Other Perelman School of Medicine Affiliations
Mahoney Institute of Neurological Science
Cell and Molecular Biology Graduate Group
Biochemistry and Biophysics Graduate Group
Neuroscience Graduate Group

Degrees
M.D., Beijing Medical University, 1986
M.S., University of Wisconsin-Madison, 1989
Ph.D., University of Wisconsin-Madison, 1992

Honors
Mahoney Fellow, Harvard Medical School, 1992-1994
Independent Scientist Award, National Institutes of Health, 1998-2003

Professional Affiliations
Biophysical Society

Research Interests
Molecular mechanisms of potassium channels and retinal cGMP-gated channels.
Mechanisms of protein-protein interactions

Research Description
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 various types of ion channels generate electrical voltage across the cell membrane. The negative electrical voltage in a resting cell is essential for both the survival and the normal function of the cell. Nerve cells, muscle cells and hormone-secreting cells can generate electrical impulses, and use the electrical impulse as a means to rapidly propagate messages.

Currently, we are studying two types of ion channels, inward-rectifier potassium channels and cyclic-nucleotide-gated channels, using techniques such as patch-clamp, two-electrode 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 the inward-rectifier potassium channels, which includes controlling the rate of the cardiac pacemaker, regulating the communications between neurons 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.

Representative Publications
Spassova, M., Lu, Z.: Coupled ion movement underlies rectification in an inward-rectifier K+ channel. Journal of General Physiology 112:211-221, 1998.

Jin, W., Lu, Z.: A novel high affinity inhibitor for inward-rectifier K+ channels. Biochemistry 37: 13291-13299, 1998.

Lu, Z., Klem, A.M., Ramu, Y. Ion conduction pore is conserved among K+ channels. Nature 413: 809-812, 2001.

Guo, D., Lu, Z.: IRK1 inward rectifier K+ channels exhibit no intrinsic rectification. Journal of General Physiology 120: 539-551, 2002

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

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

Guo, D., Lu, Z. Interaction Mechanisms between polyamines and IRK1 inward-rectifier K+ channels. Journal of General Physiology, 122: 485-500. 2003.

Click here for a full list of publications
(searches the National Library of Medicine's PubMed database.)