Transcriptional Research

Transcriptional Research

Transcription is a highly dynamic process by which a gene is expressed into a messenger RNA, the process which is regulated by a combination of RNA polymerase II, basic transcription factors and regulatory transcription factors. Modulation of gene transcription is therefore important for its response to the microenvironment and its persistence in the diseased organ.

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Control of Myofibroblast Phenotype

The NFRG described angiotensin, serotonin and Toll-like Receptor pathways that stimulate myofibroblasts to survive, produce fibrotic tissue and suppress liver regeneration. More recently we discovered how the cytokine IL-1alpha modifies myofibroblasts to adopt a highly inflammatory state that perpetuates fibrogenesis.

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c-Rel a ‘Core’ Transcriptional Regulator of Fibrosis

The NFRG discovered that c-Rel is critical for development of fibrosis in response to injury in the liver, skin and heart. Because c-Rel can be targeted with small molecule inhibitors this important discovery paves the way for the development of novel generic anti-fibrotic molecules.

Our major publications on transcriptional research

  • The c-Rel subunit of NF-κB regulates epidermal homeostasis and promotes skin fibrosis in mice View >
  • Stimulating healthy tissue regeneration by targeting the 5-HT₂B receptor in chronic liver disease View >
  • Tumor progression locus 2/Cot is required for activation of extracellular regulated kinase in liver injury and toll-like receptor-induced TIMP-1 gene transcription in hepatic stellate cells in mice View >
  • IL-1α released from damaged epithelial cells is sufficient and essential to trigger inflammatory responses in human lung fibroblasts View >