In development, the embryo generates many cell types with distinct gene expression programs, leading to heterogeneity across cells. This is fundamental to complex life, but how genes and networks encode the information for this process in mammals remains mysterious. At right, the early mouse embryo shows the beginnings of polarization (arrow) and lumen formation (dashed area), two key steps in development. Also shown is variable expression of gene Nanog (right). Our goal is to define the mechanisms by which variable expression (heterogeneity) arises. Image reproduced with permission from Shahbazi et al, Nature 2017.
Our hypothesis is that the same processes driving heterogeneity in development operate in tumors. This may be part of what makes cancer so difficult to treat - the tumor cells are following normal rules of development they learned in the embryo. We are making systematic comparisons between developmental programs and tumor programs, and using the knowledge gained to build deep learning artificial intelligence tools for precise diagnosis and treatment of cancer. Image reproduced from Moiso et al, Cancer Discovery 2022.