Dr. Roger Arce
whereas ineffective antigen presentation by immature DCs leads to sustained inflammation and bone loss characterized by strong regulatory T cells infiltration (Tregs). The expected outcome of this application is to specifically identify a protective or destructive role for DCs and T cell subsets in biofilm-induced alveolar bone loss and the mechanisms involved.
Periodontitis affects up to 47% of the US population. When untreated, periodontitis results in alveolar bone/tooth loss, sustaining a chronic proinflammatory disorder with cardiovascular consequences. A critical barrier to treat periodontitis relates to the regulation of protective vs. destructive immune responses. The goal of my current research is to understand the specific contribution of polymicrobial infections, Dendritic Cells (DCs) and T-cell subtypes in protective/destructive immune responses in a murine model of oral biofilm infection. Our central hypothesis is that the development of an effective adaptive immune response against oral pathogens is set in motion upon efficient recognition, processing and pathogen clearance by DCs. For this, DCs differentially activate, maturate and regulate a sequence of events including intracellular routing/processing, co-stimulatory molecule expression and cytokine secretion. Effective antigen presentation by mature DCs leads to polarization of CD4+ T cell response, clearance and immune homeostasis;
Exploring the effects of pathogen-differentiated dendritic cells in experimental periodontitis mouse model.
Dr. Arce prepares cells for separation.
immunologic (vaccination) therapy for modification of the clinical and inflammatory (cytokine) response of the gingiva to infection. These have included FDA studies and grants/contracts with the following health care companies: Allergan, Corixa, Proctor and Gamble, Warner-Lambert, Collagenex, Teledyne Water Pik, Parkell and Biolase.
Clinical expertise in periodontics combined with basic science focus on host-pathogen interactions and oral mucosal immunology/inflammation.
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Dr. Cutler explains periodontal disease using a skull model.
The major objective of my research program is to establish the role of human dendritic cell (DC) subsets in the oral mucosal immune response to periodontal pathogens. We isolate myeloid DCs from blood and tissues and analyze transcriptome and microbiome, with the former focused on immunomodulatory pathways. This is correlated with an in-vitro model consisting of DCs generated in vitro, including monocyte-derived DCs (MoDCs) and pathogen differentiated DCs (PDDCs). Considerable expertise lies in defining the role of pattern recognition receptors/ C-type lectin receptors in uptake of Porphyromonas gingivalis and in recognition of its agonists (LPS/ fimbriae). The ability of DCs to activate/tolerize the adaptive immune response and to express mediators of tissue destruction are established by functional, genomic and proteomic analyses. Much of my clinical research interest involves analysis of pharmacologic (anti-inflammatory, anti-bacterial), physical (oral irrigation, lasers) and
Dr. Christopher Cutler​
Periodontitis affects up to 47% of the US population. When untreated, periodontitis results in alveolar bone/tooth loss, sustaining a chronic proinflammatory disorder with cardiovascular consequences. A critical barrier to treat periodontitis relates to the regulation of protective vs. destructive immune responses. The goal of my current research is to understand the specific contribution of polymicrobial infections, Dendritic Cells (DCs) and T-cell subtypes in protective/destructive immune responses in a murine model of oral biofilm infection. Our central hypothesis is that the development of an effective adaptive immune response against oral pathogens is set in motion upon efficient recognition, processing and pathogen clearance by DCs. For this, DCs differentially activate, maturate and regulate a sequence of events including intracellular routing/processing, co-stimulatory molecule expression and cytokine secretion. Effective antigen presentation by mature DCs leads to polarization of CD4+ T cell response, clearance and immune homeostasis; whereas ineffective antigen presentation
Dr. Pachiappan Arjunan
Therefore, as part of my research interest, I propose to study the pathological interaction of degenerative diseases of the retina, bone, vascular system and mucosa with other inflammatory degenerative disorders of the body systems. The current research intent is to determine the dysbiosis caused by periodontal inflammation and its pathological association with systemic disorders, with a major emphasis on retinal inflammatory/degenerative conditions using in-vitro & in-vivo models.
Dr. Arjunan uses a microneedle to inject a mouse.
Investigating the molecular mechanisms of disruption of immune homeostasis in chronic inflammatory degenerative disorders
My primary research focus is to identify the key cellular mechanisms of disruption of immune homeostasis that occurs in response to dysbiotic pathogen Porphyromonas gingivalis. Using high-throughput sequencing and bioinformatics analysis, I have identified differentially expressed genes (DEGs) in human MoDCs in response to P. gingivalis and its fimbrial mutants, which are associated with inflammation, immune response, immunosuppression, anti-apoptosis, cell proliferation, and other significant homeostatic functions. With a reverse-translational research approach, studying the novel pathways employed in pathogen survival that involves exploitation of monocyte plasticity, lead us to discover a special long-lived DCs sub-type particularly relevant to cancer immune-surveillance. This innovation is expected to expand our knowledge in the therapeutic management of dysbiosis related immunological disorders as in chronic periodontitis and various other conditions including cancers. The inflamed periodontium is a known reservoir of infection and dissemination of inflammatory and infectious agents to distant locations cause numerous systemic disarrays.
Dr. Ahmed El-Awady
Dr. Amanda Stadler
Oral microbiome in murine model of Periodontal Disease
Using an oral infection model, we are investigating the effects of an oral biofilm on immune recognition during periodontitis, with and without the suppression of dendritic cells.