The Molecular Basis of Familial Spontaneous Pneumothorax

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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.