Patient oriented research and mentoring in COPD biomarker studies - PROJECT SUMMARY Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease, with varying contributions of emphysema and large and small airway disease. COPD patients also differ in the natural history of the disease, with some patients experiencing frequent episodes of acute exacerbations and/or rapid decline in lung function. There is an unmet need for biomarkers for COPD progression, exacerbations, and response to therapy, to fulfill the promise of precision medicine. There is a need to train physician-scientists in the full range of activities necessary for large genetic epidemiology studies: enrolling subjects, conducting detailed lung disease phenotyping, collecting biospecimens, and performing bioinformatics analysis. Dr. Craig Hersh, the Principal Investigator of this proposal, has experience directing the COPDGene clinical center at Brigham and Women’s Hospital. He has expertise in using RNA-sequencing to identify gene expression signatures associated with COPD phenotypes. This proposal will expand the PI’s skills in developing and implementing a novel study protocol to identify blood and bronchoalveolar lavage fluid biomarkers for phenotypes and acute exacerbations of COPD, in subjects undergoing bronchoscopic lung volume reduction (BLVR) and other bronchoscopy procedures. Furthermore, he has mentored multiple MD and PhD scientists in genetic epidemiology studies in COPD. Through this proposal, he will devote significant time to mentoring physician-scientists in all aspects of patient-oriented research in new and ongoing COPD studies, as well as augment his own mentoring and leadership skills. Specific aims: (1) COPD bronchoscopy biomarkers study. We will develop and implement a protocol for biospecimen collections before and after bronchoscopic lung volume reduction (BLVR). We will test the hypothesis that post-BLVR respiratory events can be used as a novel model for COPD exacerbations. In addition, we will enroll stable subjects with and without COPD undergoing other bronchoscopy procedures to study a wide range of disease severity phenotypes. Plasma proteomics will be used to identify blood biomarkers. (2) Biomarkers for progression in clinical subtypes COPD. We will test the hypothesis that COPD progression will vary depending on COPD subtypes and that large scale omics analyses will provide blood biomarkers for progression. In the COPDGene Study, we will identify clinically relevant COPD subtypes, test for disease progression using longitudinal data, and analyze RNA- sequencing and proteomics data. (3) Mentoring in COPD biomarkers research. Through this proposal, the PI will mentor physician-scientists in subject enrollment, phenotyping, sample collection, and omics data generation and bioinformatics analysis. The Channing Division of Network Medicine has an extensive history of genetics and epidemiology studies in respiratory disease, including a long-standing T32 program in systems genetics and data science in lung diseases. This proposal will complement the T32 by stressing patient-oriented research coupled with data science. The PI and his trainees will have access to educational and mentoring resources, including expertise in patient-oriented research, at BWH, Harvard Medical School and nationwide through ongoing collaborations.
