Radwanski Lab

Mission

Understanding the mechanisms underlying cardiac arrhythmias and seizures while developing safer, more effective therapies through biophysical, pharmacological, and translational approaches.

Key areas of focus

  • Cardiac & neural electrophysiology
  • Ion channel biophysics and pharmacology
  • Sodium channel isoforms and excitability
  • Isoform-selective antiarrhythmic and antiseizure therapies
  • Drug repurposing and translational therapeutics
  • Single-molecule to whole-organism approaches

Lab team

  • Przemysław Radwański, Pharm.D., Ph.D. : Principal Investigator
  • Joseph Waterman, B.S. : Research Scientist

Notable research findings

Work in our lab can be divided into two main research themes:

Role of neuronal-type sodium channels in inherited and acquired cardiac arrhythmias: A major goal of this research theme is to understand the roles of neuronal-type sodium channels in health and disease, and thereby, develop means to prevent life-threatening adverse events resulting from their dysfunction. By using cutting-edge, biophysical approaches ranging from the single ion channel level to the whole organism, my lab has identified neuronal-type sodium channels, including NaV1.6, localized within discrete cardiomyocyte nanodomains, where they play key roles in sodium/calcium homeostasis (Radwański et al., Cardiovasc Res. 2015; Struckman et al., Microsc Microanal. 2020; Tarasov et al., JCI 2023). We have discovered how dysfunction of these channels drives calcium dysregulation and life-threatening arrhythmias in inherited and acquired disease (Koleske et al., J Gen Physiol. 2018; Radwański et al., JACC Basic Transl Sci. 2016). We recently extended our insights to the clinical setting, demonstrating the antiarrhythmic efficacy and cardioprotective effects of riluzole, a drug used for amyotrophic lateral sclerosis that inhibits neuronal-type sodium channels (Munger et al., J Am Heart Assoc. 2020; Kim et al., Eur J Neurol. 2025).

In ongoing work, we aim to uncover the mechanisms underlying the formation, organization, and regulation of sodium channel clusters and how the sodium channels within these clusters cooperate to determine the biophysics of cardiac and neural excitability (Tarasov et al., Nat Commun. 2026). Additionally, we are examining the safety of various sodium channel blockers currently employed in management of various disease states, ranging from neurological disorders to heart disease (Kim et al., Sci Rep 2025; Kim et al., Pharmacotherapy 2025; Dias et al., Epilepsia 2025).

Sudden cardiac death as a contributor to sudden unexplained death in epilepsy (SUDEP): In another exciting direction for the lab, we have been investigating SUDEP, delineating the respective contributions of the heart and the brain to this phenomenon. We are discovering that, because key ion channels are expressed in both brain and heart, patients with defects in these experience two-fold dysfunction – pro-arrhythmic mishandling of sodium and calcium in the heart. We recently discovered that primary cardiac dysfunction alone is sufficient to recapitulate a major part of the sudden death phenotype in adult subjects with Dravet syndrome (King et al, JACC Clin Electrophysiol. 2024). Previous therapeutic approaches, which focused on the dysfunction in the nervous system alone, have yielded limited success. In contrast, we are developing novel therapies that target both aspects of dysfunction (i.e., the heart and brain), while minimizing the risk of pro-arrhythmia and these are showing immense promise in preclinical animal experiments. Moving forward, we are using our novel murine models of epilepsy and those previously established in the field to develop novel life-saving therapies for inherited and acquired epilepsy while avoiding potentially deadly side effects.

Equipment, technology and techniques

• Scanning ion conductance microscopy (SICM)-guided patch clamp electrophysiology
• Genetic murine models of arrhythmia, cardiomyopathy and epilepsy
• High-spatial and temporal confocal imaging
• Optical mapping
• Electrocardiography (ECG)

Active grants and research projects

  1. Defining novel mechanisms of sudden death in Dravet syndrome: Dysregulation of sodium channels in the heart.
    • Award: R01NS121234
    • Funding organization: National Institute of Health (NIH) - National Institute of Neurological Disorders and Stroke (NINDS)
  2. Regulation and dysregulation of sodium channels by calmodulin.
    • Award: R01NS121234
    • Funding organization: National Institute of Health (NIH) - National Heart, Lung, and Blood Institute (NHLBI)