James Chen received his A.B. and Ph.D. degrees in Chemistry and Chemical Biology from Harvard, and he completed his postdoctoral studies at the Department of Molecular Biology and Genetics at Johns Hopkins. He joined the Stanford faculty in 2003, and his research interests span organic chemistry, chemical biology, developmental biology, and cancer biology.
The Chen lab investigates the molecular mechanisms that underlie tissue patterning 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. Among these compounds are the first specific inhibitors of cytoplasmic dyneins, microtubule motors that regulate a signaling organelle called the primary cilium. Members of the lab have also 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.
More recently, the Chen group 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. Current research interests in the lab include small-molecule modulators of stem cell metabolism, optogenetic tools for controlling developmental signaling pathways, spermiogenesis, and male contraception.
Breslow, D. K., Hoogendoorn, S., Kopp, A. R., Morgens, D. W., Vu, B. K., Kennedy, M. C., … Nachury, M. V. (2018). A CRISPR-based screen for Hedgehog signaling provides insights into ciliary function and ciliopathies. Nature Genetics, 50(3), 460–71.
Rack, P. G., Ni, J., Payumo, A. Y., Nguyen, V., Crapster, J. A., Hovestadt, V., … Chen, J. K. (2014). Arhgap36-dependent activation of Gli transcription factors. Proceedings of the National Academy of Sciences of the United States of America, 111(30), 11061–66.
Yamazoe, S., Shestopalov, I. A., Provost, E., Leach, S. D., & Chen, J. K. (2012). Cyclic Caged Morpholinos: Conformationally Gated Probes of Embryonic Gene Function. ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 51(28), 6908–11.
See, S. K., Hoogendoorn, S., Chung, A. H., Ye, F., Steinman, J. B., Sakata-Kato, T., … Chen, J. K. (2016). Cytoplasmic Dynein Antagonists with Improved Potency and Isoform Selectivity. ACS CHEMICAL BIOLOGY, 11(1), 53–60.
Mich, J. K., & Chen, J. K. (2011). Hedgehog and retinoic acid signaling cooperate to promote motoneurogenesis in zebrafish. DEVELOPMENT, 138(23), 5113–19.
Crapster, J. A., Rack, P. G., Hellmann, Z. J., Le, A. D., Adams, C. M., Leib, R. D., … Chen, J. K. (2020). HIPK4 is essential for murine spermiogenesis. ELife, 9.
Chen, J. K. (2016). I only have eye for ewe: the discovery of cyclopamine and development of Hedgehog pathway-targeting drugs. NATURAL PRODUCT REPORTS, 33(5), 595–601.
Kowalik, L., & Chen, J. K. (2017). Illuminating developmental biology through photochemistry. NATURE CHEMICAL BIOLOGY, 13(6), 587–98.
Mich, J. K., Payumo, A. Y., Rack, P. G., & Chen, J. K. (2014). In vivo imaging of Hedgehog pathway activation with a nuclear fluorescent reporter. PLoS One, 9.
Shestopalov, I. A., Sinha, S., & Chen, J. K. (2007). Light-controlled gene silencing in zebrafish embryos. NATURE CHEMICAL BIOLOGY, 3(10), 650–51.