Voltage-gated (Cav) Ca2+ channels play pivotal roles throughout the nervous system in regulating gene transcription, neuronal excitability, and neurotransmitter release. We study Cav channels as macromolecular complexes, the components of which determine the intrinsic properties, modulation, and localization of these channels, as well as their contributions to the development and function of neural circuits.
STRUCTURE/ FUNCTION RELATIONSHIPS OF CAV CALCIUM CHANNELS
We are studying the molecular determinants and protein interactions that regulate the biophysical properties of Cav channels. Technical approaches include patch-clamp electrophysiology, voltage-clamp fluorometry, FRET, and isothermal titration calorimetry. A major goal of this project is to generate modified Cav channels to study their roles within neuronal cell-types and circuits.
CALCIUM SIGNALING MECHANISMS CONTROLLING AXONAL REGENERATION
We are investigating a novel pathway involving Cav channels and calmodulin-like Ca2+ binding proteins (CaBPs) in sensory neurons. We are determining how Cav coupling to CaBPs alters the regenerative growth of axons in vitro, and the recovery of sensory function following nerve injury in vivo. Techniques include live-cell imaging, single-cell RNAseq, and machine-learning approaches for analyzing neuronal morphology.
CAV AND OTHER ION CHANNELS IN RETINAL CIRCUIT DEVELOPMENT AND FUNCTION
We are investigating the roles of Cav channel subtypes in regulating photoreceptor synapse assembly, and how dysregulation of these channels lead to aberrant and homeostatic forms of rewiring within retinal circuits. Techniques include multi-photon imaging/electrophysiology in retinal tissue, behavioral analyses of visual function, and imaging (super-resolution and electron microscopy) of protein localization and synaptic structure.