The health of the oral cavity is maintained by salivary secretions. Our past studies have focused on understanding mechanisms of saliva formation and their alteration during pathologic processes, and developing novel methods to treat salivary dysfunction. During this reporting period we have continued our efforts to utilize gene transfer technology to alter the phenotypic behavior of salivary epithelial cells. Specifically, we have continued efforts to correct the salivary damage suffered by patients whose salivary glands are exposed to radiation during treatment for head and neck cancer. We have extended past findings using the recombinant adenovirus AdhAQP1 which leads to increased fluid secretion in irradiated rats. These new efforts have concentrated on the mechanism by which hAQP1 enhances fluid secretion and on its application to primate glands. Additionally, we have made progress in the application of recombinant adeno-associated virus constructs for salivary gland gene transfer. We have also extended studies on the systemic secretion of transgene products from transduced salivary epithelial cells. Using a dwarf mouse model, we showed that glands infected with a recombinant adenovirus encoding mouse growth hormone secrete therapeutic levels of the hormone. Additionally, this virus, AdmGH, can lead to a doubling of dwarf mouse size in 30 days after a single intramuscular injection.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Intramural Research (Z01)
Project #
1Z01DE000336-17
Application #
6104585
Study Section
Special Emphasis Panel (GTTB)
Project Start
Project End
Budget Start
Budget End
Support Year
17
Fiscal Year
1998
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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