Biomedical Summer Undergraduate Research Experience Program
(B-SURE)
The University of Texas Health Science Center at San Antonio (UTHSCSA)
STOCKAND,
James (Physiology): My laboratory is interested
in understanding the cellular and molecular mechanisms modulating the activity
of epithelial ion channels. We primarily focus on the epithelial
Na channel (ENaC). We also are interested in defining the structural
relationship between the subunits that comprise ENaC, as well as mapping
interactions between this channel and its regulatory proteins. ENaC
is a centrally positioned effector modulating systemic Na and water balance.
Thus, the activity of this channel directly impacts blood pressure and
epithelial hydration. Indeed gain of function mutations in ENaC and
its upstream regulatory pathways lead to hypertension in humans.
In contrast, loss of function mutations in this channel lead to salt wasting
and hypotension and acute respiratory distress. Most hypertension
is essential and associated with salt sensitivity. Thus, to fully
understand the cellular basis of these diseases, it is essential to understand
the control points regulating Na reabsorption mediated by ENaC. Results
from my laboratory have made significant contributions to understanding
how ENaC is modulated by small G proteins, such as K-Ras, and how phospholipid
signaling effects channel gating. Our results, as well as those of
others, have directly implicated K-Ras and phospholipid signaling in the
transduction pathway whereby aldosterone stimulates ENaC leading to Na
reabsorption in the distal nephron. More recently, we have begun
to investigate the cellular mechanisms by which EGF decreases ENaC activity.
This is mediated by tyrosine kinase signaling. This is important
for decreased ENaC activity and increased EGF levels are associated with
Polycystic Kidney Disease. A decrease in ENaC activity may, in part,
lead to inappropriate fluid secretion into the renal cysts associated with
this disease.
My laboratory
uses a combination of experimental methodologies to investigate ENaC.
We have played a central role in establishing a departmental imaging core
facility allowing us to perform evanescent field fluorescence microscopy
using a microscope with total internal reflection fluorescence. In
addition, we are well versed in electrophysiology, fluorescence imaging,
molecular biology and biochemistry. Trainees in the laboratory are
encouraged to train with every available technology and to integrate these
methods to establish a comprehensive set of experimental tools with which
to test hypotheses.
James
Stockand's Web Page.