Home > About the School > Research Activities > CRCPD
Director: Harvey A. Schenkein, DDS, Ph.D.
Co-Director: John G. Tew, Ph.D.
Center Office: Wood Building, Room 401
Phone: (804) 828-9185
Fax: (804) 828-5787
Center Clinical and Administrative Staff
Kimberly L. Hollaway, Research Specialist
Phone: (804) 828-4553
Margaret Poland, Grants Administrator
Phone: (804) 828-9185
The CRCPD studies periodontal (gum) diseases, with emphasis on a group of
diseases in teenagers and young adults called early-onset periodontitis (EOP).
This form of periodontal disease is significant because it occurs in the U.S.
mainly in the African American population, it is familial (runs in families)
and thus could have a genetic cause, and patients with the disease have some
unusual host-response, or immune function, characteristics which also could
be genetic or influenced by race. These diseases include some of the most
severe forms of periodontal disease and can lead to loss of many permanent
teeth during the teens and early 20's.
The CRCPD represents an interdisciplinary effort that involves
investigators in the Schools of Dentistry and Medicine at VCU as well as
investigators at the National Institutes of Health, who are our collaborators
in the human genetics aspects of the work. Our work on these diseases began
in the late 1970's and continues to this date, resulting in accumulation of
data and laboratory samples on the largest number of EOP patients and their
families in the world.
The goals of ongoing projects in the CRCPD include the following:
1. Genetic Epidemiology and Molecular Gene Mapping Studies of Early
Onset Periodontitis (Investigation of the underlying genetic, or inherited,
factors that may cause EOP.) Clinical investigators at VCU recruit families of
individuals with EOP, perform clinical characterizations, and send DNA samples
to the genetics laboratory at the National Institute of Dental and Craniofacial
Research. The genetics group is searching for a gene or genes that predispose
to risk for EOP. Additionally, they are utilizing data from the other CRCPD
research groups, such as information about unusual immune responses in these
patients, to search for genes that influence these immune response.
Project Director: Scott R. Diehl, Ph.D., NIDCR/NIH
2. Monocyte derived lipid mediators and cytokines in regulating IgG2
production in early-onset periodontitis (Examination of the mechanisms
explaining the unusual antibody responses observed in patients with localized
juvenile periodontitis (LJP), a form of EOP.) One of the interesting
characteristics of LJP that has been described by our group is the fact that
patients with this disease produce very high concentrations of a particular
antibody protein called IgG2. This type of antibody is usually produced by
the body during infections with many kinds of bacteria, including the ones
thought to be most involved in LJP. Furthermore, IgG2 is mainly produced as a
response against foreign carbohydrates, which are found on most bacteria. Since
very high antibody responses are characteristic of LJP patients, we are seeking
to determine why LJP patients make so much of this protein. We are examining
the various factors that influence one's ability to make IgG2, including
mediators of inflammation such as prostaglandins and other lipids, and
cytokines (which are proteins produced by cells to signal other cells).
In addition, we are closely studying a type of cell called the dendritic
cell as a possible cause of the excess IgG2 production by LJP patients.
Project Director: John G. Tew, Department of Microbiology and Immunology,
VCU School of Medicine.
3. PAF acetyl-hydrolase in localized juvenile periodontitis (Role
of the enzyme PAF-AH in IgG2 production in EOP). One of the "inflammatory
mediators" cited above that is under investigation is "platelet activating
factor" or PAF. Our studies show that PAF may be a critical molecule for
regulating IgG2 production in LJP, with high levels of PAF stimulating immune
cells to produce more IgG2. High levels of PAF could be caused by decreased
breakdown of this molecule-this is mediated by an enzyme that is abbreviated
PAF-AH. In fact, our data indicate that LJP patients make less PAF-AH so they
would have less breakdown of PAF-this would cause their cells to make more
IgG2 due to higher levels of available PAF. This project is aimed at
discovering how and why the PAF-AH enzyme in LJP patients is less active. It
also focuses on dendritic cells PAF-AH activity, because we have observed that
such cells appear to be more common in the circulation of LJP patients.
Project Director: Suzanne Barbour, Ph.D., Department of Microbiology and
Immunology, VCU School of Medicine
4. Human antibody reactivity to phosphorylcholine: modulation of
PAF-dependent biological activities, induction by phosphoryl choline-bearing
plaque bacteria, and relationship to periodontal destruction (Studies of
phosphorylcholine (PC) on oral bacteria and antibody to PC--role in periodontal
pathology). Phosphorylcholine (PC) is a small molecule present on some bacteria,
and patients with periodontal diseases have higher levels of antibody
(particularly IgG2 antibody) in their serum that reacts with PC. This project
examines the function of both the PC on oral bacteria and this antibody. We
have found that certain oral pathogens, or disease-causing bacteria, are able
to invade the cells that line the bloodstream (endothelial cells) and perhaps
enter the bloodstream because of their PC-as it happens, the reason they can
do this is that bacterial PC looks identical to these cells to PC that is
present on PAF. We are therefore studying the invasion process. Secondly, we
are studying the antibodies to PC which are found in all human sera-these
antibodies react with PAF, placing them into a category of molecules called
"autoantibodies", that is, antibodies that react with normal constituents of
the body. We are attempting to determine how these "autoantibodies" react with
normal molecules to influence immune responses such as production of IgG2.
Finally, these antibodies may also be involved in other diseases such as
cardiovascular disease since they also react with human oxidized LDL's, a well
known risk factor for stroke and heart attack. We are studying how oral
bacteria may promote the production of antibodies to PC which could then
react with LDL's to influence the course of cardiovascular disease.
Project Director: Harvey A. Schenkein, DDS, Ph.D., VCU School of Dentistry