Pirih's Lab

My laboratory focuses on understanding the basic and clinical aspects of periodontitis and peri-implantitis, with the ultimate goal of developing new strategies to prevent and treat both conditions. We conduct translational research that examines the role of genetics in patients' susceptibility to periodontitis and to better understand peri-implantitis.

Current NIH Funded Projects in the Pirih's Lab:

1R21DE023901-01A1: Mouse Genome-Wide Association Studies in LPS-Induced Bone Loss.

Periodontitis (PD) is a common inflammatory disease affecting periodontal tissues, leading to tooth support loss and potential tooth loss if untreated, with a prevalence of 47.2% in adults over 30. While bacterial biofilm is central to its pathogenesis, the host's genetic response plays a critical role, with PD being 50% heritable. This study aims to identify genetic variants contributing to PD-related bone loss through a genome-wide association study (GWAS) using the Hybrid Mouse Diversity Panel (HMDP), consisting of 100 genetically diverse mouse strains. Preliminary experiments utilizing LPS-induced bone loss models in 29 strains revealed heritability estimates and significant differences in susceptibility, supporting the genetic basis of PD. Specific aims include assessing periodontal bone loss across the HMDP and identifying genes linked to LPS-induced bone loss. Future work will validate findings and integrate genomic, transcriptomic, and proteomic approaches to advance understanding of PD susceptibility and aid in predicting genetically predisposed patients.

1R21DE031906-01A1: The role of CXCL10-CXCR3 axis in the compounding effects of diabetes mellitus in periodontitis.

Poorly controlled diabetes mellitus (DM) exacerbates the progression of periodontitis (PD), a condition that constitutes the sixth most frequent complication of DM and presents significant treatment challenges. Both conditions are linked to heightened inflammatory responses, with CXCL10 identified as a key inflammatory mediator in DM and PD. Elevated CXCL10 levels have been observed in periodontally diseased tissues and patient serum, and the CXCL10-CXCR3 signaling axis is critical for PD development. Preliminary studies show that deletion of the CXCR3 receptor or use of a CXCR3 antagonist reduces experimental periodontal bone loss (EPD) in mice. This study hypothesizes that targeting CXCL10-CXCR3 signaling can mitigate the detrimental effects of DM on PD. Specific aims include elucidating CXCL10’s role in the periodontium through genetic deletion and systemic administration, and testing the therapeutic potential of a CXCR3 antagonist (AMG-487) delivered locally via nanoparticles in DM-induced PD models. These findings aim to establish CXCL10-CXCR3 signaling as a novel therapeutic target for managing PD in patients with uncontrolled DM.

5R21DE031431-02: Genomewide association studies in peri-implant bone loss

Dental implants have transformed dentistry, but complications such as peri-implantitis (PI) affect 45% of implant recipients, with 14.5% experiencing moderate to severe cases. PI progresses more aggressively than periodontitis, often resulting in implant loss, and current treatments are only successful in resolving PI in 50% of cases. With over 5 million implants placed annually in the U.S. and a projected prevalence of 23% by 2026, PI represents a significant clinical concern. While genetics play a known role in periodontitis, their influence on PI remains largely unexplored. This study aims to identify genetic traits associated with peri-implant bone loss through Genome-Wide Association Studies (GWAS) using the Hybrid Mouse Diversity Panel (HMDP), which comprises over 100 inbred mouse strains. Preliminary studies have demonstrated strain-dependent variability in ligature-induced peri-implant bone loss, supporting the role of genetic factors. By leveraging the controlled genetic and environmental framework of the HMDP, this research seeks to uncover quantitative trait loci (QTLs) linked to PI susceptibility, treatment outcomes, and mechanistic differences from periodontitis, ultimately contributing to improved patient care and advancing scientific understanding of PI.