Spivack Lab Focusing diagnostics and therapeutics on those most likely to benefit is a key to successful intervention at both the public health and clinical levels. The translational goal of the Spivack laboratory is to identify individuals at particularly high risk for lung malignancy, and selected non-malignant lung diseases, upon whom to focus smoking/toxin exposure cessation (primary prevention), chemoprevention (secondary prevention), and early disease detection efforts (disease screening, tertiary prevention). The laboratory is currently exploring individual Gene x Environment signatures as susceptibility markers by exploring quantitative gene (mRNA) expression phenotypes, and the DNA sequence, methylation, microRNA features potentially underlying these expression phenotypes, as well as metabolic and protein downstream features, in vitro and in human populations. Discovery efforts at the ‘omics level are well underway. This is performed in the setting of defined tobacco, diet, and other exposures. Concretely, human lung biomarkers are being established by pairing lung tissue specimens with several unique, non-invasively collected surrogate airway specimens developed in the laboratory. These entail laser capture microdissected lung compartment DNA methylomes and transcriptomes by next-gen sequencing. At a more focused level, mRNA and microRNA expression signatures from brush-exfoliated buccal mucosa cells, and exhaled microRNAs are being prfiled. The exhaled microRNAs represent a new exhaled airway biomarker class, as do pilots of exhaled condensate metabolomic/proteomic signatures. These airway-derived specimens continue to accrue from a sampling (currently n>1000) of a population assembled in a lung cancer case-control, and other clinical contexts. Additionally, airway biomarker studies in COVID19 pandemic are being initiated. The airway specimens are collectively being studied with a view toward developing non-invasive assays of the lung in human populations. The overall goal is to develop informative non-invasive risk profiling, preventive, and early disease detection strategies for the lung in human populations.