Dr. Glavy studies the molecular mechanisms of the mitotic breakdown of the nuclear pore complex (NPC), with a focus on the effects of cell-cycle-dependent modifications on the regulation of nucleoporins.
His Lab analyzes the NPC; which is the principal passageway for nucleocytoplasmic macromolecular traffic. It is composed of about 30 proteins, termed nucleoporins (Nups) designated by their molecular weights in kilodaltons. These are organized into a pseudo-symmetric structure with a two-fold plane quasi-parallel to the nuclear envelope and an eight-fold axis of symmetry across the nucleo-cytoplasmic axis. Most of the Nups are part of a symmetric core structure and therefore occur in at least 16 copies per NPC. Others are present only on either the cytoplasmic or the nucleoplasmic side and are present in eight copies per NPC.
FG Nups are targets of at least nine chromosomal rearrangements found in leukemia, primarily in acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS). These chromosomal translocations further effect other related Nups, such as Nup107 and Nup133, demonstrating their interdependence which is critical during cell division. The NPC is disassembled into subcomplexes of Nups during open mitosis in higher eukaryotic cells. Mitotic disassembly is thought to be triggered by phosphorylation. The best characterized subcomplex is the vertebrate Nup107-160 and the homologous Nup84 subcomplex in Saccharomyces cerevisiae. The Nup107-160 subcomplex has 9 members (Nup160, Nup133, Nup107, Nup96, Nup75, Nup43, Nup37, Seh1 and Sec 13. In the “protocoatomer” hypothesis, this nonameric complex has been proposed to stabilize the sharp bend between the inner and outer nuclear envelope membrane.
K.H. Bui, A. von Appen, A. L. DiGuilio, L. Sparks, M. Mackmull, T. Bock, W. Hagen, A. Andrés-Pons, J. S. Glavy, and M. Beck. (Dec 5, 2013). Integrated Structural Analysis of the Human Nuclear Pore Complex Scaffold, Cell, cover. 155 (6), 1233-1243. Article Link
Kaur, S., White, T.E., DiGuilio, A.L., Glavy, J.S.. (Aug 1, 2010). The Discovery of a Werner Helicase Interacting Protein (WHIP) Association with the Nuclear Pore Complex, Cell Cycle, 9 (15), 3106-3111
Blethrow, J.D., Glavy, J.S. Morgan, D.O., and Shokat K.M.. ( 2008). Covalent capture of kinase-specific phosphopeptides reveals Cdk1-cyclin B substrates, PNAS, 105 1442-1447
Glavy, J. S., Krutchinsky, A., Cristea, I.M., Berke, I.C., Boehmer, T., Blobel, G. and Chait, B.T. ( 2007). Cell-Cycle Dependent Phosphorylation of the Nuclear Pore Nup107-160 Subcomplex, PNAS, 104 3811-3816
Selected Recent Publications
Glavy, J. S.. (Jun 15, 2010). The Discovery of a Werner Helicase Interacting Protein (WHIP) Association with the Nuclear Pore Complex, EMBL Heidelberg, Germany. EMBL Seminar
Glavy, J.S.. ( 2009). Nuclear Pore Complex, The Liver: Biology and Pathobiology, John Wiley & Sons Press. in press
Blethrow, J.D. and Glavy, J.S.. ( 2009). Purification of Cdk1-Cyclin B Kinase Targeted Phosphopeptides from the Nuclear Envelope, Methods in Molecular Biology: Nuclear Envelope: Methods and Protocols, The Humana Press Inc.. in press
Glavy, J. S.. (Aug 25, 2009). The Cell-Cycle Dependent Phosphorylation of the Nup107-160 Subcomplex, International Meeting on Nuclear Trafficking