Current Research and Scholarly Interests
The Chen laboratory integrates synthetic chemistry and developmental biology to investigate the molecular mechanisms that control tissue formation, regeneration, and oncogenic transformation. Our research group is currently focused on three major areas: (1) small-molecule and genetic regulators of Hedgehog signaling; (2) chemical tools for studying tissue patterning at the molecular and systems levels; and (3) zebrafish models of tissue biology.
Our interest in the Hedgehog pathway arises from its critical role in the patterning of multiple tissues such as the neural tube, craniofacial structures, limbs, and somites. Aberrant Hedgehog pathway activation in children and adults is also linked to several cancers, including those of the skin, brain, and blood. Since the cellular events that transduce the Hedgehog signal from the cell surface to the nucleus are not well understood, we are pursuing genetic and small-molecule screens for new Hedgehog pathway modulators with novel modes of action. These studies will provide insights into the basic mechanisms of Hedgehog signal transduction, as well as targets and chemical leads for new therapies.
Our laboratory is also investigating the molecular pathways regulate vertebrate tissue formation, homeostasis, and regeneration. We use primarily the zebrafish as a model organism for these studies, exploiting its rapid ex utero development, amenability to both chemical and genetic perturbations, and optical transparency during embryonic and larval stages. As part of these efforts, we have developed caged antisense oligonucleotides and photoactivatable signaling proteins that afford precise spatiotemporal control of gene function. We have also devised new methods for time-resolved lanthande microscopy, enabling ultrasensitive, autofluorescence-free imaging. In conjunction with genetic approaches, these chemical technologies can open new windows into the molecular mechanisms that control vertebrate development and physiology.