CAREER: Propagation of Lung Fibrosis through Mechanotransduction

本学院早期职业发展（Career）项目奖的研究目的是验证肺泡上皮细胞机械拉伸导致肺纤维化的假设。上皮损伤是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性肺损伤等纤维化肺疾病进展中的中心事件。机械应变是一个经常被低估的肺上皮损伤的贡献者。本项目将通过三个研究目标来验证这一假设，利用多尺度方法研究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导致肺泡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。除了更好地了解肺纤维化外，这些实验研究的结果将为上皮细胞的机械转导提供新的认识，这可能适用于几种不同器官和疾病的上皮。将开发一个具有上皮细胞力学生物学实践演示的学习平台，作为教育代表性不足的中学生的外展工具。作为中学模块的延伸，本项目将开发高中机械生物学课程教材。此外，这项工作将为生物医学工程的新本科和研究生课程“细胞力学和力学生物学”提供基础。此外，研究机会将通过医学科学实习计划提供给高中生，并通过荣誉暑期本科生研究计划提供给本科生。研究和教育目标将影响许多代表性不足的学生在不同的水平，并对人类纤维化肺疾病有很大的影响。

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.