Research Projects

Cannon Lab Research Areas

Mechanism of Disease Underlying Periodic Parlaysis

• Determine the alterations of ion channel function caused by disease-associated mutations

  • Are specific changes of ion channel function associated with specific clinical variants of periodic paralysis?
  • Functional expression studies to determine whether ion channel genetic variants are innocuous (benign) or later channel function to cause disease (pathogenic).

• Understand how anomalous behavior of mutant channels causes transient attacks of weakness in Periodic Paralysis

  • Computer simulation to define the effects on muscle fiber excitability
  • Pharmacologic models to validate the impact on muscle contractility

  • Genetically-engineered mouse models (knock-in mutations) as a platform to explore the basis for provoked episodes of weakness by environmental triggers (exercise, diet, K, pH, osmolality).

     

    • Hyperkalemic periodic paralysis (NaV1.4 M1592V)
    • Hypokalemic periodic paralysis (CaV1.1 R528H)

    • Hypokalemic periodic paralysis (NaV1.4 R669H)

      

Leveraging Disease Mechanism into Development of Therapeutics for Periodic Paralysis

• Quantitatively define the efficacy and feasibility of lifestyles changes (exercise, hydration, diet) to minimize the likelihood for an attack of weakness.

• Repurposing drugs to stabilize the resting membrane potential of muscle fibers and thereby prevent attacks or enhance the recovery from weakness.

• Computational chemistry to indentify novel compounds (small molecules or synthetic peptides) that attenuate the deleterious behavior of mutant channels.

• Gene therapy to remove or to correct the missense mutation of ion channel genes causing periodic paralysis.