David Culp, Ph.D.
Professor
Oral Biology

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Tissue-Specific Gene Expression and Function
There are two diverse research projects on-going in the lab:

1. We discovered a large murine gene, Smgc/Muc19. This gene encodes the apomucin, Muc19, and a smaller splice-variant , Smgc, which is regulated developmentally. Primary goals are to elucidate mechanisms regulating gene expression, using both wild type and a mutant mouse model, NFS/N-sld. In sld mice, Muc19 expression is markedly and specifically attenuated. We are producing Muc19 knockout mice to determine whether deletion of Muc19 mimics the sld phenotype, and also as a recipient model system for gene regulation studies. Current studies include: 1) determining the mechanism for attenuated Muc19 expression in sld mice (e.g., rates of transcription and degradation; and 2) delineation of cis- and trans-acting factors required for the cell-specific expression of Muc19 and for the developmentally regulated RNA splicing of Smgc/Muc19 heteronuclear RNA. Elucidation of promoter sequences that direct the specific expression of Muc19 in salivary mucous cells will aid in the design of constructs to modulate gene expression in a cell-specific manner, and thus open the door for in-vivo studies of signaling mechanisms controlling exocrine function and cytodifferentiation of this cell type. Such information will assist in biomimetic approaches to treat cancer and autoimmune patients with salivary gland dysfunction.

2. We developed a mouse model to assess caries (tooth decay) in determining the protective role of specific salivary constituents (Muc19, Muc10, and amylase). We recently produced knockout founders for Muc10 and Amy1. Experiments of Strepococcus mutans binding to hydroxyapatite beads coated with either purified glycoproteins/proteins or with strain-specific saliva's (to mimic the tooth surface), in combination with in vivo caries and infectivity studies will help identify protective role of these host factors. Reciprocal experiments are planned with strains of Strepococcus mutans in which cell surface proteins that are suspected of being caries virulence factors are deleted.

Research Diagram

Status:
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Contact Information:
office: P4-33
lab: P4-30
phone: 352-846-0800
email: dculp@dental.ufl.edu
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Biography:
David Culp received his Ph.D. in Physiology from the University of California, Berkeley in the laboratory of Dr. John Forte. In 1981 he joined the Pulmonary Unit of the Department of Medicine at the University of Rochester as a postdoc to study secretory mechanisms in the airways. He was promoted 3 years later to Assistant Professor of Medicine and of Biochemistry. He directed the undergraduate program in Biochemistry and coordinated the first semester Biochemistry course for Medical Center graduate students. His research program re-focused on the cell biology of salivary glands, a more homogeneous model system to study cellular secretory mechanisms. Shortly thereafter, he moved from Medicine to the newly emerging Department of Dental Research, followed by an additional secondary appointment in the Department of Pharmacology and Physiology and promotion to Associate Professor. He directed the graduate student seminar series in Pharmacology and Physiology, and a Pharmacology course for residents in the Eastman Department of Dentistry. After 25 years at the University of Rochester and helping to raise three wonderful children, he joined the faculty in the UF College of Dentistry in 2006 as Professor of Oral Biology.

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