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My research interests lie in the realm of control of membrane excitability by ion channel proteins, and particularly how ion channels are regulated by drugs and accessory proteins. One limb of my research program is the characterization of the molecular pharmacology of retigabine and its relatives – these are an emerging class of Kv7 potassium channel openers that are used to treat epilepsy. Using unique methods for introduction of unnatural amino acids, we are conducting experiments to reveal the detailed features of these drugs that allow them to stabilize channel opening, rather than blocking the channel pore. Key outcomes of this work have been the demonstration of a critical hydrogen bond that underlies retigabine action, and the characterization of distinct sites and mechanisms of action of subtypes of Kv7 channel activator molecules. A second emerging research theme is the identification of novel accessory proteins of ion channels using unbiased screening approaches. Using mass spectrometry of cross-linked ion channel complexes, followed by functional assays of candidate interactors, we have identified several previously unknown membrane proteins that govern the trafficking and gating of Kv1 family potassium channels. These unexpected binding partners have dramatic effects on channel function and often alter the functional outcome of disease-linked mutations. A significant outcome of this research theme is the recognition that the composition of native ion channel complexes must be considered when investigating the functional effects of disease-linked mutations.