Cell Surface Modulation of EGFR-Mediated Differentiation

EGFR 介导的分化的细胞表面调节

基本信息

批准号：
7267643
负责人：
SUIL KIM
金额：
$ 12.18万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-08-01 至 2009-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7267643
关键词：
Abnormal Cell Adenocarcinoma Adherens Junction Adhesions Advisory Committees Antibodies Apoptosis Apoptotic Biological Assay Biometry California Cardiovascular system Cell Adhesion Molecules Cell Density Cell Differentiation Inhibition Cell Differentiation process Cell Proliferation Cell Surface Receptors Cell surface Cell-Cell Adhesion Cells Cellular biology Clara cell-specific protein Condition Cyclins Development Doctor of Philosophy E-Cadherin Environment Epidermal Growth Factor Receptor Epithelial Cell Proliferation Epithelial Cells Fellowship Gel Goblet Cells Grant Growth Human Immunoblotting Immunofluorescence Immunologic Immunology In Vitro Interdisciplinary Study Internal Medicine Laboratories Lead Ligands Lung Lung diseases MUC5AC gene Malignant neoplasm of lung Maps Mass Spectrum Analysis Measures Mediating Medical Mentors Michigan Mitosis Mucins Mucous body substance Nuclear Pathway interactions Phenotype Phosphopeptides Phosphoric Monoester Hydrolases Phosphorylation Phosphotyrosine Physicians Principal Investigator Production Program Development Protein Binding Protein Tyrosine Phosphatase Proteins Pulmonology Receptor Activation Receptor Signaling Recombinants Research Research Institute Research Training Residencies Resources San Francisco Scientist Signal Pathway Surface Training Training Programs Tyrosine Phosphorylation Universities Writing airway epithelium base career in vivo inhibitor/antagonist insight lectures novel novel therapeutics programs protein expression response therapeutic target

项目摘要

DESCRIPTION (provided by applicant): The proposal describes a five-year training program for the development of an independent academic career in pulmonary cell biology. The principal investigator has acquired Ph.D. training in immunology as a Medical Scientist Training Program fellow at the University of Michigan, residency training in internal medicine at the University of Pittsburgh, and fellowship training in pulmonary medicine at the University of California, San Francisco. To gain expertise in pulmonary cell biology, he has organized a program consisting of laboratory-based research, courses, lectures, and meetings. Dr. Jay Nadel will mentor the principal investigator's scientific development. Dr. Nadel is the Director of the Multidisciplinary Research Training Program in Lung Disease and has trained more than one hundred pulmonary academicians and many of the present leaders in pulmonology worldwide. An expert scientific advisory committee consisting of highly regarded physician-scientists will provide research and career guidance. The educational program will include research seminars, research colloquia, attendance at national meetings, special courses (including lab management, grant writing, and ethical scientific conduct), and formal coursework in biostatistics and advanced cell biology. Because of its excellent resources and emphasis on multidisciplinary research, the Cardiovascular Research Institute provides an exceptional environment for the development of an academic career in pulmonary epithelial cell biology. Research will focus on the mechanisms that modulate epidermal growth factor receptor (EGFR) signaling in the airway epithelium to produce divergent responses such as differentiation (mucus hypersecretion) and proliferation (adenocarcinoma). Recently, Dr. Nadel's lab discovered a novel pathway (EGFR cascade) for the production of mucins. The application focuses on two proteins that may modulate EGFR signaling: the adhesion molecule, E-cadherin, and a protein of unknown function, Clara cell secretory protein (CCSP). The specific aims include: 1) examining the impact of E-cadherin-mediated cell-cell contact on EGFR signaling in airway epithelial cells; 2) determining whether CCSP promotes EGFR-mediated differentiation of airway epithelial cells; and 3) determining whether adherens junction-associated protein tyrosine phosphatase (PTPase) activity modulates EGFR activation.

描述（由申请人提供）：该提案描述了一个为期五年的培训计划，旨在发展肺细胞生物学的独立学术生涯。主要研究者已获得博士学位。在密歇根大学作为医学科学家培训项目研究员进行免疫学培训，在匹兹堡大学进行内科住院医师培训，在旧金山加利福尼亚大学进行肺科进修培训。为了获得肺细胞生物学方面的专业知识，他组织了一个由实验室研究、课程、讲座和会议组成的项目。 Jay Nadel 博士将指导首席研究员的科学发展。纳德尔博士是肺病多学科研究培训项目的主任，并培训了一百多名肺科院士和全球肺病学领域的许多现任领导者。由备受尊敬的医师科学家组成的专家科学咨询委员会将提供研究和职业指导。教育计划将包括研究研讨会、研究座谈会、参加全国会议、特殊课程（包括实验室管理、资助写作和道德科学行为）以及生物统计学和高级细胞生物学的正式课程。由于其优良的资源和对多学科研究的重视，心血管研究所为肺上皮细胞生物学学术生涯的发展提供了优越的环境。研究将重点关注调节气道上皮中表皮生长因子受体 (EGFR) 信号传导以产生不同反应的机制，例如分化（粘液分泌过多）和增殖（腺癌）。最近，Nadel 博士的实验室发现了一种用于产生粘蛋白的新途径（EGFR 级联）。该应用重点关注两种可能调节 EGFR 信号传导的蛋白质：粘附分子 E-钙粘蛋白和功能未知的蛋白质 Clara 细胞分泌蛋白 (CCSP)。具体目标包括：1）检查E-钙粘蛋白介导的细胞间接触对气道上皮细胞中EGFR信号传导的影响； 2)确定CCSP是否促进EGFR介导的气道上皮细胞分化； 3) 确定粘附连接相关蛋白酪氨酸磷酸酶 (PTPase) 活性是否调节 EGFR 激活。