RESEARCH
Voltage-gated (Cav) Ca2+ channels play pivotal roles throughout the nervous system in regulating gene transcription, neuronal excitability, and neurotransmitter release. We study Cav as well as other ion 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.
MOLECULAR AND NEURONAL PHYSIOLOGY OF CAV CALCIUM CHANNELS
We are studying the molecular determinants and protein interactions that regulate the biophysical properties of Cav channels. Technical approaches include mutagenesis, protein-interaction assays, and patch-clamp electrophysiology. A major goal of this project is to generate modified Cav channels to study their roles within neuronal cell-types and circuits. We are also generating novel mouse strains and immunolabeling reagents to track the protein interactions and subcellular dynamics of these channels at synapses.
MECHANISMS CONTROLLING RETINAL SYNAPSE DEVELOPMENT AND FUNCTION
We are investigating the roles of Cav channels and other synaptic molecules in regulating photoreceptor synapse assembly, and how their dysregulation 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.
CABP FAMILY OF CALCIUM SENSORS
We are studying the neurophysiological functions of a family of calmodulin-like Ca2+ binding proteins (CaBPs), which regulate Piezo, Ca2+ channels, and a variety of other targets. We have found that KO of one CaBP family member, caldendrin, causes enlarged Piezo currents and mechanical hypersensitivity in mice. We are exploring additional roles of CaBPs using live-cell imaging, single-cell RNA-seq, behavioral assays, and machine-learning approaches for analyzing neuronal morphology.