Avrum Spira, MD
The long-term objective of our research program is to explore the complex interaction of genes and the environment in human lung disease in order to develop genomic biomarkers that can directly impact clinical management of these conditions. Our current work focuses on applying high-throughput genomic and bioinformatics approaches to the study of lung cancer and Chronic Obstructive Pulmonary Disease (COPD). While cigarette smoking is the major cause of both diseases, only 10-20% of smokers develop either condition and there are currently no tools available to identify those smokers at highest risk for disease. Our lab has been exploring how cigarette smoking affects airway epithelial cell gene expression and defining lung-cancer-specific alterations in airway gene expression that can identify that subset of smokers who have, or are at risk for developing, lung cancer. We have also begun to explore how a smoker’s pattern of airway gene-expression reflects the perturbation of specific oncogenic pathways, potentially allowing for personalized approaches to chemoprevention and therapy. This disease-specific airway “field of injury” paradigm is currently being extended to COPD, with the goal of better understanding the molecular diversity of COPD both for developing subtype-targeted therapies and for developing biomarkers that would allow identification of biologically distinct forms of COPD. We have also pioneered techniques for gene-expression profiling in mouth and nasal epithelial cells, demonstrating that these sites reflect the physiological response to smoking and hold the potential for serving as non-invasive genomic screening tools that could be applied in large-scale population studies.