The health of the oral cavity is maintained by salivary secretions. The principal function of salivary glands is to produce these complex fluids. We have utilized a variety of tools to understand saliva formation and the pathologic processes that alter normal secretory events. During this reporting period, much of our effort has been directed at using recombinant adenoviruses to transfer aquaporin (AQP; water channel) genes to epithelial cells in order to increase their water permeability. Eventually, we hypothesize that this strategy could be used to correct the irreversible damage suffered by patients whose salivary glands are exposed to ionizing radiation during treatment for head and neck cancer. Radiation is a key component of therapy for such cancers, however, it destroys the fluid secreting acinar cells while the relatively water-impermeable, salt- absorbing ductal cells survive. Our second major area of study this year was related to the systemic secretion of products of genes transferred to the salivary glands. We hypothesized early that because salivary glands are naturally secretory, and are capable of producing large amounts of protein for export, we could utilize the glands to manufacture the products of transferred genes for eventual therapeutic use elsewhere in the body, ie. besides through saliva into the upper gastrointestinal tract.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Intramural Research (Z01)
Project #
1Z01DE000336-15
Application #
2572315
Study Section
Special Emphasis Panel (CIPC)
Project Start
Project End
Budget Start
Budget End
Support Year
15
Fiscal Year
1996
Total Cost
Indirect Cost
Name
National Institute of Dental & Craniofacial Research
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Zheng, Changyu; Baum, Bruce J (2008) Evaluation of promoters for use in tissue-specific gene delivery. Methods Mol Biol 434:205-19
Adriaansen, Janik; Perez, Paola; Goldsmith, Corine et al. (2008) Differential sorting of human parathyroid hormone after transduction of mouse and rat salivary glands. Hum Gene Ther :
Cotrim, Ana P; Baum, Bruce J (2008) Gene therapy: some history, applications, problems, and prospects. Toxicol Pathol 36:97-103
Samuni, Yuval; Zheng, Changyu; Cawley, Niamh X et al. (2008) Sorting of growth hormone-erythropoietin fusion proteins in rat salivary glands. Biochem Biophys Res Commun 373:136-9
Zheng, Changyu; Vitolo, Joseph M; Zhang, Weitian et al. (2008) Extended transgene expression from a nonintegrating adenoviral vector containing retroviral elements. Mol Ther 16:1089-97
Samuni, Yuval; Cawley, Niamh X; Zheng, Changyu et al. (2008) Sorting behavior of a transgenic erythropoietin-growth hormone fusion protein in murine salivary glands. Hum Gene Ther 19:279-86
Nandula, Seshagiri R; Amarnath, Shoba; Molinolo, Alfredo et al. (2007) Female mice are more susceptible to developing inflammatory disorders due to impaired transforming growth factor beta signaling in salivary glands. Arthritis Rheum 56:1798-805
Yan, Xing; Voutetakis, Antonis; Zheng, Changyu et al. (2007) Sorting of transgenic secretory proteins in miniature pig parotid glands following adenoviral-mediated gene transfer. J Gene Med 9:779-87
Voutetakis, Antonis; Zheng, Changyu; Mineshiba, Fumi et al. (2007) Adeno-associated virus serotype 2-mediated gene transfer to the parotid glands of nonhuman primates. Hum Gene Ther 18:142-50
Baum, Bruce J (2007) Inadequate training in the biological sciences and medicine for dental students: an impending crisis for dentistry. J Am Dent Assoc 138:16, 18, 20 passim

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