Investigate the pharmacology of ion channels relating to pain and epilepsy

Dr. Bean studies are helping uncover the molecular basis of ion channels and neuronal electrical firing.  These insights will be instrumental in developing novel medicines to alleviate pain, to treat epilepsy, and to address other disorders related to ion channel pathophysiology. Dr. Bean has extensive experience using neuropharmacological agents to probe mechanistic aspects of ion channels. He is an ideal collaborator for life science companies that are intent on developing new pharmaceuticals for ion-related pathologies.

Dr. Bean studies the intersection of neurophysiology and pharmacology, performing mechanistic studies with approved and investigational drugs. In collaboration with Clifford Woolf of the Massachusetts General Hospital, Dr. Bean is continuing his paradigm shifting studies on pain-selective local anesthetics through the development of novel sodium channel blockers. 

Dr. Bean’s lab is also investigating these other topics:

• Pharmacology of distinct sodium channel subtypes (Nav1.7, Nav1.8, Nav1.9, Nav1.5, Nav1.1)
• The underlying etiology of epilepsy, focusing on sodium channel dynamics
• Pharmacology of potassium channels, including Kv1, Kv3, and Kv4 families
• The ion channel blocking ability of peptide toxins
• How dopaminergic neurons use electrical signaling

Dr. Bean studies the intricate dynamics of ion channel activity in cells of the central nervous system. There are dozens of ion channels that support electrical signaling, but it is poorly understood how these channels collaborate in the context of cells and tissues. Dr. Bean has a strong interest in uncovering the essential molecular features of pacemaking, which is the process of spontaneous neuronal firing without synaptic provocation. In a recent study, the lab explored pacemaking in dopaminergic neurons by comparing electrophysiological measurements of spontaneous and ramp-dependent currents in voltage clamp. The lab found that a pacemaking feedback mechanism, involving the A-type potassium channel, curtails the ionic current. The slower ionic current promotes a slow but steady firing. 

In a high-profile landmark study recently published in Nature, Dr. Bean joined forces with Dr. Clifford Woolf of Massachusetts General Hospital to develop a more selective anesthetic formula. Dr. Bean and Dr. Woolf demonstrated that therapeutic targeting of nociceptor (that is, pain-sensing) neurons without effects on motor neurons is possible, paving the way for a new generation of local anesthetics that preserve function of non-nociceptor neurons while alleviating pain sensations.

Biological Mechanisms and Pathways

• Calcium channel •
• Dopaminergic neuron •
• Electrical signaling •
• Neurobiology •
• Neuron •
• Pain-sensing neuron •
• Potassium channel •
• Sensory neuron •
• Sodium channel •
• TRPV1 channel •
• Voltage-gated ion channel
•  

Central Nervous System

• Action potential •
• Calcium channel •
• Calcium channel blocker •
• Dopaminergic neuron •
• Epilepsy •
• Ionic current •
• Local anaesthesia •
• Local anaesthesia •
• Pacemaking •
• Pain •
• Pain-sensing neuron •
• Potassium channel •
• Sensory neuron •
• Sodium channel •
• TRPV1 channel •
• Voltage clamp technique
•  

Disease Mechanisms

• Epilepsy
•  

Therapeutic Discovery Tools and Assays

• Neuropharmacology
•  

Therapeutics

• Anti-convulsant therapy
•