Dr. Tuveson’s laboratory will use their expertise in forward genetics and mouse cancer modeling to mutagenize enterochromaffin cells (ECCs), enteroendocrine cells found in the digestive and respiratory tracts, to both generate models of NET and simultaneously identify genes and pathways that promote NET formation. The lack of model systems that accurately recapitulate the behavior of neuroendocrine cancers has long been a significant hurdle to developing targeted treatments for patients. Also, the cause of NET has been difficult to establish from previous studies of clinical specimens. In this application, Tuveson proposes to develop animal (mouse) models of NET by taking advantage of a new method of generating tumor models with “jumping genes” that are called transposons. Any NET that develops in such mice will then be studied to quickly determine the genes that cause NET, and this information will both be useful way to determine the cause of NET and to establish reproducible models of NET for the field.