Effects of Smoke Constituents on the Human Lung Transcriptome

The link between cigarette smoking and the development of chronic obstructive pulmonary disease (COPD) and lung and oral cancers is well documented. What is not known at present is which of the more than 4000 constituents of tobacco smoke poses the greatest threat to human health. Our work aims determine which components in tobacco smoke are the most active in directing changes in human lung epithelial cell gene expression. By specifically modifying smoke composition through directed genetic engineering of tobacco leaf metabolism, we hope to define the effects of individual smoke components and groups of related molecules in changing lung cell function. To monitor changes in the nature of gene expression in lung cells, the so-called “lung transcriptome”, we will use high-density gene chips made possible by the sequencing of the human genome. Documenting global changes in the lung transcriptome in response to discrete smoke constituents is a critical step in understanding the link between smoke exposure and altered cellular function. Documenting the global changes in human lung cell transcription in response to discrete smoke constituents is a critical step in understanding the link between smoke exposure and alterations in lung epithelial cell function, and may lead to the design of strategies to protect, alleviate, or reverse the harmful cellular effects and debilitating consequences of smoking on human health. These studies may also contribute to the identification of new biomarkers for smoke exposure.