The Chen lab investigates the molecular mechanisms that underlie tissue formation and tumorigenesis, guided by chemical principles and enabled by chemical technologies. For example, the Chen group has developed small-molecule inhibitors of Hedgehog signaling, a biochemical pathway that is required for multiple aspects of embryonic development and contributes to human cancer. They discovered the first specific inhibitors of cytoplasmic dyneins, microtubule motors that regulate a signaling organelle called the primary cilium, and first-in-classes inhibitors of aldehyde dehydrogenase 1B1, a mitochondrial that promotes colorectal and pancreatic cancer. In addition, members of the lab have synthesized photoactivatable antisense oligonucleotides that allow gene expression to be suppressed with spatiotemporal precision. By applying these tools in zebrafish embryos, they have elucidated the transcriptional programs that regulate formation of the notochord, somites, and other mesodermal tissues. The Chen group also collaborated with the Harbury lab to devise new methods for time-resolved lanthanide microscopy. This approach takes advantage of the long-lived photoluminescence of lanthanide chelates, and it enables ultrasensitive, autofluorescence-free imaging of whole organisms.