Reawakening of embryonic transcriptional regulatory programmes in oesophageal cancer

Oesophageal adenocarcinoma (OAC) is a devastating disease with very poor survival statistics, which is increasing in incidence in the Western world.

There are very few targeted therapeutic options available due to our lack of understanding of targetable pathways in this cancer subtype.

We have uncovered a network of transcription factors that is found in OAC [1-3] and is also operational during early oesophageal development in human embryos.

More recently, single cell transcriptomics and epigenomics work has identified a transient subpopulation of cells that arises in during early embryonic development which resembles OAC.

However, we do not know how the transcriptional networks and the underlying regulatory chromatin networks function in this context.

In this project, human stem cell differentiation models will be used and linked through to the clinic by analysis of OAC patient samples.

A combination of cellular, molecular and genome-wide approaches (including associated bioinformatics approaches) will be used to further our understanding of the transcription and chromatin regulatory networks in the developing oesophagus in the human embryo.

We will then relate these events to the cancer scenario and investigate how they relate to OAC progression from its precursor state to metastatic disease.