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
  • August 1, 2015 - July 31, 2019 - Rational design of a genetically encoded infrared fluorescent protease reporter , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01GM115399
  • September 30, 2012 - June 30, 2017 - New principle-based technologies for identifying transient protein interactions , Principal Investigator . Sponsor: NIH, Sponsor Award ID: DP2GM105446

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. Lombera JMM, Feng X, Shu X, Seiple IB. A Convergent Approach to Resorcinolic Macrolides to Expand Structural Diversity. Chemistry. 2025 May 07; e202501509.  View on PubMed
  2. Kirstin Meyer, Klaus Yserentant, Rasmi Cheloor-Kovilakam, Kiersten Ruff, Chung Chan-I, Xiaokun Shu, Bo Huang, Orion Weiner. BPS2025 - YAP charge patterning mediates signal integration through transcriptional co-condensates. Biophysical Journal. 2025 Feb 1; 124(3):29a.  View on PubMed
  3. Kirstin Meyer, Klaus Yserentant, Rasmi Cheloor-Kovilakam, Kiersten Ruff, Chung Chan-I, Xiaokun Shu, Bo Huang, Orion Weiner. BPS2025 - YAP charge patterning mediates signal integration through transcriptional co-condensates. Biophysical Journal. 2025 Feb 1; 124(3):566a.  View on PubMed
  4. Yang J, Chung CI, Koach J, Liu H, Navalkar A, He H, Ma Z, Zhao Q, Yang X, He L, Mittag T, Shen Y, Weiss WA, Shu X. Author Correction: MYC phase separation selectively modulates the transcriptome. Nat Struct Mol Biol. 2024 Nov; 31(11):1808.  View on PubMed
  5. Wu G, Ma T, Hancock CE, Gonzalez S, Aryal B, Vaz S, Chan G, Palarca-Wong M, Allen N, Chung CI, Shu X, Liu Q. Opposing GPCR signaling programs protein intake setpoint in Drosophila. Cell. 2024 Sep 19; 187(19):5376-5392.e17.  View on PubMed
  6. Meyer K, Yserentant K, Cheloor-Kovilakam R, Ruff KM, Chung CI, Shu X, Huang B, Weiner OD. YAP charge patterning mediates signal integration through transcriptional co-condensates. bioRxiv. 2024 Aug 10.  View on PubMed
  7. Yang J, Chung CI, Koach J, Liu H, Navalkar A, He H, Ma Z, Zhao Q, Yang X, He L, Mittag T, Shen Y, Weiss WA, Shu X. MYC phase separation selectively modulates the transcriptome. Nat Struct Mol Biol. 2024 Oct; 31(10):1567-1579.  View on PubMed
  8. Chung CI, Yang J, Yang X, Liu H, Ma Z, Szulzewsky F, Holland EC, Shen Y, Shu X. Phase separation of YAP-MAML2 differentially regulates the transcriptome. Proc Natl Acad Sci U S A. 2024 Feb 13; 121(7):e2310430121.  View on PubMed
  9. To TL, Li X, Shu X. Spying on SARS-CoV-2 with Fluorescent Tags and Protease Reporters. Viruses. 2023 09 27; 15(10).  View on PubMed
  10. Middha P, Wang X, Behrens S, Bolla MK, Wang Q, Dennis J, Michailidou K, Ahearn TU, Andrulis IL, Anton-Culver H, Arndt V, Aronson KJ, Auer PL, Augustinsson A, Baert T, Freeman LEB, Becher H, Beckmann MW, Benitez J, Bojesen SE, Brauch H, Brenner H, Brooks-Wilson A, Campa D, Canzian F, Carracedo A, Castelao JE, Chanock SJ, Chenevix-Trench G, CTS Consortium, Cordina-Duverger E, Couch FJ, Cox A, Cross SS, Czene K, Dossus L, Dugué PA, Eliassen AH, Eriksson M, Evans DG, Fasching PA, Figueroa JD, Fletcher O, Flyger H, Gabrielson M, Gago-Dominguez M, Giles GG, González-Neira A, Grassmann F, Grundy A, Guénel P, Haiman CA, Håkansson N, Hall P, Hamann U, Hankinson SE, Harkness EF, Holleczek B, Hoppe R, Hopper JL, Houlston RS, Howell A, Hunter DJ, Ingvar C, ABCTB Investigators, kConFab Investigators, Isaksson K, Jernström H, John EM, Jones ME, Kaaks R, Keeman R, Kitahara CM, Ko YD, Koutros S, Kurian AW, Lacey JV, Lambrechts D, Larson NL, Larsson S, Le Marchand L, Lejbkowicz F, Li S, Linet M, Lissowska J, Martinez ME, Maurer T, Mulligan AM, Mulot C, Murphy RA, Newman WG, Nielsen SF, Nordestgaard BG, Norman A, O'Brien KM, Olson JE, Patel AV, Prentice R, Rees-Punia E, Rennert G, Rhenius V, Ruddy KJ, Sandler DP, Scott CG, Shah M, Shu XO, Smeets A, Southey MC, Stone J, Tamimi RM, Taylor JA, Teras LR, Tomczyk K, Troester MA, Truong T, Vachon CM, Wang SS, Weinberg CR, Wildiers H, Willett W, Winham SJ, Wolk A, Yang XR, Zamora MP, Zheng W, Ziogas A, Dunning AM, Pharoah PDP, García-Closas M, Schmidt MK, Kraft P, Milne RL, Lindström S, Easton DF, Chang-Claude J. A genome-wide gene-environment interaction study of breast cancer risk for women of European ancestry. Breast Cancer Res. 2023 08 09; 25(1):93.  View on PubMed
  11. Chung CI, Yang J, Shu X. Chemogenetic Minitool for Dissecting the Roles of Protein Phase Separation. ACS Cent Sci. 2023 Jul 26; 9(7):1466-1479.  View on PubMed
  12. Dekker J, Alber F, Aufmkolk S, Beliveau BJ, Bruneau BG, Belmont AS, Bintu L, Boettiger A, Calandrelli R, Disteche CM, Gilbert DM, Gregor T, Hansen AS, Huang B, Huangfu D, Kalhor R, Leslie CS, Li W, Li Y, Ma J, Noble WS, Park PJ, Phillips-Cremins JE, Pollard KS, Rafelski SM, Ren B, Ruan Y, Shav-Tal Y, Shen Y, Shendure J, Shu X, Strambio-De-Castillia C, Vertii A, Zhang H, Zhong S. Spatial and temporal organization of the genome: Current state and future aims of the 4D nucleome project. Mol Cell. 2023 08 03; 83(15):2624-2640.  View on PubMed
  13. Li X, Combs JD, Salaita K, Shu X. Polarized focal adhesion kinase activity within a focal adhesion during cell migration. Nat Chem Biol. 2023 Dec; 19(12):1458-1468.  View on PubMed
  14. Li X, Chung CI, Yang J, Chaudhuri S, Munster PN, Shu X. ATM-SPARK: A GFP phase separation-based activity reporter of ATM. Sci Adv. 2023 03; 9(9):eade3760.  View on PubMed
  15. Yang J, Xiao Y, Lidsky PV, Wu CT, Bonser LR, Peng S, Garcia-Knight MA, Tassetto M, Chung CI, Li X, Nakayama T, Lee IT, Nayak JV, Ghias K, Hargett KL, Shoichet BK, Erle DJ, Jackson PK, Andino R, Shu X. Fluorogenic reporter enables identification of compounds that inhibit SARS-CoV-2. Nat Microbiol. 2023 01; 8(1):121-134.  View on PubMed
  16. Lafaye C, Aumonier S, Torra J, Signor L, von Stetten D, Noirclerc-Savoye M, Shu X, Ruiz-González R, Gotthard G, Royant A, Nonell S. Riboflavin-binding proteins for singlet oxygen production. Photochem Photobiol Sci. 2022 Sep; 21(9):1545-1555.  View on PubMed
  17. Tsz-Leung To, Xiaokun Shu. Chapter 4 Major methods and technologies for assessing cell death. . 2022 Jan 1; 93-118.  View on PubMed
  18. 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
  19. 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
  20. 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

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