Polyploid chromosome instability
Studies of yeast and cultured mammalian cells that were experimentally engineered to become polyploid showed that division of polyploid cells leads to cell division errors. This led to the hypothesis that polyploidy promotes cancer by by cell division errors and resulting aneuploidy. In contrast, naturally occurring polyploid cells typically do not divide, and this was used as an explanation for why these cells don't lead to disease. Our work helped overturn this dogma.
Beyond disease, our work has helped to show that polyploid cell division errors can occur not only in cases of disease , but also in cases of normal development. Similarly unstable polyploid cell divisions contribute to development of the liver and placenta of some mammals. A major question going forward is how such cell division errors and their consequences may be tolerated in non-diseased tissues, and whether such errors may actually serve a functional purpose in these tissues. Thus, in addition to relating our findings to polyploidy in disease, we will also uncover new functions/regulation of building a functional organ through error-prone polyploid cell division.