Perelman School of Medicine Affiliations
Mahoney Institute of Neurological Science
Cell and Molecular Biology Graduate Group
Biochemistry and Biophysics Graduate Group
Neuroscience Graduate Group
M.D., Beijing Medical University, 1986
M.S., University of Wisconsin-Madison, 1989
Ph.D., University of Wisconsin-Madison, 1992
Mahoney Fellow, Harvard Medical School, 1992-1994
Independent Scientist Award, National Institutes of Health,
Molecular mechanisms of potassium channels and retinal cGMP-gated channels.
Mechanisms of protein-protein interactions
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.
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
neurons and coupling the blood glucose level to insulin
secretion. We also investigate the molecular mechanisms
the cGMP-gated channel to mediate visual photo-transduction
in the eye.
second area of our research is to develop novel protein
inhibitors for various types of biologically
ion channels through both passive screening and active
design-and-engineering. Using the thermodynamic mutant
cycle analysis, we investigate both the molecular and
mechanisms through which protein inhibitors interact
with the channels. Also, we investigate the mechanisms
determine the molecular specificity between a given protein
and its targeting channel.
M., Lu, Z.: Coupled ion movement underlies rectification
in an inward-rectifier K+ channel.
Journal of General Physiology 112:211-221, 1998.
W., Lu, Z.: A novel high affinity inhibitor for inward-rectifier
K+ channels. Biochemistry 37: 13291-13299, 1998.
Z., Klem, A.M., Ramu, Y. Ion conduction pore is conserved
among K+ channels. Nature 413: 809-812, 2001.
D., Lu, Z.: IRK1 inward rectifier K+ channels exhibit
intrinsic rectification. Journal of General Physiology
120: 539-551, 2002
Z., Klem, A.M., Ramu, Y. Coupling between voltage sensors
and activation gate in voltage-gated
of General Physiology 120: 663-676, 2002.
D., Ramu, Y., Klem, A.M., Lu, Z. Mechanism of rectification
in inward-rectifier K+ channels. Journal
of General Physiology,
121: 261-275. 2003.
D., Lu, Z. Interaction Mechanisms between polyamines
and IRK1 inward-rectifier
General Physiology, 122: 485-500. 2003.
Click here for
a full list of publications
(searches the National Library of Medicine's PubMed database.)