Deciphering the regulation of non-coding RNAs in a hypoxic tumour microenvironment

The role of the microenvironment in driving tumour progression is increasingly recognized. Hypoxia is one of the key microenvironmental changes between tumour and normal tissue, and adaptation of cancer cells to this hostile environment contributes to their malignancy and aggressive phenotype (1).

Such adaptation is governed by many factors, including metabolic reprogramming of tumour cells. We have developed integrated approaches to identify transcriptional programs activated in response to hypoxia (2,3,4). We will use next generation sequencing (NGS) and other high-throughput methodologies to produce a comprehensive map of such response. We will interrogate not only protein-coding transcripts and micro-RNAs, which we have previously characterized (3-4), but also uncharacterized non-coding regions of the human genome (see e.g. 5).

This will elucidate for the first time the genome-wide transcriptional response to hypoxia in different cancer types. Combined analysis of cell lines with material from individual donors will identify biomarkers with immediate potential for clinical application. We expect the results generated will also have broader implications for other biological domains and diseases.

The candidate will benefit from working closely with members of Prof Buffa’s CRUK Functional Genomics and ERC Tumour Microenvironment Modelling labs, and collaboration with Prof Harris’s CRUK Hypoxia and Angiogenesis lab.

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