Gli1 in murine lung development and differentiation

Gli1 在小鼠肺发育和分化中的作用

• 批准号: 7649556
• 负责人: ANTHONY N GERBER
• 金额: $ 2.98万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-29 至 2009-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7649556
• 关键词: Academic Medical Centers; Affect; Architecture; Basic Science; Cell Culture Techniques; Cell Differentiation process; Cell Proliferation; Cell division; Clinical; Commit; Complement; Coupled; Critical Care; Development; Developmental Biology; Disease; Distal; Epithelial; Epithelial Cell Proliferation; Epithelial Cells; Epithelium; Erinaceidae; Fostering; Gene Activation; Gene Expression; Genes; Goals; Grant; Histology; In Situ Hybridization; Injury; Investigation; Laboratories; Lung; Lung diseases; Malignant neoplasm of lung; Medical; Medicine; Mesenchymal; Mesenchyme; Messenger RNA; Modeling; Morphology; Mus; Northern Blotting; Nucleic Acid Regulatory Sequences; Pathway interactions; Pattern; Physicians; Pulmonary Fibrosis; Regulation; Research Personnel; Reverse Transcriptase Polymerase Chain Reaction; Role; Scientist; Series; Signal Transduction; System; Testing; Tetracyclines; Time; Training Programs; Transgenes; Transgenic Mice; Transgenic Organisms; Universities; Washington; Work; base; career; career development; design; experience; injured; interest; lung development; lung injury; lung maturation; meetings; member; programs; promoter; response; response to injury; transcription factor

DESCRIPTION (provided by applicant): Dr. Anthony Gerber is a pulmonary and critical care physician with a well-defined interest in developmental biology that was fostered as a member of the medical scientist training program at the University of Washington. His overall career objective is to combine his clinical and basic science interests through studying the relationship between developmental pathways and lung disease in an academic medical center. This proposal is constructed to provide the framework to achieve that goal. Through a series of specific aims, Dr. Gerber will test several hypotheses regarding the role of the hedgehog (Hh) pathway, a critical developmental control network, in the lung. Specifically, he will explore the effects of transgenic misexpression of the Hh regulated transcription factor, Gli1, in the lung epithelium and mesenchyme. This will test the hyopthesis that Gli1 regulates patterning, proliferation, and differentiation in the developing lung. The hypothesis that the effects of Hh signaling in the lung vary depending on timing will be tested using temporal regulation of Gli1 mis-expression. Microarrays will also be used to identify targets of Hh signaling in the lung to test the hyopthesis that distinct subsets of genes respond to the Hh signal at different times; ultimately the effects of Gli1 on gene activation and lung injury will be assessed using mouse and cell culture models. The relevance of the proposed work to lung disease is based on the general notion that developmental pathways are activated in disease, coupled with specific recent observations that the Hh pathway is activated in response to lung injury and is expressed in lung cancer and pulmonary fibrosis. Additionally, this proposal is designed to complement Dr. Gerber's prior laboratory experience and provide him with the requisite technical and intellectual background in lung development to function as an independent investigator. A committee of physicians and scientists will oversee Dr. Gerber's progression towards independence; his scientific development will also be enriched through attendance at several seminar series at UCSF, departmental retreats, and national meetings. UCSF is committed to the development of careers in academic medicine, and at the end of the grant period, Dr. Gerber will be prepared to embark on a career as an independent physician scientist investigating developmental pathways that are active in lung disease.

描述（由申请人提供）： 安东尼·格伯（Anthony Gerber）博士是一名肺部和重症监护医师，对发育生物学的兴趣明确，被培养为华盛顿大学医学科学家培训计划的成员。 他的整体职业目标是通过研究学术医学中心的发育途径与肺部疾病之间的关系来结合他的临床和基础科学利益。 该建议的旨在提供实现该目标的框架。 通过一系列具体目标，Gerber博士将检验有关肺中关键发育控制网络的刺猬（HH）途径的作用的几个假设。 具体而言，他将探索肺上皮和间质的HH调节转录因子GLI1的转基因Misexpression的影响。 这将测试GLI1调节发育中肺部模式，增殖和分化的杂种。 HH信号在肺中的影响因时间定时而变化的假设将通过GLI1错误表达的时间调节进行测试。 微阵列还将用于识别肺中HH信号的靶标，以测试杂种，即不同时间在不同时间对HH信号响应的杂种。最终将使用小鼠和细胞培养模型评估GLI1对基因激活和肺损伤的影响。 拟议工作与肺部疾病的相关性是基于一般观念，即发育途径在疾病中被激活，再加上最新的观察结果，即HH途径因响应肺损伤而激活，并在肺癌和肺纤维化中表达。 此外，该提案旨在补充Gerber博士先前的实验室经验，并为他提供肺部发展中必不可少的技术和智力背景，以作为独立研究者的工作。 医师和科学家委员会将监督格伯博士向独立发展的发展；他的科学发展也将通过参加UCSF，部门静修和国家会议的多个研讨会系列的出席来丰富。 UCSF致力于发展学术医学的职业，在赠款期结束时，Gerber博士将准备从事独立医师科学家的职业，研究活跃于肺部疾病的发育途径。