课题基金 / 基金详情

Mentoring Patient Oriented Research in sensory disorders

Mentoring Patient Oriented Research in sensory disorders
指导以患者为导向的感觉障碍研究
批准号:
10644567
负责人:
Alan Gi-Lun Cheng
金额:
$19.67万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2023
资助国家:
美国
项目状态:
未结题
起止时间:
2023-05-01 至 2028-04-30

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中文摘要
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英文摘要
Abstract: Sensory hair cells are required for balance function. Vestibular hair cell degeneration causes balance dysfunction manifested as dizziness and vertigo. In mice, a limited degree of spontaneous regeneration occurs in the utricle, a vestibular organ detecting linear acceleration. Moreover, addition of the transcription factor Atoh1 robust enhances regeneration of hair cells in the mouse utricle, but regenerated hair cells mature only partially relative to native hair cells. In preliminary experiments, we have characterized a novel AAV-ATOH1 construct leading to regeneration of more mature hair cells in the mouse utricle. With the long-term goal of regenerating human hair cells to restore balance function, two major obstacles remain: 1) we have an incomplete understanding of the molecular signatures of human hair cells, supporting cells and hair cell precursors, 2) adult human inner ear tissues are not readily available to test promising therapeutics discovered in animal models. To overcome these obstacles, we have designed a surgical method to procure live utricles from deceased organ donors who typically have normal auditory and vestibular function. We have begun assembling their medical records, single-cell transcriptomes, and histologic sections of utricles. In parallel, we have procured utricles from vestibular schwannoma patients undergoing surgical resection. Here, we propose to increase the recruitment of organ donors and vestibular schwannoma patients and delineate and validate the transcriptomes of hair cells, supporting cells, and hair cell precursors in adult human utricles in these two cohorts (Aim 1). Furthermore, we will determine whether our novel AAV-ATOH1 enhances hair regeneration and maturation in cultured human utricles (Aim 2). Another goal of this award is to further my career as an investigator and mentor in patient- oriented research. To build on my previous experience in bench research and mentoring, this award is designed to protect my time and help me gain knowledge and skills to 1) study human hair cell regeneration and 2) mentor others pursuing patient-oriented research. In summary, we will apply state-of-the art technologies (single-cell RNA-sequencing, gene therapy, bioinformatic strategies) to study vestibular hair cell regeneration in live human utricles. We have assembled a team of collaborators and experienced mentors in patient-oriented research. At the end of this 5-year proposal, we will have 1) delineated transcriptomes of human hair cells, supporting cells, and hair cell precursors, 2) revealed whether novel AAV-ATOH1 enhances regeneration and maturation of human vestibular hair cells, and 3) enhanced my ability to perform and mentor others in patient-oriented research in sensory disorders.
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Diversification of the mechanotransduction complex in vestibular hair cells
  • 批准号:
    10734358
  • 项目类别:
  • 资助金额:
    $65.9万
  • 财政年份:
    2023
  • 负责人:
    Alan Gi-Lun Cheng
  • 依托单位:
Molecular basis of mammalian cochlear regeneration
  • 批准号:
    10682272
  • 项目类别:
  • 资助金额:
    $67.63万
  • 财政年份:
    2023
  • 负责人:
    Alan Gi-Lun Cheng
  • 依托单位:
Stanford Clinician Scientist Training Program
  • 批准号:
    10427050
  • 项目类别:
  • 资助金额:
    $35.14万
  • 财政年份:
    2022
  • 负责人:
    Alan Gi-Lun Cheng
  • 依托单位:
Stanford Clinician Scientist Training Program
  • 批准号:
    10591580
  • 项目类别:
  • 资助金额:
    $35.14万
  • 财政年份:
    2022
  • 负责人:
    Alan Gi-Lun Cheng
  • 依托单位:
海外基金