These researchers are working to exploit insertional mutagenesis for cancer gene discovery and functional genomics in the mouse. They use a vertebrate-active transposon system, called Sleeping Beauty (SB), for insertional mutagenesis in mouse somatic and germline cells, and for gene therapy. Using SB they have developed a powerful method to find new cancer genes using transgenic mouse models. This approach can be used to understand the genetic basis of many types of cancer, including brain tumors, carcinomas of the liver and gastrointestinal tract, leukemias, sarcomas, and many more. Insertional mutagenesis is also being used to identify genes and genetic pathways underlying acute myeloid leukemia (AML) development. The results of these screens have led to the identification of potential therapeutic targets. The lab has utilized and developed various CRISPR/Cas9 tools to knockout individual genes or screen for cancer related genes. In addition to identifying cancer specific anomalies, the Largaespada lab is identifying novel peptides in cancer cells for use in the development of patient specific cancer vaccines, and the development of novel approaches for adoptive immunotherapy.
Other work includes genetic studies of chemotherapy resistance and RAS pathway oncogene addiction in acute myeloid leukemia. Analysis of data also involves collaborations with MSI to develop custom programs/workflows for identifying neoantigens, such as MMuFLR and a fusion identification pipeline, and collaborations with other bioinformaticists on campus to create new analytical strategies. The lab also relies heavily on preexisting tools, such as the Galaxy suite of NGS tools and Ingenuity.
This group's research was featured on the MSI website in May 2019: A Tool to Identify Cancer Genes.