Post-transcriptional Regulation of Gene Expression in Inflammation, Hepatotoxicity, and Cancer
Innate immunity is a highly conserved response that quickly detects and attempts to clear pathogens and harmful environmental stimuli by inducing inflammatory responses. These responses are orchestrated via temporal and highly coordinated regulation of a number of genes. In addition to regulation at the transcriptional level, a majority of these genes are also regulated by post-transcriptional mechanisms that modify mRNA stability and/or translation. The focus of our research is to understand the association between environmental stimuli, post-transcriptional mechanisms of gene expression, and disease pathogenesis. We are specifically interested in:
1) Investigating how post-transcriptional mechanisms of gene expression regulate the pathogenesis of acute lung injury/acute respiratory distress syndrome.
2) Understanding the biochemical mechanisms of hepatotoxicity and carcinogenesis in the context of post-transcriptional regulation of gene expression.
Critical domains of Tristetraprolin (TTP): In the center of the figure is a schematic diagram of three critical domains of TTP: The N terminal nuclear export sequence (NES), the central tandem zinc finger domain (TZF domain), and the C terminal NOT1 binding domain (NOT1 BD). At the upper left is shown a structural model of the human TTP TZF domain bound to nine base RNA sequence. At the upper right is a diagram of the crystal structure of the C-terminal NOT1 binding domain peptide of TTP (maroon), binding to the three internal helices from the human NOT1 protein (beige).
