BLAGDEN GROUP

mRNA dysregulation in Cancer

Gene expression describes the conversion of genetic message to protein. This depends on messenger RNA (mRNA) which copies the gene sequence, shuttles into the cytoplasm, binds ribosomes and generates protein. Numerous RNA binding proteins (RBPs) attach to these mRNA transcripts and regulate their splicing, stability, subcellular localisation and rate of translation. 

In cancer cells, expression of RBPs is disrupted, driving the malignant state by preserving the stability of proto-oncogenic mRNAs while destabilising those with tumour suppressor functions. One such RBP is La-related protein 1 (LARP1). We have shown that LARP1 is capable of selectively binding transcripts involved in cancer processes and is present at high levels in some epithelial cancers. The net effect of LARP1 upregulation is to drive cancer progression. The purpose of our research is to discover more about cancer RBPs and develop therapeutics against them that can be used as anti-cancer treatments. 

 LARP1 (green) highly expressed in the cytoplasm of a cancer cell. LARP1 is associated with almost 3000 mRNAs predominantly those encoding cancer signalling proteins.
 

 Cancer Therapeutics

A crucial part of cancer drug discovery is finding the best cancer treatments for the future. 

The Oxford Early Phase Cancer Trials Unit has a long established track record of drug discovery and delivering novel therapies safely and effectively. Dr Blagden has a strong science and medical background which enables her to design clinical trials, investigate treatments (developed by academia or industry) and deliver them to cancer patients.In leading the Early Phase Trials Unit, Dr Blagden’s team investigate new treatments for patients with cancer. Potential treatments are carefully chosen on their scientific rationale, their likelihood of being effective and, most importantly, their safety profile.