Contact Information
600 South Mathews
Urbana, IL 61801
Research Interests
Research Topics
Imaging, Neurobiology, Optogenetics, Signal Transduction
Research Description
Our laboratory seeks to understand how cells process molecular information to make decisions, and how these signaling processes can be precisely measured and controlled in living systems. We combine optogenetics, quantitative live-cell imaging, protein engineering, and single-molecule/super-resolution microscopy to develop technologies that reveal the spatial and temporal organization of cellular signaling and establish causal relationships between molecular events and cell behavior.
A major focus of our research is the development of optogenetic approaches for controlling intracellular signaling with high spatial and temporal precision. We apply these tools to investigate neurotrophin and kinase signaling in neurons, asking how the dynamics of pathways such as Raf–ERK regulate neuronal function across molecular, cellular, and circuit scales. We also use light-controlled protein assembly to study necroptosis, examining how the abundance, activation, and nanoscale organization of signaling complexes determine distinct inflammatory and cell-death outcomes.
A second research direction focuses on protein homeostasis and targeted protein degradation. We engineer genetically encoded, ubiquitin-independent degradation systems that enable selective removal of endogenous proteins. By integrating these systems with optogenetic control, we aim to manipulate protein abundance with temporal precision and establish new strategies for interrogating, and potentially correcting, disease-associated signaling networks.
We are also interested in how proteins and macromolecular assemblies mediate communication between cells. One example is the neuronal protein activity-regulated cytoskeleton-associated protein or Arc, which can assemble into capsid-like structures and participate in intercellular RNA and protein trafficking. Using quantitative fluorescence imaging and nanoscale microscopy, we investigate how Arc assembly, membrane interactions, and intracellular trafficking regulate its secretion and transfer between neurons.
In summary, the Zhang lab develops quantitative and controllable approaches for understanding how molecular signaling and protein organization determine cell fate, neuronal function, and disease-associated cellular behaviors.
Education
B.S. 2002 University of Science and Technology of China (USTC), China
Ph.D. 2008 University of California, Berkeley
Postdoc. 2009-2014 Stanford University
External Links
Highlighted Publications
Representative Publications
Qing Pei, Qixin Chen, Zhiqi Tian, Le Zhu, Yang Chen, Jihong Gong, Shen Wang, Yijuan Xiang, John S. Khamo, Jiaqi Fan, Yi Rong, Yi Yu, Yuyang Qin, Shiping Wu, Youssef Faragalla, Peng Cao, Kai Zhang,* Ying Lai,* Ling-Gang Wu,* Cong Ma,* Xiaofei Yang* & Jiajie Diao,* “Munc18 modulates syntaxin phase separation to promote exocytosis” Nature Neuroscience, 2026, 29, 306–314, doi: 10.1038/s41593-025-02140-9.
Tianlu Wang, Kai Zhang,* Yubin Zhou,* “Interrogating Physiological Functions with Light and Chemicals”, Annual Review Physiology, 2026, 88(1):21-46. doi: 10.1146/annurev-physiol-042924-083733.
Tyler Camp, Zixiao Li, Yushan Li, Teak-Jung Oh, Kai Zhang* “Resolving Oligomeric States of Photoactivatable Proteins in Live Cells via Photon Counting Histogram Analysis”, iScience, 2025, 28, Issue 11, 113848. doi: 10.1016/j.isci.2025.113848.
Kritika Mehta, Henry Yentsch, Jungbin Lee, Yeeun Yook, Kwan Young Lee, Tianyu Terry Gao, Nein-Pei Tsai, and Kai Zhang*, “Phosphatidylinositol 3-phosphate mediates Arc capsids secretion through the multivesicular body pathway“, Proceedings of National Academy of Sciences (PNAS), 2024, 121 (35) e2322422121. https://www.pnas.org/doi/10.1073/pnas.2322422121
Teak-Jung Oh, Vishnu Krishnamurthy, Jeong Won Han, Junyao Zhu, Zayn Beg, Amna Mehfooz, Bryan Gworek, David J. Shapiro, Kai Zhang* “Spatiotemporal control of inflammatory lytic cell death through optogenetic induction of RIPK3 oligomerization”, Journal of Molecular Biology, 2024,436(13):168628. https://doi: 10.1016/j.jmb.2024.168628
Kangqiang Qiu, Weiwei Zou, Hongbao Fang, Mingang Hao, Kritika Mehta, Zhiqi Tian, Jun-Lin Guan*, Kai Zhang*, Taosheng Huang*, Jiajie Diao*, “Light-activated mitochondrial fission through optogenetic control of mitochondria-lysosome contacts,” Nature Communications, 2022, 13, 4303. https://doi.org/10.1038/s41467-022-31970-5.
Vishnu V. Krishnamurthy, Hyojeong Hwang, Jia Fu, Jing Yang*, Kai Zhang*, “Optogenetic control of the canonical Wnt signaling pathway during Xenopus laevis embryonic development”, Journal of Molecular Biology, 2021, 433,18,167050. https://doi.org/10.1016/j.jmb.2021.167050. (Featured Communication)
Qixin Chen, Hongbao Fang, Xintian Shao, Zhiqi Tian, Yuming Zhang, Huaxun Fan, Kai Zhang*, Weijiang He*, Zijian Guo*, Jiajie Diao*, “A dual-labeling probe to track functional mitochondria–lysosome interactions in live cells”, Nature Communications, 2020,11, 6290. https://doi.org/10.1038/s41467-020-20067-6
Qin Wang, Huaxun Fan, Feng Li, Savanna R. Sharum, Vishnu Krishnamurthy, Yuanquan Song*, Kai Zhang* “Spatiotemporal optogenetic control of neurotrophin signaling accelerates axon regeneration and functional recovery in the peripheral and central nervous system”, eLife, 2020, 9: e57395. https://doi.org/10.7554/eLife.57395.
Vishnu V. Krishnamurthy, Jia Fu, Teak-Jung Oh, John Khamo, Jing Yang*, Kai Zhang* “A Generalizable Optogenetic Strategy to Regulate Receptor Tyrosine Kinases during Vertebrate Embryonic Development”, Journal of Molecular Biology, 2020, 432, 10, 3149-3158. https://doi.org/10.1016/j.jmb.2020.03.032
Savanna S. Skeeters, Ana C. Rosu, Divyanshi, Jing Yang, Kai Zhang* “Comparative determination of cytotoxicity of sub-10-nm copper nanoparticles to prokaryotic and eukaryotic cells”, ACS Applied Materials & Interfaces, 2020,12, 45, 50203–50211. https://doi.org/10.1021/acsami.0c11052.
Tyler Camp, Kritika Mehta, Stephen Sligar*, Kai Zhang*, “Molecular Orientation Determination in Nanodiscs at the Single-Molecule Level”, Analytical Chemistry, 2019, 92, 2, 2229-2236. https://doi.org/10.1021/acs.analchem.9b04950.
Payel Mondal, Vishnu Krishnamurthy, Savanna Sharum, Neeka Haack, Huiwen Zhou, Jennifer Cheng, Jing Yang, and Kai Zhang* “Repurposing protein degradation for optogenetic modulation of protein activities”, ACS Synthetic Biology, 2019. 8, 11, 2585-2592. https://doi.org/10.1021/acssynbio.9b00285.
John S. Khamo, Vishnu V. Krishnamurthy, Qixin Chen, Jiajie Diao*, and Kai Zhang*, “Optogenetic delineation of receptor tyrosine kinase subcircuits in PC12 cell differentiation“, Cell Chemical Biology, 2019, 26, 400-410. https://doi.org/10.1016/j.chembiol.2018.11.004.
Indrajit Srivastava, John S. Khamo, Subhendu Pandit, Parinaz Fathi, Xuedong Huang, Anleen Cao, Richard T. Haasch, Shuming Nie, Kai Zhang*, Dipanjan Pan* “Influence of Electron Acceptor and Electron Donor on the Photophysical Properties of Carbon Dots: A Comparative Investigation at the Bulk‐State and Single‐Particle Level. Advanced Functional Materials, 2019, 29,1902466. https://doi.org/10.1002/adfm.201902466.
J.S. Khamo, V. V. Krishnamurthy, P. Mondal, S. R. Sharum, and K. Zhang* “Applications of optobiology in intact cells and multi-cellular organisms”, Journal of Molecular Biology, 2017, 429, 2999-3017. (DOI: 10.1016/j.jmb.2017.08.015).
V. V. Krishnamurthy, J.S. Khamo, W. Mei, A. J. Turgeon, H. M. Ashraf, P. Mondal, D. B. Patel, N. Risner, E. E. Cho, J. Yang*, and K. Zhang* “Reversible optogenetic control of kinase activity during differentiation and embryonic development” Development, 2016, 143, 4085-4094. (DOI: 10.1242/dev.140889).
Zhang K* and Cui B* (2015) Optogenetic control of intracellular signaling pathways, Trends in Biotechnology, 33, 92-100.
Recent Publications
Pei, Q., Chen, Q., Tian, Z., Zhu, L., Chen, Y., Gong, J., Wang, S., Xiang, Y., Khamo, J. S., Fan, J., Rong, Y., Yu, Y., Qin, Y., Wu, S., Faragalla, Y., Cao, P., Zhang, K., Lai, Y., Wu, L. G., ... Diao, J. (2026). Munc18 modulates syntaxin phase separation to promote exocytosis. Nature Neuroscience, 29(2), 306-314. https://doi.org/10.1038/s41593-025-02140-9
Wang, T., Zhang, K., & Zhou, Y. (2026). Interrogating Physiological Functions with Light and Chemicals. Annual review of physiology, 88(1), 21-46. https://doi.org/10.1146/annurev-physiol-042924-083733
Camp, T., Li, Z., Li, Y., Oh, T. J., & Zhang, K. (2025). Resolving oligomeric states of photoactivatable proteins in living cells via photon counting histogram analysis. iScience, 28(11), Article 113848. https://doi.org/10.1016/j.isci.2025.113848
Qiu, K., Xu, X., Zhang, K., & Diao, J. (2025). Alternating Cellular Functions by Optogenetic Control of Organelles. In Methods in Molecular Biology (pp. 175-183). (Methods in Molecular Biology; Vol. 2840). Humana Press Inc.. https://doi.org/10.1007/978-1-0716-4047-0_13
Tyoe, O., Zhang, K., & Diao, J. (2025). Molecular Dynamics Simulation for Membrane Fusion. In Methods in Molecular Biology (pp. 53-68). (Methods in Molecular Biology; Vol. 2887). Humana Press Inc.. https://doi.org/10.1007/978-1-0716-4314-3_3
