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The electrical current
generated across cellular membranes is a key conduit for physiological
signaling between the internal and external environments of the cell. The
Li lab employs state-of-the-art technologies to elucidate the biology and
pharmacology of potassium channels, central players in determining membrane
excitability.
Macromolecular Assembly and Organization of Potassium
Channels
The
functional diversity of potassium channels is achieved through contribution
to a host of regulatory pathways. We are conducting research on modulatory
proteins that regulate potassium channels. Specifically we are working on
macromolecular organization of channel complexes and molecular mechanisms by
which accessory proteins exert regulatory effects on channel activity. (Publications)
Regulation
of Forward Transport
Synthesis of
membrane proteins such as potassium channels is initiated from cytosol and
completed in the endoplasmic reticulum (ER). Through vesicular transport,
the channel proteins eventually reach the site of action – cell surface.
Complex regulatory steps are implicated in determining ER exit, speed of
transport, number of molecules and specific subcellular location. We are
working on the signals and machinery that mediate forward transport. (Publication)
Chemical
Biology of Potassium Channels
Small molecules and toxins are
often targeted to potassium channels. These interactions provide useful
entry points and tools to learn about the biology of potassium channels and
useful for development of therapeutics. In
addition, a large collection of drugs have now shown to regulate potassium
channels, thereby causing severe side effects. We are
working to identify and understand the mechanism of action of bioactive
compounds that regulate potassium channel trafficking and function. (Publication)
Assay and
Target Technologies
Ion channels are important proteins for both biology and drug development.
Methodologies for assaying channel activity, such as electrophysiological
recording, are extremely sensitive and content-intensive, but with low
throughput. Hence they are not amenable to large-scale molecular screens.
We are pursuing the development of enabling assay technologies to
effectively screen and isolate protein and chemical modulators of ion
channels. (Publications)
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