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Metabolic Reprogramming in Laryngotracheal Stenosis

Metabolic Reprogramming in Laryngotracheal Stenosis
喉气管狭窄的代谢重编程
批准号:
9590279
负责人:
Alexander Hillel
金额:
$16.38万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2018
资助国家:
美国
项目状态:
已结题
起止时间:
2018-07-05 至 2021-06-30

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中文摘要
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英文摘要
Summary Dr. Alexander Hillel is a faculty member in the Department of Otolaryngology-Head & Neck Surgery at the Johns Hopkins School of Medicine where his clinical practice is dedicated to the medical and surgical management of voice and airway disorders. With the support of an Early Career Research Award, Dr. Hillel seeks to better understand metabolic mechanisms of laryngotracheal stenosis (LTS) and apply regenerative medicine techniques to its treatment. Specifically, Dr. Hillel will be focusing on glutamine metabolism and targeted inhibition of glutamine as a novel approach to treating LTS in vitro on human LTS-scar fibroblasts and in vivo in a validate mouse model of LTS. As a part of this study, he plans to utilize a drug-eluting stent to target these metabolic mechanisms in a preclinical model. Aim 1 will be performed in mice to determine the ability of 6-diazo-5-oxo-l-norleucine (DON), a glutamine inhibitor, to prevent fibrosis. Systemic DON therapy will be compared with topical DON administration via a drug eluting stent. One of the enzymes DON blocks is glutaminase, which converts glutamine into glutamate. Aim 2 will specifically investigate glutaminase inhibition in human tracheal fibroblasts in vitro and in LTS mice in vivo. Preclinical validation of glutamine inhibition as a treatment for LTS is a critical step prior to translation to human studies.
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Role of E-cadherin in epithelial barrier dysfunction and fibrosis in idiopathic subglottic stenosis
  • 批准号:
    10756248
  • 项目类别:
  • 资助金额:
    $15.41万
  • 财政年份:
    2023
  • 负责人:
    Alexander Hillel
  • 依托单位:
Targeting mTOR regulation of T-lymphocytes and fibroblasts in Laryngotracheal Stenosis
  • 批准号:
    10594621
  • 项目类别:
  • 资助金额:
    $0.94万
  • 财政年份:
    2020
  • 负责人:
    Alexander Hillel
  • 依托单位:
Targeting mTOR regulation of T-lymphocytes and fibroblasts in Laryngotracheal Stenosis
  • 批准号:
    10384685
  • 项目类别:
  • 资助金额:
    $8.49万
  • 财政年份:
    2020
  • 负责人:
    Alexander Hillel
  • 依托单位:
Targeting mTOR regulation of T-lymphocytes and fibroblasts in Laryngotracheal Stenosis
  • 批准号:
    10635043
  • 项目类别:
  • 资助金额:
    $8.43万
  • 财政年份:
    2020
  • 负责人:
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  • 依托单位:
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