Research Interests
Dr. Boucher is a pioneer in gene therapy for cystic fibrosis. He and his colleagues have been instrumental in developing strategies for clinical deployment of gene therapy techniques in inherited disease and are now focusing these same tools and expertise on the treatment of lung cancer and malignant pleural effusions. He has compared the transduction of non-small lung cancer cells by adenoviral and retroviral vectors and found that Ad vectors transduce squamous, adenoquamous and malignant mesothelial cells better than adenocarcinoma or large cells. Sensitive cells appear to have specificity for the Ad fiber knob. Retroviral transduction appears to be more efficient for adenocarcinoma cells metastic to the pleural space. Further investigation of the use of retroviral gene transfer in malignant pleural effusions demonstrated proteoglycans/glycosaminoglycans in effusions were inhibitory to viral transduction due to direct interaction with the vector. These results suggested that drainage of the pleural cavity may be necessary before attempting retroviral gene transfer into metastatic tumor cells. Dr. Boucher has also explored the transfer of several pro-drug metabolizing enzymes into adenocarcinoma cell lines and demonstrated superior efficacy of cytosine deaminase in association with its prodrug, 5-fluorocystine.

Publications
Clark, L.L., T. Chinet, & R.C. Boucher. Extracellular ATP stimulated K+ secretion across cultured human airway epithelium. Am J Physiol (Lung Cell Mol Physiol) 272:L11710-11715, 1997.

Watt, W.C., E.R. Lazarowski, and R.C. Boucher. CFTR-independent release of ATP: Its implications for the regulation of P2U2 receptors in airway epithelia. J Bio Chem 273:14053-14058, 1998.

Matsui, H., S.H. Randell, S.W. Perett, C.W. Davis, & R.C. Boucher. Coordinated clearance of periciliary liquid and mucus from airway surfaces. J Clin Invest (In press), 1998.

Hoganson, D.K., H. Matsui, R.K. Batra, & R.C. Boucher. Toxin gene-mediated growth inhibition of lung adenocarcinoma in an animal model of pleural malignancy. Human Gene Therapy 9:1143-1156, 1998.

Pickles, R.J., D. McCarty, H. Matsui, P.J. Hart, S.H. Randell, & R.C. Boucher. Limited entry of adenovirus vectors into well-differentiated airway epithelium is responsible for inefficient gene transfer. J Virology 72:6014-6023, 1998.

E-mail: rboucher@med.unc.edu
Telephone: (919) 966-1077
Address: 7011 Thurston-Bowles Chapel Hill, NC

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