“Investigating regulatory landscapes in oesophageal adenocarcinoma”

Oesophageal cancer is the 14th most prevalent cancer and the 7th most common cause of cancer death in the UK. Oesophageal Adenocarcinoma (OAC) is the most common subtype within Western populations. A poor understanding of the disease drives poor patient outcomes. The disease is thought to arise from a pre-cancerous state known as Barrett’s Oesophagus (BO).

Changes in the regulation of transcription and chromatin environment have been identified in the transition from regular oesophageal tissue to BO to OAC. This includes evidence of reversion to an embryonic developmental cell state.

Additionally, Little is known about the changes in gene regulatory networks and chromatin environment which initiates and maintains metastatic cancer state.

I will use functional genomics approaches to identify elements which play a role in transcriptional regulation such as enhancers, super-enhancers and silencers.

This will include developing bioinformatics methods to scale up existing unsupervised clustering methods and experimentally validating bioinformatics results e.g. endogenous reporter assays for enhancers.

I will compare the regulatory landscape in regular and metastatic OAC, and embryonic tissue from the oesophagus, stomach and duodenum.

This will help elucidate the origins of OAC and molecular drivers of OAC metastasis and provide bioinformatics tools potentially applicable to other diseases.