Research in the Min Li lab has been focused on molecular mechanisms and regulation of bioelectrical ion currents. Biological phenomena - ranging from neuronal action potential, to rhythmic cardiac contraction, to sensory transduction, to hormone secretion - are ultimately controlled by one class of proteins: the ion channels. Changes of ion channel activities by genetic mutations or by drugs are causes for human diseases and basis for therapeutics.  Our work is primarily focused on the class of ion channels with exquisite selection for potassium ions - known as potassium channels.  They are very diverse membrane proteins and function as oligomers, normally consisting of four subunits.  More than 160 different human genes encode potassium channels and in many cases, they can form hetero-oligomers which further increase their functional diversity.  Human mutations in potassium channel genes cause brain and heart diseases including arrhythmias, epilepsy and ataxia.  Almost all human mutations result in loss or reduction of potassium channel activity on cell surface.  Thus, investigation of potassium channel assembly and membrane trafficking is essential for understanding both the development of membrane excitability and mechanisms of human diseases. 

        Our earlier work has identified molecular determinants that confer specific interactions between different subunits (Science 257:1225 & 285:1565; Cell 103:169).  Recent effort in our lab has been focused on identification of signal motifs that regulate protein surface expression.  Taking advantage of genetic screen and proteomics technologies, we have found new motifs that potently confer membrane protein expression on the cell surface (Shikano et al., 2003 & 2005).  We further discovered that activity of these motifs is directly coupled to activation of protein kinases (Coblitz et al., 2005, Shikano et al., 2006).  On-going experiments are concentrated on studying their mechanisms of action.  Another line of research on-going in our lab has been focused on chemical modulation of membrane excitability and rescue of mutant potassium channels.  Here, we use a chemical biology approach to screen large chemical libraries of existing drugs and novel structures to isolate compounds with unique properties that either augment or inhibit potassium channel activity (Sun et al., 2004 & 2006).  These probes have now been used for functional studies and for testing their effectiveness in rescuing human mutant channels (Xiong et al., 2007).  Our general objectives are to understand plasticity of potassium channel subunit assembly and biogenesis, dynamics of cellular localization and density, and chemical regulation and therapeutics.

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            We are with the Solomon H. Snyder Department of Neuroscience and High Throughput Biology Center at Johns Hopkins University School of Medicine.   For information concerning Hopkins Facility for High Throughput Compound Screening, please click ChemCORE.