# Molecular Imaging of Gingipain Activity in Advanced Periodontitis

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2021 · $190,057

## Abstract

PROJECT SUMMARY
This objective of this proposal is an activatable photoacoustic contrast agent to map and measure the
gingipain proteases released by P. gingivalis during periodontitis. While P. gingvalis is easy to measure with
PCR it cannot mapped in the mouth. Here, photoacoustic ultrasound will be used to report the quantity and
location of gingipains released by P. gingivalis and improve diagnosis and response to therapy. We are
motivated by studies showing that dental pain dramatically decreases quality of life but that nearly 50% of
Americans have some form of periodontitis. Our rationale is that current approaches to monitoring oral health
only measure the results and symptoms of gingipains (tooth loss, pocket depth, etc.). We argue that by
imaging and measuring a molecular cause of periodontal disease—i.e., the gingipains secreted by P.
gingivalis—new insights will be gained into the basic biology of this condition as well as better diagnostic and
treatment-monitoring plans. This improved diagnostic insight will better guide therapy, and non-invasive
imaging will increase patient compliance ultimately translating into earlier and better treatment of periodontitis.
The workflow will include two parts: Aim 1 will build the contrast agent and validate it with recombinant
gingipains, bacterial culture, and saliva from healthy subjects. Aim 2 will test the probe with gingival crevicular
fluid (GCF) samples collected by Dr. Chen during routine cleanings. We will resuspend these samples and
quantitate the gingipains using the probe validated in Aim 1. We hypothesize that the photoacoustic signal of
our probe will increase linearly with gingipain concentration in vitro. We hypothesize that photoacoustic
imaging can stratify GCF samples as a function of oral health status. This approach is innovative because
this contrast agent will be the first molecular imaging technique for periodontal disease. It will detect disease
prior to anatomical damage. As such, we will be able to map and measure the extent of pathogenic activity
caused by P. gingivalis in the subgingival space in real time. It will also triage the disease in early stages.
Current periodontal charting can only assess pocket depths and bleeding on probing, but detection of early-
stage pathogenic activity will allow easy and inexpensive intervention to lower the clinical burden of
periodontitis and improve patient outcomes. The clinical impact is a tool to detect early-stage changes in the
oral microbiota to guide/monitor therapy. This technique could also answer questions about the impact of
gingipains on inflammation, immune loading, pocket deepening, and alveolar bone loss in situ. We all well
positioned to perform this work because of Dr. Jokerst’s skills in photoacoustic contrast media and Dr. Chen’s
leadership position at the USC School of Dentistry; we have already published together on related research.

## Key facts

- **NIH application ID:** 10259849
- **Project number:** 5R21DE029917-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Jesse Vincent Jokerst
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $190,057
- **Award type:** 5
- **Project period:** 2020-09-09 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10259849

## Citation

> US National Institutes of Health, RePORTER application 10259849, Molecular Imaging of Gingipain Activity in Advanced Periodontitis (5R21DE029917-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10259849. Licensed CC0.

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