Assistant Investigator Anesthesia, Critical Care and Pain Medicine, Mass General Research Institute

Assistant Professor of Anaesthesia Harvard Medical School

epilepsy; etomidate; gabaa receptors; general anesthesia; ion channels; noradrenergic neurotransmission; seizures; serotonergic neurotransmission; sudden unexpected death in epilepsy; sudep

Research Areas

• Mechanism and prevention of sudden unexpected death in epilepsy (SUDEP)
• Molecular mechanism of general anesthetics 

Description of Research

We investigate the mechanism underlying SUDEP in animal models.  Using cutting-edge cell-type specific technologies such as optogenetics and designer receptors exclusively activated by designer drugs (DREADD), we dissect the monoaminergic circuitry that is involved in seizure-induced sudden death.  Our study observed that optogenetic activation of serotonergic neurons in the midbrain dorsal raphe suppresses seizure-induced sudden death in transgenic DBA/1 mice.  We also seek targeted pharmacological interventions to prevent SUDEP.  Our work showed that certain widely used medications and food supplements, including atomoxetine and 5-hydroxytryptophan, alleviate seizure-induced sudden death.  These compounds are therefore potentially useful to protect patients with epilepsy from SUDEP.  

We study the mechanism of general anesthesia.  We test the modulation of GABAA receptors, especially the alphabetadelta GABAA receptor that mediates the tonic inhibition, by general anesthetics using molecular biology, biochemistry and electrophysiology techniques.  The receptor kinetic properties, including desensitization and deactivation, are examined using a rapid drug application device and patch-clamp recordings.  Shifts of GABA concentration responses are measured using two electrode voltage-clamp technique and allosteric co-agonist modeling.