Xiaoyu Shi

Picture of Xiaoyu Shi
Associate Professor, Developmental & Cell Biology
Charlie Dunlop School of Biological Sciences
Associate Professor, Chemistry
School of Physical Sciences
Associate Professor, Biomedical Engineering
The Henry Samueli School of Engineering
Ph.D., University of Californian, Davis, 2012, Physical Chemistry
Phone: (949)824-7638
Email: xiaoyu.shi@uci.edu
University of California, Irvine
2403 Natural Sciences 1
Mail Code: 2300
Irvine, Ca 92697
Research Interests
Structural Biology, Super-Resolution Microscopy, Cell Biology, Systems Biology, Single-cell spatial Multiomics, Alzheimer's Desease, Neural Disorders, Cell Signaling, Cilia Biology, Bioimaging, Biophysics
Appointments
Postdoc, University of California, San Francisco
Research Abstract
Cells are the essential building blocks of life. They participate in the development and function of organs at all spatial scales – from molecular signaling to tissue patterning. The mission of Shi’s lab is to elucidate how cells drive developmental mechanisms across all scales. To answer these questions, we leverage super-resolution microscopy and chemical synthesis to develop novel cutting-edge imaging and multiomics methods and apply these methods to study the following specific topics:
I. How cellular machineries are organized at the molecular scale?
Seeing is believing. A major objective of our research program is to directly visualize how cells organize proteins, RNA, and DNA in space and time. We have developed a series of super-resolution microscopy methods to dissect the architecture of cellular structures at molecular resolution and with high labeling efficiency, brightness, and detection sensitivity. We are particularly interested in the structure-function relationships of the nuclear lamina, chromatin, cytoplasmic vesicles, lysosomes, and cellular protrusions called cilia.
Methods: Expansion Microscopy (ExM), Stochastic Optical Reconstruction Microscopy (STORM), Structured Illumination Microscopy (SIM), Airyscan Microscopy, live-cell imaging
II. How single-cell multiomic data are organized at the spatial scale?
Over the last few years, we are witnessing rapid advances in the fields of single-cell transcriptomics, genomics, and proteomics. However, most tissues and organs are solid, with cells encased within a complex extracellular matrix network. Studying single cells from solid tissues usually requires their mechanical and enzymatic disaggregation. As a result, the positional information is lost, which is otherwise essential for a proper understanding of how cells cooperate in tissues. We take optical and chemical approaches to develop novel, spatially-resolved multiomic methods, which isolate cells without homogenization, enable cell phenotyping with super-resolution, and allow multiomics in the same single cells. This novel platform will significantly advance our knowledge of how cell phenotypes are maintained in native tissue and become perturbed in disease.
III. New and better biomarkers for diagnosis and precision medicine
We are dedicated to discovering new and better biomarkers to advance diagnosis and precision medicine related to aging, including Alzheimer’s disease, schizophrenia, depression, and solid tumors. By employing unbiased discovery methods developed in our lab, such as spatial proteomics, spatial multiomics, super-resolution imaging, and nanomaterial interfaces, we aim to identify novel biomarkers that directly lead to improved diagnostic tools and more effective, personalized precision medicine strategies.
Awards and Honors
Chan Zuckerberg Imaging Scientist Residency, Chan Zuckerberg Biohub, 2026
National Alzheimer's Coordinating Center Rising Star Award (one of two awardees), 2025
NSF CAREER Award, 2024
Research Education Component (REC) Scholar, UCI Alzheimer's Disease Research Center, 2024, 2025
Advancing Imaging through Collaborative Projects Award, Chan Zuckerberg Initiative (one of 14 winning teams worldwide), 2023
Proof of Product (PoP) Award, UCI Beall Applied Innovation, 2022
NIH Director's New Innovator Award (DP2), NIH Office of the Director, 2022
Hellman Fellow, Hellman Foundation, 2022
Selected Fellow, Education and Training (MET) Program, UCI Chao Family Comprehensive Cancer Center, 2021
Frontiers of Imaging Award for Visual Proteomics Imaging, Chan Zuckerberg Initiative (one of 14 winning teams worldwide), 2021
NIH Pathway to Independence Award (K99/R00), NIGMS, 2018
Mary Anne Koda-Kimble Seed Award for Innovation, UCSF, 2018
Chinese Government Award for Outstanding Self-Financed Students Abroad (0.1% selection rate among 500,000 students in 33 countries), 2013
Silver Medal, 18th China National Invention Exhibition (youngest medalist of the 2009 Exhibition), 2009
Short Biography
Dr. Xiaoyu Shi is an Associate Professor in the departments of Developmental and Cell Biology, Chemistry, and BME at UC Irvine. She earned her Ph.D. in Chemistry and Astrophysics from UC Davis, under Professor Cheuk Ng. Her postdoctoral research took her to UCSF, where she worked with Professor Bo Huang to develop adaptive-optical STORM. In 2019, Dr. Shi established her laboratory at UC Irvine. Her research program integrates optical and chemical methods to advance spatial multiomics and imaging technologies for biomarker discovery in neurodegenerative diseases and cancers. In the imaging direction, her lab develops Expansion Microscopy methods to visualize aging mechanisms in cells and tissues at super resolution. Dr. Shi has been recognized with prestigious awards for her biotechnologies, including the NIH Director’s New Innovator Award, the NSF CAREER Award, two Chan Zuckerberg Initiative awards, and the National Alzheimer’s Coordination Center Rising Star Award.
Publications
1. E. Tom, F. Gao, C.N. Franco, A. Wong, N. Kemmerer, Z. Wang, A. Jairaman, Q. Xu, Y. Zhuang, S.W. Du, G. Palczewska, K. Palczewski, I. Budin, S. Othy, X. Shi, V.L. Bonilha, J. Schoeneberg, K.J. Wahlin, L.V. Albrecht, D. Skowronska-Krawczyk#, Lipid-driven membrane remodeling engages a lysosome-dependent adaptive repair program during retina aging, Mol. Neurodegener. 21, 56, 2026.
2. R.T.A. Pedersen, Y. Zhuang, A.V. Reyes, S.-L. Xu, X. Shi, Y. Zheng#, Reconstitution of lamin assembly on nuclear pore complex-containing membranes, J. Cell Sci. jcs265192, 2026.
3. Y. Zhuang, Z. Zhang, Z. Dai, X. Shi#, Landscape Expansion Microscopy Reveals Interactions between Membrane and Phase-Separated Organelles, J. Cell Biol. 225, e202502035, 2026.
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4. X. Zhao#, V. Mouilleau, Y. Wang, A.C. Solak, J.Q. Garcia, X. Chen, X. Shi, C.J. Wilkinson, L.A. Royer#, Z. Dong#, S. Guo#, PCM1 coordinates centrosome asymmetry with polarized endosome dynamics to regulate daughter cell fate, Nat. Commun. 16, 10728, 2025.
5. J.A. Woytash, A.E.Y.T. Lefebvre, Z. Zhang, B. Xu, S.A. Harchenko, H.T. Le, A.R. McColloch, X. Shi, M.A. Digman, O.V. Razorenova, CDCP1/mitochondrial Src axis increases electron transport chain function to promote metastasis in triple-negative breast cancer, Br. J. Cancer 133, 1265, 2025.
6. E.G. Stokes, J.J. Vasquez, G. Azouz, M. Nguyen, A. Tierno, Y. Zhuang, V.M. Galinato, M. Hui, M. Toledano, I. Tyler, X. Shi, R.F. Hunt, J. Aoto, K.T. Beier, Cationic peptides cause memory loss through endophilin-mediated endocytosis, Nature 638, 479, 2025.
7. Y. Yoon, E. Bournique, L.V. Soles, H. Yin, H.-F. Chu, C. Yin, Y. Zhuang, X. Liu, L. Liu, J. Jeong, C. Yu, M. Valdez, L. Tian, L. Huang, X. Shi, G. Seelig, F. Ding, L. Tong, R. Buisson, Y. Shi, RBBP6 anchors pre-mRNA 3' end processing to nuclear speckles for efficient gene expression, Mol. Cell 85, 555, 2025.
8. S. Park, X. Wang, Y. Mo, S. Zhang, X. Li, K.C. Fong, C. Yu, A.A. Tran, L. Scipioni, Z. Dai, X. Huang, L. Huang, X. Shi#, Proximity Labeling Expansion Microscopy (PL-ExM) resolves structure of the interactome, Journal of Materials Chemistry B, 12, 8335, 2024.
9. Y. Zhuang, X. Shi#, Label-Retention Expansion Microscopy (LR-ExM) for Enhanced Fluorescent Signals using Trifunctional Probes, Current Protocols 4, e973, 2024.
10. Y. Zhuang, X. Shi#, Expansion microscopy: A chemical approach for super-resolution microscopy, Current Opinion in Structural Biology 81, 102614, 2023.
11. S. Park, X. Shi#, Expansion microscopy of ciliary proteins, Cilia Methods and Protocols, Methods in Molecular Biology, Chapter 4, Springer Nature, 2023.
12. S. Park, Y. Zhuang, X. Shi#, Label-retention expansion microscopy (LR-ExM) enables super-resolution imaging and high-efficiency labeling, the Journal of Visualized Experiments (JoVE), e63793, 2022.
13. X. Shi * #, Q Li *, Z. Dai, A.A.Tran, S. Feng, A.D. Ramirez, Z. Lin, X. Wang, T.T. Chow, J. Chen, D. Kumar, A.R. McColloch, J.F. Reiter, E.J. Huang, I.B. Seiple #, B. Huang #, Label-Retention Expansion Microscopy, J. Cell Biol. 220, e202105067, 2021.
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14. X. Zhao, J.Q. Garcia, K. Tong, X. Chen, B. Yang, Q. Li, Z. Dai, X. Shi, I.B. Seiple, B. Huang, S. Guo#, Polarized endosome dynamics engage cytoplasmic Par-3 that recruits dynein during asymmetric cell division, Science Advances 7, eabg1244, 2021
15. D. Kumar, A. Rains, V. Herranz-Pérez, Q. Lu, X. Shi, D.L. Swaney, E. Stevenson, N.J. Krogan, B. Huang, C. Westlake, J.M. Garcia-Verdugo, B. Yoder, J.F. Reiter#, A ciliopathy complex builds distal appendages to initiate ciliogenesis. J. Cell Biol. 220, e202011133, 2021.
16. A. Tulpule*, J. Guan*, D.S. Neel*, H.R. Allegakoen, Y.P. Lin, A. Heslin, D. Brown, Y.-T. Chou, A. Heslin, N. Chatterjee, S. Perati, S. Menon, T.A. Nguyen, J. Debnath, A.D. Ramirez, X. Shi, B. Yang, S. Feng, S. Makhija, D. Brown, B. Huang#, T.G. Bivona#, Cytoplasmic protein granules organize kinase-mediated RAS signaling. Cell 184, 2649, 2021.
17. J. Zhang, D. Velmeshev, K. Hashimoto, Y.-H. Huang, J. W. Hofmann, X. Shi, J. Chen, A. M. Leidal, J. G. Dishart, M. K. Cahill, K. W. Kelley, S. A. Liddelow, W. W. Seeley, B. L. Miller, T. C. Walther, R. V. Farese Jr., J. P. Taylor, E. M. Ullian, B. Huang, J. Debnath, T. Wittmann, A. R. Kriegstein, E. J. Huang#, Neurotoxic microglia promote TDP-43 proteinopathy in progranulin deficiency, Nature 588, 459, 2020.
18. X. Huang, X. Shi, M.E. Hansen, C.L. Nemeth, A. Ceili, B. Huang, T. Mauro, M. Koval, T.A. Desai#, Nanotopography enhances dynamic remodeling of tight junction proteins through cytosolic complexes, ACS Nano 14, 13192, 2020.
Prior to UCI:
19. X. Shi, G. Garcia, Y. Wang, J. Reiter, B. Huang#, Alignment of super-resolution images for semi-flexible structures in 3D, PLoS One 0212735, 2019.
20. X. Shi*, H. Gao*, Q.-Z. Yin, Y.-C. Chang, R. C. Wiens, W. M. Jackson, C. Y. Ng#, Branching ratio measurements of the predissociation of 12C16O by time-slice velocity-map ion imaging in the energy region from 106,250 to 107,800 cm-1, J. Phys. Chem. A 122, 8136, 2018.
Cover image
21. T. Chow, X. Shi, J.H. Wei, J. Guan, G. Stadler, B. Huang, E. Blackburn#, Local enrichment of HP1alpha at telomeres alters their structure and regulation of telomere protection,
Nat. Commun. 9, 3583, 2018.
22. X. Shi *, G. Garcia *, J. C. Van De Weghe, R. McGorty, G. J. Pazour, D. Doherty, B. Huang#, J. F. Reiter#, Super-resolution microscopy reveals that disruption of ciliary transition zone architecture is a cause of Joubert syndrome, Nat. Cell Biol. 19, 1178, 2017.
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23. X. Shi, Q.-Z. Yin, H. Gao, Y. C. Chang, W. M. Jackson, R. Wiens and C. Y. Ng#, A Predissociation Branching Ratio Comparison of CO and N2: Implications for Oxygen Nitrogen Isotope Evolution in the Early Solar System, Astrophys. J. 850, 48, 2017.
24. J. Guan, H. Liu, X. Shi, S. Feng, B. Huang#, Tracking multiple genomic elements using correlative CRISPR imaging and sequential DNA FISH, Biophys. J. 112,1077, 2017.
Highlighted as New and Notable
25. H. Huang, H. Wang, Z. Luo, X. Shi, Y.-C. Chang, C. Y. Ng#. A High-Resolution Vacuum Ultraviolet Laser Photoionization and Photoelectron Study of the Co Atom, Astrophys. J. 833, 205, 2016.
26. H. Gao, Y. Song, Y.-C. Chang, X. Shi, Q.-Z. Yin, R. C. Wiens, W. M. Jackson, C. Y. Ng#, Branching Ratio Measurements for Vacuum Ultraviolet Photodissociation of 12C16O, J. Phys. Chem. A 117, 6185, 2013.
27. H. Huang, Y.-C. Chang, Z. Luo, X. Shi, C.-S. Lam, K.-C. Lau, and C. Y. Ng#, Rovibronically selected and resolved two-color laser photoionization and photoelectron study of cobalt carbide cation, J. Chem. Phys. 138, 094301, 2013.
28. K.-C. Lau, Y. Pan, C.-S. Lam, H. Huang, Y.-C. Chang, Z. Luo, X. Shi, and C. Y. Ng#, High-level ab initio predictions for the ionization energy, bond dissociation energies and heats of formation of cobalt carbide (CoC) and its cation (CoC+), J. Chem. Phys. 138, 094302, 2013.
29. X. Shi, H. Huang, B. Jacobson, Y. C. Chang, Q.-Z. Yin, and C. Y. Ng#, A High-Resolution Photoionization and Photoelectron Study of 58Ni using a Vacuum Ultraviolet Laser, Astrophys. J. 747, 20, 2012.
30. H. Gao, Y. Song, L. Yang, X. Shi, Q.-Z. Yin, C. Y. Ng#, and W. M. Jackson, Branching Ratio measurements of the Predissociation of 12C16O by Time-Slice Velocity-Map Ion Imaging in the Vacuum Ultraviolet region from 108 000 to 110 500 cm-1, J. Chem. Phys. 137, 034305, 2012.
31. H. Gao, Y. Song, L. Yang, X. Shi, Q.-Z. Yin, C. Y. Ng, and W. M. Jackson#, Communication: Branching Ratio measurements in the Predissociation of 12C16O by Time-Slice Velocity-Map Ion Imaging in the Vacuum Ultraviolet region, J. Chem. Phys. 135, 221101, 2011.
32. Y. C. Chang, X. Shi, K-C Lau, Q.-Z. Yin, H. T. Liou, and C. Y. Ng#, Rovibronically Selected and Resolved Two-color Laser Photoionization and Photoelectron study of Nickel Carbide Cation, J. Chem. Phys. 133, 054310, 2010.
33. K.-C. Lau, Y. C. Chang, X. Shi, C. Y. Ng#, High-level ab initio predictions for the ionization energy, bond dissociation energies and heats of formations of Nickel carbide (NiC) and its cation (NiC+), J. Chem. Phys. 133, 114304, 2010.
34. Q.-Z. Yin#, X. Shi, C. Chang, C. Y. Ng, Comment on ''Experimental test of self-shielding in vacuum ultraviolet photodissociation of CO'', Science 324, 1516, 2009.
35. W. M. Jackson#, X. Yang, X. Shi, and A. L. Cochran, The temporal changes in the emission spectrum of Comet 9P/ Tempel 1 after Deep Impact, Astrophys. J. 698, 1609, 2009.
36. Y. Zhu, M. Tang#, X. Shi, Y. Zhao, Quantum chemical study of cyclic dipeptides, Int. J. Quantum Chem. 3, 745, 2007.
Grants
NIH R01 (R01HL186358), NHLBI, 2026-2030
NSF CAREER Award, 2024-2029
Advancing Imaging Through Collaborative Projects Award, Chan Zuckerberg Initiative, 2023-2025
NIH Director's New Innovator Award (DP2), 2022-2027
Frontiers of Imaging Award, Chan Zuckerberg Initiative, 2021-2023
NIH Pathway to Independence Award (K99/R00), NIGMS; 2018-2023
NIH R01 (R01AG100878), NIA, 2026-2031
Professional Societies
Biophysical Society (BPS)
American Chemical Society (ACS)
American Society for Cell Biology (ASCB)
Other Experience
Postdoc
University of California, San Francisco 2013—2019
Graduate Programs
Biomedical Engineering
Cellular and Molecular Biosciences
Mathematical, Computational and Systems Biology
Research Centers
Center for Complex Biological Systems (CCBS)
NSF-Simons Center for Multiscale Cell Fate Research (CMCF)
Chao Family Comprehensive Cancer Center (CFCCC)
Memory Impairments and Neurological Disorders (MIND)
The Center for Neural Circuit Mapping (CNCM)
Center for Aging Research in Down Syndrome (CAR-DS)
Noel Drury, MD Institute for Translational Depression Discoveries
Last updated
09/23/2026