A Developmental Basis for Chronic Obstructive Lung Disease

慢性阻塞性肺病的发育基础

基本信息

批准号：
8307848
负责人：
Alvin Thong-Juak Kho
金额：
$ 14.85万
依托单位：
BOSTON CHILDREN'S HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-09-01 至 2013-10-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): The applicant describes a 5-year career development program leading to independent academic research in basic respiratory research as a biological mathematician under co-mentors Isaac Kohane and Scott Weiss, leaders in biomedical informatics and respiratory pathobiology respectively. The 2 goals of this program are (1) to gain the foundational biological knowledge and skills to become an independent researcher in lung development and pathobiology - for the career development half, and (2) to develop a comprehensive molecular-functional taxonomy of lung development as a framework for characterizing the developmental basis of constituent phenotypes of chronic obstructive pulmonary disease (COPD) - in the research half. The candidate will have full access to the rich multi-disciplinary resources at Children's Hospital Boston and the Channing Laboratory for academic growth. RESEARCH: We address the association between molecular developmental milestones in lung ontogeny and the molecular pathology of chronic obstructive pulmonary disease (COPD) in an effort to understand the molecular-developmental basis underlying COPD phenotypic heterogeneity. Our premise builds on successful prior work of the applicant in using mouse developmental models to investigate human malignancies. Our central hypothesis is that the molecular events that describe disease progression in COPD reflect embryonic lung development programs but in a dysfunctional rather than an ordered program. We resolve this hypothesis via 3 specific aims which: (1) Define the molecular taxonomy of mammalian lung development, that (2) Maps the molecular hallmarks for each lung development phase from (1) to ontologic / functional attributes, and (3) Identify the developmental correlates - defined in (1-2) - inherent to each constituent phenotype of COPD that will be used to create a prognostic model for COPD phenotypes. Our approach will use integrative genomics as a practical scaffold to synthesize large multi-factorial datasets. RELEVANCE: If successful, our approach could provide a novel molecular signature (developmentally-based or otherwise) for COPD phenotypes. Such a definition could lead to a much needed refinement of our current definitions of COPD, which are based on the inherent imprecision of clinical phenotyping. Such definitions could prove of value in both descriptive and interventional studies in COPD. (End of Abstract)

描述（由申请人提供）：申请人描述了一个为期 5 年的职业发展计划，该计划导致作为生物数学家在基础呼吸研究方面进行独立学术研究，共同导师 Isaac Kohane 和 Scott Weiss 分别是生物医学信息学和呼吸病理学领域的领导者。该计划的 2 个目标是 (1) 获得基础生物学知识和技能，成为肺部发育和病理生物学的独立研究人员 - 职业发展的一半，以及 (2) 开发肺部发育的全面分子功能分类法作为描述慢性阻塞性肺病 (COPD) 构成表型的发育基础的框架 - 在研究中。候选人将可以充分利用波士顿儿童医院和钱宁实验室丰富的多学科资源来促进学术发展。研究：我们探讨肺个体发育的分子发育里程碑与慢性阻塞性肺疾病（COPD）的分子病理学之间的关联，以努力了解 COPD 表型异质性的分子发育基础。我们的前提建立在申请人之前使用小鼠发育模型研究人类恶性肿瘤的成功工作之上。我们的中心假设是，描述慢性阻塞性肺病疾病进展的分子事件反映了胚胎肺发育程序，但是功能失调的而不是有序的程序。我们通过 3 个具体目标解决了这一假设：(1) 定义哺乳动物肺部发育的分子分类学，(2) 绘制每个肺部发育阶段的分子标志，从 (1) 到本体/功能属性，以及 (3) 识别(1-2) 中定义的发育相关性是 COPD 的每个组成表型所固有的，将用于创建 COPD 表型的预后模型。我们的方法将使用综合基因组学作为实用的支架来合成大型多因素数据集。相关性：如果成功，我们的方法可以为慢性阻塞性肺病表型提供一种新的分子特征（基于发育的或其他的）。这样的定义可能会导致我们当前对 COPD 的定义进行急需的完善，这些定义是基于临床表型固有的不精确性。这些定义在慢性阻塞性肺病的描述性研究和干预性研究中都具有价值。（摘要完）

项目成果

期刊论文数量（2）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Gene expression analysis in Fmr1KO mice identifies an immunological signature in brain tissue and mGluR5-related signaling in primary neuronal cultures.

DOI：
10.1186/s13229-015-0061-9
发表时间：
2015
期刊：
Molecular autism
影响因子：
6.2
作者：
Prilutsky D;Kho AT;Palmer NP;Bhakar AL;Smedemark-Margulies N;Kong SW;Margulies DM;Bear MF;Kohane IS
通讯作者：
Kohane IS