Rapid biological signaling processes, such as visual recognition and pain sensation, achieve the speed by transmitting electrical pulses through neuronal pathways. The molecular machines that mediate the electrical signals are ion channels. Abnormalities of ion channel function can cause diseases like epilepsies and cardiac arrhythmias, and modulation of ion channel activity can provide treatments for pathological pain and diseases such as diabetes. We study the mechanisms of ion channel function and seek to identify and understand pharmacological modulators that may lead to improved therapies.
- Dynamic subunit stoichiometry confers a progressive continuum of pharmacological sensitivity by KCNQ potassium channels.
Yu, H., Lin, Z. et al., Proc. Natl. Acad. Sci. USA(2013)
- Modulation of hERG potassium channel gating normalizes action potential duration prolonged by dysfunctional KCNQ1 potassium channel.
Zhang, H., Zou, B., et al., Proc. Natl. Acad. Sci. USA 109 (29), 11866-11871(2012)
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- hERGcentral: A large database to store, retrieve, and analyze compound-human ether-a-go-go related gene channel interactions to facilitate cardiotoxicity assessment in drug development.
Du, F., Yu H., et al., Assay Drug Dev. Technol. 9:580-588 (2011) (Cover Article)
- Zinc pyrithione-mediated activation of voltage-gated KCNQ potassium channels rescues epileptogenic mutants.
Xiong, Q., Sun, H., and Li, M., Nature Chemical Biol. 3, 287-296 (2007)
- Chronic inhibition of cardiac Kir2.1 and hERG potassium channels by celastrol with dual effects on both ion conductivity and protein trafficking.
Sun, H., Liu, X., et al., J. Biol. Chem. 281, 5877-5884 (2006) (featured cover story)
- Genetic selection of trafficking signals that direct cell surface expression.
Shikano, S. Coblitz, B., Sun, H. & Li, M. Nat Cell Biol. 7, 985-992 (2005)
- Phosphatidylinositol 4,5-bisphosphate alters pharmacological selectivity for epilepsy-causing KCNQ potassium channels..
Zhou, P., Yu, H. et al., Proc. Natl. Acad. Sci. USA(2013)
- A theoretical model for calculating voltage sensitivity of ion channels and the application on Kv1.2 potassium channel.
Yang, H., Gao, Z., et al., Biophysical Journal 102 (8), 1815-1825 (2012)
- Identification of ML204 – a novel potent antagonist that selectively modulates native TRPC4/C5 channels.
Miller, M., Shi, J., et al., J Biol Chem 286(38), 33436-46 (2011)
- Combinatorial Activation of KCNQ potassium channels by synthetic chemical ligands.
Xiong, Q., Sun, H., Nan, F. and Li, M, Proc. Natl. Acad. Sci. USA 105, 3128-3133 (2008)
- Isoform-specific prolongation of Kv7 (KCNQ) potassium channel opening mediated by new molecular determinants for drug-channel interactions.
Gao, Z., Zhang, T, et al., J Biol Chem 210(36), 28322-28332 (2010)
- Profiling diverse compounds by flux-based and electrophysiology-based primary screens for inhibition of hERG potassium channels.
Zou, B., Yu, H., et al., Assay Drug Dev. Technol. 8(6), 743-754 (2010) (Cover article accompanied with PROFILE interview)
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