Injured Lung and its Influence on Bone Marrow Cell Phenotype

这项建议描述了一个五年的培训计划，以发展实验室的学术生涯。 医药。我在布朗大学完成了肺部和重症监护医学的奖学金， 获得了这两个专业的董事会认证，现在将通过应用我的 对罗德岛医院急性肺损伤修复研究的两个子专业的知识 布朗大学的教学分支机构。这个程序将检查受伤的细胞之间的通讯 肺细胞和骨髓细胞以及这种通讯在以骨髓细胞为基础的 肺损伤的肺修复。Peter Quesenberry博士将指导我的科学发展；我还将获得 干细胞生物学和肺部生物学方面的专家顾问的指导。奎森伯里博士是世界卫生组织 罗德岛医院的血液科和肿瘤科；他培养了许多博士后 干细胞相关项目的研究员和内科科学家。我们实验室的研究已经证明 说明成年小鼠的骨髓细胞是受损小鼠肺的宿主，并参与肺细胞的修复。我们 肺损伤细胞通过肺细胞释放诱导骨髓细胞表型改变的假设 随后骨髓细胞摄取肺细胞衍生的微泡，从而诱导骨髓细胞 假定为肺细胞表型。具体目标是：1.我们将定义骨髓细胞种群 肺源性微泡，主要集中在全骨髓细胞和某些造血细胞群体 干细胞。2.我们将测定肺源性微泡的成分(RNA、DNA、蛋白质) 导致骨髓细胞的表型改变。3.我们将定义细胞周期对细胞功能的影响。 骨髓细胞摄取肺来源的微泡。4.我们将确定骨髓细胞移植是否 摄取肺来源的微泡可以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 岛屿医院和布朗医学院为培训内科科学家提供了理想的环境 将不同学科的专业知识纳入定制培训计划。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。

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.