| We apply multidisciplinary approaches (morphological, physiological, pharmacological, biochemical, molecular and genetic) to study the biology of salivary glands, with an emphasis on the synthesis, secretion and functions of mucins. Mucins are major constituents of mucus layers of the body and function as a defense mechanism against invading microorganisms. These glycoproteins are secreted by the highly specialized mucous cell phenotype, which are under complex parasympathetic control. We recently discovered and characterized the gene, Muc19/Smgc, which encodes the mucin (Muc19) that is selectively expressed by mouse sublingual salivary glands. Coincidently, we genetically mapped an autosomal recessive mutation, sld, to a 1 megabase critical region of chromosome 15. The sld phenotype is characterized by the developmental delay and attenuated expression of Muc19. Interestingly, the critical region contains Muc19/Smgc. We are currently delineating whether Muc19 indeed harbors the sld mutation, through construction of knockout mouse models and by bioinformatic/gene expression analysis of the critical region. We are also investigating the associated genetic lesion to determine mechanism(s) by which steady-state levels of Muc19 transcripts are regulated.
We recently initiated a project to induce distinct targeted gene deletions of specific salivary constituents (e.g., Muc19) in mice to test their functions in protecting teeth against the oral pathogen, Streptococcus mutans. Genetic manipulations of the bacteria are also being carried out to test putative S. mutans virulence factors in caries development. Determination of the influence of specific bacterial and host determinants in caries development in vivo may ultimately provide important targets for therapeutic intervention in the treatment of patients at high risk for caries.
Graduate Education:
Lecturer, GMS 6161, Oral Biology II
Extramural Professional Activities:
Member, Editorial Board of the Journal of Dental Research
Member, Oral, Dental and Craniofacial Sciences, NIH Study Section.
Sponsored-research Support:
NIH (DE014730) “Salivary Mucous Cell Gene Expression” (PI)
NIH (DE016362) “Oral Infectious Disease: Virulence and Host Determinants” (PI).
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Culp, D.J., Quivey, R.G., Bowen, W.H., Fallon, M.A., Pearson, S.K., Faustoferri, R. 2005. A mouse caries model and evaluation of Aqp5 -/- knockout mice. Caries Research 39(6): 448-454.
Latchney, L.R., Fallon, M.A., Culp, D.J., Gelbard, H.A., and Dewhurst, S. (2004) Immunohistochemical assessment of fractalkine, inflammatory cells and human herpes virus 7 in human salivary glands. J. Histochem. Cytochem. 52(5):671–681.
Culp, D.J., Latchney, L.R., Fallon, M., P.A., Denny, P.C., Couwenhoven, R.I., and Chuang, S. (2004) The gene encoding mouse Muc19: cDNA, genomic organization and relationship to Smgc. Physiol. Genomics 9:303-18.
Reviews and Book Chapters:
Melvin, J.E. and Culp, D.J. (2004) Salivary Gland Physiology. In: Encyclopedia of Gastroenterology, ed., J.A. Williams, Academic Press Inc., San Diego, CA, pp.318-325.
Presentations:
April 2005 “Muc-en Around With Mice" Department of Oral Biology, School of Dental Medicine , University at Buffalo , The State University of New York
February 2005 “Controlling Mucous Cell Differentiation and Development" Gordon Research Conference, Salivary Glands and Exocrine Secretion, Ventura, California
February 2005 “Mucous Cell Differentiation: Insights from the sld Mutation" School of Medicine and the School of Veterinary Medicine Joint Seminar Series, University of California, Davis |
