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We are just starting to grasp the complexity of human cancer. Different tumor types tend to harbor mutations in different genes but how tissue specific selective damaging and aging processes result in specific combinations of mutated genes and how these processes are influenced by cell diversity and functionality remain poorly explored. Our research program will focus on understanding how tissue and organ degeneration, regeneration defects, and decline in regenerative capacity affect the initiation of cancer. We will use the liver as the target organ as it has several important characteristics that will facilitate tackling the above barriers. The liver has high endogenous regenerative capacity after damage resulting from trauma, toxicity or infection. Development of liver cancer is tightly linked to chronic liver damage and regenerative responses. Additionally, the liver is very amenable to experimental manipulation, not only by genetic tools but also by using viruses or even naked DNA.