Injured Lung and its Influence on Bone Marrow Cell Phenotype

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，在实验室医学的学术生涯的发展。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委员会认证，现在将通过应用我在这两个亚专业的知识来扩展我的科学技能，在布朗大学的主要教学附属机构罗得岛医院研究急性肺损伤的修复。该项目将研究受损肺细胞和骨髓细胞之间的细胞间通讯，以及这种通讯有助于以骨髓细胞为基础的肺修复肺损伤的机制。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生物学专家顾问的指导。Quesenberry博士是罗得岛医院血液学和肿瘤学部门的主任;他在干细胞相关项目中培训了许多博士后研究员和医生科学家。本实验室的研究表明，成年小鼠骨髓细胞可归巢于受损的肺组织，并参与肺组织细胞的修复。我们假设，损伤的肺细胞诱导骨髓细胞的表型修饰，从肺细胞释放和随后的肺细胞衍生的微泡的骨髓细胞的摄取，从而诱导骨髓细胞承担肺细胞表型。具体目标是：1.我们将定义吸收肺源性微泡的骨髓细胞群，重点是全骨髓细胞和某些造血干细胞群。2.我们将确定导致骨髓细胞表型改变的肺源性微泡（RNA，DNA，蛋白质）的组分。3.我们将确定细胞周期对骨髓细胞吸收肺源性微泡能力的影响。4.我们将确定移植吸收了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特性，为目前有效治疗方法很少的肺部疾病提供了一种新的治疗选择。罗得岛医院和布朗医学院通过将不同学科的专业知识纳入定制的培训计划，为培训医生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，建立一个科学的利基，这将是我未来学术生涯的基础。(End摘要）

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)