Since the early 1990’s, Dr. Jon Aster has been interested in the molecular biology of cancers of the blood and blood-forming elements, including leukemia and lymphoma. His laboratory conducts research on Notch, a fundamental signaling pathway that controls the way cells communicate with one another and respond to their external environment. This pathway plays a central role in regulating many aspects of normal cellular development. It is also important in certain forms of leukemia, most notably T-cell acute lymphoblastic leukemia (T-ALL). Newly made Notch receptors reside on the surface of the cell, but when activated by ligand proteins expressed on adjacent cells, part of the receptor moves to the nucleus where it activates gene expression. Notch is one of a handful of signaling pathways that permit cells to respond to cues from their environment. These instructive signals regulate normal behavior and often go awry in cancer and other diseases. Dr. Aster’s laboratory published a seminal paper in the journal Science in 2004 that described the discovery of mutations in the Notch1 receptor in T-ALL. These mutations increase Notch signaling and drive the growth of the leukemia cells. To date, this finding remains the best example of an abnormality in the Notch pathway that leads to a human cancer.