Dr. Stephen Blacklow

Biography

Stephen Blacklow is the Gustavus Adolphus Pfeiffer Professor of Biological Chemistry and Molecular Pharmacology at Harvard Medical School. His research focuses on understanding the molecular logic of signal transduction, particularly how proteins are implicated in human disease. His laboratory emphasizes structure-function studies in Notch signaling while maintaining an ongoing interest in oncogenic signaling pathways. Notch proteins act as single-pass transmembrane receptors that convey signals upon activation by transmembrane ligands expressed in neighboring cells. The signals transduced by Notch receptors play a central role in cell fate decisions during embryonic development and adult tissue homeostasis. Binding of ligands initiates signaling, leading to a process called regulated intramembrane proteolysis, which releases the intracellular part of Notch (ICN) from the membrane. In canonical Notch signaling, ICN ultimately enters the nucleus, assembling a transcriptional activation complex that induces the expression of Notch target genes. Notch receptors are a large and complex family containing an extracellular ligand-binding domain, a conserved juxtamembrane region that maintains the receptor's resting conformation before ligand-induced activation, and an intracellular ankyrin repeat domain necessary for transcriptional activation. Mutations in the juxtamembrane region can lead to increased signaling, which occurs in human T-cell acute leukemias (T-ALL), thus identifying Notch as a therapeutic target for these tumors. Current efforts are directed towards understanding the ligands that induce activation and the factors that regulate target gene transcription, as well as inhibiting Notch1 as a potential treatment for aberrant signaling noted in more than half of human T-ALLs.

Research Interests

Experience