Innovations in the Baboon Model of Liver Cancer

This project aims to create a Liver Cancer baboon model by trying two complementary strategies. In the first strategy, common genetic mutations seen in human liver tumors will be recreated in baboon liver cells in vitro. We will use a new gene editing method called CRISPR to inactivate tumor suppressor genes (genes that normally limit cellular replication). The cells will be implanted into mouse livers to determine oncogenic potential. In the second strategy, transposons (genetic elements that randomly insert DNA into the genome) will be used to mutate thousands of cells. The resulting library of mutated cells can be directly injected into mice to generate tumors. Malignant cells will be sequenced to determine the cancer causing mutations. In addition, tumor cells can then be isolated from the mice and transplanted back into donor baboons to drive tumor formation in a way that has not been possible with our previous approaches.