Notch signaling plays a central role in cell fate determination during embryogenesis and adult tissue homeostasis (1 and 2). The mechanism of Notch signaling is highly conserved and consists of Notch receptors and transmembrane ligands which reside on neighboring cells and interact to achieve cell-to-cell communication. Signaling via the Notch pathway is iterative and functions in a variety of developmental events (2). The canonical Notch signaling pathway begins at the cell surface where an interaction between Notch and one of its ligands, such as Delta or Serrate on the surface of a neighboring cell, engages the Notch receptor to undergo a proteolytic event. Cleavage of the Notch receptor results in the release of the notch intracellular domain (NICD) from the membrane. The NICD translocates into the nucleus where it assembles into a transcriptional activation complex with RBP_J (also known as CSL or C-promoter binding factor) and Mastermind-like coactivator proteins for the regulation of gene expression. The critical role of notch signaling during development has been demonstrated in variety of model organisms such as flies, worms, and mice. In these organisms deficiencies in the Notch pathway result in embryonic lethality. In humans several diseases have been linked to defects in genes involved in notch signaling. Human T-cell acute lymphoblastic leukemia has been found to be caused by gain-of-function mutations in the Notch1 receptor leading to activation and oncogenic activity (3). The requirement of Notch signaling during development as well as the association between Notch signaling and human diseases establishes this pathway as a critical subject of study.