Dissecting the Spatial Origins of Biliary Intraepithelial Neoplasms

• Dr Luke Boulter, MRC Human Genetics Unit, Institute of Genetics and Cancer
• Prof Tim Kendall, Centre for Inflammation Research, Institute for Regeneration and Repair

October 1^st (Expected start date Jan 2026)

Funding information (students eligible to apply) UK and EU 

Application details - When applying please specify within the application this project so we can easily identify.

The liver contains a network of tubes called bile ducts which move fluids from the liver into the intestine. In some people, these ducts form an aggressive cancer called cholangiocarcinoma which, for most patients, cannot be treated. The treatment of this disease would be greatly improved if it was diagnosed earlier and if we had medicines that we could use to prevent the cancer growing at very early stages, rather than later, once the cancer had already formed.

We know that at the beginning of cholangiocarcinoma growth, bile ducts change and develop pre-cancers; our work using animal models of cholangiocarcinoma has found a particular type of cell in the diseased bile duct which becomes cancer. We have also shown that in human samples these pre-cancer cells exist and are found in “high-risk” groups of patients, who are more likely to develop cholangiocarcinoma. Importantly, what makes these cancer-starting cells different to normal cells is that they change how they communicate with immune cells (which are normally used to fight off infections). We think that understanding how early cancer cells talk to immune cells will be key in stopping cholangiocarcinoma forming.

In this project we will expand our analysis of human tissue to further investigate tumour-starting cells. To do this, we will use samples from patients who have pre-cursor cells and use a tool called spatial transcriptomics to 1. Find which immune cells are next to cancer-starting cells and 2. Understand how the cancer-starting cells are talking to these immune cells. Once we have done this, we will take cancer cells (which we have in our laboratory) and introduce them to immune cells in a dish. We can then discover whether these cancer cells use immune cells to grow. Based on the information from human tissue, we will treat these cancer-immune cell mixtures with new medicines to determine if stopping these conversations reduces how cholangiocarcinoma starts.

• Cancer
• Cholangiocarcinoma
• Liver
• Spatial Transcriptomics
• Pathology