# Modulation of MMPs gene expression and activity by the microbiome in caries

> **NIH NIH K08** · UNIVERSITY OF IOWA · 2022 · $144,990

## Abstract

Project Summary/Abstract
Caries is a multifactorial disease that results from an imbalance between the microbiome and the host leading
to demineralization of the dental hard tissues. After a lesion initiates in enamel, further tissue demineralization
will lead to cavitation and involvement of the dentin. The etiology of caries attributes lesion progression to diet-
and pH-dependent processes. However, enamel and dentin differ in terms of mineral content, structure and
composition, and the degradation of the organic matrix of dentin seems to be a more complex mechanism than
currently accepted. In vitro studies from the candidate’s research group and from others have shown in-
creased presence and activity of endogenous proteases, such as matrix metalloproteases (MMPs), in caries
dentin. Novel and important preliminary data suggest that while some MMPs may contribute for tissue degra-
dation, specific MMPs might be important to favor reparative processes in dentin, even though tissue repair
does not overcome degradation in advanced caries lesions. Fundamental questions remain concerning the
regulatory mechanisms that drive MMPs expression and activation and how these mechanisms respond to
bacterial infiltration as caries lesion advances. This proposal will address these issues by: (a) filling the gap in
knowledge regarding the breadth of the contribution of specific MMPs to caries lesion progression; (b) defining
the role of odontoblast-produced and dentin-released MMPs in caries; and (c) determining how the shift in the
oral microbiome can modulate MMPs expression and/or activation as the lesion progresses. These studies will
provide essential baseline information to facilitate the candidate’s long-term research goal, which is the devel-
opment of new dental therapies based on modulation of MMPs activity in caries. The candidate aims to be-
come an independent researcher to pursue the creation of novel therapeutic targets based on selective inhibi-
tion of damaging endogenous mechanisms and promotion of repair mechanisms that would fundamentally
change the way in which we manage and surgically treat dentin caries. This application for a K08 award will
provide the candidate protected time and training to support her research goals and to ensure her career de-
velopment. The candidate has assembled an outstanding group of mentor, co-mentors, collaborators, consult-
ant, and advisors with expertise in microbiology, genomics, proteomics, and bioinformatics. This K08 award
will facilitate the candidate’s career development by providing the structure and the guidance for expanding
and acquiring: (1) advanced knowledge on dentin organic matrix composition and biochemical properties in
health and caries disease, (2) experience with methodologies for the study of oral proteins and microorganisms
in caries, including genomics and proteomics, (3) skills in leadership and scientific communication including
writing, oral presentations and mentorship, and (4) t...

## Key facts

- **NIH application ID:** 10440511
- **Project number:** 5K08DE029490-02
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** Cristina De Mattos Pimenta Vidal
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $144,990
- **Award type:** 5
- **Project period:** 2021-07-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10440511

## Citation

> US National Institutes of Health, RePORTER application 10440511, Modulation of MMPs gene expression and activity by the microbiome in caries (5K08DE029490-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10440511. Licensed CC0.

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