Development and maintenance of the alveolar type 1 cell

这项新的研究者提案描述了一项为期 5 年的职业发展培训计划 肺科医师科学家。首席研究员已完成了一项研究金 波士顿大学肺科和重症监护医学专业，并获得为期一年的研究奖学金 他目前在斯坦福大学生物化学系担任医学讲师 医学部肺科和重症监护科。 在进行拟议的研究时，首席研究员将获得肺组织学方面的专业知识， 小鼠遗传学、分子生物学和基因组方法。 Mark A. Krasnow 博士将指导校长 研究者的科学发展。他是斯坦福大学生物化学系教授兼主席， 霍华德休斯医学研究所的研究员，培训了许多已经离开的人 建立自己的实验室并成功竞争独立资助。校长 研究人员还聘请了肺上皮细胞领域三位国际公认的权威人士 生物学、肺泡发育和小鼠遗传学方面分别担任顾问。他将与 导师和顾问，以确保实现特定目标。高级顾问委员会 斯坦福大学的研究人员也已集结，将提供科学和职业建议。 研究重点是肺泡 1 型 (AT 1) 细胞的发育和维持。具体目标 包括：1) 使用分子标记鉴定和表征 AT 1 细胞的假定双潜能祖细胞 小鼠肺部并确定它出现的时间和地点，以及它在肺部发育过程中如何变化，2) 使用 小鼠转基因技术标记和追踪成熟 AT 2 细胞的命运，以确定 AT 2 是否 细胞是 AT 1 细胞的专性祖细胞，3) 通过使用 RNA 来鉴定 AT 1 命运的潜在调节因子 原位杂交筛选在终端空域选择性表达的转录因子基因 AT 1 形态发生时的上皮细胞。 通过汇集多个部门的独特资源，该计划整合了专业的 确保实现特定目标的专业领域。这项工作将与 了解并最终治疗肺气肿、肺癌和肺纤维化等肺部疾病。

This new investigator proposal describes a 5 year training program for the development of a career as a Dhysician scientist in pulmonary medicine. The principal investigator has completed a fellowship in pulmonary and critical care medicine at Boston University and a one year research fellowship in the Department of Biochemistry at Stanford University, where he now continues as an Instructor in Medicine the Pulmonary and Critical Care division of the Department of Medicine. In carrying out the proposed research, the Principal Investigator will acquire expertise in lung histology, mouse genetics, molecular biology, and genomic approaches. Dr. Mark A. Krasnow will mentor the Principal Investigator's scientific development. He is Professor and Chairman of Biochemistry at Stanford and an Investigator in the Howard Hughes Medical Institute who has trained numerous individuals who have gone on to establish their own laboratories and successfully compete for independent funding. The Principal Investigator has also enlisted three internationally recognized authorities in the fields of lung epithelial cell biology, alveolar development and mouse genetics, respectively, as consultants. He will work closely with the mentor and consultants to ensure fulfillment of the specific aims. An advisory committee of senior investigators at Stanford has also been assembled and will provide scientific and career advice. Research will focus on development and maintenance of the alveolar type 1 (AT 1) cell. Specific aims include: 1) Identify and characterize using molecular markers the putative bi-potential progenitor of AT 1 cells in mouse lung and determine when and where it arises, and how it changes during lung development, 2) Use mouse transgenic techniques to label and trace the fate of mature AT 2 cells to determine whether the AT 2 cell is an obligate progenitor to the AT 1 cell, 3) To identify potential regulators of AT 1 fate by using RNA in situ hybridization to screen for transcription factor genes that are selectively expressed in terminal airspace epithelium at the time of AT 1morphogenesis. By bringing together unique resources from multiple departments, this program integrates specialized areas of expertise that will ensure fulfillment of the specific aims. This work will be relevant for understanding and ultimately treating lung diseases like emphysema, lung cancer, and pulmonary fibrosis.