Marie E. Egan, M.D.

Associate Professor of Pediatrics
Associate Director, Cystic Fibrosis Care Center

Address:
Section of Respiratory Medicine
Department of Pediatrics
Yale University School of Medicine
333 Cedar Street, FMP 503
New Haven, CT 06520

E-Mail: marie.egan@yale.edu
Office Phone: (203) 785-2480
Fax: (203) 785-6337
Appointments: (203) 785-4081


Marie E. Egan received her medical degree from the Mount Sinai School of Medicine in 1986. She completed her pediatric internship and residency at The Johns Hopkins Hospital from 1986-1989. After her finishing her pediatric residency training, she went on to complete her pediatric pulmonary medicine fellowship at the Johns Hopkins Medical Center before joining the faculty at Yale in 1992.

Clinical Interests: Cystic Fibrosis, asthma, bronchopulmonary dysplasia, ciliary dyskinesia and flexible bronchoscopy.

Research interests: 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 (δF508) 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 δF508-CFTR protein can be released 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.

Publications (last three years):

Original Articles

  1. McNicholas, C.M., M.W. Nason, W.B. Guggino, E.M. Schwiebert, S.C. Hebert, G.H. Giebisch & M.E. Egan. A Functional CFTR-NBF1 is Required for ROMK2-CFTR Interaction, American Journal of Physiology: Renal, Fluid and Electrolyte Physiology, 273: F843-F848, 1997.
  2. Rubinstein, R., M.E. Egan, P.L. Zeitlin. In Vitro restoration of CFTR-mediated chloride transport with sodium 4-Phenylbutyrate in cystic fibrosis epithelial cells containing δF508-CFTR, Journal of Clinical Investigation, 100: 2457-2465, 1997.
  3. Schwiebert, E.M., S.S. Allen, M.M. Morales, S. Devidas, M.E. Egan, and W.B. Guggino. Chloride channel and chloride conductance regulator domains of CFTR, the cystic fibrosis transmembrane conductance regulator, Proceedings of the National Academy of Science, 95:2674-2679, 1998.
  4. 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.
  5. 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.
  6. 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.
  7. 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. in press.

Chapters & Reviews

  1. Devine, L., M.E. Egan, & T. Fung. Cystic Fibrosis. In The Yale Guide to Children's Nutrition, W. Tamborlane, J. Weiswasser, T. Fung, N. Held, T. Liskov (editors). Yale University Press, New Haven, 1997.
  2. Schwiebert, E.M., M.E. Egan, and W.B. Guggino. Assays to study the dynamics, mechanisms, and regulation of ATP release from epithelial and non-epithelial cells. Methods in Enzymology, 292:664-675, 1998.
  3. Schweibert, E.M, D. Benos, M.E. Egan, M.J. Stutts, & W.B. Guggino. CFTR is Indeed a "Conductance Regulator", Physiological Reviews, 79(1), S145-S166, January 1999.

      Last updated February 09, 2001.