Recent/Current
Research Funding

Cystic Fibrosis

Glaxo, Smith and
Kline

National Institute
of Health

Graduate Group Affiliations

Comparative Pathology

Molecular, Cellular and
Integrative Physiology

Research Interests

Our laboratory studies the epithelium of human airways. Altered function of this epithelium is at the heart of a number of respiratory diseases, including cystic fibrosis, asthma and chronic bronchitis. We obtain human tracheas post mortem or after surgery, and extract whatever epithelial cells are still living. These are then cultured until a tissue closely resembling the original epithelium is recreated. We have successfully cultured both the surface epithelium and epithelium from the airway mucous glands. We then use these cell cultures to study human airway diseases. Twenty years ago, we determined that airway epithelial cultures obtained from patients dying of cystic fibrosis were unable to secrete chloride ions. The main cause of death of patients with cystic fibrosis is the gradual blockage of airways with sticky mucous secretions, and much of our research has been directed at determining how a defect in chloride ion transport results in this pathology. More recently, we have been using the same cell cultures in asthma research. It is well known that the common colds trigger asthma attacks. Therefore, we have been infecting our cell cultures with the cold virus to determine whether this induces any changes in function that could potentially induce asthma.

 

Representative Publications

Widdicombe, J. H., M. J. Welsh, and W. E. Finkbeiner. 1985. Cystic fibrosis decreases the apical membrane chloride permeability of monolayers cultured from cells of tracheal epithelium. Proc. Natl. Acad. Sci., USA. 82:6167-6171.

Barthelson, R. A., and J. H. Widdicombe. 1987. Cyclic adenosine monophosphate-dependent kinase in cystic fibrosis tracheal epithelium. J. Clin. Invest. 80:1799-1802.

Yamaya, M., W. E. Finkbeiner, S. Y. Chun, and J. H. Widdicombe. 1992. Differentiated structure and function of cultures from human tracheal epithelium. Am J. Physiol. 262:L713-L724.

Uyekubo, S. N., H. Fischer, A. Maminishkis, B. Illek, S. S. Miller, and J. H. Widdicombe. 1998. Cyclic AMP-dependent absorption of chloride across airway epithelium. Am. J. Physiol 275:L1219-L1227.

Widdicombe, J. H., L. L.-K. Chen, H. Sporer, H. K. Choi, I. S. Pecson and S. J. Bastacky. 2001. Distribution of tracheal and laryngeal mucous glands in some rodents and the rabbit. J. Anat. 198: 207-221.

Lopez-Souza, N., G. Dolganov, R. Dubin, L.A Sachs, L. Sassina, H. Sporer, S. Yagi, D. Schnurr, H. A. Boushey and J. H. Widdicombe. 2004. Resistance of differentiated human airway epithelium to infection by rhinovirus. Am J Physiol. 286:L373-L381.

Rajagopal, M., H. Fischer, and J. H. Widdicombe. 2008. Hormonal and purinergic stimulation of bicarbonate secretion in oviducts of rhesus monkeys.Am. J. Physiol. 294:E55-E62.

 

Recent/Current Teaching

Freshman Seminar Series
HPH400, Human Physiology
MCP200L, Molecular, Cellular and Integrative Physiology Rotations Course
MCP210A, Advanced Physiology
PMI285, Cellular Basis of Disease