Ovitt Lab
Catherine Ovitt
Ph. D. 1987 Washington University
Associate Professor of Biomedical Genetics (BMG) in the
Center for Oral Biology (COB)
Research Overview
Salivary Gland Development and Regeneration
The overarching goal of my laboratory is to identify and characterize progenitor cells of the salivary gland, which may be harnessed for the repair or repopulation of damaged glands. Using mouse genetics and cell biological methods, we have identified a population of progenitor cells with the potential to regenerate specific salivary gland cell types in the adult organism. Our long-term goal is to aid in the development of treatments for xerostomia caused by radiation therapy for head and neck cancers.
Projects
Salivary gland precursor cells: We have identified a multipotent progenitor cell population in the salivary glands that generates both secretory acinar and ductal cells (Figure 1). Although apparently not required for salivary gland development, these progenitor cells contribute to the maintenance of the adult glands. The ability of these cells to function in salivary gland repair and regeneration is currently under investigation. Preliminary results of these studies present compelling evidence that salivary gland homeostasis is effected by multiple progenitor cell populations. Current research is underway to isolate and determine the extent of involvement of alternate progenitor cell populations.
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Physiology of mucous-secreting glands: The development of interventions to restore gland secretory function first requires a basic understanding of their molecular physiology. The characterization of transporter regulation and functional interactions in both salivary glands and the mucous-secreting glands of the olfactory epithelium is ongoing. Specific interactions within ion transport protein complexes are being explored through proteomic analysis. Lineage tracing has demonstrated that Ascl3-expressing progenitor cells are precursors of mucous-secreting glands (Figure 2). Ascl3 activity is thereby linked to regulation of the molecular program required for mucous cell identity. Additional components of this program are being explored.
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Development of gene-based therapeutic strategies for salivary gland repair: The salivary glands are critical for the maintenance of oral health. Age, drug treatments, diseases such as Sjogren's syndrome, and radiation treatment of patients with head and neck cancers, cause cellular damage in the salivary glands that is usually severe, and irreversible. The unique accessibility of the salivary glands allows us to test gene-based therapeutic strategies for treating these conditions. For example, we are investigating the targeted delivery of siRNAs via nanoparticles for protecting the cells from radiation damage (Figure 3). We are also exploring the rescue of saliva production through transduction of critical transporter genes into mutant mouse models. Successful delivery to salivary gland tissues will serve as a critical step in future studies on the functional restoration of the salivary glands. |
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Recent Publications
Arany S, Benoit DS, Dewhurst S, Ovitt CE (2013) Nanoparticle-mediated Gene Silencing Confers Radioprotection to Salivary Glands In Vivo. Mol Ther. 2013 Mar 19. doi: 10.1038/mt.2013.42. [Epub ahead of print] View article in PubMed
Rugel-Stahl A, Elliott ME, Ovitt CE (2012) Ascl3 marks adult progenitor cells of the mouse salivary gland. Stem Cell Res 8(3):379-387 View article in PubMed
Arany S, Xu Q, Hernady E, Benoit DS, Dewhurst S, Ovitt CE (2012) Pro-apoptotic gene knockdown mediated by nanocomplexed siRNA reduces radiation damage in primary salivary gland cultures. J Cell Biochem 113(6):1955-1965 View article in PubMed
Arany S, Catalan MA, Roztocil E, Ovitt CE (2011) Ascl3 knockout and cell ablation models reveal complexity of salivary gland maintenance and regeneration. Dev Biol, 353(2):186-193 View article in PubMed
Lan Y, Liu H, Ovitt CE, Jiang R. (2011) Generation of Osr1 conditional mutant mice. Genesis Feb 22. doi: 10.1002/dvg.20734. [Epub ahead of print] View article in PubMed
Bullard, T., Koek, L., Roztoci, E., Kingsley, P.D., Mirels, L., and Ovitt, C.E. (2008) Ascl3 expression marks a progenitor population of both acinar and ductal cells in mouse salivary glands. Dev Biol 320:72-78 View article in PubMed.
Nakamoto T., Srivastava A., Romanenko V.G., Ovitt C.E., Perez Cornejo P., Arreola J., Begenisich T., and Melvin J.E. (2007) Functional and molecular characterization of the fluid secretion mechanism in human parotid acinar cells. Am. J. Physiol. Regul. Integr. Comp. Physiol. 292, R2380-2390 View article in PubMed.
Lan, Y., Ovitt, C. E., Cho, E.-S., Maltby, K. M., Wang, Q., and Jiang, R. (2004) Odd-skipped related 2 (Osr2) encodes a key intrinsic regulator of secondary palate growth and morphogenesis. Development 131:3207-3216. View article in PubMed.
More papers: 
Graduate Program Affiliations
Contact
Catherine Ovitt
University of Rochester
School of Medicine and Dentistry
601 Elmwood Ave., Box 611
Rochester, NY 14642
Office: KMRB G-9639
Phone: (585) 275-2920
Lab: (585) 273-3076
Fax: (585) 276-0190
catherine_ovitt@urmc.
rochester.edu
Lab Members
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Mridula Vinjamuri Graduate student |
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Michael Rogers Technician |
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Marit Aure Post-doctoral fellow |
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Seo-Kyoung (Katie) Hwang graduate student |
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Pei-Lun Weng graduate student |
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Tiffany Wendt under-graduate |
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Alin Vonica, M.D., Ph.D. Research Assistant Professor |
