# Investigating the role of Tumor Necrosis Factor-Receptor Associated Factor 3 Interacting Protein 2

> **NIH NIH R00** · UNIVERSITY OF IOWA · 2021 · $241,099

## Abstract

PROJECT SUMMARY
The candidate is a dual-trained periodontist scientist who is committed to an academic career dedicated to
study periodontal disease and improve oral health. Periodontitis is a polygenetic, inflammatory response
towards bacterial pathogens at the gingival surface and affects 47% of the adult population in the United
States. This common oral disease, without effective management, eventually leads to tooth loss and is
significantly associated with systemic conditions such as diabetes. Analysis of a Genome Wide Association
Study (GWAS) for periodontitis has identified Tumor necrosis factor Receptor-Associated Factor 3 Interacting
Protein 2 (TRAF3IP2) as a target gene of interest. TRAF3IP2 dysfunction, such as induced by key genetic
variants, is significantly associated with a periodontal inflammation phenotype defined by a high pathogen
burden in plaque and local inflammation.TRAF3IP2 is a non-redundant adaptor molecule in the IL-17 pathway,
which plays a critical role in mucosal defense. The objective of this research proposal is to acquire knowledge
of the TRAF3IP2-mediated IL-17 response in gingival barrier defense mechanisms and the variant-induced
functional defects in the IL-17 pathway. The candidate hypothesizes that loss of TRAF3IP2-IL17 signaling
compromises the oral epithelial barrier and mucosal inflammatory signature and promotes dysbiotic
microbiome overgrowth. This hypothesis will be tested by both in vitro and in vivo genetic approaches. Using
Traf3ip2 ablated mice, the candidate will first determine the role of the IL-17/TRAF3IP2 pathway-modulated
immune response and microbial community structure in a periodontal pathogen-induced murine alveolar bone
loss model (Aim1). The candidate will then investigate the role of the IL-17/TRAF3IP2 pathway in mucosal
physical barrier function and mechanism of IL-17-regulated tight junction structure (Aim 2). The candidate will
further determine the TRAF3IP2 variant effect on immune response as reflected by the transcriptional and
post-transcriptional regulation of chemokine synthesis and barrier function in genetically engineered, human
gingival epithelial cells (Aim 3). The implementation of this research proposal requires additional training
including complex microbial community structure analysis, Th17/IL-17 immunobiology, epithelial biology and
molecular genomics. Strong mentorship by experts in each field and the exceptional environment at the
University of North Carolina at Chapel Hill will foster the accomplishment of this research proposal and
expedite the career development of the candidate. The scientific component and training outlined in this
proposal provide a pathway to achieving not only the candidate's short-term goal, which is to transition into an
independent investigator at a tenure track faculty position with R01 funding support, but also the long-term
goal, which is to update understanding of host-pathogen interactions at the mucosal surface. The expertise
gain...

## Key facts

- **NIH application ID:** 10180936
- **Project number:** 5R00DE027086-05
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** Shaoping Zhang
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $241,099
- **Award type:** 5
- **Project period:** 2019-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10180936

## Citation

> US National Institutes of Health, RePORTER application 10180936, Investigating the role of Tumor Necrosis Factor-Receptor Associated Factor 3 Interacting Protein 2 (5R00DE027086-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10180936. Licensed CC0.

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