Mfge8 and the Role of Apoptotic Cell Clearance in Lung Injury

该提案概述了一项为期五年的职业发展计划，旨在为Atabai博士的职业生涯做好准备 作为一名肺部医学的学术内科医生兼科学家。Atabai博士有兴趣研究 损伤和修复的潜在机制，特别是与肺相关的机制。急性肺损伤(ALL)是 常见且具有破坏性的炎症状态，可导致肺纤维化。尽管死亡率很高 几乎没有有效的治疗方法，因为最近的证据都表明细胞凋亡在糖尿病的发病中起着重要作用 人类ALI与肺纤维化。在他的导师迪恩·谢泼德博士的指导下，阿塔巴伊博士 我一直在研究MfgeS的作用，MfgeS是一种整合素结合分子，可以促进凋亡细胞吞噬，在 肺损伤。Atabai博士发现，缺乏功能性MfgeS的小鼠会出现夸大的肺纤维化 气管内注射博莱霉素后。博莱霉素诱导上皮细胞凋亡、炎症和 肺纤维化。Atabai博士的假设是，MfgeS通过以下方式调节肺损伤和炎症 促进细胞凋亡的清除。检验这一假说的具体目的是：1)确定 MfgeS在肺细胞凋亡清除中的作用；2)确定MfgeS在调节中的作用 炎症和肺损伤的严重程度，3)确定磷脂酰丝氨酸残基在 MfgeS介导的细胞凋亡与吞噬细胞表面AVP、Av(35)整合素的表达 活着。Atabai博士将使用成熟的体外和体内技术来实现这些目标，包括细胞 培养，重组蛋白的产生，免疫组织化学，免疫细胞化学，DNA表达 阵列、实时荧光定量聚合酶链式反应、酶联免疫吸附试验和免疫印迹。阿塔巴伊博士的导师迪恩·谢泼德博士是一位 多产且资金雄厚的科学家，在整合素生物学、炎症和纤维化方面具有专业知识 阿龙。谢泼德博士在培养成功的学术内科医生方面有着出色的记录。忠告 由备受尊敬的科学家组成的小组将在奖项期间向Atabai博士提供进一步的指导。一个 教学课程培训和参加地方和国家科学会议的详细计划将 成为该计划的最终组成部分。Atabai博士得到了加州大学旧金山分校 医学和肺生物中心关于职业发展和获得所有资源的情况 这是成功完成这项工作所必需的。

This proposal outlines a five-year career development program designed to prepare Dr. Atabai for a career as an academic physician-scientist in pulmonary medicine. Dr. Atabai is interested in studying the mechanisms underlying injury and repair, particularly as they relate to the lung. Acute Lung Injury (All) is a common and devastating inflammatory condition that can lead to pulmonary fibrosis. Despite high mortality rates few effective therapies exist for ALL Recent evidence has implicated a pathogenic role for apoptosis in human ALI and pulmonary fibrosis. Under the guidance of his mentor, Dr. Dean Sheppard, Dr. Atabai has been examining the role of MfgeS, an integrin binding molecule that facilitates apoptotic cell engulfment, in lung injury. Dr. Atabai has found that mice lacking functional MfgeS develop exaggerated pulmonary fibrosis after intratracheal bleomycin administration. Bleomycin induces epithelial cell apoptosis, inflammation and pulmonary fibrosis. Dr. Atabai's hypothesis is that MfgeS modulates injury and inflammation in the lung by facilitating apoptotic cell clearance. The specific aims designed to test this hypothesis are 1) determining the role of MfgeS in apoptotic cell clearance in the lung, 2) determining the role of MfgeS in regulating inflammation and the severity of lung injury, 3) determining the role of phosphatidylserine residues on apoptotic cells and the avps and av(35 integrins on phagocytes in MfgeS-mediated apoptotic cell clearance in vivo. Dr. Atabai will use well-established in vitro and in vivo techniques to achieve these aims including cell culture, generation of recombinant proteins, immunohistochemistry, immunocytochemistry, DNA expression arrays, Real-Time PCR, ELISA, and immunoblotting. Dr. Atabai's mentor, Dr. Dean Sheppard, is a productive and well-funded scientist with expertise in integrin biology and inflammation and fibrosis in the lung. Dr. Sheppard has an outstanding track record of training successful academic physicians. An advisory panel of highly regarded scientists will provide further guidance to Dr. Atabai for the duration of the award. A detailed program of didactic course training and participation in local and national scientific conferenceswill be the final component of the program. Dr. Atabai has the full commitment of the UCSF Department of Medicine and the Lung Biology Center with regard to career development and access to all the resources necessary for the successful completion of this work.