Research Summary

The Shu lab believes in what Richard Feynman said "If you're not having fun, you are not learning. There's a pleasure in finding things out." Thus, having fun is an essential part of our research life. Our students and postdoc trainees and the PI always find unexpected fun in their biological adventures because we are an interdisciplinary lab, focusing on visualizing inner life of living cells and animals. The cells' inner life is like a glowing beautiful world of Avatar, after we label many proteins in the cell with multicolor fluorescent reporters.

Our research interests span the fields of Physical Biology, Chemical Biology, Structural Biology, Protein Engineering, Cell & Molecular Biology, Developmental Biology, and Drug Discovery. We apply Physics, Chemistry and Engineering to design biological tools for visualizing and manipulating dynamic cell signaling in vivo in order to understand animal development and homeostasis, because dynamical features of signaling are the essence of living organisms. Effector proteins such as proteases and kinases regulate almost every major signaling pathways, and protein-protein interactions (PPIs) define specificity of signal transduction from extracellular cues to the appropriate intracellular effector proteins. We have developed new classes of fluorescent reporters of proteases, kinases, and PPIs. These reporters achieve large dynamic range, high brightness and fast kinetics, in addition being genetically encoded requiring no exogenous cofactor for non-invasive imaging. Our reporters enable robust and rapid imaging of dynamic signaling in living cells and animals with unexpected fun, identifying small molecules that inhibit dysregulated signaling in disease such as cancer. Other biological tools we are developing include: chemogenetic tools for manipulating protein interaction and liquid-liquid phase separation; a genetically encoded photosensitizer for activating caspase and apoptosis signaling and ablating single cells in live animals; singlet oxygen-mediated proximity labeling technologies for identifying weak and transient PPIs by mass spectrometry. We are applying these novel technologies to explore exciting biology and therapeutics. We also collaborate with many biologists and chemists. We have shared our tools by depositing them to not-for-profit organizations, e.g. Addgene, Bloomington Stock Center.

Together let's explore fascinating biology and discover life-saving therapeutics while having fun in the biological adventures!

Research Funding

  • April 1, 2021 - March 31, 2026 - Imaging and manipulating oncoprotein phase separation and compartmentalization, Principal Investigator. Sponsor: NIH, Sponsor Award ID: R01CA258327
  • September 15, 2020 - June 30, 2025 - Modulation and functional characterization of protein condensation in chromatin organization, Co-Principal Investigator. Sponsor: NIH, Sponsor Award ID: U01DK127421
  • June 1, 2019 - May 31, 2024 - Designing a new class of fluorescent reporters for imaging dynamic cell signaling in live animals, Principal Investigator. Sponsor: NIH, Sponsor Award ID: R35GM131766
  • May 4, 2018 - March 31, 2022 - Rational design of fluorescent kinase reporters for visualizing dynamic kinase signaling in vivo, Principal Investigator. Sponsor: NIH, Sponsor Award ID: R01GM127664

Education

Sichuan University, Chengdu, China, B.S., 2000, Theoretical Physics
Fudan University, Shanghai, China, M.S., 2003, Condensed Matter Physics
University of Oregon, Eugene, OR, Ph.D., 2007, Biophysics
University of California-San Diego, San Diego, CA, Postdoc, 2010, Biochemistry

Honors & Awards

  • 2012
    NIH Director’s New Innovator Award
  • 2018-2020
    Dean’s Apple Award for Excellence in Teaching (UCSF)
  • 2019
    Maximizing Investigators’ Research Award (NIGMS)

Selected Publications

  1. Li X, Lidsky PV, Xiao Y, Wu CT, Garcia-Knight M, Yang J, Nakayama T, Nayak JV, Jackson PK, Andino R, Shu X. Ethacridine inhibits SARS-CoV-2 by inactivating viral particles. PLoS Pathog. 2021 09; 17(9):e1009898.  View on PubMed
  2. Li X, Lidsky P, Xiao Y, Wu CT, GarciaKnight M, Yang J, Nakayama T, Nayak JV, Jackson PK, Andino R, Shu X. Ethacridine inhibits SARS-CoV-2 by inactivating viral particles in cellular models. bioRxiv. 2020 Nov 02.  View on PubMed
  3. Guo WH, Qi X, Yu X, Liu Y, Chung CI, Bai F, Lin X, Lu D, Wang L, Chen J, Su LH, Nomie KJ, Li F, Wang MC, Shu X, Onuchic JN, Woyach JA, Wang ML, Wang J. Enhancing intracellular accumulation and target engagement of PROTACs with reversible covalent chemistry. Nat Commun. 2020 08 26; 11(1):4268.  View on PubMed
  4. Shu X. Imaging dynamic cell signaling in vivo with new classes of fluorescent reporters. Curr Opin Chem Biol. 2020 02; 54:1-9.  View on PubMed
  5. Zhang Q, Schepis A, Huang H, Yang J, Ma W, Torra J, Zhang SQ, Yang L, Wu H, Nonell S, Dong Z, Kornberg TB, Coughlin SR, Shu X. Designing a Green Fluorogenic Protease Reporter by Flipping a Beta Strand of GFP for Imaging Apoptosis in Animals. J Am Chem Soc. 2019 03 20; 141(11):4526-4530.  View on PubMed
  6. Torra J, Lafaye C, Signor L, Aumonier S, Flors C, Shu X, Nonell S, Gotthard G, Royant A. Tailing miniSOG: structural bases of the complex photophysics of a flavin-binding singlet oxygen photosensitizing protein. Sci Rep. 2019 02 20; 9(1):2428.  View on PubMed
  7. Chung CI, Zhang Q, Shu X. Dynamic Imaging of Small Molecule Induced Protein-Protein Interactions in Living Cells with a Fluorophore Phase Transition Based Approach. Anal Chem. 2018 12 18; 90(24):14287-14293.  View on PubMed
  8. Zhang SQ, Huang H, Yang J, Kratochvil HT, Lolicato M, Liu Y, Shu X, Liu L, DeGrado WF. Designed peptides that assemble into cross-α amyloid-like structures. Nat Chem Biol. 2018 09; 14(9):870-875.  View on PubMed
  9. Zhang Q, Zheng YW, Coughlin SR, Shu X. A rapid fluorogenic GPCR-β-arrestin interaction assay. Protein Sci. 2018 04; 27(4):874-879.  View on PubMed
  10. Shao-Qing Zhang, Lijun Liu, Junjiao Yang, Marco Lolicato, Huong Kratochvil, Xiaokun Shu, William F. DeGrado. De Novo Design of Cross-a Amyloid-Like Fibrils with Cellular Activity. Biophysical Journal. 2018 Feb 1; 114(3):410a.  View on PubMed
  11. Zhang Q, Huang H, Zhang L, Wu R, Chung CI, Zhang SQ, Torra J, Schepis A, Coughlin SR, Kornberg TB, Shu X. Visualizing Dynamics of Cell Signaling In Vivo with a Phase Separation-Based Kinase Reporter. Mol Cell. 2018 01 18; 69(2):334-346.e4.  View on PubMed
  12. To TL, Shu X. Detecting Activity at Different Length Scales: From Subdiffraction to Whole-Animal Activity. Biochemistry. 2017 10 03; 56(39):5163-5164.  View on PubMed
  13. Makhijani K, To TL, Ruiz-González R, Lafaye C, Royant A, Shu X. Precision Optogenetic Tool for Selective Single- and Multiple-Cell Ablation in a Live Animal Model System. Cell Chem Biol. 2017 Jan 19; 24(1):110-119.  View on PubMed
  14. Rodriguez EA, Campbell RE, Lin JY, Lin MZ, Miyawaki A, Palmer AE, Shu X, Zhang J, Tsien RY. The Growing and Glowing Toolbox of Fluorescent and Photoactive Proteins. Trends Biochem Sci. 2017 02; 42(2):111-129.  View on PubMed
  15. Erik A Rodriguez, Geraldine N Tran, Larry A Gross, Jessica L Crisp, Xiaokun Shu, John Y Lin, Roger Y Tsien. Erratum: Corrigendum: A far-red fluorescent protein evolved from a cyanobacterial phycobiliprotein. Nature Methods. 2016 Oct 1; 13(10):890-890.  View on PubMed
  16. Rodriguez EA, Tran GN, Gross LA, Crisp JL, Shu X, Lin JY, Tsien RY. A far-red fluorescent protein evolved from a cyanobacterial phycobiliprotein. Nat Methods. 2016 09; 13(9):763-9.  View on PubMed
  17. Feliks M, Lafaye C, Shu X, Royant A, Field M. Structural Determinants of Improved Fluorescence in a Family of Bacteriophytochrome-Based Infrared Fluorescent Proteins: Insights from Continuum Electrostatic Calculations and Molecular Dynamics Simulations. Biochemistry. 2016 08 09; 55(31):4263-74.  View on PubMed
  18. To TL, Schepis A, Ruiz-González R, Zhang Q, Yu D, Dong Z, Coughlin SR, Shu X. Rational Design of a GFP-Based Fluorogenic Caspase Reporter for Imaging Apoptosis In Vivo. Cell Chem Biol. 2016 07 21; 23(7):875-882.  View on PubMed
  19. To TL, Medzihradszky KF, Burlingame AL, DeGrado WF, Jo H, Shu X. Photoactivatable protein labeling by singlet oxygen mediated reactions. Bioorg Med Chem Lett. 2016 07 15; 26(14):3359-3363.  View on PubMed
  20. To TL, Zhang Q, Shu X. Structure-guided design of a reversible fluorogenic reporter of protein-protein interactions. Protein Sci. 2016 Mar; 25(3):748-53.  View on PubMed

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