Contact

All Publications

  • Small-molecule modulators of HIPK4 activity and proteostasis bioRxiv Zhuang, Z., Togashi, R. K., Kearney, P., Pass, I., Swick, S. M., Zeng, F., Bobkov, A. A., Fujimoto, L. M., Dutta, S., Zerva, A., Rain, N. D., Saha, D., Emami, A., Schwalm, M. P., Moon, B. K., Howard, S. T., Knapp, S., Hanke, T., Chung, T., Chen, J. K. 2026

    View details for DOI 10.64898/2026.05.12.724395

  • Bicyclic caged morpholino oligonucleotides for optical gene silencing ChemBioChem Pattanayak, S., Sarode, B. R., Deiters, A., Chen, J. K. 2022

    View details for DOI 10.1002/cbic.202200374

  • Targeting colorectal cancer with small-molecule inhibitors of ALDH1B1 Nature Chemical Biology Feng, Z., Hom, M. E., Bearrood, T. E., Rosenthal, Z. C., Fernández, D., Ondrus, A. E., Gu, Y., McCormick, A. K., Tomaske, M. G., Marshall, C. R., Chen, C., Mochly-Rosen, D., Kuo, C. J., Chen, J. K. 2022

    View details for DOI 10.1038/s41589-022-01048-w

  • A CRISPR-based screen for Hedgehog signaling provides insights into ciliary function and ciliopathies Nat. Genet. Breslow, D. K., Hoogendoorn, S., Kopp, A. R., Morgens, D. W., Vu, B. K., Han, K., Li, A., Hess, G. T., Bassik, M. C., Chen, J. K., V, N. M. 2018; Epub ahead of print: 460–71

    Abstract

    Primary cilia organize Hedgehog signaling and shape embryonic development, and their dysregulation is the unifying cause of ciliopathies. We conducted a functional genomic screen for Hedgehog signaling by engineering antibiotic-based selection of Hedgehog-responsive cells and applying genome-wide CRISPR-mediated gene disruption. The screen can robustly identify factors required for ciliary signaling with few false positives or false negatives. Characterization of hit genes uncovered novel components of several ciliary structures, including a protein complex that contains δ-tubulin and ε-tubulin and is required for centriole maintenance. The screen also provides an unbiased tool for classifying ciliopathies and showed that many congenital heart disorders are caused by loss of ciliary signaling. Collectively, our study enables a systematic analysis of ciliary function and of ciliopathies, and also defines a versatile platform for dissecting signaling pathways through CRISPR-based screening.

    View details for DOI 10.1038/s41588-018-0054-7

    View details for PubMedCentralID PMC5862771

  • Ultrasensitive optical imaging with lanthanide lumiphores Nat. Chem. Biol. Cho, U., Riordan, D. P., Ciepla, P., Kocherlakota, K. S., Chen, J. K., Harbury, P. B. 2018; 14: 15-21

    Abstract

    In principle, the millisecond emission lifetimes of lanthanide chelates should enable their ultrasensitive detection in biological systems by time-resolved optical microscopy. In practice, however, lanthanide imaging techniques have provided no better sensitivity than conventional fluorescence microscopy. Here, we identified three fundamental problems that have impeded lanthanide microscopy: low photon flux, inefficient excitation, and optics-derived background luminescence. We overcame these limitations with a new lanthanide imaging modality, transreflected illumination with luminescence resonance energy transfer (trLRET), which increases the time-integrated signal intensities of lanthanide lumiphores by 170-fold and the signal-to-background ratios by 75-fold. We demonstrate that trLRET provides at least an order-of-magnitude increase in detection sensitivity over that of conventional epifluorescence microscopy when used to visualize endogenous protein expression in zebrafish embryos. We also show that trLRET can be used to optically detect molecular interactions in vivo. trLRET promises to unlock the full potential of lanthanide lumiphores for ultrasensitive, autofluorescence-free biological imaging.

    View details for DOI 10.1038/nchembio.2513

    View details for PubMedCentralID PMC5726931