The Molecular Basis of Familial Spontaneous Pneumothorax

这个以患者为导向的导师研究职业发展奖的全球目标是建立 候选人作为一名学术内科科学家的职业生涯，并帮助她过渡到一名独立的 调查员。为了实现这些目标，候选人和她的导师制定了一个综合计划 包括尖端科学和以患者为中心的研究技术的高级培训。这 该奖项将为候选人提供翻译研究所需的时间、资源和技能 肺部医学领域。在这项授权中，提出家族性自发性气胸(FSP)是一种 有别于其他已知的单基因疾病的疾病。为了验证这一假设，许多研究将 将确定受影响个体的临床和分子特征，以及他们的 一级亲属。将建立一个没有α-L抗胰蛋白酶的FSP家系集合 缺乏症、马凡综合征或其他已知的与自发性有关的单基因疾病 )气胸。这种疾病的临床特征将由以下特征决定 通过人体测量、呼吸测量和胸部CT扫描来确定他们的 身体习性，肺损伤程度，以及X线片的模式和位置--明显 肺气肿。此外，还将使用分子技术来定义遗传基础 这种混乱的症状。将对较大的家系进行全基因组连锁扫描，以确定 与这种表型分离的基因组。这一罕见病例的临床和遗传学特征 疾病可能为更常见的肺气肿亚型的发病机制提供新的见解。在……里面 此外，以患者为中心的研究中的高级培训与深入研究的结合 重要的临床问题将为候选人作为一名独立研究员的长期职业生涯做好准备。

The global objective of this Mentored Patient-Oriented Research Career Development Award is to build the career of the candidate as an academic physician-scientist and to faciliate her transition to an independent investigator. To accomplish these goals, the candidate and her mentors have developed an integrated plan including cutting-edge science and advanced training in the techniques of patient-oriented research. This award will provide the candidate with time, resources, and skills necessary for translational research in the field of pulmonary medicine. In this grant, it is proposed that familial spontaneous pneumothorax (FSP) is a disease distinct from other known monogenetic disorders. To test this hypothesis, a number of studies will be performed that will characterize both the clinical and molecular features of affected individuals and their first degree relatives. A collection of families with FSP will be established without alpha-l-antitrypsin deficiency, Marfan syndrome, or other known monogenetic disorders associated with spontaneous )neumothoraces. The clinical features of this disease will be determined by the characterization of ndividuals with anthropomorphic measurements, spirometry, and CT scans of the chest to determine their body habitus, degree of pulmonary impairment, and pattern and location of radiographic-apparent emphysema, respectively. In addition, molecular techniques will be used to define the genetic underpinning of this disorder. Genome-wide linkage scans will be performed on the larger families to identify regions of the genome segregating with this phenotype. Characterization of the clinical and genetic features of this rare disease may provide novel insights into the mechanism of more common subtypes of emphysema. In addition, the combination of advanced training in patient-oriented research and in-depth study of an important clinical problem will prepare the candidate for a long-term career as an independent investigator.