Cystic Fibrosis and Stem Cells
The gene responsible for cystic fibrosis (CF), CFTR, was identified to be camp-dependent chloride channel. Clinically, CF patients develop chronic lung infections and small airway obstruction, which is the major cause of mortality. The link between the chloride channel defect and persistent lung infection has not been established. Towards this end my laboratory has discovered that neutrophils in CF patients are defective in chlorination of phagocytosed bacteria. Development of novel probe to measure chloride concentrations in phagolysosomes has facilitated this finding.  Stem cells-based therapy represents a new platform. In collaboration with the Tulane Gene Therapy Center, my laboratory has discovered that marrow-derived mesenchymal stem cells (MSCs) have the capacity to differentiate into airway epithelial cells. CFTR-gene corrected CF MSCs contribute to chloride transport from the basolateral side to the apical side, which suggests the possibility of restoration on the altered airway surface liquid composition. In spite of promising results, methods to enhance MSCs to home and engraft into CF airways have not been developed. My laboratory has found that human MSCs express the N-formyl peptide receptors, which direct the stem cells to migrate towards formyl peptides. This results suggests the possibility of engineering MSCs with the receptors to direct the recruitment of MSCs to inflammatory sites such as CF lungs.

Cancer
Cancer cells typically demonstrate high telomerase activity which can be differentiated from their normal counterparts. This feature can be used to specifically target tumor cells. Towards this end, we have developed a replication-competent adenoviral vector whose replication is driven by the telomerase promoter. This vector can be used singly or in combination with other tumor-targeting vectors to achieve tumor suppression or eradication.

Selected publications

Viswanathan, A., Painter, R.G., Lanson, N.A., and Wang, G.  Functional expression of N-formyl peptide receptors in human bone marrow-derived mesenchymal stem cells. Stem Cells, (2007)

Painter, R.G., Valentine, V.G., Lanson, N.A., Leidal, K., Zhang, Q., Lombard, G., Thompson, C., Viswanathan, A., Nauseef, W.M., and Wang, G. CFTR expression in human neutrophils and phagolysosomal chlorination defect in cystic fibrosis. Biochemistry, (2006) 45(34):102600-102609

Painter, R.G. and Wang, G. Direct measurement of free chloride concentrations in the phagolysosomes of human neutrophils. Analytical Chemistry, (2006) 78(9):3133-3137

Painter, R.G., Lanson, N.A. Jr, Jin, Z., Park F., and Wang, G. Conditional expression of a suicide gene by the telomere reverse transcriptase promoter for potential post-therapeutic deletion of tumorigenesis. Cancer Science, (2005) 96(9):607-613

Wang, G., Bunnell, B.A., Painter, R., Tom, S., Lanson, N.A., Spees, J.L., Bertucci, D., Peister, A., Wiess, D.J., Valentine, V.G., Prockop, D.J., and Kolls, J.K. Human adult stem cells from bone marrow stroma differentiate into airway epithelial cells: potential for cystic fibrosis therapy. Proceedings of the National Academy of Sciences USA, (2005) 102:186-191