Understanding the Influence of Regenerative Capacity on Cancer
It is widely assumed that cancer risk increases with regenerative capacity, but we expect the relationship is more complicated. In mammals, chronic organ damage in the skin, lung, intestine and liver is strongly associated with cancer, but it is possible that the potent regenerative abilities of these organs serve to preserve tissue integrity, reduce inflammation and resist transformation in the context of recurrent injury. Causative mechanisms have been difficult to study because animals with different regenerative capabilities are often evolutionarily or genetically distant. A general strategy is to develop mice that possess enhanced or altered organ regeneration in order to understand how modulating regeneration influences carcinogenesis in the liver.
This work is inspired by the clinical problem of hepatocellular carcinoma (HCC), a malignancy that arises from a highly regenerative organ that experiences recurrent injury. Although HCC is the third leading cause of cancer death in the world, scientific understanding of HCC is limited — a fact that our inability to predict outcomes, much less treat advanced cases, reflects. A goal for our lab is to understand how influences on regeneration may be employed to control cancer development.