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Regulation of ion transport across the airway epithelia. Dr.
Egan's primary research interest is to understand the regulation of ion transport
across the airway epithelia in health and disease. Transepithelial ion transport
is responsible for maintaining the airway surface fluid, i.e. the periciliary
fluid layer, which controls mucociliary clearance. Abnormalities in the ion channels
and regulators of these channels can alter mucociliary clearance, leading to retained
secretions, mucus plugging, infection, and lung destruction, as seen in cystic
fibrosis. In CF, it is the abnormal function of the cystic fibrosis transmembrane
conductance regulator (CFTR), a multifunctional protein encoded by the gene that
is affected in cystic fibrosis (CF) that underlies the abnormal ion transport
in affected organs.
The Egan lab uses a variety of electrophysiologic
techniques to examine how CFTR expression affects transepithelial ion transport
in airway epithelial cells. They have shown that CFTR can modulate other ion channels
and, as its name implies, act as a conductance regulator. In addition, they have
been very interested in understanding and identifying the mechanism(s) that underlie
these interactions and the lab has been examining proteins related to CFTR with
the hopes of identify regions/domains that are common to these proteins and are
necessary for these interactions. Potentially, these domains/motifs may be targeted
for therapeutic intervention. Lastly, the laboratory in interested in examining
how mutations in CFTR affect its ability to function. For instance, the most common
mutation (?F508) results in a protein which is unable to fold correctly and assume
its appropriate tertiary structure. Consequently, the protein is retained in the
endoplasmic reticulum, and then degraded. The laboratory has demonstrated that
under certain conditions including reducing incubation temperature, or after exposure
to certain drugs such as phenylbutyrate the ?F508-CFTR protein can be r eleased
from the ER and targeted to the plasma membrane. When the protein is expressed
on the plasma membrane it retains partial function. These data suggest that it
may be possible to partially correct the CF phenotype. Recent
publications: Cahill,
P, M.W. Nason, Jr., M. T.Y. Yao, C. Ambrose, P. Thomas, M.E. Egan. Identification
of the CFTR Domain that are important for interactions with ROMK2. Journal
of Biological Chemistry, 275, 16697-16701, 2000.
Schneider, S.W. , M.E.
Egan, B.P. Jena, W.B. Guggino, H. Oberleithner, J.P. Geibel. Continuous
direct measurement of extracellular ATP on living cells using Atomic Force Microscopy.
Proceedings of the National Academy of Science, 96(21), 12180-12185, 1999. Weyler,
R.T., K.A. Yyrko-Mauro, R. Rubenstein, W.J.W. Kollen, W. Reenstra, M.E. Egan,
A.E. Mulberg. CFTR
is functionally acitve in GnRH-expressing GT-7 hypothalamic neurons. American
Journal of Physiology: Cell Physiology, 46(3), C563-571, 1999. Nasonkin,
I., A. Alikisafoglu, C. Ambrose, P. Cahill, M. Chen, A. Sarniak, M.E. Egan, &
P. M. Thomas. A
novel sulfonylurea receptor family member expressed in the embryonic Drosophila
dorasl vessel and tracheal system. Journal of Biological Chemistry, 274(41),
29420- 29425, 1999. marie.egan@yale.edu http://www.med.yale.edu/pediat/respmed/marie.html |  |