Dr. Chen's laboratory integrates synthetic chemistry and developmental biology to interrogate the molecular mechanisms that control embryonic patterning, tissue regeneration, and oncogenesis. Their research group is currently focused on three major areas: the identification of small-molecule and genetic regulators of Hedgehog signaling, the development of chemical technologies for perturbing and observing the molecular programs of embryonic patterning and tumorigenesis, and the study of tissue regeneration using zebrafish as a model organism.

Their 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 gut. Since the cellular events that transduce the Hedgehog signal from the cell surface to the nucleus are not well understood, they are pursuing genetic and small-molecule screens for new Hedgehog pathway modulators with novel modes of action. These studies will not only provide insights into the basic mechanisms of Hedgehog signal transduction but also provide chemical leads for the development of next-generation chemotherapies and reveal new “druggable” targets within this tumor-promoting pathway.

Their laboratory is also investigating how Hedgehog signaling and other developmental pathways regulate tissue formation and regeneration in vertebrates. We use the zebrafish as a model organism for these studies, exploiting its rapid ex utero development and amenability to real-time imaging. As part of these efforts, we have developed new strategies for activating and silencing gene expression in zebrafish embryos with unprecedented spatial and temporal precision. These methods utilize chemical probes developed by our research group, including caged reagents that allow light-controlled gene silencing in whole organisms. In conjunction with conventional genetic approaches, these chemical technologies will help us elucidate the genetic programs that control vertebrate development and physiology.