THE ROLE OF ALPHA-DEFENSINS IN CYSTIC FIBROSIS LUNG DISE

点击翻译按钮获取中文摘要

As the principal investigator of this K23 proposal, I will complete fellowship training in pediatric pulmonology at the University of Florida in June 1999. I have accepted a faculty position in the same division effective in July 1999. Having completed 3 years of full-time research in basic and applied sciences in addition to residency and accelerated clinical and research fellowship training, my immediate career goals are to pursue further training in methodology designed to translate investigative findings of biomedical research to clinically useful applications. The proposed training program consists of an early period of relevant didactic training and initiation of research efforts, and culminates in 3 years of mentored research at 80 percent effort. The skills and experience obtained during this 5 year training program will provide opportunities for further research and funding in an independent manner. The proposed research is designed to characterize the role of neutrophil or alpha-defensins in cystic fibrosis (CF) lung disease. Our preliminary data indicates that alpha-defensin levels are significantly elevated in the airways of CF patients compared to healthy volunteers. These peptides possess cytotoxic and inflammatory properties, and may play a role in chronic endobronchial infection in CF. Using bronchoscopic evaluation of the lungs and bronchoalveolar lavage, we plan to define the specific and net effect of alpha-defensins in CF lung disease. We also plan to explore the possibility of modulation of deleterious effects of alpha-defensin with aerosolized alpha1- antitypsin, a molecule that may possess a wide range of therapeutic properties in CF lung disease. The methodology of this project is diverse, consisting of patient selection and recruitment, research bronchoscopy and specimen processing, complimentary ex vivo assays and experiments, collection of clinical data, clinical trial design and administration, and a broad range of statistical analysis methods. Structured didactic training will complement this project in providing multidisciplinary training geared towards independence in the conductance of patient-oriented research. Following completion of this training and research, my long-term career interest will remain in the area of pathogenesis and applied clinical intervention of neutrophil-mediated pulmonary disease in pediatric patients.