Research

My 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. I will use several novel approaches, which modify the phosphoinositides directly and rapidly, in combination with electrophysiology, confocal imaging, and FRET techniques.

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.

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. I 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.

 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, I will assess membrane functions in cation-permeable ion channel modulation and cellular excitability in DRG and dorsal horn cells. This advancing knowledge about the role of receptor signaling in channel function also will contribute significantly to understanding biophysical properties of plasma membrane phospholipids in pain signaling.

Phosphoinositides are minor phospholipids localized mainly in the cytoplasmic leaflet of the plasma membrane, and are essential for regulating many cellular signaling activities and for targeting of peripheral membrane proteins. My research goal is to define the functional actions of PIP2 on signal transduction pathways in living cells, focusing mainly on voltage-gated ion channels in neurons. I will utilize two phospholipid modifying approaches (rapamycin-induced translocation & voltage-sensitive phosphatases) to test the function of PI lipids in live cells. These two methods are very specific to PI lipid modifications and permit observation of PI modulation of channel activity without activating any other signaling pathways.