Injured Lung and its Influence on Bone Marrow Cell Phenotype

描述(由申请人提供)： 这项建议描述了一项五年的培训计划，以发展实验室医学的学术生涯。我在布朗大学完成了肺部和重症监护医学的奖学金，获得了两个专业的董事会证书，现在将通过将我在两个子专业的知识应用于布朗大学的主要教学附属机构罗德岛医院的急性肺损伤修复研究来扩展我的科学技能。这个项目将研究受损的肺细胞和骨髓细胞之间的细胞间通讯，以及这种通讯在肺损伤的骨髓细胞肺修复中的作用机制。Peter Quesenberry博士将指导我的科学发展；我还将接受干细胞生物学和肺部生物学专家顾问的指导。奎森伯里博士是罗德岛医院血液科和肿瘤科的主任；他在干细胞相关项目中培训了许多博士后研究员和内科科学家。本实验室的研究表明，成人骨髓细胞是受损小鼠肺的归宿细胞，参与肺细胞的修复。我们假设，受损的肺细胞通过从肺细胞释放并随后被骨髓细胞摄取肺细胞来源的微泡来诱导骨髓细胞的表型改变，从而诱导骨髓细胞呈现肺细胞表型。具体目标是：1.我们将定义肺源性微泡的骨髓细胞群，重点是整个骨髓细胞和某些造血干细胞群。2.我们将确定引起骨髓细胞表型修饰的肺源性微泡的成分(RNA、DNA、蛋白质)。3.我们将确定细胞周期对骨髓细胞摄取肺源性微泡能力的影响。4.我们将确定移植已摄取肺源性微泡的骨髓细胞是否能减轻辐射和弹性蛋白酶诱导的肺损伤，从而改善肺功能。我们的假设是，骨髓细胞具有足够的修复能力，为肺部疾病提供了一种新的治疗选择，目前几乎没有有效的治疗方法。罗德岛医院和布朗医学院通过将不同学科的专业知识整合到定制的培训计划中，为培训内科科学家提供了理想的环境。这样的环境将最大限度地发挥我的潜力，建立一个科学利基，这将是我未来学术生涯的基础。(摘要结束)

DESCRIPTION (provided by applicant): This proposal describes a five year training program for development of an academic career in laboratory medicine. I have completed a fellowship in pulmonary and critical care medicine at Brown University, received board certifications in both specialties, and will now expand my scientific skills by applying my knowledge of both subspecialties to research in repair of acute lung injury at Rhode Island Hospital, a major teaching affiliate of Brown University. This program will examine cell-to-cell communication between injured lung cells and bone marrow cells and mechanisms by which this communication aids in marrow cell-based lung repair of lung injury. Dr. Peter Quesenberry will mentor my scientific development; I will also receive guidance from expert consultants in stem cell biology and lung biology. Dr. Quesenberry is the director of the division of hematology and oncology at Rhode Island Hospital; he has trained numerous postdoctoral fellows and physician-scientists in stem cell-related projects. Research frm our laboratory has demonstrated that adult bone marrow cells home to injured murine lung and participate in the restoration of lung cells. We hypothesize that injured lung cells induce phenotypic modifications of marrow cells by release from lung cells and subsequent uptake by marrow cells of lung cell-derived microvesicles, thereby inducing marrow cells to assume a lung cell phenotype. The specific aims are: 1. We will define marrow cell populations that take up lung-derived microvesicles, focusing on whole bone marrow cells and certain populations of hematopoietic stem cells. 2. We will determine the component of lung-derived microvesicles (RNA, DNA, protein) that causes phenotypic modification of marrow cells. 3. We will define the influence of cell cycle on the ability of marrow cells to take up lung-derived microvesicles. 4. We will determine if transplantation of marrow cells that have taken up lung-derived microvesicles attenuates radiation and elastase-induced lung injury, thereby improving lung function. Our hypothesis is that marrow cells possess sufficient reparative properties to provide a novel therapeutic option for pulmonary diseases with few currently effective treatments. Rhode Island Hospital and Brown Medical School provide an ideal setting for training physician-scientists by incorporating expertise from diverse disciplines into customized training programs. Such an environment will maximize my potential to establish a scientific niche that will be the basis of my future academic career. (End of Abstract)