Lab focus: Transcriptional cycle regulation and targeting

Accurate control of gene expression is essential for health and deregulation of this process results in human disease, including cancer. The recognition that gene dysregulation causes many human diseases has spurred the development of small-molecule inhibitors of key regulatory components to restore normal gene expression. Despite the importance of tightly regulated gene expression and the clinical promise of therapies targeting this process, the mechanistic control of this process remains incompletely understood.

My laboratory aims to:

• Discover new fundamental regulatory mechanisms of gene expression
• Determine how these are dysregulated in disease
• Develop novel therapies targeting transcriptional components to correct dysregulated gene expression networks in disease.

Research interest

The Vervoort lab aims to understand how RNA Polymerase II driven transcription cycles are controlled by large regulatory complexes and epigenetic cues. We study how the dysregulation of this normally tightly controlled process results in human disease and explore therapeutic avenues to correct this aberrant transcriptional-state.

To achieve this, the lab uses state-of-the art genomics approaches and nascent RNA methods with single-nucleotide resolution to characterize the epigenetic and transcriptional landscape. This is combined with novel genome-wide CRISPR screens, Cas9 genome-engineering, and bioinformatics approaches to functionally dissect transcriptional and epigenetic complexes. The therapeutic targeting of novel regulatory complexes will subsequently be explored in the context of human diseases, including cancer, in pre-clinical disease models.

This work builds on our recent discoveries which have uncovered novel mechanisms of transcriptional regulation and have demonstrated that inhibitors of core-transcriptional components can correct transcriptional dysregulation in disease, and in cancer, reduce disease burden in solid and haematopoietic malignancies (Vervoort et al. Cell 2021).