# The impact of the aging immune system on periodontal disease

> **NIH NIH K08** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2021 · $130,858

## Abstract

Project Summary
This is an application for Dr. Daniel Clark for a Mentored Clinical Scientist Research Career Development Award
(K08). Dr. Clark has been training to establish himself as an investigator in basic science research of
osteoimmunology, and this award will provide Dr. Clark with the support and opportunities necessary to reach
his career goal of being an independent researcher. In pursuit of his career goal, the K08 award will allow Dr.
Clark to: (1) to become an expert in osteoimmunology; (2) develop an independent research program through
novel application of osteoimmunology to the investigation of periodontal disease; (3) create a productive and
impactful publication record; (4) enhance grant writing skills and create a record of successful utilization of past
and current awards. Towards his career goal, Dr. Clark has established a transdisciplinary team to provide their
expertise in research training and mentorship in career development. Primary mentor Dr. Ralph Marcucio (expert
in bone biology) and co-mentor Dr. Mary Nakamura (immunologist and expert in osteoimmunology) will provide
foundational training in osteoimmunology, and co-mentor Dr. Yvonne Kapila (leading dentist-scientist and
periodontal basic science researcher) will provide expertise and guidance for osteoimmunological applications
to periodontal disease research. In addition, collaborators Drs. Marina Sirota, Eben Alsberg, and Saul Villeda
will provide their expertise of bioinformatics, cell-based therapeutics, and aging biology respectively. Immune
system dysfunction increases with age and is associated with an increased prevalence and severity of
inflammatory conditions in elderly populations, including periodontal disease. The cellular and molecular process
regulating the inflammatory response that become perturbed by age are unknown. Dr. Clark's long term goal is
to identify cellular and molecular targets for immunomodulatory treatment of periodontal disease. The objective
of this proposal is to understand how a key cellular regulator of the innate inflammatory response, macrophages,
interacts with mesenchymal stem cells (MSCs) and Th17 cells, to regulate inflammation in bone and how these
processes become dysregulated with age. Dr. Clark will utilize primary cell lines from young and old mice and a
periodontal disease mouse model to investigate (1) the extent to which macrophages and MSCs interact through
triggering receptor expressed on myeloid cells-2 (TREM2) to downregulate inflammation; (2) the extent to which
an aged macrophage phenotype drives pathogenic Th17 cell expansion; (3) and demonstrate the effect of
immunomodulation with cell-based therapeutics that target age-related perturbations to rejuvenate the immune
response in periodontal disease. Further single cell analysis and bioinformatics techniques will produce
transcriptomic datasets to identify gene expression signatures associated with aging and inflammatory
dysregulation. Findings from this proj...

## Key facts

- **NIH application ID:** 10531708
- **Project number:** 7K08DE029505-03
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Daniel R. Clark
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $130,858
- **Award type:** 7
- **Project period:** 2022-01-17 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10531708

## Citation

> US National Institutes of Health, RePORTER application 10531708, The impact of the aging immune system on periodontal disease (7K08DE029505-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10531708. Licensed CC0.

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