Post-transcriptional regulation of protein expression by the aryl hydrocarbon receptor

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The long-term goal of my research program is to understand the biological role of the aryl hydrocarbon receptor (AhR), a protein that is found in almost all cells. Although the AhR responds to environmental chemicals, scientists do not know what the role of the AhR is under normal biological conditions. The goal of this project is to understand, at the cellular and molecular levels, how the AhR stop inflammatory proteins from being produced. Cigarette smoke is a wide-spread environmental contaminant that can increase the expression of numerous proteins such as cyclooxygenase-2 (Cox-2). Long-term increases in Cox-2 are associated diseases such as cancer and arthritis. Recent research from our laboratory has shown the AhR stops Cox-2 protein from being expressed when cells called fibroblasts are exposed to cigarette smoke. Fibroblasts are a type of cell found in organs such as the lung that help to give the organ structure. We hypothesize that the AhR controls protein synthesis, including that of Cox-2, by a process called post-transcriptional regulation. This process directs how much protein is generated from mRNA, rather than controlling protein expression by transcription (DNA to mRNA). Newly-discovered microRNAs (miRNAs) are a large group of non-coding RNAs that can down-regulate protein expression by causing degradation of the mRNA. It is not known if or how the AhR directly controls miRNA and the ability of miRNA to regulate protein synthesis. Cigarette smoke generated in the laboratory, together with in vitro cell culture models and cell-, molecular-, pharmacological- and biochemical techniques, will be used to understand the biological role of the AhR in controlling protein expression.