2026 Award

Dr. Rachel Guest
University of Edinburgh, Edinburgh, Scotland

DH1/2 mutations in liver cell plasticity and cholangiocarcinoma

Cholangiocarcinoma, or bile duct cancer, is an aggressive cancer that is difficult to treat. Surgery is currently the only potential cure, but many patients are not eligible. Like many cancers, it develops when changes, or mutations, occur in DNA. Dr. Rachel Guest’s research focuses on a group of genes called IDH, which are involved in some bile duct cancers. The goal is to better understand why certain IDH mutations are more common, how they lead to cancer, and whether those differences can be used to develop new treatments.

To do this, Dr. Guest has created new mouse models that allow specific IDH mutations to be turned on in liver cells and tracked as cancer develops. This helps researchers study how these mutations affect the cells, especially how they change the way cells use energy. A key focus is a substance called D-2HG, which is produced by these mutations and may need to be at just the right level for cancer to grow.

Using advanced lab techniques, Dr. Guest will study these changes and explore whether D-2HG can be detected in blood, urine, or bile. This could help doctors find bile duct cancer earlier and lead to more targeted, effective treatments in the future.

Supported by Paul Sidenblad in memory of Kathleen Sidenblad