# Bioinformatic Approaches for Understanding Macrophage Plasticity and Microbiome in Oral Diseases

> **NIH NIH K18** · STATE UNIVERSITY OF NEW YORK AT BUFFALO · 2020 · $94,393

## Abstract

PROJECT SUMMARY
Research: With advancing age, the immune system undergoes dynamic changes characterized by both
impairment of adaptive immunity and activation of low-grade chronic inflammation. This chronic activation of
inflammation associated with aging or `inflammaging'. Tristetraprolin (TTP) is an RNA binding protein that post-
translationally binds to adenylate-uridylate–rich elements in the 3′-UTR of target mRNAs (including key pro-
inflammatory mRNAs e.g. TNFα, COX-2 and IL-6) to promote their rapid turnover. Importantly, the project
laboratory has demonstrated that failure to regulate expression of cytokines at the posttranscriptional level
contributes to chronic inflammation and spontaneous alveolar bone loss with age in TTP-/- mice compared to
age/sex match controls. Thus, TTP expression appears to be essential for alveolar bone homeostasis in an age-
dependent manner. Data in this application and recently published data strongly support the concept that
macrophages and myeloid-derived suppressor cell (MDSC) populations are expanded with age in TTP-/- mice,
with concomitant reduction in lymphocyte populations. Taken together, these results support the notion that TTP
may be a critical intrinsic factor of inflammaging and myeloid lineage expansion/differentiation that contributes
towards skeletal homeostasis. For this K18 application, it is proposed to use data sets generated already under
5R01DE028258, to examine the role of the microbiome in contributing towards the TTP null hyperinflammatory
phenotype and understand if MDSC populations from oral and non-oral sources have different expression
profiles by single cell RNA sequencing.
Fellowship training plan/environment: The applicant has assembled a strong mentoring team who have a
long history of working together and training scientists to become successful independent investigators. The
proposed project will allow the applicant to integrate his translation research portfolio with bioinformatics, which
will foster the perspectives and skills necessary to continue to be a successful oral biologist.

## Key facts

- **NIH application ID:** 9952990
- **Project number:** 1K18DE029526-01
- **Recipient organization:** STATE UNIVERSITY OF NEW YORK AT BUFFALO
- **Principal Investigator:** Keith L Kirkwood
- **Activity code:** K18 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $94,393
- **Award type:** 1
- **Project period:** 2020-04-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9952990

## Citation

> US National Institutes of Health, RePORTER application 9952990, Bioinformatic Approaches for Understanding Macrophage Plasticity and Microbiome in Oral Diseases (1K18DE029526-01). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/9952990. Licensed CC0.

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