Some viruses do more than make us sick: they can rewire our cells in ways that lead to cancer and, in some cases, shield cancer cells from the immune system. Dr. Ondrej Belan’s project seeks to explore exactly how viruses do that in the context of the complex mammalian immune response.
Using a groundbreaking genetic screening technology, Dr. Belan has tested genes from over 400 viruses in immune-competent mouse cancer models to identify which viral proteins promote tumor growth and immune escape. One standout was a gene called NS5, which is from the same viral family that includes the liver cancer-causing hepatitis C virus. NS5 drives cancer cells to produce Lect2, a molecule that shields them from immune detection. In this project, Dr. Belan will further explore how NS5 and Lect2 help cancer cells to evade the immune system and whether this viral program can be disrupted to stop liver tumor growth. “This work has the potential to guide future virus-associated cancer prevention, diagnosis and treatment strategies,” he states. Dr. Belan trained at The Francis Crick Institute, where he pioneered single-molecule imaging systems to monitor DNA repair, the process cells use to fix genetic damage. His work revealed how proteins like BRCA2 and RAD51 regulate repair pathways and how mutations in those genes can lead to cancer, including breast and ovarian cancer. Now, he’s turning to viruses – not just as infectious agents, but as evolutionary experts in genetic manipulation – to uncover how cancer cells learn to hide from the immune system.
Sponsor
Stephen Elledge, PhD
Research Focus
Hepatocellular carcinoma, hepatitis C virus, immune evasion
Projects and Grants
Exploring novel mechanisms of tumor immune evasion using a synthetic virome library
