I am a physician scientist focused on the genetic epidemiology of chronic obstructive pulmonary disease (COPD). The primary goal of my research has been to combine field, laboratory, and analytical approaches to address the challenging problems involved in elucidating the genetic influences in complex lung diseases, primarily chronic obstructive pulmonary disease (COPD). Field work involves the development and collection of relevant phenotypes in obstructive lung diseases, including clinical and imaging assessments. Laboratory work includes supervising genotyping, sequencing, and functional molecular studies. Analytical work involves a range of methods including assessment of risk to relatives, linkage analysis, association studies, and rare variant analysis. Training of post-doctoral fellows and collaborating investigators in genetic epidemiology research is a central component of my work. I am the director the COPD genetics research program at the Channing Division of Network Medicine (CDNM). Since 1994, I have been the Principal Investigator of an extended pedigree study designed to identify novel genetic determinants of early-onset COPD (Boston Early-Onset COPD Study). I am the Principal Investigator of the Transcontinental COPD Genetics Study, which is investigating genetic determinants of COPD in diverse ethnic groups, and I am one of two national Principal Investigators of the Genetic Epidemiology of COPD Study (COPDGene), which has created a cohort of more than 10,000 COPD cases and controls with comprehensive pulmonary phenotyping (including chest CT scans) for genome-wide association analysis. In addition, I was the Principal Investigator of a collaborative study to identify genetic modifiers of severe alpha-1 antitrypsin deficiency. Key research contributions from our group include: 1) Demonstration that the development of lung disease in alpha-1 antitrypsin deficiency is highly variable and influenced by genetic modifiers as well as gender and asthma; 2) Showing that COPD clusters in families, likely due to genetic factors; and 3) Identifying several genetic determinants of COPD, including IREB2, HHIP, and FAM13A. New areas of investigation for our group include: 1) Developing a program through the Respiratory Genetics Research Center at BWH (which I lead) to identify the functional variants and to investigate the biological impact, using both cell-based and murine models, of COPD genetic determinants identified by genetic association studies and DNA sequencing approaches; and 2) Employing systems biology approaches to dissect COPD heterogeneity by incorporating CT imaging phenotypes and genetic variation.