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Enfu Hui

Research

As an essential part of the immune system, T cells are able to recognize and destroy tumorous and virus infected cells. T cell mediated immunity is dictated by signals transduced through many different receptors on its surface that binds to their respective ligands from the target cell. One type of signal is generated by the T cell antigen receptor (TCR) which recognizes peptide antigens (Signal 1). The second type of signal comes from a number of coreceptors that regulate the T cell mediated immune response either positively or negatively (Signal 2). Cancer and viruses are able to hijack some coreceptors to escape immune attack. Perturbation of the coreceptor-ligand interactions using antibodies have proven durable clinical benefit in a variety of cancer indications. Despite the huge clinical success of extracellular antibodies in cancer immunotherapy, the fundamental intracellular mechanisms of coreceptor signaling remain poorly understood. We have developed a membrane reconstitution system to investigate the precise mechanism of T cell signaling. This reconstitution system, combined with live cell imaging and cell culture assays, has allowed us to identify a costimulatory receptor, rather than the TCR, as the major target for the immune checkpoint receptor programmed-cell-death-protein-1 (PD-1), which is a viable cancer immunotherapy target. Currently, the Hui lab at UCSD is in the process of understanding the mechanisms of coreceptor pathways in T cells. Knowledge from our research will guide rational design of immunotherapy.

Publications

  • Hui E, Cheung J, Zhu J, Su X, Taylor MJ, Wallweber HA, Sasmal DK, Huang J, Kim JM, Mellman I, Vale RD. T cell co-stimulatory receptor CD28 is a primary target for PD-1–mediated inhibition. Science. In press
  • 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;352(6285):595-9. doi: 10.1126/science.aad9964.
  • Hui E, Vale RD. In vitro membrane reconstitution of the T-cell receptor proximal signaling network. Nature structural & molecular biology. 2014;21(2):133-42. doi: 10.1038/nsmb.2762
  • Hui E, Gaffaney JD, Wang Z, Johnson CP, Evans CS, Chapman ER. Mechanism and function of synaptotagmin-mediated membrane apposition. Nature structural & molecular biology. 2011;18(7):813-21. doi: 10.1038/nsmb.2075.
  • Zhang Z, Hui E, Chapman ER, Jackson MB. Regulation of exocytosis and fusion pores by synaptotagmin-effector interactions. Molecular biology of the cell. 2010;21(16):2821-31. doi: 10.1091/mbc.E10-04-0285.
  • Zhang Z, Hui E, Chapman ER, Jackson MB. Phosphatidylserine regulation of Ca2+-triggered exocytosis and fusion pores in PC12 cells. Molecular biology of the cell. 2009;20(24):5086-95. doi: 10.1091/mbc.E09-08-0691.
  • Hui E, Johnson CP, Yao J, Dunning FM, Chapman ER. Synaptotagmin-mediated bending of the target membrane is a critical step in Ca(2+)-regulated fusion. Cell. 2009;138(4):709-21. doi: 10.1016/j.cell.2009.05.049.
  • Shahin V, Datta D, Hui E, Henderson RM, Chapman ER, Edwardson JM. Synaptotagmin perturbs the structure of phospholipid bilayers. Biochemistry. 2008;47(7):2143-52. doi: 10.1021/bi701879g. PubMed PMID: 18205405; PubMed Central PMCID: PMC3095487.
  • Paddock BE, Striegel AR, Hui E, Chapman ER, Reist NE. Ca2+-dependent, phospholipid-binding residues of synaptotagmin are critical for excitation-secretion coupling in vivo. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2008;28(30):7458-66. doi: 10.1523/JNEUROSCI.0197-08.2008.
  • Gaffaney JD, Dunning FM, Wang Z, Hui E, Chapman ER. Synaptotagmin C2B domain regulates Ca2+-triggered fusion in vitro: critical residues revealed by scanning alanine mutagenesis. The Journal of biological chemistry. 2008;283(46):31763-75. doi: 10.1074/jbc.M803355200.
  • Chicka MC, Hui E, Liu H, Chapman ER. Synaptotagmin arrests the SNARE complex before triggering fast, efficient membrane fusion in response to Ca2+. Nature structural & molecular biology. 2008;15(8):827-35. doi: 10.1038/nsmb.1463.
  • Hui E, Bai J, Chapman ER. Ca2+-triggered simultaneous membrane penetration of the tandem C2-domains of synaptotagmin I. Biophysical journal. 2006;91(5):1767-77. doi: 10.1529/biophysj.105.080325.
  • Hui E, Bai J, Wang P, Sugimori M, Llinas RR, Chapman ER. Three distinct kinetic groupings of the synaptotagmin family: candidate sensors for rapid and delayed exocytosis. Proceedings of the National Academy of Sciences of the United States of America. 2005;102(14):5210-4. doi: 10.1073/pnas.0500941102.

Biography

Enfu Hui obtained his Ph.D. in 2009 from UW Madison and was a recipient of the American Heart Association Fellowship. He then completed his postdoctoral training at UC San Francisco, supported by postdoctoral fellowships from the Leukemia & Lymphoma Society and Genentech Inc. He joined the Division of Biological Sciences at UC San Diego in July 2016.