# Monocyte and Macrophage Signaling in the Pathogenesis of Periodontitis in Diabetes

> **NIH NIH R03** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2021 · $162,000

## Abstract

PROJECT SUMMARY
Type 2 diabetes mellitus (T2DM) and periodontitis are chronic diseases affecting millions of people globally
and have long been considered biologically linked. Periodontitis is a complex inflammatory disease, initiated by
subgingival microbial agents in a susceptible host, which can lead to tooth loss and contribute to systemic
inflammation. Diabetes is an established risk factor for periodontitis. Importantly, periodontitis has also been
shown to adversely affect glycemic control and to contribute to incident T2DM and the development of its
complications. The innate immune system, including monocytes and macrophages, plays a pivotal role in the
pathogenesis of both diseases. Functionally, macrophages can be categorized as classic pro-inflammatory
macrophages (M1) or anti-inflammatory/resolution macrophages (M2). Our preliminary results indicate
disruption of monocyte/macrophage homeostasis in periodontitis and T2DM and distinct RNA signature in
cellular subtypes. We also found a decrease in JMJD3 and IRF4 in monocytes/macrophages of T2DM patients
compared to subjects without T2DM. Downregulation of the JMJD3-IRF4 pathway has been linked to the
suppression of M2 macrophage polarization. Taken together these findings indicate the need for a more
comprehensive understanding of the role of monocyte/macrophage signaling in periodontitis with or without
T2DM and for mechanistic studies to delineate perturbed pathways. In this proposal, in Aim 1, we will use
single-cell RNA-sequencing and immune cell barcoding to first match the gene expression profile to the cellular
sub-types of myeloid-derived immune cells in gingival tissue (locally) and immune cells in blood (systemically)
with the vision of understanding their specific changes and their role in the pathogenesis of periodontitis in
T2DM. Moreover, we will identify the molecular signaling events that affect the phenotype and function of
monocytes/macrophages in the pathogenesis of periodontitis and T2DM. In Aim 2, We will use CRISPR/CAS9
activators to engineer monocytes/macrophages to restore JMJD3-IRF4 levels and modulate their functional
profile ex-vivo towards a resolution (M2) phenotype. The results of the proposed studies will lead to an in-depth
understanding of the heterogeneity in molecular signature and function of myeloid cells and their interactions
and roles in the pathogenesis of periodontitis with and without T2DM and provide mechanistic tools to
modulate macrophage phenotype to treat periodontitis with or without T2DM. The long-term vision of these
studies is the development of actionable targeted molecular therapies that can modulate
monocyte/macrophage phenotype and function in affected individuals. The proposed work is novel; it will
inform future directions for in vivo studies and produce valuable data that will serve as preliminary work for an
R01 grant application.

## Key facts

- **NIH application ID:** 10145651
- **Project number:** 5R03DE029546-02
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Fatemeh Momen Heravi
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $162,000
- **Award type:** 5
- **Project period:** 2020-05-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10145651

## Citation

> US National Institutes of Health, RePORTER application 10145651, Monocyte and Macrophage Signaling in the Pathogenesis of Periodontitis in Diabetes (5R03DE029546-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10145651. Licensed CC0.

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