# Defining the mutational pathogenesis of oral preneoplasia

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2021 · $569,530

## Abstract

Project Summary:
 Oral potentially preneoplastic diseases are common with worldwide prevalence of approximately 4%,
and millions of cases in the United States alone. A large subset of these harbor the histopathological features
of oral dysplasia, the lesions most likely to progress to oral squamous cell carcinoma. Despite years of
research on these lesions, the approach to management of these lesions is quite variable. In particular,
because we lack a clear molecular classification of these lesions, we do not have good, clinically applicable
biomarkers that predict which lesions are likely to progress to cancer (and therefore require treatment) and
which are likely to not progress (and therefore can be observed). Further, we lack a full understanding of the
identity of the mutations responsible for reprogramming cells from normal oral keratinocytes into dysplastic oral
keratinocytes, and subsequently to carcinoma cells. We also do not understand how these mutations interact
in order to give rise to dysplasia, or how this knowledge could be harnessed to generate novel therapeutic
approaches to oral dysplasia. The work proposed within this grant aims to address these questions. First, we
will perform next generation sequencing on a large panel of oral dysplasias in order to define the mutational
landscape of oral dysplasias in general. Next, we propose performing next generation sequencing on biopsies
from a group of patients followed longitudinally over the arc of years whose oral dysplasias ultimately
progressed to cancer. We next take advantage of novel gene editing systems in primary human oral
keratinocytes combined with optimized organotypic model systems to generate “designer” oral dysplastic
lesions and validate the causative mutational events in these lesions. Finally, we leverage our optimized
organotypic model systems to predict a precision medicine approach using FDA-approved medications. Once
complete, this work will serve as the foundational data resource for the oral dysplasia research community, and
will introduce novel, flexible, and powerful model systems to address key questions in oral preneoplastic
progression.

## Key facts

- **NIH application ID:** 10217102
- **Project number:** 5R01DE029890-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Aaron Tward
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $569,530
- **Award type:** 5
- **Project period:** 2020-07-15 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10217102

## Citation

> US National Institutes of Health, RePORTER application 10217102, Defining the mutational pathogenesis of oral preneoplasia (5R01DE029890-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10217102. Licensed CC0.

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