Development and maintenance of the alveolar type 1 cell

肺泡 1 型细胞的发育和维持

基本信息

批准号：
8207255
负责人：
Tushar Jasubhai DESAI
金额：
$ 13.21万
依托单位：
STANFORD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-01-04 至 2012-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8207255
关键词：
Adult Advisory Committees Alveolar Alveolar Cell Alveolus Antibodies Area Biochemistry Boston Cell Culture Techniques Cell Cycle Kinetics Cell Differentiation process Cells Cellular biology Chairperson Critical Care Databases Defect Development Differentiation Antigens Disease Distal Embryo Embryonic Development Ensure Epithelial Cells Epithelium Event Fellowship Funding Gases Gene Expression Gene Expression Profile Genes Genetic Genetic Recombination Genetic Techniques Genomics Goals Health Histology In Situ Hybridization Indirect Immunofluorescence Individual Institutes Label Laboratories Lung Lung diseases Maintenance Malignant neoplasm of lung Medical Medicine Mentors Molecular Molecular Biology Molecular Genetics Mouse Strains Mus Natural regeneration Pathway interactions Pattern Phenotype Physiology Play Pregnancy Principal Investigator Program Development Protocols documentation Pulmonary Emphysema Pulmonary Fibrosis Pulmonary Surfactant-Associated Protein C Pulmonology RNA Research Research Personnel Resources Respiratory Failure Role Scientist Series Signal Transduction Site Specific qualifier value Staging Stem cells Techniques Testing Time Tissues Training Training Programs Transcription factor genes Transgenic Mice Undifferentiated Universities Work authority base career cell type in vivo instructor lung Carcinoma lung development molecular marker mouse development mouse genome professor progenitor programs recombinase research study selective expression surfactant transcription factor

项目摘要

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.

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，并在该大学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的教授兼主席，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。

项目成果

期刊论文数量（3）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Reconstructing lineage hierarchies of the distal lung epithelium using single-cell RNA-seq.

DOI：
10.1038/nature13173
发表时间：
2014-05-15
期刊：
Nature
影响因子：
64.8
作者：
通讯作者：

Keeping it together: Pulmonary alveoli are maintained by a hierarchy of cellular programs.

DOI：
10.1002/bies.201500031
发表时间：
2015-09
期刊：
BioEssays : news and reviews in molecular, cellular and developmental biology
影响因子：
0
作者：
Logan CY;Desai TJ
通讯作者：
Desai TJ

Alveolar progenitor and stem cells in lung development, renewal and cancer.

肺发育、更新和癌症中的肺泡祖细胞和干细胞。