Grant: Fellowship - Priority Announcement: Fanconi Anemia (SHOPP)

Fanconi Anemia (FA) is a genetic disease characterized by a predisposition to develop anemia and cancer. To learn more about how Fanconi Anemia develops and to identify new therapies, we are studying the genes responsible for FA in a simple organism, Caenorhabditis elegans. C. elegans is a nematode worm and has many of the same genes as humans. The worm has proven to be extremely useful in studying diseases that affect people as the worm has many of the same biological processes and genes. By studying how worm FA genes function, we can learn a lot that is relevant to FA and FA therapy in humans. My proposed research has two major aims. 1) I will study FA gene mutations in the worm to gain a better understanding of the biological role of FA genes in the development of anemia and cancer. The worm has many of the key genes associated with Fanconi Anemia in humans and mutations of these genes results in consequences similar to those observed in FA patients. The research tools available to study the worm will allow me to investigate the results of these FA mutations in a whole live organism. Previous work in my lab, led to the discovery that the worm FA protein, FANCJ/DOG-1, unwinds problematic DNA sequences. This was a very important finding and has been shown to be true in human cells. 2) I will use the worm to look for other genes that could be targeted to specifically kill FA tumour cells. These would be genes that when disrupted kill FA tumour cells but not normal cells. These FA-lethal genes would be excellent therapeutic targets for the development of novel drugs to kill FA and non-FA tumours. In summary, this research will add to the understanding of how disrupting FA genes compromises the mechanisms which maintain genomic stability and prevent tumour formation. This knowledge, combined with screens to identify new targets for development of therapeutics, will advance our understanding of FA and our ability to develop treatments for FA derived tumours.