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William Kaelin wants to understand how tumor suppressor gene mutations cause cancer. Kaelin and his team study the functions of the proteins encoded by specific tumor suppressor genes, with the long-term goal of helping to develop new anticancer therapies. Specifically, the team focuses on proteins associated with the von Hippel-Lindau (VHL) cancer syndrome causing kidney cancers and blood vessel tumors of the brain and eye, and the retinoblastoma tumor-suppressor protein. The team uses genetic and biochemical approaches with both human and mouse cells, including genetically engineered mouse models.