The focus of our research is to understand how post-transcriptional mechanisms of gene expression regulate the pathogenesis of Environmentally-induced Hepatic and Pulmonary inflammation.
We are specifically investigating RNA-Binding-Proteins of the Zinc Finger Protein 36 (ZFP36) family. Zinc Finger Protein 36 (ZFP36), also commonly known as Tristetraprolin (TTP) post-transcriptionally regulates gene expression by binding to AU-rich elements (AREs) within the 3′-untranslated regions (3’UTRs) of certain mRNAs and causing their rapid turnover. Therefore, changes in the expression of TTP family proteins could have severe consequences in terms of downstream gene expression as well as tissue pathology.
We use various models of liver and lung injury and inflammation to test these hypotheses.
Liver Injury and Inflammation: We use carbon tetrachloride (CCl4) to model hepatotoxicant-induced liver injury, inflammation, and fibrosis. We have found that certain hepatotoxicants, including CCl4, suppress the expression of TTP family RBPs in the liver indicating this as one potential mechanism of hepatotoxicity. We have generated liver-specific deletions of TTP family proteins in mice to investigate the potential mechanisms.
We are testing the hypothesis that certain hepatotoxicants dysregulate TTP family RBP expression, that results in their target mRNA stabilization and associated pathology.
Lung Injury and Inflammation: Second, we are testing how TTP, the master regulator of inflammation, regulates the pathogenesis, including initiation, progression, and resolution of ozone- and allergen-induced lung inflammation. We have generated various knockout mice of cell-specific TTP deficiency to answer some of these questions. Besides, bone-marrow chimeras are generated to test the cell-lineage specificity of TTP action.
We use various methodologies in the lab that includes transcriptomics, bioinformatics, digital pathology including quantitative histological and immunohistochemical techniques, RNAScope in situ hybridization, and mouse genetics to test our hypotheses.