CAREER: Propagation of Lung Fibrosis through Mechanotransduction

这项教师早期职业发展(Career)计划奖的研究目标是检验机械拉伸肺泡上皮细胞传播肺纤维化的假设。上皮损伤是纤维化肺疾病发展过程中的中心事件，如急性呼吸窘迫综合征、肺纤维化、支气管肺发育不良和呼吸机相关性肺损伤。机械劳损是导致肺上皮损伤的一个经常被低估的因素。这个项目将通过三个研究目标来验证这一假设，利用多尺度方法从肺组织变形到亚细胞分子信号的机械转导。这些研究将通过解释肺泡II型上皮细胞异常修复和纤维化的机制来提高基础科学知识。除了更好地了解肺内的纤维化，这些实验研究的结果还将提供对上皮细胞机械转导的新理解，这可能适用于几种不同器官和疾病的上皮。将开发一个带有上皮细胞机械生物学动手演示的学习平台，作为向代表性不足的中学生提供教学的外展工具。作为中学模块的延伸，该项目将为高中机械生物学教育开发课程材料。此外，这项工作将为生物医学工程的新的本科生和研究生课程“细胞力学和机械生物学”提供基础。此外，高中生将通过医学实习计划获得研究机会，本科生通过荣誉暑期本科生研究计划获得研究机会。研究和教育目标将在不同程度上影响许多代表性不足的学生，并对人类纤维性肺病产生很大影响。

The research objective of this Faculty Early Career Development (CAREER) Program award is to test the hypothesis that mechanical stretch of alveolar epithelial cells propagates lung fibrosis. Epithelial injury is a central event in the progression of fibrotic lung diseases like acute respiratory distress syndrome, pulmonary fibrosis, bronchopulmonary dysplasia, and ventilator induced lung injury. Mechanical strain is an often underappreciated contributor to lung epithelial injury. This project will test the hypothesis through three research goals utilizing a multi-scale approach toward mechanotransduction from lung tissue deformation to sub-cellular molecular signaling. These studies will improve fundamental scientific knowledge by explaining mechanisms that are responsible for aberrant repair and fibrosis in alveolar type II epithelial cells.In addition to providing a better understanding of fibrosis in the lung, the results of these experimental studies will provide a new understanding of the mechanotransduction of epithelial cells that may be applicable to the epithelium of several different organs and diseases. A learning platform with hands-on demonstrations of epithelial cell mechanobiology will be developed as an outreach tool to teach under-represented middle school students. As an extension of the middle school modules, this project will develop course materials for high school education in mechanobiology. Furthermore, this work will provide a basis for a new Undergraduate and Graduate Course offering in Biomedical Engineering, "Cell Mechanics and Mechanobiology". Additionally, research opportunities will be available for high school students through the Medical Sciences Internship Program and to undergraduates through the Honors Summer Undergraduate Research Program. The research and educational goals will impact many under-represented students at a variety of levels and have high impact on human fibrotic lung disease.