Don Cleveland

Summary

Affiliation: University of California
Country: USA

Publications

  1. ncbi request reprint Elevation of the Hsp70 chaperone does not effect toxicity in mouse models of familial amyotrophic lateral sclerosis
    Jian Liu
    Ludwig Institute for Cancer Research and Department of Neurosciences, University of California, San Diego, La Jolla, 92093, USA
    J Neurochem 93:875-82. 2005
  2. ncbi request reprint Determinants of rapid disease progression in ALS
    Koji Yamanaka
    Neurology 65:1859-60. 2005
  3. pmc CENP-E combines a slow, processive motor and a flexible coiled coil to produce an essential motile kinetochore tether
    Yumi Kim
    Ludwig Institute for Cancer Research, University of California, San Diego, La Jolla, CA 92093, USA
    J Cell Biol 181:411-9. 2008
  4. pmc Esperanto for histones: CENP-A, not CenH3, is the centromeric histone H3 variant
    W C Earnshaw
    Wellcome Trust Centre for Cell Biology, University of Edinburgh, Mayfield Road, Edinburgh, Scotland, UK
    Chromosome Res 21:101-6. 2013
  5. pmc Beyond nuclear transport. Ran-GTP as a determinant of spindle assembly
    J A Kahana
    Ludwig Institute for Cancer Research and Departments of Medicine and Neuroscience, University of California at San Diego School of Medicine, La Jolla, California 92093 0660, USA
    J Cell Biol 146:1205-10. 1999
  6. pmc CENP-meta, an essential kinetochore kinesin required for the maintenance of metaphase chromosome alignment in Drosophila
    J K Yucel
    Ludwig Institute for Cancer Research, University of California, San Diego, La Jolla, California 92093, USA
    J Cell Biol 150:1-11. 2000
  7. pmc Chaperone-facilitated copper binding is a property common to several classes of familial amyotrophic lateral sclerosis-linked superoxide dismutase mutants
    L B Corson
    Predoctoral Program in Human Genetics, Johns Hopkins University, Baltimore, MD 21205, USA
    Proc Natl Acad Sci U S A 95:6361-6. 1998
  8. ncbi request reprint Centromeres and kinetochores: from epigenetics to mitotic checkpoint signaling
    Don W Cleveland
    Ludwig Institute for Cancer Research and Department of Cellular and Molecular Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
    Cell 112:407-21. 2003
  9. ncbi request reprint Progressive spinal axonal degeneration and slowness in ALS2-deficient mice
    Koji Yamanaka
    Ludwig Institute for Cancer Research and Department of Medicine and Neurosciences, University of California, San Diego, La Jolla, 92093 0670, USA
    Ann Neurol 60:95-104. 2006
  10. ncbi request reprint Centromere identity maintained by nucleosomes assembled with histone H3 containing the CENP-A targeting domain
    Ben E Black
    Ludwig Institute for Cancer Research, University of California, San Diego, La Jolla, CA 92093, USA
    Mol Cell 25:309-22. 2007

Research Grants

  1. Mammalian Centromere Assembly
    Don Cleveland; Fiscal Year: 2007
  2. Mammalian Centromere Assembly
    Don Cleveland; Fiscal Year: 2009
  3. Mammalian Centromere Assembly
    Don W Cleveland; Fiscal Year: 2010
  4. MICROTUBULE REGULATION
    Don W Cleveland; Fiscal Year: 2010
  5. MICROTUBULE REGULATION
    Don Cleveland; Fiscal Year: 2009
  6. Neurofilaments, SOD1 and Motor Neuron Diseases
    Don Cleveland; Fiscal Year: 2007
  7. MICROTUBULE REGULATION
    Don Cleveland; Fiscal Year: 2007
  8. Neurofilaments, SOD1 and Motor Neuron Diseases
    Don Cleveland; Fiscal Year: 2004
  9. NEUROFILAMENTS, SOD1 AND MOTOR NEURON DISEASE
    Don Cleveland; Fiscal Year: 2000

Collaborators

Detail Information

Publications87

  1. ncbi request reprint Elevation of the Hsp70 chaperone does not effect toxicity in mouse models of familial amyotrophic lateral sclerosis
    Jian Liu
    Ludwig Institute for Cancer Research and Department of Neurosciences, University of California, San Diego, La Jolla, 92093, USA
    J Neurochem 93:875-82. 2005
    ..Therefore, increasing Hsp70 to a level that is protective in mouse models of acute ischemic insult and selected neurodegenerative disorders is not sufficient to ameliorate mutant SOD1-mediated toxicity...
  2. ncbi request reprint Determinants of rapid disease progression in ALS
    Koji Yamanaka
    Neurology 65:1859-60. 2005
  3. pmc CENP-E combines a slow, processive motor and a flexible coiled coil to produce an essential motile kinetochore tether
    Yumi Kim
    Ludwig Institute for Cancer Research, University of California, San Diego, La Jolla, CA 92093, USA
    J Cell Biol 181:411-9. 2008
    ..We propose that the highly processive microtubule-dependent motor activity of CENP-E serves to power chromosome congression and provides a flexible, motile tether linking kinetochores to dynamic spindle microtubules...
  4. pmc Esperanto for histones: CENP-A, not CenH3, is the centromeric histone H3 variant
    W C Earnshaw
    Wellcome Trust Centre for Cell Biology, University of Edinburgh, Mayfield Road, Edinburgh, Scotland, UK
    Chromosome Res 21:101-6. 2013
    ....
  5. pmc Beyond nuclear transport. Ran-GTP as a determinant of spindle assembly
    J A Kahana
    Ludwig Institute for Cancer Research and Departments of Medicine and Neuroscience, University of California at San Diego School of Medicine, La Jolla, California 92093 0660, USA
    J Cell Biol 146:1205-10. 1999
  6. pmc CENP-meta, an essential kinetochore kinesin required for the maintenance of metaphase chromosome alignment in Drosophila
    J K Yucel
    Ludwig Institute for Cancer Research, University of California, San Diego, La Jolla, California 92093, USA
    J Cell Biol 150:1-11. 2000
    ....
  7. pmc Chaperone-facilitated copper binding is a property common to several classes of familial amyotrophic lateral sclerosis-linked superoxide dismutase mutants
    L B Corson
    Predoctoral Program in Human Genetics, Johns Hopkins University, Baltimore, MD 21205, USA
    Proc Natl Acad Sci U S A 95:6361-6. 1998
    ....
  8. ncbi request reprint Centromeres and kinetochores: from epigenetics to mitotic checkpoint signaling
    Don W Cleveland
    Ludwig Institute for Cancer Research and Department of Cellular and Molecular Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
    Cell 112:407-21. 2003
    ....
  9. ncbi request reprint Progressive spinal axonal degeneration and slowness in ALS2-deficient mice
    Koji Yamanaka
    Ludwig Institute for Cancer Research and Department of Medicine and Neurosciences, University of California, San Diego, La Jolla, 92093 0670, USA
    Ann Neurol 60:95-104. 2006
    ..The goal of this study was to elucidate how the motor system is affected by the deletion of ALS2...
  10. ncbi request reprint Centromere identity maintained by nucleosomes assembled with histone H3 containing the CENP-A targeting domain
    Ben E Black
    Ludwig Institute for Cancer Research, University of California, San Diego, La Jolla, CA 92093, USA
    Mol Cell 25:309-22. 2007
    ..These data offer direct support for centromere identity maintained by a unique nucleosome that serves to distinguish the centromere from the rest of the chromosome...
  11. pmc Centromere-associated protein-E is essential for the mammalian mitotic checkpoint to prevent aneuploidy due to single chromosome loss
    Beth A A Weaver
    Ludwig Institute for Cancer Research, 3080 CMM East, 9500 Gilman Drive, La Jolla, CA 92093 0670, USA
    J Cell Biol 162:551-63. 2003
    ..Thus, CENP-E is required for enhancing recruitment of its binding partner BubR1 to each unattached kinetochore and for stimulating BubR1 kinase activity, implicating it as an essential amplifier of a basal mitotic checkpoint signal...
  12. ncbi request reprint The neuroprotective factor Wlds does not attenuate mutant SOD1-mediated motor neuron disease
    Christine Vande Velde
    Ludwig Institute for Cancer Research and Departments of Medicine and Neuroscience, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
    Neuromolecular Med 5:193-203. 2004
    ..However, presynaptic endings in both the presence and absence of Wld(s) showed high accumulations of mitochondria and synaptic vesicles, implicating errors of retrograde transport as a consequence of SOD1-mutant damage to axons...
  13. pmc Toxicity from different SOD1 mutants dysregulates the complement system and the neuronal regenerative response in ALS motor neurons
    Christian S Lobsiger
    Ludwig Institute and Department of Medicine, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
    Proc Natl Acad Sci U S A 104:7319-26. 2007
    ..Alteration of these mutant SOD1-induced pathways identified a set of targets for therapies for inherited ALS...
  14. pmc Altered axonal architecture by removal of the heavily phosphorylated neurofilament tail domains strongly slows superoxide dismutase 1 mutant-mediated ALS
    Christian S Lobsiger
    Ludwig Institute for Cancer Research and Department of Medicine, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
    Proc Natl Acad Sci U S A 102:10351-6. 2005
    ....
  15. pmc Astrocytes as determinants of disease progression in inherited amyotrophic lateral sclerosis
    Koji Yamanaka
    Ludwig Institute for Cancer Research and Department of Medicine and Neuroscience, University of California at San Diego, 9500 Gilman Drive, La Jolla, California 92093 0670, USA
    Nat Neurosci 11:251-3. 2008
    ..These findings demonstrate that mutant astrocytes are viable targets for therapies for slowing the progression of non-cell autonomous killing of motor neurons in ALS...
  16. ncbi request reprint Mutant SOD1 causes motor neuron disease independent of copper chaperone-mediated copper loading
    Jamuna R Subramaniam
    Department of Pathology, The Johns Hopkins University School of Medicine, 558 Ross Research Building, 720 Rutland Avenue, Baltimore, Maryland 21205, USA
    Nat Neurosci 5:301-7. 2002
    ..Hence, CCS-dependent copper loading of mutant SOD1 plays no role in the pathogenesis of motor neuron disease in these mouse models...
  17. ncbi request reprint Onset and progression in inherited ALS determined by motor neurons and microglia
    Severine Boillee
    Ludwig Institute for Cancer Research and Departments of Medicine and Neuroscience, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
    Science 312:1389-92. 2006
    ....
  18. pmc Mutant dynein (Loa) triggers proprioceptive axon loss that extends survival only in the SOD1 ALS model with highest motor neuron death
    Hristelina S Ilieva
    Ludwig Institute for Cancer Research, University of California at San Diego, La Jolla, CA 92093, USA
    Proc Natl Acad Sci U S A 105:12599-604. 2008
    ..These findings support a noncell autonomous, excitotoxic contribution from proprioceptive sensory neurons that modestly accelerates disease onset in inherited ALS...
  19. ncbi request reprint Medicine. Treating neurodegenerative diseases with antibiotics
    Timothy M Miller
    Ludwig Institute for Cancer Research and the Department of Medicine and Neurosciences, University of California, San Diego, La Jolla, CA 92093, USA
    Science 307:361-2. 2005
  20. pmc Non-cell autonomous toxicity in neurodegenerative disorders: ALS and beyond
    Hristelina Ilieva
    Ludwig Institute for Cancer Research and Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA
    J Cell Biol 187:761-72. 2009
    ....
  21. ncbi request reprint The human CENP-A centromeric nucleosome-associated complex
    Daniel R Foltz
    Ludwig Institute for Cancer Research, University of California at San Diego, La Jolla, CA 92093 0670, USA
    Nat Cell Biol 8:458-69. 2006
    ..The CENP-A NAC is essential, as disruption of the complex causes errors of chromosome alignment and segregation that preclude cell survival despite continued centromere-derived mitotic checkpoint signalling...
  22. ncbi request reprint Toxicity of familial ALS-linked SOD1 mutants from selective recruitment to spinal mitochondria
    Jian Liu
    Ludwig Institute for Cancer Research, Department of Neurosciences, Medicine, and Cellular and Molecular Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
    Neuron 43:5-17. 2004
    ..These findings implicate damage from action of spinal cord-specific factors that recruit mutant SOD1 to spinal mitochondria as the basis for their selective toxicity in ALS...
  23. pmc Mutant SOD1 in cell types other than motor neurons and oligodendrocytes accelerates onset of disease in ALS mice
    Koji Yamanaka
    Ludwig Institute for Cancer Research and Department of Medicine and Neuroscience, University of California at San Diego, La Jolla, CA 92093, USA
    Proc Natl Acad Sci U S A 105:7594-9. 2008
    ..Disease onset is therefore non-cell autonomous, and mutant SOD1 damage within cell types other than motor neurons and oligodendrocytes is a central contributor to initiation of motor neuron degeneration...
  24. ncbi request reprint ALS: a disease of motor neurons and their nonneuronal neighbors
    Severine Boillee
    Ludwig Institute for Cancer Research and Departments of Medicine and Neuroscience, University of California, San Diego, La Jolla, California 92093, USA
    Neuron 52:39-59. 2006
    ..Damage within motor neurons is enhanced by damage incurred by nonneuronal neighboring cells, via an inflammatory response that accelerates disease progression. These findings validate therapeutic approaches aimed at nonneuronal cells...
  25. pmc Misfolded mutant SOD1 directly inhibits VDAC1 conductance in a mouse model of inherited ALS
    Adrian Israelson
    Ludwig Institute for Cancer Research and Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA 92093 0670, USA
    Neuron 67:575-87. 2010
    ..Taken together, our results establish a direct link between misfolded mutant SOD1 and mitochondrial dysfunction in this form of inherited ALS...
  26. pmc Revisiting oxidative damage in ALS: microglia, Nox, and mutant SOD1
    Severine Boillee
    Ludwig Institute for Cancer Research, Department of Medicine, and Department of Neuroscience, UCSD, La Jolla, California 92030, USA
    J Clin Invest 118:474-8. 2008
    ..Diminishing ROS by treatment with the microglial Nox inhibitor apocynin or by elimination of Nox extends survival in ALS mice, reviving the proposal that ROS mediate ALS pathogenesis, but with a new twist: it's ROS produced by microglia...
  27. pmc Gene transfer demonstrates that muscle is not a primary target for non-cell-autonomous toxicity in familial amyotrophic lateral sclerosis
    Timothy M Miller
    Ludwig Institute for Cancer Research, La Jolla, CA 92093, USA
    Proc Natl Acad Sci U S A 103:19546-51. 2006
    ..Thus, SOD1-mutant-mediated damage within muscles is not a significant contributor to non-cell-autonomous pathogenesis in ALS, and enhancing muscle mass and strength provides no benefit in slowing disease onset or progression...
  28. pmc Selective association of misfolded ALS-linked mutant SOD1 with the cytoplasmic face of mitochondria
    Christine Vande Velde
    Ludwig Institute and Departments of Medicine and Neuroscience, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093 0670, USA
    Proc Natl Acad Sci U S A 105:4022-7. 2008
    ....
  29. pmc Propagation of centromeric chromatin requires exit from mitosis
    Lars E T Jansen
    Ludwig Institute for Cancer Research and Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA
    J Cell Biol 176:795-805. 2007
    ....
  30. ncbi request reprint Amyotrophic lateral sclerosis and gene therapy
    Timothy M Miller
    Department of Neurosciences, Ludwig Institute for Cancer Research, University of California, San Diego, La Jolla, CA 92093 0670, USA
    Nat Clin Pract Neurol 2:462-3. 2006
  31. pmc Schwann cells expressing dismutase active mutant SOD1 unexpectedly slow disease progression in ALS mice
    Christian S Lobsiger
    Department of Medicine and Neuroscience, Ludwig Institute for Cancer Research, University of California at San Diego, La Jolla, CA 92093, USA
    Proc Natl Acad Sci U S A 106:4465-70. 2009
    ..Thus, therapeutic down-regulation of dismutase active mutant SOD1 in familial forms of ALS should be targeted away from Schwann cells...
  32. ncbi request reprint Does aneuploidy cause cancer?
    Beth A A Weaver
    Ludwig Institute for Cancer Research, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093 0670, USA
    Curr Opin Cell Biol 18:658-67. 2006
    ..Cumulatively, the current evidence suggests that aneuploidy promotes tumorigenesis, at least at low frequency, but a definitive test has not yet been reported...
  33. pmc Unattached kinetochores catalyze production of an anaphase inhibitor that requires a Mad2 template to prime Cdc20 for BubR1 binding
    Anita Kulukian
    Ludwig Institute for Cancer Research, University of California at San Diego, La Jolla, CA 92093, USA
    Dev Cell 16:105-17. 2009
    ..Our results support a model in which immobilized Mad1/Mad2 at kinetochores provides a template for initial assembly of Mad2 bound to Cdc20 that is then converted to a final mitotic checkpoint inhibitor with Cdc20 bound to BubR1...
  34. ncbi request reprint Comment on "A centrosome-independent role for gamma-TuRC proteins in the spindle assembly checkpoint"
    Beth A A Weaver
    Ludwig Institute for Cancer Research and Department of Cellular and Molecular Medicine, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093 0670, USA
    Science 316:982; author reply 982. 2007
    ....
  35. pmc Centromere-specific assembly of CENP-a nucleosomes is mediated by HJURP
    Daniel R Foltz
    Ludwig Institute for Cancer Research, La Jolla, CA 92093 0670, USA
    Cell 137:472-84. 2009
    ..We propose HJURP to be a cell-cycle-regulated CENP-A-specific histone chaperone required for centromeric chromatin assembly...
  36. pmc Microtubule capture by CENP-E silences BubR1-dependent mitotic checkpoint signaling
    Yinghui Mao
    Ludwig Institute for Cancer Research, University of California at San Diego, La Jolla, CA 92093, USA
    J Cell Biol 170:873-80. 2005
    ..Together, this reveals that CENP-E is the signal transducing linker responsible for silencing BubR1-dependent mitotic checkpoint signaling through its capture at kinetochores of spindle microtubules...
  37. ncbi request reprint Unstable kinetochore-microtubule capture and chromosomal instability following deletion of CENP-E
    Frances R Putkey
    Ludwig Institute for Cancer Research, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
    Dev Cell 3:351-65. 2002
    ..CENP-E is thus essential for the maintenance of chromosomal stability through efficient stabilization of microtubule capture at kinetochores...
  38. pmc Abnormal neurofilament transport caused by targeted disruption of neuronal kinesin heavy chain KIF5A
    Chun hong Xia
    Department of Cellular and Molecular Medicine, Howard Hughes Medical Institute, University of California, San Diego, La Jolla, CA 92093 0683, USA
    J Cell Biol 161:55-66. 2003
    ..These data support the hypothesis that a conventional kinesin plays a role in the microtubule-dependent slow axonal transport of at least one cargo, the NF proteins...
  39. ncbi request reprint Activating and silencing the mitotic checkpoint through CENP-E-dependent activation/inactivation of BubR1
    Yinghui Mao
    Ludwig Institute for Cancer Research, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
    Cell 114:87-98. 2003
    ..This supports bifunctional roles for BubR1 in the checkpoint: an enzymatic one requiring CENP-E-dependent activation of its kinase activity at kinetochores and a stoichiometric one as a direct inhibitor of Cdc20...
  40. pmc A chemical tool box defines mitotic and interphase roles for Mps1 kinase
    Weijie Lan
    Ludwig Institute for Cancer Research, Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA
    J Cell Biol 190:21-4. 2010
    ....
  41. pmc Unstable mutants in the peripheral endosomal membrane component ALS2 cause early-onset motor neuron disease
    Koji Yamanaka
    Ludwig Institute for Cancer Research and Departments of Medicine and Neuroscience, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
    Proc Natl Acad Sci U S A 100:16041-6. 2003
    ..Thus, mutations in the ALS2 gene linked to early-onset motor neuron disease uniformly produce loss of activity through decreased protein stability of this endosomal GEF...
  42. ncbi request reprint Gene therapy for ALS delivers
    Severine Boillee
    Ludwig Institute for Cancer Research and Departments of Cellular and Molecular Medicine and Neurosciences, University of California, 9500 Gilman Drive, La Jolla, CA 92093 0670, USA
    Trends Neurosci 27:235-8. 2004
    ..With the clinical safety of both IGF-1 and AAV already established, this provides real hope for an effective treatment of ALS...
  43. pmc Lethality to human cancer cells through massive chromosome loss by inhibition of the mitotic checkpoint
    Geert J P L Kops
    Ludwig Institute for Cancer Research and Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA 92093 0670, USA
    Proc Natl Acad Sci U S A 101:8699-704. 2004
    ..Thus, suppression of mitotic checkpoint signaling is invariably lethal as the consequence of massive chromosome loss, findings that have implications for inhibiting proliferation of tumor cells...
  44. ncbi request reprint Structural determinants for generating centromeric chromatin
    Ben E Black
    Ludwig Institute for Cancer Research, University of California, San Diego, La Jolla, California 92093, USA
    Nature 430:578-82. 2004
    ..Thus, the centromere-targeting domain of CENP-A confers a unique structural rigidity to the nucleosomes into which it assembles, and is likely to have a role in maintaining centromere identity...
  45. ncbi request reprint Mutations in neurofilament genes are not a significant primary cause of non-SOD1-mediated amyotrophic lateral sclerosis
    Michael L Garcia
    Ludwig Institute for Cancer Research and Department of Neurosciences, University of California at San Diego, 9500 Gilman Drive, CMM E Room 3072, La Jolla, CA 92093 0670, USA
    Neurobiol Dis 21:102-9. 2006
    ..Thus, mutations in neurofilaments are possible risk factors that may contribute to pathogenesis in ALS in conjunction with one or more additional genetic or environmental factors, but are not significant primary causes of ALS...
  46. pmc Requirements for NuMA in maintenance and establishment of mammalian spindle poles
    Alain D Silk
    Ludwig Institute for Cancer Research, Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA
    J Cell Biol 184:677-90. 2009
    ..Thus, NuMA is a defining feature of the mammalian spindle pole and functions as an essential tether linking bulk microtubules of the spindle to centrosomes...
  47. pmc ZW10 links mitotic checkpoint signaling to the structural kinetochore
    Geert J P L Kops
    Ludwig Institute for Cancer Research and Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA 92093, USA
    J Cell Biol 169:49-60. 2005
    ..Thus, ZW10 functions as a linker between the core structural elements of the outer kinetochore and components that catalyze generation of the mitotic checkpoint-derived "stop anaphase" inhibitor...
  48. pmc Virus-delivered small RNA silencing sustains strength in amyotrophic lateral sclerosis
    Timothy M Miller
    Ludwig Institute for Cancer Research, University of California, San Diego, USA
    Ann Neurol 57:773-6. 2005
    ....
  49. pmc An epigenetic mark generated by the incorporation of CENP-A into centromeric nucleosomes
    Ben E Black
    Ludwig Institute for Cancer Research, University of California at San Diego, La Jolla, CA 92093, USA
    Proc Natl Acad Sci U S A 104:5008-13. 2007
    ..Thus, the targeting information directing CENP-A deposition at the centromere produces a structurally distinct nucleosome, supporting a CENP-A-driven self-assembly mechanism that mediates maintenance of centromere identity...
  50. pmc Rethinking ALS: the FUS about TDP-43
    Clotilde Lagier-Tourenne
    Department of Cellular and Molecular Medicine, University of California San Diego, Ludwig Institute for Cancer Research, La Jolla, CA 92093 0670, USA
    Cell 136:1001-4. 2009
    ..TDP-43 and FUS/TLS have striking structural and functional similarities, implicating alterations in RNA processing as a key event in ALS pathogenesis...
  51. pmc ALS-associated mutations in TDP-43 increase its stability and promote TDP-43 complexes with FUS/TLS
    Shuo Chien Ling
    Ludwig Institute for Cancer Research and Department of Neuroscience, University of California at San Diego, La Jolla, CA 92093 0670, USA
    Proc Natl Acad Sci U S A 107:13318-23. 2010
    ..Taken together, abnormal stability of mutant TDP-43 and its enhanced binding to normal FUS/TLS imply a convergence of pathogenic pathways from mutant TDP-43 and FUS/TLS in ALS...
  52. pmc Aurora kinases and protein phosphatase 1 mediate chromosome congression through regulation of CENP-E
    Yumi Kim
    Ludwig Institute for Cancer Research, University of California, San Diego, La Jolla, CA 92093, USA
    Cell 142:444-55. 2010
    ....
  53. pmc Aneuploidy: instigator and inhibitor of tumorigenesis
    Beth A A Weaver
    Ludwig Institute for Cancer Research and Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA 92093 0670, USA
    Cancer Res 67:10103-5. 2007
    ..These findings confirm that aneuploidy can act oncogenically and reveal a previously unsuspected role for aneuploidy as a tumor suppressor...
  54. pmc Polo-like kinase 4 kinase activity limits centrosome overduplication by autoregulating its own stability
    Andrew J Holland
    Ludwig Institute for Cancer Research, La Jolla, CA, USA
    J Cell Biol 188:191-8. 2010
    ..We propose that kinase-mediated, autoregulated instability of Plk4 self-limits Plk4 activity so as to prevent centrosome amplification...
  55. pmc Boveri revisited: chromosomal instability, aneuploidy and tumorigenesis
    Andrew J Holland
    Ludwig Institute for Cancer Research and Department of Cellular and Molecular Medicine, University of California, 9500 Gilman Drive, San Diego, La Jolla, California 92093 0670, USA
    Nat Rev Mol Cell Biol 10:478-87. 2009
    ..A clearer understanding of the tumour suppressive function of aneuploidy might reveal new avenues for anticancer therapy...
  56. pmc Double-strand DNA breaks recruit the centromeric histone CENP-A
    Samantha G Zeitlin
    Ludwig Institute for Cancer Research, Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA 92093, USA
    Proc Natl Acad Sci U S A 106:15762-7. 2009
    ..Finally, since cell survival after radiation-induced DNA damage correlates with CENP-A expression level, we propose that CENP-A may have a function in DNA repair...
  57. pmc Removal of Spindly from microtubule-attached kinetochores controls spindle checkpoint silencing in human cells
    Reto Gassmann
    Ludwig Institute for Cancer Research Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, California 92093, USA
    Genes Dev 24:957-71. 2010
    ..In the absence of Spindly, a second mechanism silences the checkpoint; this mechanism is likely evolutionarily ancient, as fungi and higher plants lack kinetochore dynein...
  58. pmc TDP-43 and FUS/TLS: emerging roles in RNA processing and neurodegeneration
    Clotilde Lagier-Tourenne
    Department of Cellular and Molecular Medicine, University of California, La Jolla, CA 92093 6070, USA
    Hum Mol Genet 19:R46-64. 2010
    ..Their association with ALS and other neurodegenerative diseases is redirecting research efforts toward understanding the role of RNA processing regulation in neurodegeneration...
  59. pmc Glial cells as intrinsic components of non-cell-autonomous neurodegenerative disease
    Christian S Lobsiger
    Ludwig Institute for Cancer Research and Department of Medicine and Neurosciences, University of California at San Diego, La Jolla, California 92093, USA
    Nat Neurosci 10:1355-60. 2007
    ..The disease mechanism is non-cell-autonomous, with toxicity derived from glia as a prominent contributor driving disease progression and in some instances even disease initiation...
  60. pmc Antisense oligonucleotide therapy for neurodegenerative disease
    Richard A Smith
    Ludwig Institute for Cancer Research, University of California, San Diego, La Jolla, California, USA
    J Clin Invest 116:2290-6. 2006
    ..This suggests that direct delivery of antisense oligonucleotides could be an effective, dosage-regulatable means of treating neurodegenerative diseases, including ALS, where appropriate target proteins are known...
  61. ncbi request reprint Decoding the links between mitosis, cancer, and chemotherapy: The mitotic checkpoint, adaptation, and cell death
    Beth A A Weaver
    Ludwig Institute for Cancer Research and Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA 92093, USA
    Cancer Cell 8:7-12. 2005
    ..These lead to chronic mitotic arrest from sustained activation of the mitotic checkpoint. Here, we review the linkage between the mitotic checkpoint, aneuploidy, adaptation from mitotic arrest, and antimitotic drug-induced cell death...
  62. pmc Unstable microtubule capture at kinetochores depleted of the centromere-associated protein CENP-F
    Pascale Bomont
    Department of Cellular and Molecular Medicine and Ludwig Institute for Cancer Research, University of California at San Diego, La Jolla, CA 92093, USA
    EMBO J 24:3927-39. 2005
    ..Others rebind YFP-Mad1 intermittently so as to produce 'twinkling', demonstrating cycles of mitotic checkpoint reactivation and silencing and a crucial role for CENP-F in efficient assembly of a stable microtubule-kinetochore interface...
  63. ncbi request reprint Aneuploidy acts both oncogenically and as a tumor suppressor
    Beth A A Weaver
    Ludwig Institute for Cancer Research and Department of Cellular and Molecular Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
    Cancer Cell 11:25-36. 2007
    ..These findings reveal a role of aneuploidy and chromosomal instability in preventing tumorigenesis...
  64. ncbi request reprint Cell biology: nondisjunction, aneuploidy and tetraploidy
    Beth A A Weaver
    Ludwig Institute for Cancer Research and Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, California 92093 0670, USA
    Nature 442:E9-10; discussion E10. 2006
    ..We suggest that chromatin trapped in the cytokinetic cleavage furrow is the more likely reason for furrow regression and tetraploidization...
  65. pmc NF-M is an essential target for the myelin-directed "outside-in" signaling cascade that mediates radial axonal growth
    Michael L Garcia
    Ludwig Institute for Cancer Research, Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA 92093, USA
    J Cell Biol 163:1011-20. 2003
    ..This has revealed that the tail domain of NF-M, with seven KSP motifs, is an essential target for the myelination-dependent outside-in signaling cascade that determines axonal caliber and conduction velocity of motor axons...
  66. pmc RCADiA: simple automation platform for comparative multidimensional protein identification technology
    Aaron O Bailey
    Department of Cell Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, SR11, La Jolla, California 92037, USA
    Anal Chem 79:6410-8. 2007
    ..We demonstrate this device by performing a comparative analysis of mitochondria enriched from rat liver and spinal cord...
  67. ncbi request reprint Has gene therapy for ALS arrived?
    Timothy M Miller
    Nat Med 9:1256-7. 2003
  68. ncbi request reprint Motoneuron death triggered by a specific pathway downstream of Fas. potentiation by ALS-linked SOD1 mutations
    Cedric Raoul
    INSERM U 382, Developmental Biology Institute of Marseille, CNRS INSERM Univ Mediterranee, Campus de Luminy, Case 907, 13288 Marseille Cedex 09, France
    Neuron 35:1067-83. 2002
    ..Thus, triggering of a motoneuron-restricted cell death pathway by neighboring cells might contribute to motoneuron loss in ALS...
  69. ncbi request reprint High molecular weight neurofilament proteins are physiological substrates of adduction by the lipid peroxidation product hydroxynonenal
    Takafumi Wataya
    Institute of Pathology and Departments of Physiology and Biophysics, and Chemistry, Case Western Reserve University, Cleveland, Ohio 44106, USA
    J Biol Chem 277:4644-8. 2002
    ....
  70. ncbi request reprint Hindlimb gait defects due to motor axon loss and reduced distal muscles in a transgenic mouse model of Charcot-Marie-Tooth type 2A
    Scott A Detmer
    Division of Biology, California Institute of Technology, 1200 East California Boulevard, MC114 96, Pasadena, CA 91125, USA
    Hum Mol Genet 17:367-75. 2008
    ..This transgenic line recapitulates key motor features of CMT2A and provides a system to dissect the function of mitochondria in the axons of mammalian motor neurons...
  71. ncbi request reprint Unraveling the mechanisms involved in motor neuron degeneration in ALS
    Lucie I Bruijn
    ALS Association, Guilford, Connecticut 06437, USA
    Annu Rev Neurosci 27:723-49. 2004
    ....
  72. pmc Modest loss of peripheral axons, muscle atrophy and formation of brain inclusions in mice with targeted deletion of gigaxonin exon 1
    Florence Dequen
    CHUL Research Centre and Department of Anatomy and Physiology, Laval University, Quebec City, Quebec, Canada
    J Neurochem 107:253-64. 2008
    ..This new mouse model should provide a useful tool to test potential therapeutic approaches for GAN disease...
  73. pmc Motor neuron disease: The curious ways of ALS
    Magdalini Polymenidou
    Nature 454:284-5. 2008
  74. pmc ALS-causing SOD1 mutants generate vascular changes prior to motor neuron degeneration
    Zhihui Zhong
    Center for Neurodegenerative and Vascular Brain Disorders and Department of Neurosurgery, University of Rochester Medical Center, Kornberg Medical Research Bldg, 601 Elmwood Avenue, Box 670, Rochester, New York 14642, USA
    Nat Neurosci 11:420-2. 2008
    ..SOD1 mutant-mediated endothelial damage accumulated before motor neuron degeneration and the neurovascular inflammatory response occurred, indicating that it was a central contributor to disease initiation...
  75. ncbi request reprint Low rates of aneuploidy promote tumorigenesis while high rates of aneuploidy cause cell death and tumor suppression
    Beth A A Weaver
    Cell Oncol 30:453. 2008
  76. pmc Common molecular signature in SOD1 for both sporadic and familial amyotrophic lateral sclerosis
    Arie Gruzman
    Bioconformatics Laboratory and Department of Neuroscience, California Pacific Medical Center Research Institute, San Francisco, CA 94107, USA
    Proc Natl Acad Sci U S A 104:12524-9. 2007
    ..Our results identify a shared molecular event involving a known target gene and suggest a common step in the pathogenesis between SALS and FALS...
  77. pmc Focal loss of the glutamate transporter EAAT2 in a transgenic rat model of SOD1 mutant-mediated amyotrophic lateral sclerosis (ALS)
    David S Howland
    Department of Molecular Genetics, Wyeth Research, CN8000, Princeton, NJ 08543, USA
    Proc Natl Acad Sci U S A 99:1604-9. 2002
    ..These transgenic rats provide a valuable resource to pursue experimentation and therapeutic development, currently difficult or impossible to perform with existing ALS transgenic mice...
  78. ncbi request reprint CENP-A-containing nucleosomes: easier disassembly versus exclusive centromeric localization
    Natalia Conde e Silva
    Institut Jacques Monod UMR CNRS 7592, 2 place Jussieu, 75251 Paris Cedex 05, France
    J Mol Biol 370:555-73. 2007
    ..This dual relative instability is proposed to facilitate the progressive clearance of CENP-A nucleosomes that assemble promiscuously in euchromatin, especially as is seen following CENP-A transient over-expression...
  79. ncbi request reprint Intercellular miscommunication in polyglutamine pathogenesis
    Christopher A Ross
    Nat Neurosci 9:1205-6. 2006
  80. ncbi request reprint Dynamics of centromere and kinetochore proteins; implications for checkpoint signaling and silencing
    Jagesh V Shah
    Ludwig Institute for Cancer Research, Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA 92093 USA
    Curr Biol 14:942-52. 2004
    ..Mad2 and Cdc20, two candidate proteins for components of a diffusible wait signal, have previously been shown to be recruited to and rapidly released from unattached kinetochores...
  81. ncbi request reprint An immunological epitope selective for pathological monomer-misfolded SOD1 in ALS
    Rishi Rakhit
    Department of Biochemistry, University of Toronto and Ontario Cancer Institute, 101 College Street, Toronto, Ontario M5G 1L7, Canada
    Nat Med 13:754-9. 2007
    ..Despite ubiquitous expression, misfolded SOD1 was found primarily within degenerating motor neurons. Misfolded SOD1 appeared before the onset of symptoms and decreased at the end stage of the disease, concomitant with motor neuron loss...
  82. ncbi request reprint Human Zwint-1 specifies localization of Zeste White 10 to kinetochores and is essential for mitotic checkpoint signaling
    Hongmei Wang
    CAS Key Laboratory for Structure Biology and Hefei National Laboratory for Physical Sciences at Microscale, Hefei 230027, China
    J Biol Chem 279:54590-8. 2004
    ..As ZW10 and Zwint-1 are absent from yeast, we reasoned that metazoans evolved an elaborate spindle checkpoint machinery to ensure faithful chromosome segregation in mitosis...
  83. ncbi request reprint VEGF: multitasking in ALS
    Christine Vande Velde
    Nat Neurosci 8:5-7. 2005
  84. ncbi request reprint On the road to cancer: aneuploidy and the mitotic checkpoint
    Geert J P L Kops
    Laboratory of Experimental Oncology, Department of Medical Oncology, University Medical Center, Utrecht, 3584 CG, The Netherlands
    Nat Rev Cancer 5:773-85. 2005
    ..Defects in the mitotic checkpoint generate aneuploidy and might facilitate tumorigenesis, but more severe disabling of checkpoint signalling is a possible anticancer strategy...
  85. ncbi request reprint Novel missense mutation in ALS2 gene results in infantile ascending hereditary spastic paralysis
    Eleonore Eymard-Pierre
    Institut National de la Sante et de la Recherche M├ędicale U384 and Human Genetics Department, CHU, Clermont Ferrand, France
    Ann Neurol 59:976-80. 2006
    ..The goal of this study is to identify novel disease-causing ALS2 mutations...
  86. ncbi request reprint Neurodegeneration and neuroprotection in multiple sclerosis and other neurodegenerative diseases
    Suhayl Dhib-Jalbut
    UMDNJ Robert Wood Johnson Medical School, New Brunswick, NJ 08901, and The Cleveland Clinic, OH, USA
    J Neuroimmunol 176:198-215. 2006
    ..Elucidating the mechanisms that orchestrate neuronal diseases should facilitate development of neuroprotective and neurorestorative strategies...
  87. pmc Chromosomal instability by inefficient Mps1 auto-activation due to a weakened mitotic checkpoint and lagging chromosomes
    Nannette Jelluma
    Department of Physiological Chemistry and Cancer Genomics Centre, UMC Utrecht, Utrecht, The Netherlands
    PLoS ONE 3:e2415. 2008
    ..Two of the causes of CIN are weakened mitotic checkpoint signaling and persistent merotelic attachments that result in lagging chromosomes during anaphase...

Research Grants27

  1. Mammalian Centromere Assembly
    Don Cleveland; Fiscal Year: 2007
    ....
  2. Mammalian Centromere Assembly
    Don Cleveland; Fiscal Year: 2009
    ..abstract_text> ..
  3. Mammalian Centromere Assembly
    Don W Cleveland; Fiscal Year: 2010
    ....
  4. MICROTUBULE REGULATION
    Don W Cleveland; Fiscal Year: 2010
    ..Finally, since some successful anti-tumor drugs in humans chronically activate the mitotic checkpoint, the mechanisms tha determine cell fate, cell death or adaptation, when so arrested will be determined. ..
  5. MICROTUBULE REGULATION
    Don Cleveland; Fiscal Year: 2009
    ..Finally, since some successful anti-tumor drugs in humans chronically activate the mitotic checkpoint, the mechanisms tha determine cell fate, cell death or adaptation, when so arrested will be determined. ..
  6. Neurofilaments, SOD1 and Motor Neuron Diseases
    Don Cleveland; Fiscal Year: 2007
    ..Finally, following from our discovery of selective mutant association with spinal mitochondria, the mechanism for this and its role in toxicity will be determined with purified components. ..
  7. MICROTUBULE REGULATION
    Don Cleveland; Fiscal Year: 2007
    ..abstract_text> ..
  8. Neurofilaments, SOD1 and Motor Neuron Diseases
    Don Cleveland; Fiscal Year: 2004
    ....
  9. NEUROFILAMENTS, SOD1 AND MOTOR NEURON DISEASE
    Don Cleveland; Fiscal Year: 2000
    ..Experiments will test directly whether the toxic properties of SOD1 mutations arise through an effect on neurofilament accumulation and transport. ..