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RESEARCH

Ion channels play pivotal roles throughout the nervous system in regulating gene transcription, neuronal excitability, and neurotransmitter release. We study 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 VOLTAGE-GATED CA2+ CHANNELS

We are studying the molecular determinants and protein interactions that regulate the biophysical properties of Ca2+ 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.

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Lee and Dolphin, Nat Rev Neurosci 2020, 21(4):213-229

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MECHANISMS CONTROLLING SYNAPSE FORMATION AND FUNCTION

We are investigating the roles of Ca2+ 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. 

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Lopez et al., 2023 Sci Rep, 13(1):2608. doi: 10.1038/s41598-023-29622-9

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Lopez et al., 2024 J Neurosci, 44(10):e1402232023. doi: 10.1523/JNEUROSCI.1402-23.2023.

ION CHANNEL DYSREGULATION IN NEURODEVELOPMENTAL DISORDERS

We are studying the neurophysiological functions of caldendrin, a Ca2+ sensor that regulates voltage-gated Ca2+ channels and mechanically gated Piezo channels. We have found that knockout of caldendrin causes enlarged Piezo currents and mechanical hypersensitivity in mice. We are exploring how abnormal somatosensory function in caldendrin KO mice is linked to behaviors associated with autism spectrum disorder and impaired learning and memory.

©2020 by the Lee Laboratory.

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