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Xiaokun Shu, PhD

Title(s)Professor, Pharmaceutical Chemistry
SchoolSchool of Pharmacy
Address555 Mission Bay Blvd South
San Francisco CA 94158
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    Collapse Biography 
    Collapse Awards and Honors
    National Institute of Health2012NIH Director's New Innovator Award

    Collapse Overview 
    Collapse Overview
    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!

    Collapse Research 
    Collapse Research Activities and Funding
    Designing a new class of fluorescent reporters for imaging dynamic cell signaling in live animals
    NIH/NIGMS R35GM131766Jun 1, 2019 - May 31, 2024
    Role: Principal Investigator
    Rational design of fluorescent kinase reporters for visualizing dynamic kinase signaling in vivo
    NIH/NIGMS R01GM127664May 4, 2018 - Mar 31, 2022
    Role: Principal Investigator
    Rational design of a genetically encoded infrared fluorescent protease reporter
    NIH/NIGMS R01GM115399Aug 1, 2015 - Jul 31, 2019
    Role: Principal Investigator
    New principle-based technologies for identifying transient protein interactions
    NIH/NIGMS DP2GM105446Sep 30, 2012 - Jun 30, 2017
    Role: Principal Investigator

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    Collapse Publications
    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Researchers can login to make corrections and additions, or contact us for help. to make corrections and additions.
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    Altmetrics Details PMC Citations indicate the number of times the publication was cited by articles in PubMed Central, and the Altmetric score represents citations in news articles and social media. (Note that publications are often cited in additional ways that are not shown here.) Fields are based on how the National Library of Medicine (NLM) classifies the publication's journal and might not represent the specific topic of the publication. Translation tags are based on the publication type and the MeSH terms NLM assigns to the publication. Some publications (especially newer ones and publications not in PubMed) might not yet be assigned Field or Translation tags.) Click a Field or Translation tag to filter the publications.
    1. Enhancing intracellular accumulation and target engagement of PROTACs with reversible covalent chemistry. Nat Commun. 2020 08 26; 11(1):4268. 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. PMID: 32848159.
      View in: PubMed   Mentions:    Fields:    Translation:HumansCells
    2. Imaging dynamic cell signaling in vivo with new classes of fluorescent reporters. Curr Opin Chem Biol. 2020 02; 54:1-9. Shu X. PMID: 31678813.
      View in: PubMed   Mentions: 1     Fields:    Translation:HumansAnimalsCells
    3. 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. 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. PMID: 30821975.
      View in: PubMed   Mentions: 3     Fields:    Translation:HumansAnimalsCells
    4. Tailing miniSOG: structural bases of the complex photophysics of a flavin-binding singlet oxygen photosensitizing protein. Sci Rep. 2019 02 20; 9(1):2428. Torra J, Lafaye C, Signor L, Aumonier S, Flors C, Shu X, Nonell S, Gotthard G, Royant A. PMID: 30787421.
      View in: PubMed   Mentions: 4     Fields:    Translation:Cells
    5. 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. Chung CI, Zhang Q, Shu X. PMID: 30431263.
      View in: PubMed   Mentions: 3     Fields:    Translation:HumansCells
    6. Designed peptides that assemble into cross-a amyloid-like structures. Nat Chem Biol. 2018 09; 14(9):870-875. Zhang SQ, Huang H, Yang J, Kratochvil HT, Lolicato M, Liu Y, Shu X, Liu L, DeGrado WF. PMID: 30061717.
      View in: PubMed   Mentions: 7     Fields:    Translation:HumansCells
    7. A rapid fluorogenic GPCR-ß-arrestin interaction assay. Protein Sci. 2018 04; 27(4):874-879. Zhang Q, Zheng YW, Coughlin SR, Shu X. PMID: 29411438.
      View in: PubMed   Mentions: 3     Fields:    Translation:HumansCells
    8. De Novo Design of Cross-a Amyloid-Like Fibrils with Cellular Activity. Biophysical Journal. 2018 Feb 1; 114(3):410a. Shao-Qing Zhang, Lijun Liu, Junjiao Yang, Marco Lolicato, Huong Kratochvil, Xiaokun Shu, William F. DeGrado. .
      View in: Publisher Site   Mentions:
    9. Visualizing Dynamics of Cell Signaling In Vivo with a Phase Separation-Based Kinase Reporter. Mol Cell. 2018 01 18; 69(2):334-346.e4. Zhang Q, Huang H, Zhang L, Wu R, Chung CI, Zhang SQ, Torra J, Schepis A, Coughlin SR, Kornberg TB, Shu X. PMID: 29307513.
      View in: PubMed   Mentions: 7     Fields:    Translation:HumansAnimalsCells
    10. Detecting Activity at Different Length Scales: From Subdiffraction to Whole-Animal Activity. Biochemistry. 2017 10 03; 56(39):5163-5164. To TL, Shu X. PMID: 28915023.
      View in: PubMed   Mentions:    Fields:    Translation:HumansAnimalsCells
    11. 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. Makhijani K, To TL, Ruiz-González R, Lafaye C, Royant A, Shu X. PMID: 28065655.
      View in: PubMed   Mentions: 9     Fields:    Translation:HumansAnimalsCells
    12. The Growing and Glowing Toolbox of Fluorescent and Photoactive Proteins. Trends Biochem Sci. 2017 02; 42(2):111-129. Rodriguez EA, Campbell RE, Lin JY, Lin MZ, Miyawaki A, Palmer AE, Shu X, Zhang J, Tsien RY. PMID: 27814948.
      View in: PubMed   Mentions: 71     Fields:    Translation:HumansAnimals
    13. Erratum: Corrigendum: A far-red fluorescent protein evolved from a cyanobacterial phycobiliprotein. Nature Methods. 2016 Oct 1; 13(10):890-890. Erik A Rodriguez, Geraldine N Tran, Larry A Gross, Jessica L Crisp, Xiaokun Shu, John Y Lin, Roger Y Tsien. .
      View in: Publisher Site   Mentions:
    14. A far-red fluorescent protein evolved from a cyanobacterial phycobiliprotein. Nat Methods. 2016 09; 13(9):763-9. Rodriguez EA, Tran GN, Gross LA, Crisp JL, Shu X, Lin JY, Tsien RY. PMID: 27479328.
      View in: PubMed   Mentions: 27     Fields:    Translation:HumansCells
    15. 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. Feliks M, Lafaye C, Shu X, Royant A, Field M. PMID: 27471775.
      View in: PubMed   Mentions: 3     Fields:    Translation:Cells
    16. Rational Design of a GFP-Based Fluorogenic Caspase Reporter for Imaging Apoptosis In Vivo. Cell Chem Biol. 2016 07 21; 23(7):875-882. To TL, Schepis A, Ruiz-González R, Zhang Q, Yu D, Dong Z, Coughlin SR, Shu X. PMID: 27447051.
      View in: PubMed   Mentions: 6     Fields:    Translation:HumansAnimalsCells
    17. Photoactivatable protein labeling by singlet oxygen mediated reactions. Bioorg Med Chem Lett. 2016 07 15; 26(14):3359-3363. To TL, Medzihradszky KF, Burlingame AL, DeGrado WF, Jo H, Shu X. PMID: 27220724.
      View in: PubMed   Mentions: 1     Fields:    Translation:Cells
    18. Structure-guided design of a reversible fluorogenic reporter of protein-protein interactions. Protein Sci. 2016 Mar; 25(3):748-53. To TL, Zhang Q, Shu X. PMID: 26690964.
      View in: PubMed   Mentions: 7     Fields:    Translation:HumansCells
    19. Rational design of a monomeric and photostable far-red fluorescent protein for fluorescence imaging in vivo. Protein Sci. 2016 Feb; 25(2):308-15. Yu D, Dong Z, Gustafson WC, Ruiz-González R, Signor L, Marzocca F, Borel F, Klassen MP, Makhijani K, Royant A, Jan YN, Weiss WA, Guo S, Shu X. PMID: 26549191.
      View in: PubMed   Mentions: 7     Fields:    Translation:HumansAnimalsCells
    20. A naturally monomeric infrared fluorescent protein for protein labeling in vivo. Nat Methods. 2015 Aug; 12(8):763-5. Yu D, Baird MA, Allen JR, Howe ES, Klassen MP, Reade A, Makhijani K, Song Y, Liu S, Murthy Z, Zhang SQ, Weiner OD, Kornberg TB, Jan YN, Davidson MW, Shu X. PMID: 26098020.
      View in: PubMed   Mentions: 27     Fields:    Translation:HumansAnimalsCells
    21. Rationally designed fluorogenic protease reporter visualizes spatiotemporal dynamics of apoptosis in vivo. Proc Natl Acad Sci U S A. 2015 Mar 17; 112(11):3338-43. To TL, Piggott BJ, Makhijani K, Yu D, Jan YN, Shu X. PMID: 25733847.
      View in: PubMed   Mentions: 22     Fields:    Translation:HumansAnimalsCells
    22. Singlet oxygen triplet energy transfer-based imaging technology for mapping protein-protein proximity in intact cells. Nat Commun. 2014 Jun 06; 5:4072. To TL, Fadul MJ, Shu X. PMID: 24905026.
      View in: PubMed   Mentions: 4     Fields:    Translation:AnimalsCells
    23. An improved monomeric infrared fluorescent protein for neuronal and tumour brain imaging. Nat Commun. 2014 May 15; 5:3626. Yu D, Gustafson WC, Han C, Lafaye C, Noirclerc-Savoye M, Ge WP, Thayer DA, Huang H, Kornberg TB, Royant A, Jan LY, Jan YN, Weiss WA, Shu X. PMID: 24832154.
      View in: PubMed   Mentions: 48     Fields:    Translation:HumansAnimalsCells
    24. Self-assembly of VPS41 promotes sorting required for biogenesis of the regulated secretory pathway. Dev Cell. 2013 Nov 25; 27(4):425-37. Asensio CS, Sirkis DW, Maas JW, Egami K, To TL, Brodsky FM, Shu X, Cheng Y, Edwards RH. PMID: 24210660.
      View in: PubMed   Mentions: 21     Fields:    Translation:HumansAnimalsCells
    25. Singlet Oxygen Triplet Energy Transfer (STET) Based Imaging Technologies for Mapping Protein-Protein Proximity and Interactions in Intact Cells. Biophysical Journal. 2013 Jan 1; 104(2):501a. Tsz-Leung To, Xiaokun Shu. .
      View in: Publisher Site   Mentions:
    26. Fluorescent and photo-oxidizing TimeSTAMP tags track protein fates in light and electron microscopy. Nat Neurosci. 2012 Dec; 15(12):1742-51. Butko MT, Yang J, Geng Y, Kim HJ, Jeon NL, Shu X, Mackey MR, Ellisman MH, Tsien RY, Lin MZ. PMID: 23103964.
      View in: PubMed   Mentions: 28     Fields:    Translation:HumansAnimalsCells
    27. A structural basis for the assembly and functions of a viral polymer that inactivates multiple tumor suppressors. Cell. 2012 Oct 12; 151(2):304-19. Ou HD, Kwiatkowski W, Deerinck TJ, Noske A, Blain KY, Land HS, Soria C, Powers CJ, May AP, Shu X, Tsien RY, Fitzpatrick JA, Long JA, Ellisman MH, Choe S, O'Shea CC. PMID: 23063122.
      View in: PubMed   Mentions: 42     Fields:    Translation:HumansAnimalsCells
    28. Advances in Correlated Light and Electron Microscopy Imaging Probes. Microscopy and Microanalysis. 2012 Jul 1; 18(S2):834-835. T.J. Deerinck, E. Bushong, R. Tsien, M. Ellisman, X. Shu. .
      View in: Publisher Site   Mentions:
    29. Photo-inducible cell ablation in Caenorhabditis elegans using the genetically encoded singlet oxygen generating protein miniSOG. Proc Natl Acad Sci U S A. 2012 May 08; 109(19):7499-504. Qi YB, Garren EJ, Shu X, Tsien RY, Jin Y. PMID: 22532663.
      View in: PubMed   Mentions: 65     Fields:    Translation:AnimalsCells
    30. Picking faces out of a crowd: genetic labels for identification of proteins in correlated light and electron microscopy imaging. Methods Cell Biol. 2012; 111:139-55. Ellisman MH, Deerinck TJ, Shu X, Sosinsky GE. PMID: 22857927.
      View in: PubMed   Mentions: 17     Fields:    Translation:HumansAnimalsCells
    31. Bridging Gaps in Imaging by Applying EM Tomography and Serial Block Face SEM, Including a New Genetically Encoded Tag for Correlated Light and 3D Electron Microscopy of Intact Cells, Tissues and Organisms: Integrating the Resulting Correlated Image Data Using the Whole Brain Catalog. Microscopy and Microanalysis. 2011 Jul 1; 17(S2):2-3. M Ellisman, X Shu, V Lev-Ram, T Deerinck, R Tsien, S Lamont, J Martinez, M Berlanga, E Bushong, M Martone, S Larson. .
      View in: Publisher Site   Mentions:
    32. A genetically encoded tag for correlated light and electron microscopy of intact cells, tissues, and organisms. PLoS Biol. 2011 Apr; 9(4):e1001041. Shu X, Lev-Ram V, Deerinck TJ, Qi Y, Ramko EB, Davidson MW, Jin Y, Ellisman MH, Tsien RY. PMID: 21483721.
      View in: PubMed   Mentions: 229     Fields:    Translation:AnimalsCells
    33. Enhancing Serial Block-Face Scanning Electron Microscopy to Enable High Resolution 3-D Nanohistology of Cells and Tissues. Microscopy and Microanalysis. 2010 Jul 1; 16(S2):1138-1139. TJ Deerinck, EA Bushong, V Lev-Ram, X Shu, RY Tsien, MH Ellisman. .
      View in: Publisher Site   Mentions:
    34. Genetically Encoded Singlet Oxygen Generator (SOG) Requiring No Exogenous Cofactors. Biophysical Journal. 2010 Jan 1; 98(3):612a. Xiaokun Shu, Varda Lev-Ram, Guido M. Gaietta, Thomas J. Deerinck, Ericka B. Ramko, Michael W. Davidson, Mark H. Ellisman, Roger Y. Tsien. .
      View in: Publisher Site   Mentions:
    35. Mammalian expression of infrared fluorescent proteins engineered from a bacterial phytochrome. Science. 2009 May 08; 324(5928):804-7. Shu X, Royant A, Lin MZ, Aguilera TA, Lev-Ram V, Steinbach PA, Tsien RY. PMID: 19423828.
      View in: PubMed   Mentions: 216     Fields:    Translation:HumansAnimalsCells
    36. Unique interactions between the chromophore and glutamate 16 lead to far-red emission in a red fluorescent protein. Protein Sci. 2009 Feb; 18(2):460-6. Shu X, Wang L, Colip L, Kallio K, Remington SJ. PMID: 19165727.
      View in: PubMed   Mentions: 23     Fields:    Translation:Cells
    37. An alternative excited-state proton transfer pathway in green fluorescent protein variant S205V. Protein Sci. 2007 Dec; 16(12):2703-10. Shu X, Leiderman P, Gepshtein R, Smith NR, Kallio K, Huppert D, Remington SJ. PMID: 17965188.
      View in: PubMed   Mentions: 14     Fields:    
    38. Ultrafast excited-state dynamics in the green fluorescent protein variant S65T/H148D. 1. Mutagenesis and structural studies. Biochemistry. 2007 Oct 30; 46(43):12005-13. Shu X, Kallio K, Shi X, Abbyad P, Kanchanawong P, Childs W, Boxer SG, Remington SJ. PMID: 17918959.
      View in: PubMed   Mentions: 19     Fields:    Translation:Cells
    39. Ultrafast excited-state dynamics in the green fluorescent protein variant S65T/H148D. 2. Unusual photophysical properties. Biochemistry. 2007 Oct 30; 46(43):12014-25. Shi X, Abbyad P, Shu X, Kallio K, Kanchanawong P, Childs W, Remington SJ, Boxer SG. PMID: 17918960.
      View in: PubMed   Mentions: 16     Fields:    
    40. Ultrafast excited-state dynamics in the green fluorescent protein variant S65T/H148D. 3. Short- and long-time dynamics of the excited-state proton transfer. Biochemistry. 2007 Oct 30; 46(43):12026-36. Leiderman P, Genosar L, Huppert D, Shu X, Remington SJ, Solntsev KM, Tolbert LM. PMID: 17918961.
      View in: PubMed   Mentions: 8     Fields:    
    41. Novel chromophores and buried charges control color in mFruits. Biochemistry. 2006 Aug 15; 45(32):9639-47. Shu X, Shaner NC, Yarbrough CA, Tsien RY, Remington SJ. PMID: 16893165.
      View in: PubMed   Mentions: 171     Fields:    Translation:Animals
    42. Kindling fluorescent protein from Anemonia sulcata: dark-state structure at 1.38 A resolution. Biochemistry. 2005 Apr 19; 44(15):5774-87. Quillin ML, Anstrom DM, Shu X, O'Leary S, Kallio K, Chudakov DM, Remington SJ. PMID: 15823036.
      View in: PubMed   Mentions: 40     Fields:    Translation:AnimalsCells
    43. Surface alloying of immiscible metals induced by surface state shift. Surface Science. 2003; 545(3):199-210. X.K.Shu, P. Jiang, J.G. Che.View Publication.
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