The Molecular Basis of Familial Spontaneous Pneumothorax

这个指导患者为导向的研究职业发展奖的全球目标是建立 作为一个学术物理学家，科学家的候选人的职业生涯，并促进她过渡到一个独立的 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 包括尖端科学和以病人为导向的研究技术的高级培训。这 该奖项将为候选人提供时间，资源和必要的翻译研究的技能， 肺医学领域。在这项拨款中，提出家族性自发性气胸（FSP）是一种 与其他已知的单基因疾病不同的疾病。为了验证这一假设，一些研究将 将表征受影响个体的临床和分子特征及其 一级亲属将在无α-l-抗胰蛋白酶的情况下建立FSP家族集合 缺乏症、马凡氏综合征或其他已知的与自发性 ）气胸。这种疾病的临床特征将通过以下特征来确定： 与拟人测量，肺功能测定和胸部CT扫描，以确定其 体型、肺损伤程度以及X线片明显 肺气肿。此外，分子技术将用于确定遗传基础 这种混乱。将对较大的家族进行全基因组连锁扫描，以确定 基因组与这种表型分离。这种罕见的临床和遗传特征的表征 疾病可能提供新的见解更常见的亚型肺气肿的机制。在 此外，结合先进的培训，以病人为导向的研究和深入研究， 重要的临床问题将准备候选人作为一个独立的研究者的长期职业生涯。

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.