Discovered selective chemical inhibitors for microtubule-based motor proteins in both the kinesin and dynein superfamilies, previously ‘undrugged’ targets required for cell division. These chemical probes are now widely used to analyze cellular dynamics. Relevant Publication
Developed DrugTargetSeqR, an approach that combines genomics and genome-editing to identify physiological targets and validate mechanisms of action of chemical inhibitors. This approach helps address a major challenge in chemical biology and drug discovery. Relevant Publication
B. Unraveling Cellular Mechanisms.
Dissected how syntelic errors, which occur when both sister chromatids improperly attach to one end of the bipolar spindle, are corrected to prevent chromosome loss during mitosis. Addressing this long-standing question required an innovative use of chemical inhibitors and state-of-the-art microscopy. Relevant Publication
Provided the first evidence that a spatial phosphorylation gradient is established during anaphase by Aurora kinase, a conserved cell cycle regulator and anti-cancer drug target. This micron-scale phosphorylation gradient provides essential cues for error-free mitosis. Relevant Publication
Measured, for the first time, the vertebrate metaphase spindle’s timescale-dependent viscoelastic properties. By using force-calibrated microneedles, our analyses explain how this dynamic structure generates force to segregate chromosomes and also accommodates large deformations caused by chromosome motion. Relevant Publication
Showed that PRC1 and kinesin-4, microtubule associated proteins required for cytokinesis, generate filament length-dependent tags. We deciphered the biochemical basis and provided the first evidence for such a filament marking and measuring mechanism in dividing cells. Relevant Publication