Department of Physiology and Pharmacology
Jeffrey S. Fedan
Adjunct Professor of Pharmacology
University of Alabama at Birmingham, Ph.D., 1974
Postdoctoral Fellowship: NIH and American Heart Association Postdoctoral Fellowships at the Department of Pharmacology and Toxicology at WVU
Phone: 304-285-5766
Email: jsf2@cdc.gov
Research Interests
This pharmacology laboratory is investigating the mechanisms of asthma, particularly the mechanisms in airway epithelium responsible for airway hyperreactivity. Specifically, the reactivity of airway smooth muscle to exogenous and endogenous agents is under the control of the respiratory epithelium through the release of epithelium-derived relaxing factor (EpDRF), which causes smooth muscle to relax. We are interested in the cellular pathways involved in the release and effects of EpDRF in response to hypertonic solution. This release is accompanied by bioelectric changes in the epithelium, i.e., by a change in ion transport in the cells. The release of EpDRF may be closely coupled to signaling pathways used by epithelial cells to control their volume. Such pathways may be defective in the asthmatic patient.
Description of Research
The research conducted has drawn upon the use of several different techniques, and a multi-disciplinary integrated approach has been employed to test hypotheses. These techniques involve in vivo measurement of pulmonary function measurement in animal models. A number of unique methods are employed in in vitro experiments, including the isolated, perfused trachea model and airway strip preparations for measurement of both contractile activity of the smooth muscle and bioelectric changes in the epithelium. The measurement of epithelial bioelectric properties is measured using Ussing preparations using fresh airway segments and cultured airway epithelial cells. Molecular biology techniques are used to explore in detail the transduction pathways involved in EpDRF release.
Recent Publications
Zhang, X.-D., Fedan, J.S., Lewis, D.M., Siegel, P.D.: Asthma-like
biphasic airway response in Brown Norway rats sensitized via dermal
exposure to dry trimellitic anhydride powder.
J. Allergy Clin. Immunol.
113:320-326, 2004.
Fedan, J.S., Dowdy, J.A., Johnston, R.A. and Van Scott, M.R.: Hyperosmolar solution effects in guinea-pig airways. I. Mechanical responses to relative changes in osmolarity.
J. Pharmacol. Exp. Ther.
308:10-18, 2004.
Wu, D.X.-Y., Johnston, R.A., Rengasamy, A., Van Scott, M.R. and Fedan,
J.S.: Hyperosmolar solution effects in guinea-pig airways. II. Bioelectric responses to relative changes in osmolarity.
J. Pharmacol. Exp. Ther.
308:19-29, 2004.
Fedan, J.S., Dowdy, J.A., Van Scott, M.R., Wu, D.X.-Y. and Johnston,
R.A.: Hyperosmolar solution effects in guinea-pig airways. III. Studies on the identity of epithelium-derived relaxing factor in isolated, perfused trachea using pharmacological agents.
J. Pharmacol. Exp. Ther.
308:30-36, 2004.
Johnston, R.A., Van Scott, M.R., Kommineni, C., Millecchia, L.L., Dortch-Carnes, J. and Fedan, J.S.: Hyperosmolar solution effects in guinea-pig airways. IV. Lipopolysaccharide-induced alterations in airway reactivity and epithelial bioelectric responses to methacholine and hyperosmolarity.
J. Pharmacol. Exp. Ther.
308:37-46, 2004.
Fedan J.S., Wu, D.X.-Y., and Van Scott, M.R. Phenotypic changes in ion
transport and responsiveness to methacholine and hyperosmolarity in guinea-pig tracheal epithelium induced by air-interface culture.
J.Pharmacol. Exp. Ther., Submitted.
Fedan, J.S., Dowdy, J.A., Fedan, K.B. and Hubbs, A.F. Popcorn worker's
lung: In vitro exposure to diacetyl, an ingredient in microwave popcorn
butter flavoring, damages guinea-pig tracheal epithelium and increases
reactivity to methacholine. In preparation.
|
