Jie Yang
- Website: https://jieyang-lab.com/
Primary Appointment
Assistant Professor, Biochemistry and Molecular Genetics
Education
- BS, Biological Sciences, Wuhan University, China
- PhD, Biophysics, Case Western Reserve University. Cleveland, Ohio
- Postdoc, Structural Biology, Scripps Research. La Jolla, CA
Research Disciplines
Alzheimer's Disease, Biochemistry, Biophysics, Biophysics & Structural Biology, Biotechnology, Cancer Biology, Cardiovascular Biology, Cell and Developmental Biology, Computational Biology, Molecular Biology, Structural Biology
Research Interests
Structural biology, Cryo-EM, Mitochondrial stress, Integrated stress response, De novo protein design, Drug development, Neurodegeneration, Heart disease, Cancer
Research Description
Our research seeks to understand how cells detect, integrate, and adapt to stress at the molecular level. We combine cryo-electron microscopy, structural biology, biochemistry, cell biology, and protein engineering to elucidate the molecular architecture and regulatory mechanisms of stress-sensing signaling complexes. Our work focuses on mitochondrial stress signaling and the integrated stress response, with particular emphasis on how these pathways coordinate protein homeostasis, cellular metabolism, signal transduction, and cell fate decisions. By uncovering fundamental mechanisms of stress adaptation, we aim to develop innovative therapeutic strategies for cancer, neurodegenerative diseases, cardiometabolic disorders, and other stress-associated human diseases.
Selected Publications
2026
Yang, R., Zheng K., Metts M., Wang Y., Yin D., Li K.P., Prazmowska, A.A., Kashatus D.F., Kuhlman B., Yang, J. (2026). De novo design of protein binders that target DELE1 to inhibit the mitochondrial stress response. eLife, doi: doi.org/10.7554/eLife.111905.
Zhang, Q., Zhang H., Hirschi M., Li S., Lander, G.C., Yang J.*, Yang X.* (2026). A metabolite-bridged complex between SerRS and SIRT2 couples NAD+ metabolism to translation control. *co-coresponding author. Nature Communications, doi: 10.1038/s41467-026-75266-4
Chen, W., Lander, G. C.*, Yang, J.* (2026). Cryo-EM structures of human ClpXP reveal mechanisms of assembly and proteolytic activation. *co-coresponding author. Nature Communications, doi:10.1038/s41467-025-67010-1, highlighted by the editors: https://www.nature.com/collections/hhfigaahch
2025
Yang, R., Zheng K., Metts M., Wang Y., Yin D., Li K.P., Prazmowska, A.A., Kashatus D.F., Kuhlman B., Yang, J. (2025). De novo design of protein binders that target DELE1 to inhibit the mitochondrial stress response. bioRxiv, doi: https://www.biorxiv.org/content/10.64898/2025.12.22.695711v1
Zhang, Q., Zhang H., Hirschi M., Li S., Lander, G.C., Yang J.*, Yang X.* (2025). Human SerRS/SIRT2 complex structure reveals cross regulation between translation and NAD+ metabolism. *co-coresponding author. bioRxiv, doi: 10.1101/2025.09.23.677902
2024
Chen, W., Yang., J., Lander, G. C. (2024). Cryo-EM structures of human ClpXP reveal mechanisms of assembly and proteolytic activation. bioRxiv, doi:10.1101/2024.11.12.623337
2023
Yang, J., Baron, K. R., Pride, D. E., Schneemann, A., Guo, X., Chen, W., . . . Lander, G. C. (2023). DELE1 oligomerization promotes integrated stress response activation. NATURE STRUCTURAL & MOLECULAR BIOLOGY, 30(9), 1295-+. doi:10.1038/s41594-023-01061-0
2022
Li, Y., Liu, Z., Zhao, Y., Yang, J., Xiao, T. S., Conlon, R. A., & Wang, Z. (2023). PD-L1 expression is regulated by ATP-binding of the ERBB3 pseudokinase domain. GENES & DISEASES, 10(4), 1702-1713. doi:10.1016/j.gendis.2022.11.003
Yang, J., Song, A. S., Wiseman, R. L. C., & Lander, G. (2022). Cryo-EM structure of hexameric yeast Lon protease (PIM1) highlights the importance of conserved structural elements. JOURNAL OF BIOLOGICAL CHEMISTRY, 298(3). doi:10.1016/j.jbc.2022.101694
2020
Liu, Z., Wang, C., Yang, J., Chen, Y., Zhou, B., Abbott, D. W., & Xiao, T. S. (2020). Caspase-1 Engages Full-Length Gasdermin D through Two Distinct Interfaces That Mediate Caspase Recruitment and Substrate Cleavage. IMMUNITY, 53(1), 106-+. doi:10.1016/j.immuni.2020.06.007
2019
Liu, Z., Wang, C., Yang, J., Zhou, B., Yang, R., Ramachandran, R., . . . Xiao, T. S. (2019). Crystal Structures of the Full-Length Murine and Human Gasdermin D Reveal Mechanisms of Autoinhibition, Lipid Binding, and Oligomerization. IMMUNITY, 51(1), 43-+. doi:10.1016/j.immuni.2019.04.017
2018
Rathkey, J. K., Zhao, J., Liu, Z., Chen, Y., Yang, J., Kondolf, H. C., . . . Abbott, D. W. (2018). Chemical disruption of the pyroptotic pore-forming protein gasdermin D inhibits inflammatory cell death and sepsis. SCIENCE IMMUNOLOGY, 3(26). doi:10.1126/sciimmunol.aat2738
Yang, J., Liu, Z., Wang, C., Yang, R., Rathkey, J. K., Pinkard, O. W., . . . Xiao, T. S. (2018). Mechanism of gasdermin D recognition by inflammatory caspases and their inhibition by a gasdermin D-derived peptide inhibitor. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 115(26), 6792-6797. doi:10.1073/pnas.1800562115
Liu, Z., Wang, C., Rathkey, J. K., Yang, J., Dubyak, G. R., Abbott, D. W., & Xiao, T. S. (2018). Structures of the Gasdermin D C-Terminal Domains Reveal Mechanisms of Autoinhibition. STRUCTURE, 26(5), 778-+. doi:10.1016/j.str.2018.03.002
2017
Rathkey, J. K., Benson, B. L., Chirieleison, S. M., Yang, J., Xiao, T. S., Dubyak, G. R., . . . Abbott, D. W. (2017). Live-cell visualization of gasdermin D-driven pyroptotic cell death. JOURNAL OF BIOLOGICAL CHEMISTRY, 292(35), 14649-14658. doi:10.1074/jbc.M117.797217
2016
Yang, J., Liu, Z., & Xiao, T. S. (2017). Post-translational regulation of inflammasomes. CELLULAR & MOLECULAR IMMUNOLOGY, 14(1), 65-79. doi:10.1038/cmi.2016.29