David J. Culp, Ph.D.
Department of Oral Biology
- Ph.D., University of California, Berkeley, Physiology, 1981
- B.S., University of California, Berkeley, Biology, 1974
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). Coincidently, the gene encoding human MUC19 was identified, with expression found in human submandibular and sublingual glands. In a screen of multiple tissues in mice, we find Muc19 is expressed primarily in salivary mucous glands. On-going efforts are devoted to understanding the transcriptional regulation of expression of Muc19 transcripts.
Alternative splicing of Muc19/Smgc produces a smaller gene product, of SMGC. In murine sublingual glands, this secretory glycoprotein is expressed only during periods of gland growth. Accumulating evidence suggests SMGC is a product of glandular cells during the latter stages of acinar cell differentiation. Moreover, we find Smgc-like transcripts in human submandibular glands, suggesting species conservation for two distinct splice-variants in the gene encoding MUC19. We are interested in exploring the function of SMGC and in determining how alternative splicing of Muc19/Smgc is controlled.
We have generated knockout mice with targeted gene deletions of specific constituents of saliva (i.e., Muc19, Muc10 and amylase). Knockout mice will be used in in vivo caries experiments to test the influence of each salivary molecule 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 may ultimately provide important targets for therapeutic intervention in the treatment of patients at high risk for caries.
- Member, IDP Admissions Committee
- Director and Lecturer, GMS 6160, Oral Biology I
- Lecturer, GMS 6161, Oral Biology II
Extramural Professional Activities
- Member, Editorial Board of the Journal of Dental Research
- NIH (DE014730) “Salivary Mucous Cell Gene Expression” (PI)
- NIH (DE016362) “Oral Infectious Disease: Virulence and Host Determinants” (PI).
- 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.
- 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