Kidney cancer is the seventh most common cancer in the UK. The course of disease is clinically unpredictable and metastatic disease is currently considered incurable. The most common kidney cancer subtype is clear cell renal cell carcinoma (ccRCC), which is characterised by inactivation of the VHL gene. VHL encodes a ubiquitin ligase subunit, which targets hypoxia inducible factors (HIF) for degradation in an oxygen-dependent manner. When VHL is inactivated – either by low oxygen tension (hypoxia) or genetic/epigenetic deregulation as observed in ccRCC – HIF is stable and functions as a transcription factor to induce hundreds of genes with diverse functions. Although HIF is important in controlling appropriate cellular responses to hypoxia, it also alters many features of tumour behaviour. However, HIF activation alone is insufficient to drive ccRCC, and so the molecular basis of disease is incompletely understood. I am using next-generation sequencing (NGS) -based multi-omics to understand the interplay between genetic/epigenetic signals, HIF activity and the ccRCC cell phenotype. This will shed light on the molecular mechanisms driving ccRCC, which could aid development of better cancer treatments and identification of molecular markers.
I obtained my PhD from the University of Dundee in 2017, where I investigated the interplay between oncogenic signalling pathways and mRNA capping enzymes, with a particular interest in the oncogenic transcription factor C-MYC. I also investigated the mechanisms of transcriptional regulation by mRNA capping enzymes.
I enjoy participating in public engagement events.
Hypoxia drives glucose transporter 3 expression through hypoxia-inducible transcription factor (HIF)-mediated induction of the long noncoding RNA NICI.
Lauer V. et al, (2020), The Journal of biological chemistry, 295, 4065 - 4078
Co-incidence of RCC-susceptibility polymorphisms with HIF cis-acting sequences supports a pathway tuning model of cancer
Schmid V. et al, (2019), Scientific Reports, 9
Oncogenic PIK3CA mutations increase dependency on the mRNA cap methyltransferase, RNMT, in breast cancer cells.
Dunn S. et al, (2019), Open biology, 9
mRNA Cap Methyltransferase, RNMT-RAM, Promotes RNA Pol II-Dependent Transcription
Varshney D. et al, (2018), Cell Reports, 23, 1530 - 1542