of the available structural data indicated that the Na_V1.5 IQ motif can only accommodate interaction with one protein at a time. Our NMR data were consistent with the Na_V1.5 C-terminal domain (CTD) and the Ca²⁺- sensing protein calmodulin (CaM) engaging the same binding site surface of the Na_V1.5 IQ motif. Titrations of IQ motif peptide into a 1:1 mixture of ¹⁵N CTD : CaM sample revealed the Na_V1.5 channel is biophysically distinct from neuronal Na_V1.2 as Ca²⁺ enhanced CaM's ability to sequester the Na_V1.5 IQ motif from the Na_V1.5 CTD. Stopped-flow kinetic measurements quantified Ca²⁺ release rates from the CaM-IQ and CaM-inactivation gate (IGATE) complexes to provide insight into complex lifetimes. Our work advanced understanding the molecular machinery that underlies Na_V1.5 gating (CTD-IGATE and CTD-IQ motif interactions) and provided insight into the structural details of CaM-facilitated Na_V1.5 modification (CaM-IQ motif and CaM-IGATE interactions).

  PublisherOA PDFDOI

• BPS2025 - Mechanisms underlying distinct cardiac arrhythmia phenotypes caused by calmodulin mutation D132E in Calm2 and Calm3 genes

  Biophysical Journal · 2025-02-01

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  PublisherDOI

• BPS2025 - Spatial compartmentalization of the expression of CaM genes supports versatile Ca2+-CaM signaling in cardiac myocytes

  Biophysical Journal · 2025-02-01

  article
  PublisherDOI

• Biophysical characterization of anion channels in mitochondrion-endoplasmic-reticulum contact sites

  Biophysical Journal · 2025-04-06 · 2 citations

  articleOpen access
  PublisherOA PDFDOI

• Transforming Growth Factors in Venous Thrombus Formation and Resolution

  Arteriosclerosis Thrombosis and Vascular Biology · 2025-03-20 · 3 citations

  reviewOpen access1st authorCorresponding

  Deep vein thrombosis (DVT) and pulmonary embolism are vascular occlusive disorders categorized under the term venous thromboembolism. Venous thromboembolism affects ≈900 000 people per year in the United States alone. Understanding of the multifaceted process of DVT has improved in recent years, and current DVT treatments reduce thrombus propagation, but they also increase bleeding risk and fail to accelerate natural venous thrombus resolution. Multiple inflammatory cytokines regulate the development and subsequent resolution of DVT. One family of cytokines involved in DVT and venous thrombus resolution is the TGF-β (transforming growth factor-β) family. A comprehensive understanding of the control of venous thrombus formation and resolution by the TGF-β family could lead to the development of novel treatments for DVT that target ≥1 of the TGF-β isoforms. The aim of this review is to describe studies of the roles of the TGF-β isoforms in venous thrombus formation and resolution and to highlight opportunities for future research. TGF-β isoforms include TGF-β1, TGF-β2, and TGF-β3. TGF-β1 has a well-characterized role in the positive regulation of venous thrombus formation and the negative regulation of venous thrombus resolution. Further research is necessary, however, to understand the potential roles of TGF-β2 and TGF-β3 in venous thrombus formation and resolution. Given that TGF-β1 expression increases during venous thrombosis and that inhibition or knockdown of TGF-β1 reduces thrombus burden, TGF-β1 represents a potential diagnostic marker for DVT and a putative target for therapies that aim to prevent or treat DVT.

  PublisherOA PDFDOI

• BPS2025 - Localized synthesis of cardiac excitation-contraction coupling proteins: A dual role for the sarcoplasmic reticulum

  Biophysical Journal · 2025-02-01

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  PublisherDOI

Recent grants

• NIH Grant R21AG051913

  NIH · $424k · 2018

• NIH Grant R56HL091986

  NIH · $379k · 2017

• NIH Grant R01HL132213

  NIH · $1.5M · 2021

• NIH Grant R01HL091986

  NIH · $1.9M · 2015

• Regulation and Dysregulation of Cardiac EC coupling by Calmodulin

  NIH · $6.1M · 2017–2027

Frequent coauthors

• Paul M.L. Janssen

  The Ohio State University

  73 shared

• Svetlana B. Tikunova

  The Ohio State University

  72 shared

• Gary H. Wikfors

  Rogers (United States)

  56 shared

• Brandon J. Biesiadecki

  The Ohio State University

  48 shared

• Mark T. Ziolo

  The Ohio State University

  42 shared

• Sándor Györke

  The Ohio State University

  41 shared

• Sean C. Little

  Bristol-Myers Squibb (United States)

  41 shared

• James C. Widman

  National Oceanic and Atmospheric Administration

  40 shared