Controlling endogenous ion channels, neurotransmitter receptors, and neuronal signaling in the brain and retina with light
My research is focused on the molecular engineering of light-regulated ion channels and receptors, and applying these as tools for basic neurobiology and translational medicine. We use a combination of synthetic photoswitch compounds and molecular biology to confer light sensitivity onto specific voltage-gated and ligand-gated ion channels. This enables us to probe their neural functions with high spatial, temporal, and biochemical precision. We also use photoswitches to restore visual sensitivity in blind mammals that have lost their retinal rods and cones to degenerative disease. Recent studies have revealed a remarkable feature of photoswitches: they photosensitize blind retinas in which the rods and cones have died, but they have no effect on healthy retinas that still possess intact rods and cones. We seek to understand the molecular events that underlie the degeneration-specific action of photoswitches, and we are exploiting selective photosensitization to re-animate damaged portions of the retina, while sparing regions that remain healthy. Our findings identify new drug targets and introduce new drug candidates for human blinding diseases such as retinitis pigmentosa and age-related macular degeneration.