Defining the mutational pathogenesis of oral preneoplasia

定义口腔癌前病变的突变发病机制

基本信息

  • 批准号:
    10217102
  • 负责人:
  • 金额:
    $ 56.95万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2020
  • 资助国家:
    美国
  • 起止时间:
    2020-07-15 至 2025-04-30
  • 项目状态:
    未结题

项目摘要

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.
项目总结:

项目成果

期刊论文数量(0)
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会议论文数量(0)
专利数量(0)

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Aaron Tward其他文献

Aaron Tward的其他文献

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{{ truncateString('Aaron Tward', 18)}}的其他基金

Defining the mutational pathogenesis of oral preneoplasia
定义口腔癌前病变的突变发病机制
  • 批准号:
    10681505
  • 财政年份:
    2022
  • 资助金额:
    $ 56.95万
  • 项目类别:
Defining the mutational pathogenesis of oral preneoplasia
定义口腔癌前病变的突变发病机制
  • 批准号:
    10380083
  • 财政年份:
    2020
  • 资助金额:
    $ 56.95万
  • 项目类别:
Tympanic membrane progenitor cells in homeostasis in injury
鼓膜祖细胞在损伤中的稳态
  • 批准号:
    10378139
  • 财政年份:
    2020
  • 资助金额:
    $ 56.95万
  • 项目类别:
Tympanic membrane progenitor cells in homeostasis in injury
鼓膜祖细胞在损伤中的稳态
  • 批准号:
    9973797
  • 财政年份:
    2020
  • 资助金额:
    $ 56.95万
  • 项目类别:
Defining the mutational pathogenesis of oral preneoplasia
定义口腔癌前病变的突变发病机制
  • 批准号:
    10819716
  • 财政年份:
    2020
  • 资助金额:
    $ 56.95万
  • 项目类别:
Defining the mutational pathogenesis of oral preneoplasia
定义口腔癌前病变的突变发病机制
  • 批准号:
    10037424
  • 财政年份:
    2020
  • 资助金额:
    $ 56.95万
  • 项目类别:
Tympanic membrane progenitor cells in homeostasis in injury
鼓膜祖细胞在损伤中的稳态
  • 批准号:
    10599161
  • 财政年份:
    2020
  • 资助金额:
    $ 56.95万
  • 项目类别:
Defining the mutational pathogenesis of oral preneoplasia
定义口腔癌前病变的突变发病机制
  • 批准号:
    10614397
  • 财政年份:
    2020
  • 资助金额:
    $ 56.95万
  • 项目类别:

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