What happens when the pancreas tries to heal but gets it wrong? Pancreatic ductal adenocarcinoma, one of the deadliest cancers in the world, does not appear out of nowhere. It often begins with a regenerative response gone awry. When acinar cells are damaged, they can undergo acinar-to-ductal metaplasia, a process that under normal circumstances is reversible. But when a combination of genetic mutations and microenvironmental signals is present, this regenerative detour becomes a one-way road toward precancerous lesions and eventually invasive carcinoma.

This pillar builds directly on our work in exocrine regeneration. We investigate how the transition from normal repair to malignant transformation occurs at the molecular and cellular level. What tips the balance? Which signals tell a damaged cell to regenerate normally, and which push it toward a cancerous fate? We are particularly interested in the earliest stages of this process. We hope to develop new accurate diagnostics to target PDAC at the earliest possible stage and through chemical screening approaches identify new lead molecules to target these pre-cancerous fate.