Research Aims

  Our research goal is to determine the molecular mechanism and biophysical properties of ion channel modulation by membrane lipid metabolism in neuronal excitability and synaptic transmission, and then to examine the functional significance of membrane biology in epilepsy and pain signaling. We will use several novel approaches, which modify the phosphoinositides directly and rapidly, in combination with electrophysiology, confocal imaging, and FRET techniques.

Aim 1. Voltage-Gated Ca2+ Channels: Molecular Mechanism of Modulation

  The research goal is to understand the functional significance of membrane lipids for receptor signaling pathways and modulation of voltage-gated Ca2+ channels in neurons. We will use several novel and powerful tools that modify the phosphoinositides within seconds in living cells. Our results will elucidate the functional roles of membrane phospholipids in the physiological implication on synaptic transmission and will provide new insight into the development of drugs for Ca2+-related diseases.

Aim 2. KCNQ K+ Channels and Epilepsy: From Molecules to Medication

  KCNQ channels are highly expressed in hippocampal and cortical pyramidal neurons. Mutation of these channels results in the development of several inherited diseases, such as early-stage epilepsy (BFNC) in childhood. The understanding of KCNQ channel modulation and its control of cellular excitability in primary cells is essential for the physiological and pathophysiological understanding of channel functions in epilepsy. We will investigate the fundamental functions of membrane phosphoinositides in the regulation of KCNQ channels and neuronal excitability in SCG and hippocampal neurons. These experiments will provide new insight into the physiological significance of phospholipids in KCNQ-channel regulation of cell excitability and epilepsy.

 

Aim 3. ASIC Channels: Pain Signaling in Nociceptive Neurons

  The research direction is to understand the functional role of receptor-mediated modification of membrane phospholipids in ion channel modulation, neurosecretion and synaptic transmission in nociceptive neurons. VGCCs, KCNQ, TRPV1, ASICs and P2X channels are highly expressed in DRG neurons and differentially involved in either analgesia or hyperalgesia. These channels are known to be regulated by GPCRs and phospholipids in other tissues. Thus, We will assess membrane functions in cation-permeable ion channel modulation and cellular excitability in DRG and dorsal horn cells.

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