# Diabetes-enhanced Experimental Periodontitis

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2022 · $437,509

## Abstract

Abstract: Diabetes increases the risk and frequency of bacterial infection and alters the adaptive immune
response. Surprisingly little is known about the impact of diabetes on dendritic cells and how it may increase
susceptibility to periodontitis. The lack of understanding until recently has been hampered by limited technical
ability to define the specific behavior of dendritic cells and interactions with other cell types during active
periodontal disease. New advances in single cell transcriptomics such as single cell RNA-seq (scRNA-seq) have
provided an exponential increase in our ability to dissect the behavior of specific cell types under various disease
conditions. The studies proposed will elucidate how diabetes alters dendritic cell function in a way that
contributes to periodontitis. New Prel Data has been added resulting a completely revised proposal
demonstrating that diabetes alters dendritic cell gene expression in vivo as assessed by scRNA-seq. The studies
proposed involve sophisticated bioinformatic analysis of scRNA-seq data very recently obtained and a new
experimental approach, spatially resolved transcriptomics, to provide new insight on how diabetes may affect
dendritic cell activity. The risk in this approach in Aim 1 is mitigated by Prel Data that have identified potential
key genes that are up- or down-regulated in the periodontium in dendritic cells during active periodontal disease
progression, which will be further investigated by bioinformatic analysis of scRNA-seq results. In addition,
translational studies are proposed in Aim 1 as a preclinical step for therapeutic intervention. Functional studies
are proposed in Aim 2 to examine gene candidates in vitro to establish cause and effect relationships between
candidate genes and functional outcomes. Experiments in Aim 3 will use spatial transcriptomics to define how
diabetes may alter the spatial compartments in which DC and other leukocytes are found during the initiation of
periodontitis and investigate co-localization of cells and pattern of inflammatory gene expression to better
understand their interaction. Taken together this proposal combines an unbiased approach for hypothesis
discovery with functional in vitro and in vivo methods for hypothesis testing and establishing mechanisms.

## Key facts

- **NIH application ID:** 10375888
- **Project number:** 2R01DE017732-12A1
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** DANA T GRAVES
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $437,509
- **Award type:** 2
- **Project period:** 2007-07-01 → 2027-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10375888

## Citation

> US National Institutes of Health, RePORTER application 10375888, Diabetes-enhanced Experimental Periodontitis (2R01DE017732-12A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10375888. Licensed CC0.

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