Gene expression control is vital for health; deregulation causes diseases, including cancer. RNA Polymerase II (RNAPII) creates temporary RNA messages from DNA, instructing cellular processes, a process which is called transcription.
Cancer cells hijack RNAPII for aggressive growth and when control over the transcriptional process is lost, uncontrolled RNAPII activity may boost cancer growth.
We aim to identify how the transcription process is regulated and use this understanding to find anti-cancer therapeutics. These novel therapeutics are aimed at restoring transcriptional control and thereby halting tumor growth.
Our goal is to uncover more checkpoints, find novel targets, develop therapies, and positively impact patient outcomes.
From fundamental discoveries to translation!
Discovery and Targeting of Novel Regulators of RNA Polymerase II in Cancer
We are the Vervoort Lab, an interdisciplinary scientific research laboratory at the Walter and Eliza Hall Institute (WEHI) in Melbourne, Australia. We aim to identify novel fundamental mechanisms of RNA Polymerase II (RNAPII)-mediated gene regulation in normal conditions and explore how these can be dysregulated in the context of cancer.
Our goal is to identify critical vulnerabilities in cancer cells and exploit these therapeutically. Our research uses advanced genomics technologies and genome-wide CRISPR-screening technologies which we combine with bioinformatics analyses methods and relevant pre-clinical cancer models.
From Textbook Knowledge to Disease Understanding and novel Therapeutics.
The lab’s work has had significant scientific and commercial impact in the field of molecular control of RNA Polymerase II (RNAPII)-mediated transcription in health and disease. These accomplishments have been recognized through various grants, awards, fellowships, invited seminars, and media features.
The lab employs state-of-the-art genome-engineering, genome-wide CRISPR-Cas9 screening, advanced genomics technologies, and bioinformatics analysis methods in relevant pre-clinical in vitro and in vivo cancer and immune models.
It has discovered numerous novel regulatory mechanisms controlling RNAPII, including the novel PP2A-integrator submodule (Cell 2021), CDK12/13-mediated regulation of the elongation phase of transcription (Science Advances 2020) and the interplay between P300/CBP-controlled histone acetylation and RNAPII (Mol Cell 2021). A conceptual framework for transcriptional targeting in cancer was recently published in Nature Reviews Cancer 2022.
Tight control of gene expression is critical for normal development and homeostasis. Consequently, many layers of transcriptional regulation have evolved to control RNA Polymerase II (RNAPII) mediated RNA synthesis. When transcriptional control is lost, the ensuing dysregulation of gene-expression networks invariably results in human disease, including cancer. This notion has spurred the development of novel therapies that target transcriptional complexes.
In recent work we have combined genome-wide CRISPR-screening approaches with state-of-the-art genomics and molecular biological approaches to discover, characterise and target new transcriptional regulatory complexes (Vervoort et al. Cell 2021).
This project will combine unbiased screening approaches, with innovative bio-sensors and CRISPR-Cas9 genome-engineering to uncover novel coding and non-coding regulators of transcription and carefully delineate their molecular role through structural, molecular and genomics technologies.
The Vervoort lab joined WEHI at the start of 2022. We are enthusiastic, energetic and motivated to make ground-breaking discoveries that will feature in future molecular biology textbooks on transcription.
We aim to use these new insights to deepen our understanding of transcriptional dysregulation in disease and find ways to exploit this therapeutically.
Our team of researchers are making important discoveries in our area of focus. While everyone is working in their particular field, our collaborative scientific research laboratory means that we are all working towards a common goal. Read on to find out more.
As a member of our team you will receive in-depth supervision on your project and get trained in all the new genomics technologies and the bioinformatics analysis. Your success is our success!
We strongly encourage motivated PhD students and postdocs with an interest in genomics, CRISPR technologies and bioinformatics to apply.