# GAS6-Mediated Regulation of Oral Tissue Regeneration

> **NIH NIH K99** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2021 · $139,320

## Abstract

Project Summary
Tooth loss from trauma or disease remains a significant world-wide concern due to poor esthetics and loss of
function. Addressing this issue is not trivial because regeneration of alveolar bone and oral tissue is not
predictable, partially due to the complexity of the process. Bone regeneration of these defects remains
unpredictable and understanding the physiological mechanisms that guide bone marrow biology and
inflammatory resolution will increase the therapeutic reliability of these regenerative techniques in the future.
We have observed a previously unknown role for Growth Arrest Specific 6 (GAS6) in controlling alveolar bone
and soft tissue regeneration following extraction. GAS6-deficient mice showed markedly worse healing
following extraction, which was associated with aberrant bone and immune phenotypes. The primary goal for
this K99/R00 proposal is to test the critical role of GAS6 in oral tissue healing. Two specific aims are proposed
based on our previous observations. We hypothesize that GAS6 acts directly on mesenchymal stem cells to
prime them towards a osteoblastic phenotype. This hypothesis will be tested through measurement of healing
following extraction in mice with mesenchymal stem cells deficient in GAS6 signaling, along with associated
experiments on primary cells derived from patients following extraction. We also hypothesize that increased
neutrophil infiltrate in GAS6-deificiency impedes soft tissue healing. We will employ conditional knockout
models of neutrophils and neutrophil functions to test this hypothesis. The K99 portion will be dedicated to
developing new tools for studying tissue and immune cell-specific GAS6 signaling and building upon my prior
work in osteoblast biology, while the R00 portion will deploy these tools to study inflammation and connect
alveolar regeneration with GAS6 signaling. This award will provide a significant contribution to the
understanding of the physiology of healing in the oral cavity while providing significant training to the candidate
in the use of genetic mouse models and immunology, ultimately leading to an independent career as a dental
clinician-scientist specializing in treatment of systemically compromised patients.

## Key facts

- **NIH application ID:** 10234139
- **Project number:** 5K99DE029756-02
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Ann Marie Decker
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $139,320
- **Award type:** 5
- **Project period:** 2020-08-10 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10234139

## Citation

> US National Institutes of Health, RePORTER application 10234139, GAS6-Mediated Regulation of Oral Tissue Regeneration (5K99DE029756-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10234139. Licensed CC0.

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