The Notch4 protein is thought to stimulate growth of breast cancer stem cells, the cells responsible for chemotherapy resistance and even tumor spread. However, it is not clear whether this is true for all forms of breast cancer. Indeed, the term breast cancer describes a very heterogeneous collection of diseases, some of which are metastatic and lethal. Most commonly, the aggressive subtypes express the HER2 receptor, a mutation in an enzyme known as PI3 kinase, or express proteins found in so-called basal cells of the mammary gland. The Egan lab has mouse models for each of these three types, and will use these models to directly test whether Notch4 is required in each disease. Furthermore, experiments are designed to determine how Notch4 functions to control stem cell behavior in the mammary gland. There are few treatment options for patients with aggressive types of breast cancer; results from these studies will help determine which forms of human breast cancer are likely to be effectively targeted by new therapies against Notch4.