The UCLA-Boston University Lung Cancer Biomarker Development Laboratory (UCLA-BU BDL) is a multidisciplinary, transiational research program designed to develop and characterize new biomarkers and assays through transiational research in the molecular pathogenesis of lung cancer. By drawing from the vast academic and clinical resources at our two institutions, the UCLA-BU BDL will advance new discoveries and transform them into early detection tools for lung cancer. This discovery-translational continuum is facilitated by a multidisciplinary team of UCLA and BU investigators whose expertise encompasses biological sciences, biostatistics, bioinformatics, translational and clinical pulmonary medicine, pathology and oncology. By joining a seamless collaboration between these investigators, we anticipate that this team will develop biomarkers whose application will disrupt major barriers in early detection and diagnosis of lung cancer. The aims of our research that will achieve these goals Include: 1) Identify mRNA and microRNA expression profiles in the airways and protein profiles in peripheral blood that can serve as non-invasive diagnostic biomarkers for lung cancer. 2) Develop airway and peripheral blood-based biomarkers capable of preclinical detection of lung cancer among high-risk current and former smokers. 3) Using prospectively collected cohorts, evaluate the classification accuracy of the diagnostic and preclinical detection biomarkers identified in the airway and blood in Alms 1 and 2. We hypothesize that chronic Injury, inflammation and aberrant epithelial repair result in a field of injury that supports lung carcinogenesis and that the molecular, biochemical and cellular events associated with these processes will allow for the detection of early stage lung cancer in non-invasively collected biospecimens, including the mouth, nose and blood. Our proposed studies utilize novel and complementary approaches to solve the clinical problem of early detection of lung cancer in high-risk patients. We are well positioned to perform these studies given: a) the synergy of our groups and institutions which bring together extensive experience in lung cancer chemoprevention and early detection studies; b) our expertise in gene expression profiling and computational biology, c) our access to unique prospective cohorts of high-risk current and former smokers and those with suspect lung cancer in which intra/extra-thoracic airway and blood samples are being collected; d) our preliminary data showing feasibility of the proposed airway and blood biomarker studies as well as the existing collaborations between our investigators and e) the powerful potential of combined multi-compartment, non-invasive testing.