Research

We investigate the biophysical principles through which voltage-gated ion channels control electrical signaling. A major focus is the relationship among channel gating, resting membrane potential, channel availability, and cellular excitability.

We examine how the electrical operating state of a cell determines the contribution of individual sodium-channel isoforms and how perturbations in channel behavior alter action-potential initiation and repetitive firing. These studies seek to connect molecular channel properties with emergent cellular behavior in health and disease.

We seek to translate ion-channel mechanisms into new approaches for treating chronic pain. Our studies examine how small molecules modulate pain-relevant sodium channels and sensory-neuron excitability, with the goal of identifying pharmacological properties that improve functional and molecular selectivity.

Our work on nonpsychotomimetic phytocannabinoids has defined mechanisms through which cannabidiol (CBD), cannabigerol (CBG), and cannabinol (CBN) modulate sodium-channel function. More recently, we identified Nav1.8 as an important analgesic target for this class of compounds. We are extending these studies toward the discovery and characterization of new ion-channel modulators with improved therapeutic properties.

We study naturally occurring and disease-associated ion-channel variants to determine how changes in channel biophysics produce abnormal cellular excitability and neurological phenotypes.

By integrating functional characterization with genetic and clinical information, we seek to establish mechanistic links among genotype, channel behavior, cellular physiology, and disease. These variants also provide naturally occurring experiments that can reveal fundamental principles of ion-channel function.

We investigate the mechanisms through which small molecules interact with ion channels and their surrounding membrane environment. Our studies examine state-dependent inhibition, pore interactions, membrane-mediated effects, and the physicochemical properties that influence pharmacological activity.

These mechanistic insights are used to understand drug-channel interactions and to inform the design and selection of more selective ion-channel modulators.

Our experimental platforms include automated high-throughput patch-clamp electrophysiology, conventional voltage- and current-clamp electrophysiology, freshly isolated sensory neurons, molecular biology and mutagenesis, molecular pharmacology, multielectrode-array approaches, and computational modeling.

We have also developed scalable approaches for combined voltage-clamp and current-clamp characterization of freshly isolated neurons, enabling systematic analysis of ion-channel function, neuronal excitability, and pharmacological responses in native cellular environments.