As a recently established TTI at the NCI, only very preliminary ideas in this project can be presented: -We planned to perform chemical and genetic screenings to identify compounds and genes involved in totipotency using pluripotent cells such as mouse embryonic stem cells as a model. For these screens we generated different reporter cell lines. We obtained from a Craig Thomas, one of our intramural collaborators, a library of chemical compounds for epigenetic targets to explore the existence of compounds inducing totipotent-like features. In our screen, we identify 20 compounds that are being further evaluated in secondary validation screens. -In addition, we planned to generate a new mouse model in which we will express in a doxycycline-dependent manner a gene (Dux) highly expressed in totipotent cells. In collaboration with Lino Tesarollo, one of our intramural collaborators, we are very close to establish these mouse model lines. -Finally, we are exploring the formation of embryo-like structures in vitro from mouse totipotent-like cells in a high-throughput manner. We follow on the idea that the totipotent state might be relevant somehow during cancer formation and progression. Therefore, by defining the molecular players involved in the maintenance of totipotency we expect by extension, find new ways to understand and thus, attack cancer.
