Division of Periodontology

Anna Dongari-Bagtzoglou, D.D.S., M.S., Ph.D.

Professor and Chair

Degrees, Year Attained and University Attended

• Ph.D. in Microbiology, 1997, University of Texas Health Science Center, San Antonio
• Certificate in Periodontology, 1996, University of Texas Health Science Center, San Antonio
• M.S. in Oral Biology, 1990, University of California, Los Angeles
• D.D.S., 1988, Aristotle University of Thessaloniki, Greece

Brief Chronology of Professional Career

• 2011 - Present: Head, Department of Oral Health and Diagnostic Sciences
• 2010 - Present: Professor, Department of Oral Health Sciences, Division of Periodontology, School of Dental Medicine, University of Connecticut Health Center
• 2006 - Present: Chair, Division of Periodontology
• 2005 - 2010: Associate Professor, Division of Periodontology, School of Dental Medicine, University of Connecticut Health Center
• 2002 - 2005: Assistant Professor, Department of Periodontology, School of Dental Medicine, University of Connecticut Health Center
• 2003 - Present: Faculty Member, Graduate School, Ph.D. Program in Skeletal, Craniofacial and Oral Biology, School of Dental Medicine, University of Connecticut Health Center
• 1997 - 2002: Assistant Professor, Divisions of Oral Biology and Periodontics, Columbia University

Main Responsibilities

Research, administration, teaching, patient care.

Courses Taught

• Oral Diseases and Infections, Curriculum Leader
• Introduction to Periodontal Diagnosis and Therapy, Course Director

Major Research Interests

Pathogenesis of oral opportunistic infections in the immunocompromised host. Oral infection-induced inflammation. Innate immune factors limiting oral fungal infections.

On-going Research Projects

A. Oral thrush (pseudomembranous candidiasis) continues to afflict an unacceptably high percentage of immunocompromised individuals, particularly children. In this infection a breakdown of the mucosal innate defenses and decreased neutrophil cell number or function result in the transition from oral commensalism to mucosal infection. The overall goal of this project is to study the oral mucosal inflammatory responses to Candida and the regulatory role of these responses on the function of innate immune cells and Candida clearance. In these studies we are using novel tissue engineering approaches and animal models of oroesophageal infection to model host-pathogen interactions. We are interested in both the host response to infection and the role of specific Candida gene products in facilitating oral mucosal tissue colonization, local invasion and damage. Because superficial mycoses characterized by Candida biofilm formation on the surface of stratified epithelia affect other GI tract mucosal sites, which may be more vulnerable to invasion, our studies may have far reaching implications in preventing disseminated infection. We envision that our studies will lead to the development of new oral anti-mycotic agents which target pathways of mucosal virulence by C. albicans and/or promote local neutrophil antifungal functions.

Recent Significant Discoveries

• The development of a three-dimensional in vitro tissue model of the human oral mucosa and submucosa, which faithfully reproduces the histologic and cellular characteristics of its in vivo counterpart.
• The identification of a cytokine communication network between oral epithelial cells, fibroblasts and innate immune cells with potentially important consequences in the clearance of this infection in vivo.
• The discovery of a new mechanism of invasion of C. albicans into the oral mucosa through the degradation of E-cadherin from oral epithelial cell junctions, mediated by the fungal transcription factor Rim101 and secreted aspartyl proteases.
• The discovery that oral mucosal invasion by Candida intensifies the host inflammatory response to infection.
  

B. Over the last several years, compelling evidence is accumulating which associates chronic elevation of serum markers such as IL-6 and CRP in periodontitis patients with a systemic inflammatory state that may contribute to cardiovascular or cerebrovascular disease. For the first time, we hypothesized that the same inflammatory processes may contribute to graft atherosclerotic changes leading to chronic cardiac or renal allograft failure in transplant recipients with untreated chronic periodontal infections. In this clinical research project we are studying the periodontal condition of solid organ transplant recipients and examining the relationship between serum and periodontal tissue inflammatory markers, such as IL-6, with the history of chronic transplant rejection.

Recent Significant Discoveries

• IL-6 and CRP serum levels are elevated in solid organ transplant recipients with periodontitis.
• Periodontal tissue mRNA and serum protein IL-6 levels are highly correlated in transplant recipients with periodontitis.

Selected Recent Publications

1. Sinha-Morton R., Dongari-Bagtzoglou A.I. “Cyclooxygenase-2 Expression is Upregulated in Inflamed Gingival Tissues.” Journal of Periodontology, 2001; 72:461-469.

2. Dongari-Bagtzoglou A.I., Thienel U., Yellin M.J. CD40 Ligation Triggers COX-2 Expression in Endothelial Cells: Evidence that CD40-Mediated IL-6 Synthesis is COX-2-Dependent. Inflammation Research, 2003; 52(1):18-25.

3. Dongari-Bagtzoglou A.I., Kashleva H., “Candida albicans Triggers Interleukin-8 Secretion by Oral Epithelial Cells.” Microbial Pathogenesis, 2003; 34(4): 169-177.

4. Dongari-Bagtzoglou A.I., Kashleva H., Villar C.C. “Bioactive interleukin-1α is cytolytically released from Candida albicans-infected oral epithelial cells.” Medical Mycology, 2004; 42(6):531-541.

5. Villar C.C., Kashleva H., Dongari-Bagtzoglou A.I. “Role of Candida albicans polymorphism in the interactions with oral epithelial cells.” Oral Microbiology and Immunology, 2004; 19:262-269.

6. Villar C.C., Kashleva H., Mitchell A.P., Dongari-Bagtzoglou A.I. “Invasive phenotype of Candida albicans affects the host proinflammatory response to infection.” Infection and Immunity, 2005; 73(8):4588-4595.

7. Dongari-Bagtzoglou A.I. “Innate Defense Mechanisms in Oral Candidiasis”, In Fidel PLJr. and Huffnagle G. eds “Fungal Immunology from an Organ Perspective”, p. 13-35, Springer Science+Business Media Inc, New York, 2005.

8. Dongari-Bagtzoglou A.I., Villar C.C., Kashleva H. “Candida albicans-infected oral epithelial cells augment the anti-fungal activity of human neutrophils in vitro”. Medical Mycology, 2005; 43(6): 545-549.

9. Dongari-Bagtzoglou A.I., Fidel P.L. “The host cytokine responses and protective immunity in oropharyngeal candidiasis”. Journal of Dental Research 2005; 84(11): 966-977.

10. Dongari-Bagtzoglou A.I., Kashleva H. “Development of a Novel Three-Dimensional in vitro Model of Oral Candida Infection”. Microbial Pathogenesis, 2006; 40(6): 271-278.

11. Dongari-Bagtzoglou A.I., Kashleva H. “Development of a Highly reproducible 3D Organotypic Model of the Oral Mucosa”, Nature Protocols, 2006; 1(4): 2012-2018.

12. Li L., Redding S., Dongari-Bagtzoglou A.I. Candida glabrata, an Emerging Oral Opportunistic Pathogen. Journal of Dental Research, 2007; 86(3): 204-15.

13. Li L., Kashleva H., Dongari-Bagtzoglou A.I. Cytotoxic and Cytokine-Inducing Properties of Candida glabrata in Single and Mixed Oral Infection Models. Microbial Pathogenesis, 2007; 42(4):138-47.

14. Villar C.C., Kashleva, H Nobile, C.J., Mitchell, AP, Dongari-Bagtzoglou, AI. Mucosal Tissue Invasion by Candida albicans is Associated with E-cadherin Degradation, Mediated by Transcription Factor Rim101 and Protease Sap5. Infection and Immunity, 2007; 75(5):2126-35.