Cellular & Molecular Physiology: Epithelial Transport of Ions and Solutes | Membrane Protein Sorting and Trafficking | Membrane Proteins - Ion Channels | Physiology of Human Disease
Stem Cells and Tissue Repair
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. Lastly, the laboratory is interested in examining how mutations in CFTR affect its ability to function.
- Bruscia E., PX. Zhang, A. Satoh, C. Caputo, R. Medzhitov, A. Shenoy, M.E. Egan D.S. Krause. Abnormal trafficking and degradation of TLR4 underlie the elevated inflammatory response in cystic fibrosis, Journal of Immunology. 186: 6990-6998, 2011. (D.S.K.
- Bruscia E, Zhang P-X, Ferreira E, Caputo C, Emerson J, Krause D, Egan ME. Macrophages directly contribute to the hyper pro-inflammatory response in Cftr -/- mice. Am J Resp Cell & Mol Biol, 40:295-304, 2009.
- Egan ME, Pearson M, Weiner S, Rubin D, Lukcas G, Du K, Rajendran V, Glockner-Pagel J, Canny S, Caplan MC. Curcumin, a major constituent of the spice tumeric, corrects cystic fibrosis defects. Science, 304:600-2, 2004.
- Bruscia EM, Grove JE, Chang EC, Weiner S, Caputo C, Ferreira EC, Egan ME, Krause DS. Assessment of CFTR activity in CFTR-null mice after bone marrow transplantation, Proc Natl Acad Sci, 103:2965-70, 2006.
- Egan ME, Ambrose CA, Cahill PA, Glockner-Pagel J, Balamuth N, Pappoe L, Cho T, Wagner CA, Geibel J, Caplan MC. Calcium pump inhibitors induce functional expression of DF508-CFTR in cystic fibrosis epithelial cells. Nature Med, 8:485-92, 2002.
- Weiner SA, Caputo C, Bruscia E, Ferreira E, Price JE, Krause DS, Egan ME. Rectal potential difference measurements and the functional expression of CFTR in the gastrointestinal epithelia of cystic fibrosis models, Ped Res, 63(1):73-8, 2008.