Xiaolei Su, PhD

TitlePostdoctoral Scholar
SchoolUCSF School of Medicine
DepartmentCellular Molecular Pharmacology
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    Harvard UniversityPh.D.2012Biological and Biomedical Sciences
    Marine Biological LaboratorySummer course2009Physiology
    Peking UniversityB.S.2006Biological Sciences
    Collapse Awards and Honors
    Keystone Symposia2015Keystone Symposia Future of Science Fund Scholarship
    Cancer Research Institute2014  - 2017Cancer Research Institute Irvington Fellowship
    Harvard University2012Richard J. Herrnstein Prize for dissertation
    Marine Biological Laboratory2009Lola Ellis Robertson Endowed Scholarship
    Peking University2006Graduates with honors
    China Scholarship Council2004Hewlett-Packard Scholarship
    Peking University2002  - 2006Mingde Scholarship

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    I have a long-term interest in exploring protein dynamics and understanding how spatial organization of molecules affects cell physiology. I did my PhD under the mentorship of David Pellman at Harvard. My graduate work aimed to address two long-standing questions in the field of cytoskeleton: 1. how are lengths of microtubule polymers matched to their cellular functions? 2. how are individual microtubules organized into complex structures like mitotic spindles? I focused on a universal microtubule length regulator kinesin-8. I discovered a tethering mechanism explaining the super-processivity of kinesin-8 on microtubules, which is essential for the motor to reach microtubule ends to control microtubule length and promotes chromosome congression during mitosis. The other part of my graduate work reveals a novel function of kinesin-8 in organizing microtubules and promoting spindle assembly. Using combined approaches of biochemistry, single molecule imaging and genetics, I found kinesin-8 contains a secondary microtubule binding domain on the tail, which mediates kinesin-8’s microtubule sliding activity in vitro and spindle pole separating function in vivo. These experiences trained me well in comprehensive skills of cell biology and strengthened my confidence in doing basic science as a future career.

    As a postdoctoral fellow in Ron Vale's Lab at UCSF, I have been interested in understanding how protein clustering regulates the T cell receptor signaling, a question remained in the field for almost two decades. I led a team in the HHMI Summer Institute at the Marine Biological Laboratory to develop an in vitro reconstitution system for studying the mechanisms and functional consequences of T cell microclusters. We successfully reconstituted a TCR-LAT-actin signaling pathway on a synthetic membrane using 12 purified proteins. We found that T cell microclusters are phase separated structures formed through multivalent protein-protein interactions. These clusters enrich kinases but exclude phosphatases, thus promoting phosphorylation. The clusters also facilitate actin polymerization by recruiting and organizing actin regulators on the membrane. These findings connected phase transition, a classical phenomenon in physical chemistry, to the cell signaling field and provided a new perspective in understanding the mechanism of signal transduction.

    My future research will follow two directions. 1. engineering T cell activation responses. My previous work suggested T cell activation is affected by protein clustering. I am developing an inducible protein clustering system based on the SunTag technology, aiming to alter the threshold of T cell activation. This will help to understand how T cells differentially respond to foreign versus self antigens. It could also provide new tools for T cell-based cancer immunotherapy. 2. Understanding endomembrane signaling. Cell surface signaling pathways have been well-studied whereas our knowledge about signaling events on the endomembrane system is very limited. I will use the in vitro reconstitution system I developed, together with live cell imaging to investigate the spatial organization of receptors, kinases, and phosphatase on the membrane of endoplasmic reticulum and nuclear envelope. I aim to understand how the interactions of these proteins regulate calcium flux, lipid transport, and transcription.

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    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.
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    1. Hui E, Cheung J, Zhu J, Su X, Taylor MJ, Wallweber HA, Sasmal DK, Huang J, Kim JM, Mellman I, Vale RD. T cell costimulatory receptor CD28 is a primary target for PD-1-mediated inhibition. Science. 2017 03 31; 355(6332):1428-1433. PMID: 28280247.
      View in: PubMed
    2. Su X, Ditlev JA, Hui E, Xing W, Banjade S, Okrut J, King DS, Taunton J, Rosen MK, Vale RD. Phase separation of signaling molecules promotes T cell receptor signal transduction. Science. 2016 Apr 29; 352(6285):595-9. PMID: 27056844; PMCID: PMC4892427 [Available on 10/29/16].
    3. Su X, Arellano-Santoyo H, Portran D, Gaillard J, Vantard M, Thery M, Pellman D. Microtubule-sliding activity of a kinesin-8 promotes spindle assembly and spindle-length control. Nat Cell Biol. 2013 Aug; 15(8):948-57. PMID: 23851487; PMCID: PMC3767134.
    4. Su X, Ohi R, Pellman D. Move in for the kill: motile microtubule regulators. Trends Cell Biol. 2012 Nov; 22(11):567-75. PMID: 22959403; PMCID: PMC3482944.
    5. Su X, Qiu W, Gupta ML, Pereira-Leal JB, Reck-Peterson SL, Pellman D. Mechanisms underlying the dual-mode regulation of microtubule dynamics by Kip3/kinesin-8. Mol Cell. 2011 Sep 02; 43(5):751-63. PMID: 21884976; PMCID: PMC3181003.
    6. Wang Q, Teng J, Shen B, Zhang W, Guo Y, Su X, Zhang C, Yu AC, Chen J. Characterization of kinesin-like proteins in silkworm posterior silk gland cells. Cell Res. 2010 Jun; 20(6):713-27. PMID: 20368730.
      View in: PubMed
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