DENTRITIC CELLS IN PERIODONTAL HEALTH AND DISEASE

DESCRIPTION (provided by applicant): This proposal for a mentored patient-oriented research career development award will provide the candidate the knowledge and skills required to design, conduct, and analyze clinical research projects. The educational, clinical, and research resources at Stony Brook University's School of Dental Medicine, School of Medicine (SOM), School of Health Technology and Management (SHTM), and General Clinical Research Center (GCRC) will provide the candidate a robust environment for career development. A systematic plan has been developed that incorporates didactic courses provided by the GCRC, SHTM, and SOM with supervised research that includes clinical studies and complimentary laboratory analysis. The acquisition of both basic and applied research skills is essential for the candidate to transition into an independent investigator who can interface with basic scientists to design studies that evaluate novel hypotheses and ultimately translate this information into new diagnostic and therapeutic modalities. The research plan includes human studies to address a novel hypothesis regarding the role of dendritic cells (DC) in the pathogenesis of gingivitis and chronic periodontitis (CP). The hypothesis is that species in the plaque biofilm such as Porphyromonas gingivalis may promote the development of organized lymphoid aggregates in the lamina propria around the dentition, described as oral lymphoid follicles (OLF). Preliminary data indicate that Langerhans Cells (LC), mature dendritic cells, and T cells are the principal cellular components of the OLF. Furthermore, the transition from periodontal health to gingivitis to CP involves different stages in the development of OLF, as initiated by the plaque biofilm, propagated by cytokine/chemokine milieu, and induced by LCs. The specific aims of this proposal will use 2 longitudinal studies to establish the changes that occur in DCs and their trafficking molecules during 1) experimental gingivitis (EG) and 2) CP. In Aim 1, periodontally healthy subjects will be restored to gingival health following the EG protocol, and in Aim 2, CP subjects will receive conventional treatment and then be enrolled in a maintenance program. The information generated in this training program will further elucidate the role of the host response in periodontal diseases and potentially lead to the development of therapies aimed at prevention and treatment of these conditions.