One of the most fundamental questions in cell biology is how proteins travel from one intracellular membrane compartment to another (and sometimes get secreted) in a regulated fashion. My laboratory investigates a particularly important membrane-mediated trafficking event that takes place in mast cells.
Mast cells, which are often found in connective and mucosal tissues, play a critical role in innate and adaptive immunity, and have been associated with allergy, autoimmune disease, cardiovascular disorders, and cancer. In response to pathogens and toxins, mast cells rapidly release a wide range of mediators (e.g., histamine) via compound exocytosis/degranulation, a process that comprises two membrane fusion reactions: the homotypic fusion of secretory granules to one another and their heterotypic fusion to the cell surface. These highly regulated fusion reactions, coupled intimately to the signaling cascades, are not well understood at the molecular level, despite the identification of a number of proteins that are involved.
My research team will unravel the catalytic and regulatory machineries of mast cell degranulation, initially building a reconstitution system to identify and characterize important regulators. Our ultimate goals are to combine biochemical, molecular and cell biology approaches to delineate the signaling cascades that control mast cell degranulation, and to establish functional assays for proteins that are potential drug targets for the control of allergic inflammation.
Xu, H and Wickner, W (2012) The N-terminal Domain of the Vacuolar SNARE Vam7p Promotes trans-SNARE Complex Assembly. Proc Natl Acad Sci U S A: 109(44): 17936-17941.
Xu, H, Zick, M, Wickner, W and Jun, Y (2011) A lipid-anchored SNARE supports membrane fusion. Proc Natl Acad Sci U S A 108(42): 17325-17330.
Xu, H and Wickner, W (2010) Phosphoinositides function asymmetrically for membrane fusion, promoting tethering and 3Q-SNARE subcomplex assembly. J Biol Chem 285(50): 39359-39365.
Xu, H, Jun, Y, Thompson, J, Yates J and Wickner, W (2010) HOPS prevents the disassembly of trans-SNARE complexes by Sec17p/Sec18p during membrane fusion. EMBO J 29(12): 1948-1960.
Mima, J, Hickey, C, Xu, H, Jun, Y and Wickner, W (2008) Reconstituted membrane fusion requires regulatory lipids, SNAREs and synergistic SNARE chaperones. EMBO J 27(15): 2031-2042.
Jun, Y, Xu, H, Thorngren, N and Wickner, W (2007) Sec18p and Vam7p remodel trans-SNARE complexes to permit a lipid-anchored R-SNARE to support yeast vacuole fusion. EMBO J 26(24): 4935-4945.
Xu, H and Wickner, W (2006) Bem1p is a positive regulator of the homotypic fusion of yeast vacuoles. J Biol Chem 281(37): 27158-27166.
Xu, H, Brill, JA, Hsien, J, McBride, R, Boulianne, GL and Trimble, WS (2002) Syntaxin 5 is required for cytokinesis and spermatid differentiation in Drosophila. Developmental Biology 251(2): 294-306.
Xu, H, Boulianne, GL and Trimble, WS (2002) Drosophila syntaxin 16 is a Q-SNARE implicated in Golgi dynamics. J Cell Sci 115(23): 4447-4455.
Xu, H, Boulianne, GL and Trimble, WS (2002) Membrane trafficking in cytokinesis. Semin Cell Dev Biol 13(2): 77-82.