Zhe Lu
Professor, Dept of Physiology

Cell Biology and Physiology Program

Address

D302A Richards Building (Office)
D300 Richards Building (Lab)
3700 Hamilton Walk
Philadelphia, PA 19104-6085

Office tel.: 215 573-7711
Lab tel.: 215 573-7712
Fax: 215 573-1940
E-mail: zhelu@mail.med.upenn.edu


EDUCATION

University of Wisconsin-Madison: Ph.D., 1992.

Beijing Medical University: M.D., 1986.

RESEARCH INTERESTS

• Molecular and biophysical mechanisms of ion channels.

Key words: Ion channels, inhibitors, ion permeation and selectivity, channel gating.

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DESCRIPTION OF RESEARCH

Our laboratory investigates the molecular and biophysical mechanisms of ion channels and develops novel 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 nerve, muscle and endocrine cells.

Currently, we are studying three types of ion channels, i.e., potassium channels, the cGMP-gated cation channel, and the cystic fibrosis conductance regulator chloride channel. Using a combined approach of biophysics, biochemistry and molecular biology, we investigate the mechanisms underlying the ability of potassium channels to perform various important biological tasks, such as generating action potentials, modulating the communications between neurons, controlling the rate of the cardiac pacemaker, and coupling the blood glucose level to insulin secretion. We also examine the mechanisms that enable the cGMP-gated channel to mediate visual photo-transduction in the eye. Recently, we have ventured into the area of how phospholipases regulate ion channel function, a venture that has provided us with new insight into the pathogenesis of cystic fibrosis. Another 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 examine the molecular mechanisms of channel inhibition, mechanisms that give rise to the molecular specificity between a given inhibitor and its targeting channel.

RECENT PUBLICATIONS

Lu, Z., Klem, A.M., Ramu, Y. (2001) Ion conduction pore is conserved in K+ channels. Nature, 413: 809-813.

Lu, Z., Klem, A.M., Ramu, Y. (2002) Coupling between voltage sensors and activation gate in voltage-gated K+ channels. Journal of General Physiology. 120, 663-676.

Guo, D., Ramu, Y., Klem, A.M., Lu, Z. (2003). Mechanism of rectification in inward-rectifier K+ channels. Journal of General Physiology. 121, 261-275.

Ramu, Y., Xu, Y., Lu, Z. (2006) Enzymatic activation of voltage-gated K+ channels. Nature. 442, 696-699.

Ramu, Y., Xu, Y., Lu, Z. (2007). Inhibition of CFTR Cl- channel function caused by enzymatic hydrolysis of sphingomyelin. Proceedings of National Academy of Sciences of the United State of America, 104, 6448-6453

Lab:

ROTATION PROJECTS

Rotating students will participate in the studies of ion channel mechanisms. The projects will involve molecular biological, protein-biochemical and electrophysiological techniques such as gene construction, site-directed mutagenesis, expression of recombinant proteins in bacterium, high performance liquid chromatography (HPLC), two-electrode voltage-clamp and patch-clamp.

PERSONNEL

Mr. Juan Ramon Martinez-Francois, Graduate Student
Dr. Yajamana Ramu, Senior Research Investigator
Dr. Marriane Shin, Senior Research Investigator
Dr. Yanping Xu, Senior Research Investigator