Mechanisms of impaired mucociliary transport in CF airway disease

CF 气道疾病中粘膜纤毛运输受损的机制

基本信息

  • 批准号:
    9223992
  • 负责人:
  • 金额:
    $ 16.02万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2017
  • 资助国家:
    美国
  • 起止时间:
    2017-02-01 至 2022-01-31
  • 项目状态:
    已结题

项目摘要

PROJECT SUMMARY/ABSTRACT Impaired mucociliary transport (MCT) is a common feature of multiple airway diseases, including cystic fibrosis (CF). Effective MCT requires functional cilia and mucus. The mechanical properties of mucus influence MCT. In CF, loss of bicarbonate transport in the airway epithelium decreases the pH of the airway surface liquid (ASL). The acidic ASL changes the electrostatic interactions of mucus, making the mucus more viscous. This defect is present at birth prior to the onset of infection and inflammation. Newborn CF pigs also have impaired MCT. We predict that the viscous mucus in newborn CF pigs gives rise to defective MCT. In the current application, the candidate will probe the biophysical properties of freshly isolated porcine airway mucus using agents that alter mucus electrostatic interactions. He will assess the biophysical properties using passive microrheology. Concomitantly, he will measure MCT in newborn CF pigs using computed tomography (CT) and correlate how altered biophysical properties of mucus influence MCT. The candidate's long-term career goal is to become a leader in the fields of airway biology and airway disease. He plans to advance both fields by utilizing advanced imaging techniques and porcine models. The selection of the porcine model is particularly relevant because the airway anatomy and physiology more closely resemble humans than traditional rodent models. In the current K08 application, the candidate will gain multiple intellectual, professional and technical skills to foster his development into an independent and successful physician scientist. He has an outstanding mentor and advisory committee that will guide him in learning passive microrheology of mucus and whole animal CT. This topic is highly significant as mucus biophysical properties influence MCT, and thus the candidate's work can shed light on basic biology and also potential therapeutics. In addition, the candidate will continue to develop his manuscript and grant writing abilities through reviewing of manuscripts and grants under Dr. Welsh's guidance. He will also take coursework in biomedical and biochemical engineering to advance his understanding of the complex principles of rheology and imaging analyses. Lastly, the candidate will continue to cultivate his own mentoring skills through learning how to manage timelines and budgets, as well as train junior scientists. In summary, this award will greatly enrich the candidate's career by providing him with additional tools necessary to become an independent and successful physician scientist that contributes to the betterment of human health.
项目总结/文摘

项目成果

期刊论文数量(0)
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Mahmoud Abou Alaiwa其他文献

Mahmoud Abou Alaiwa的其他文献

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{{ truncateString('Mahmoud Abou Alaiwa', 18)}}的其他基金

Contribution of Small Airways to Mucociliary Transport Dysfunction
小气道对粘膜纤毛运输功能障碍的影响
  • 批准号:
    10659465
  • 财政年份:
    2023
  • 资助金额:
    $ 16.02万
  • 项目类别:
Mechanisms of impaired mucociliary transport in CF airway disease
CF 气道疾病中粘膜纤毛运输受损的机制
  • 批准号:
    10117037
  • 财政年份:
    2017
  • 资助金额:
    $ 16.02万
  • 项目类别:
Core C: Imaging-Abou Alaiwa
核心C:成像-Abou Alaiwa
  • 批准号:
    10470208
  • 财政年份:
    2008
  • 资助金额:
    $ 16.02万
  • 项目类别:
Core C: Imaging-Abou Alaiwa
核心C:成像-Abou Alaiwa
  • 批准号:
    10226935
  • 财政年份:
    2008
  • 资助金额:
    $ 16.02万
  • 项目类别:

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