Zhe Lu, MD, PhD

Portal to the Penn Neuroscience Community Home MINS Members MINS News Weekly Events MINS Colloquium Schedule History Community Outreach Programs Neuroscience Graduate Group Other Educational Activities Society for Neuroscience Classified Ads


				MINS Members

				Zhe Lu, M.D., Ph.D. Professor, Dept of Physiology School of Medicine D302A Richards Building (215) 573-7711 (office) (215) 573-7712 (lab) email: zhelu@mail.med.upenn.edu Click here for selected publications since Dr. Lu's arrival at Penn RESEARCH INTERESTS Molecular mechanisms of potassium channels and retinal cGMP-activated channels RESEARCH TECHNIQUES Molecular Biology: Site-directed mutagenesis and heterologous expression of ion channel genes. Biochemistry: Protein purification (HPLC and FPLC), recombinant protein production, protein design-and engineering. Electrophysiology: Patch-clamp and voltage-clamp. RESEARCH SUMMARY Our laboratory investigates the molecular and biophysical mechanisms of ion channels and develops novel protein inhibitors for ion channels. Ion channels are a class of highly specialized membrane proteins that allow ions to flow across the cell membrane in a selective manner. The opening and closing of ion channels are precisely regulated by the intricate cell signaling system. Ionic currents through ion channels generate electrical voltage across the cell membrane which underlies the electrical impulses in neurons, muscle and hormone-secreting cells. Currently, we are studying two types of ion channels - K+ channels and cyclic-nucleotide-gated channels - using techniques such as patch-clamp, voltage-clamp, heterologous gene expression, recombinant protein production and site-directed mutagenesis. With this combined approach of biophysics, biochemistry and molecular biology, we investigate both the molecular and the biophysical mechanisms underlying the various important biological functions of K+ channels, such as generating action potential, modulating the communications between neurons, controlling the rate of the cardiac pacemaker and coupling the blood glucose level to insulin secretion. We also investigate the molecular mechanisms that enable the cGMP-gated channel to mediate visual photo-transduction in the eye. The second area of our research is to develop novel protein inhibitors for various types of biologically important ion channels through both passive screening and active protein design-and-engineering. Using the thermodynamic mutant cycle analysis, we investigate both the molecular and the biophysical mechanisms through which protein inhibitors interact with the channels. Also, we investigate the mechanisms that determine the molecular specificity between a given protein inhibitor and its targeting channel. KEY WORDS: voltage-gated K+ channel, inward-rectifier K+ channel, retinal cGMP-activated channel, gene expression, site-directed mutagenesis, protein purification, protein recombination, protein design and engineering, patch-clamp, voltage clamp