Research Interests:

The Biology of IgA in Lung Disease
The mucosal epithelium of the lung forms a barrier that interfaces between the internal and external environments. Epithelial cells are polarized: the apical surface (adjacent to the external environment) has a different protein, lipid and ion channel content than the basolateral surface (facing the internal environment). These epithelial cells express the polymeric immunoglobulin receptor (pIgR) which serves to transcytose IgA from the submucosa (basolateral surface) to the lumenal (apical) surface. IgA is an important first line of host immune defense, while recruitment of neutrophils (PMN) from submucosal blood vessels across the epithelium is a secondary line of defense. PMN are characteristic of the airway inflammation seen in patients with bronchitis, bronchiectasis, cystic fibrosis and asthma. The cells that abundantly express the pIgR also express the cystic fibrosis transmembrane conductance regulator (CFTR) - a chloride channel which is abnormal in patients with cystic fibrosis.

Madin-Darby canine kidney (MDCK) cells  grown on permeable cell culture inserts serve as a well-established model system of an epithelium for studies on protein trafficking and cell polarity. The laboratory uses MDCK cells transfected with the cDNA for human pIgR, non-transfected MDCK cells, and airway cell lines that endogenously express pIgR and CFTR. We employ methods in protein biochemistry, immunology, cell and molecular biology to address the following questions:

Ongoing projects:
1. Drug delivery: Is receptor-mediated macromolecule delivery to the lung via the pIgR feasible?
2. Cystic fibrosis:  Does mutant CFTR alter protein trafficking of IgA across airway epithelial cells?
3. Asthma and chronic obstructive lung disease:  How does IgA affect epithelial-neutrophil interactions?
4. Asthma: Does IgA play a role in bronchial hyperreactivity?

PubMed Listed Publication

Lab Email: jre_lab@hotmail.com