Albert R La Spada

Summary

Affiliation: University of Washington
Country: USA

Publications

  1. pmc Polyglutamine-expanded androgen receptor truncation fragments activate a Bax-dependent apoptotic cascade mediated by DP5/Hrk
    Jessica E Young
    Department of Laboratory Medicine, University of Washington, Seattle, Washington 98195 7110, USA
    J Neurosci 29:1987-97. 2009
  2. pmc CTCF cis-regulates trinucleotide repeat instability in an epigenetic manner: a novel basis for mutational hot spot determination
    Randell T Libby
    Department of Laboratory Medicine, University of Washington Medical Center, Seattle, WA, USA
    PLoS Genet 4:e1000257. 2008
  3. ncbi request reprint Polyglutamine-expanded ataxin-7 antagonizes CRX function and induces cone-rod dystrophy in a mouse model of SCA7
    A R La Spada
    Department of Laboratory Medicine, University of Washington Medical Center, Seattle, WA 98195, USA
    Neuron 31:913-27. 2001
  4. ncbi request reprint Dynamic mutations on the move in Banff
    Albert R La Spada
    Department of Laboratory Medicine, University of Washington, Box 357110, Room NW120, Seattle, Washington 98195 7110, USA
    Nat Genet 36:667-70. 2004
  5. ncbi request reprint Neurodegeneration: a case of arrested development?
    Albert R La Spada
    Department of Laboratory Medicine, University of Washington, Seattle, WA 98195, USA
    Cell 127:669-71. 2006
  6. pmc Huntington's disease and neurogenesis: FGF-2 to the rescue?
    Albert R La Spada
    Department of Laboratory Medicine, University of Washington Medical Center, Seattle, 98195 7110, USA
    Proc Natl Acad Sci U S A 102:17889-90. 2005
  7. ncbi request reprint Polyglutamines placed into context
    Albert R La Spada
    Department of Laboratory Medicine, Division of Medical Genetics Medicine University of Washington Medical Center, Seattle, WA 98195, USA
    Neuron 38:681-4. 2003
  8. pmc Reduction of mutant ataxin-7 expression restores motor function and prevents cerebellar synaptic reorganization in a conditional mouse model of SCA7
    Stephanie A Furrer
    Departments of Neurology, University of Washington, Seattle, WA 98195, USA
    Hum Mol Genet 22:890-903. 2013
  9. pmc Spinocerebellar ataxia type 7 cerebellar disease requires the coordinated action of mutant ataxin-7 in neurons and glia, and displays non-cell-autonomous bergmann glia degeneration
    Stephanie A Furrer
    Department of Neurology, Biochemistry, University of Washington, Seattle, Washington 98195, USA
    J Neurosci 31:16269-78. 2011
  10. ncbi request reprint Loss of endogenous androgen receptor protein accelerates motor neuron degeneration and accentuates androgen insensitivity in a mouse model of X-linked spinal and bulbar muscular atrophy
    Patrick S Thomas
    Department of Laboratory Medicine, University of Washington Medical Center, Seattle, 98195 7110, USA
    Hum Mol Genet 15:2225-38. 2006

Collaborators

Detail Information

Publications42

  1. pmc Polyglutamine-expanded androgen receptor truncation fragments activate a Bax-dependent apoptotic cascade mediated by DP5/Hrk
    Jessica E Young
    Department of Laboratory Medicine, University of Washington, Seattle, Washington 98195 7110, USA
    J Neurosci 29:1987-97. 2009
    ....
  2. pmc CTCF cis-regulates trinucleotide repeat instability in an epigenetic manner: a novel basis for mutational hot spot determination
    Randell T Libby
    Department of Laboratory Medicine, University of Washington Medical Center, Seattle, WA, USA
    PLoS Genet 4:e1000257. 2008
    ....
  3. ncbi request reprint Polyglutamine-expanded ataxin-7 antagonizes CRX function and induces cone-rod dystrophy in a mouse model of SCA7
    A R La Spada
    Department of Laboratory Medicine, University of Washington Medical Center, Seattle, WA 98195, USA
    Neuron 31:913-27. 2001
    ..Our results suggest that CRX transcription interference accounts for the retinal degeneration in SCA7 and thus may provide an explanation for how cell-type specificity is achieved in this polyglutamine repeat disease...
  4. ncbi request reprint Dynamic mutations on the move in Banff
    Albert R La Spada
    Department of Laboratory Medicine, University of Washington, Box 357110, Room NW120, Seattle, Washington 98195 7110, USA
    Nat Genet 36:667-70. 2004
  5. ncbi request reprint Neurodegeneration: a case of arrested development?
    Albert R La Spada
    Department of Laboratory Medicine, University of Washington, Seattle, WA 98195, USA
    Cell 127:669-71. 2006
    ..Their intriguing results suggest that derailing a transcription program during embryonic development may render adult neurons more susceptible to toxic insults...
  6. pmc Huntington's disease and neurogenesis: FGF-2 to the rescue?
    Albert R La Spada
    Department of Laboratory Medicine, University of Washington Medical Center, Seattle, 98195 7110, USA
    Proc Natl Acad Sci U S A 102:17889-90. 2005
  7. ncbi request reprint Polyglutamines placed into context
    Albert R La Spada
    Department of Laboratory Medicine, Division of Medical Genetics Medicine University of Washington Medical Center, Seattle, WA 98195, USA
    Neuron 38:681-4. 2003
    ..Indeed, an intimate and inextricable relationship may exist between polyglutamine neurotoxicity and the normal interactions, domains, modifications, and functions of the respective disease proteins...
  8. pmc Reduction of mutant ataxin-7 expression restores motor function and prevents cerebellar synaptic reorganization in a conditional mouse model of SCA7
    Stephanie A Furrer
    Departments of Neurology, University of Washington, Seattle, WA 98195, USA
    Hum Mol Genet 22:890-903. 2013
    ....
  9. pmc Spinocerebellar ataxia type 7 cerebellar disease requires the coordinated action of mutant ataxin-7 in neurons and glia, and displays non-cell-autonomous bergmann glia degeneration
    Stephanie A Furrer
    Department of Neurology, Biochemistry, University of Washington, Seattle, Washington 98195, USA
    J Neurosci 31:16269-78. 2011
    ..These findings indicate that SCA7 disease pathogenesis involves a convergence of alterations in a variety of different cell types to fully recapitulate the cerebellar degeneration...
  10. ncbi request reprint Loss of endogenous androgen receptor protein accelerates motor neuron degeneration and accentuates androgen insensitivity in a mouse model of X-linked spinal and bulbar muscular atrophy
    Patrick S Thomas
    Department of Laboratory Medicine, University of Washington Medical Center, Seattle, 98195 7110, USA
    Hum Mol Genet 15:2225-38. 2006
    ..Our studies indicate that SBMA disease pathogenesis, both in the nervous system and the periphery, involves two simultaneous pathways: gain-of-function misfolded protein toxicity and loss of normal protein function...
  11. pmc The zinc-binding domain of Nna1 is required to prevent retinal photoreceptor loss and cerebellar ataxia in Purkinje cell degeneration (pcd) mice
    Lisa Chakrabarti
    Department of Laboratory Medicine, University of Washington Medical Center, Seattle, WA, USA
    Vision Res 48:1999-2005. 2008
    ..In conclusion, Nna1 is required for survival of retinal photoreceptors and other neuron populations that degenerate in pcd mice. A functional zinc-binding domain is crucial for Nna1 to support neuron survival...
  12. ncbi request reprint Genomic context drives SCA7 CAG repeat instability, while expressed SCA7 cDNAs are intergenerationally and somatically stable in transgenic mice
    Randell T Libby
    Department of Laboratory Medicine, University of Washington Medical Center, Seattle, WA 98195 7110, USA
    Hum Mol Genet 12:41-50. 2003
    ..As large somatic repeat expansions are absent from the brains of SCA7 cDNA mice, our results indicate that neurodegeneration can occur without marked somatic mosaicism, at least in these mice...
  13. ncbi request reprint Bergmann glia expression of polyglutamine-expanded ataxin-7 produces neurodegeneration by impairing glutamate transport
    Sara K Custer
    Department of Laboratory Medicine, University of Washington Medical Center, Seattle, Washington 98195, USA
    Nat Neurosci 9:1302-11. 2006
    ..Our studies indicate that impairment of glutamate transport secondary to glial dysfunction contributes to SCA7 neurodegeneration, and suggest a similar role for glial dysfunction in other polyglutamine diseases and SCAs...
  14. pmc Molecular pathogenesis and cellular pathology of spinocerebellar ataxia type 7 neurodegeneration
    Gwenn A Garden
    Department of Neurology, University of Washington, Seattle, Washington 98195 7110, USA
    Cerebellum 7:138-49. 2008
    ....
  15. ncbi request reprint A SCA7 CAG/CTG repeat expansion is stable in Drosophila melanogaster despite modulation of genomic context and gene dosage
    Stephen M Jackson
    Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA
    Gene 347:35-41. 2005
    ..In all cases, perfect repeat stability was preserved, suggesting that Drosophila may not be a suitable system for determining the molecular basis of SCA7 CAG repeat instability...
  16. ncbi request reprint Polyglutamine-expanded ataxin-7 promotes non-cell-autonomous purkinje cell degeneration and displays proteolytic cleavage in ataxic transgenic mice
    Gwenn A Garden
    Department of Neurology, University of Washington Medical Center, Seattle, Washington 98195 7110, USA
    J Neurosci 22:4897-905. 2002
    ..The non-cell-autonomous nature of the Purkinje cell degeneration in our SCA7 mouse model indicates that polyglutamine-induced dysfunction in adjacent or connecting cell types contributes to the neurodegeneration...
  17. pmc Autophagy activation and enhanced mitophagy characterize the Purkinje cells of pcd mice prior to neuronal death
    Lisa Chakrabarti
    Department of Laboratory Medicine, University of Washington, Seattle, WA, USA
    Mol Brain 2:24. 2009
    ..However, our results support a role for dysregulated autophagy activation in pcd, and suggest that increased or aberrant mitophagy contributes to the Purkinje cell degeneration in pcd mice...
  18. ncbi request reprint The Purkinje cell degeneration 5J mutation is a single amino acid insertion that destabilizes Nna1 protein
    Lisa Chakrabarti
    Department of Laboratory Medicine, University of Washington, Seattle, Washington 98195 7110, USA
    Mamm Genome 17:103-10. 2006
    ....
  19. pmc CTCF regulates ataxin-7 expression through promotion of a convergently transcribed, antisense noncoding RNA
    Bryce L Sopher
    Department of Laboratory Medicine, University of Washington, Seattle, WA 98195, USA
    Neuron 70:1071-84. 2011
    ..Discovery of this pathway underscores the importance of altered epigenetic regulation for disease pathology at repeat loci exhibiting bidirectional transcription...
  20. ncbi request reprint Thermoregulatory and metabolic defects in Huntington's disease transgenic mice implicate PGC-1alpha in Huntington's disease neurodegeneration
    Patrick Weydt
    Department of Laboratory Medicine, University of Washington, Seattle, Washington 98195, USA
    Cell Metab 4:349-62. 2006
    ..Finally, HD striatal neurons expressing exogenous PGC-1alpha were resistant to 3-nitropropionic acid treatment. Altered PGC-1alpha function may thus link transcription dysregulation and mitochondrial dysfunction in HD...
  21. ncbi request reprint Androgen receptor YAC transgenic mice recapitulate SBMA motor neuronopathy and implicate VEGF164 in the motor neuron degeneration
    Bryce L Sopher
    Department of Laboratory Medicine, University of Washington Medical Center, Seattle, WA 98195 USA
    Neuron 41:687-99. 2004
    ..Our results suggest that SBMA motor neuronopathy involves altered expression of VEGF, consistent with a role for VEGF as a neurotrophic/survival factor in motor neuron disease...
  22. pmc Intercellular (mis)communication in neurodegenerative disease
    Gwenn A Garden
    Department of Neurology, University of Washington, Seattle, WA 98195, USA
    Neuron 73:886-901. 2012
    ....
  23. pmc Nutrient deprivation induces neuronal autophagy and implicates reduced insulin signaling in neuroprotective autophagy activation
    Jessica E Young
    Department of Laboratory Medicine, Center for Neurogenentics and Neurotherapeutics, University of Washington Medical Center, Seattle, WA 98195, USA
    J Biol Chem 284:2363-73. 2009
    ..Our results indicate that nutrient deprivation can be used to understand the regulatory basis of neuronal autophagy and implicate diminished insulin signaling in the activation of neuronal autophagy...
  24. ncbi request reprint The power of the dark side: Huntington's disease protein and p53 form a deadly alliance
    Albert R La Spada
    Department of Laboratory Medicine, University of Washington, Seattle, WA 98195, USA
    Neuron 47:1-3. 2005
    ..In this issue of Neuron, Bae et al. present data implicating p53 in HD pathogenesis. This intriguing study may thus provide a link between nuclear transcription dysregulation and mitochondrial abnormalities in HD...
  25. ncbi request reprint Beta-synuclein modulates alpha-synuclein neurotoxicity by reducing alpha-synuclein protein expression
    Yuxin Fan
    Department of Laboratory Medicine, University of Washington Medical Center, Seattle, WA, USA
    Hum Mol Genet 15:3002-11. 2006
    ..As increased expression of alpha-synuclein may cause or contribute to PD pathogenesis in sporadic and familial forms of disease, this observation has important implications for the development of therapies for PD...
  26. ncbi request reprint Familial dementia with lewy bodies: a clinical and neuropathological study of 2 families
    Debby W Tsuang
    Department of Veterans Affairs Northwest Network Mental Illness Research, Education, and Clinical Center, VA Puget Sound Health Care System, 1660 S Columbian Way, Mailstop 116MIRECC, Seattle, WA 98108, USA
    Arch Neurol 59:1622-30. 2002
    ..Few families with DLB have been described with detailed clinical, pathological, and genetic assessments...
  27. pmc ALS motor phenotype heterogeneity, focality, and spread: deconstructing motor neuron degeneration
    John M Ravits
    Section of Neurology, Virginia Mason Medical Center, Seattle, WA, USA
    Neurology 73:805-11. 2009
    ..This also suggests opportunities for translational research to seek pathobiology directly in the less affected regions of the nervous system...
  28. pmc Visceral neuropathy and intestinal pseudo-obstruction in a murine model of a nuclear inclusion disease
    Christine M Clarke
    Department of Laboratories, Children s Hospital and Regional Medical Center, Seattle, Washington, USA
    Gastroenterology 133:1971-8. 2007
    ..The enteric neuropathology of PrP-SCA7-92Q mice was investigated after observing that they develop signs of intestinal pseudo-obstruction...
  29. doi request reprint Androgen receptor function in motor neuron survival and degeneration
    Gregory A Cary
    Department of Laboratory Medicine, University of Washington Medical Center, Box 357110, Room NW 120, Seattle, WA 98195 7110, USA
    Phys Med Rehabil Clin N Am 19:479-94, viii. 2008
    ..A thorough understanding of androgen receptor signaling in motor neurons should provide important inroads toward the development of effective treatments for a variety of devastating motor neuron diseases...
  30. ncbi request reprint Efficient recombination-based methods for bacterial artificial chromosome fusion and mutagenesis
    Bryce L Sopher
    Department of Laboratory Medicine, University of Washington Medical Center, Seattle, WA 98195, USA
    Gene 371:136-43. 2006
    ..With "hybrid recombineering", we believe that the power and utility of the classical 'pop-in/pop-out' approach -- so commonly and efficiently employed in yeast for decades -- can now be achieved with BACs...
  31. ncbi request reprint Development of selective nutrient deprivation as a system to study autophagy induction and regulation in neurons
    Jessica E Young
    Department of Laboratory Medicine, University of Washington Medical Center, Seattle, WA 98195, USA
    Autophagy 5:555-7. 2009
    ..As highlighted herein, our system for autophagy induction should contribute to efforts aimed at understanding the regulatory basis of autophagy activation in neurons...
  32. ncbi request reprint Targeting protein aggregation in neurodegeneration--lessons from polyglutamine disorders
    Patrick Weydt
    University of Washington Medical Center, Department of Laboratory Medicine, Box 357110, Room NW 120, Seattle, WA 98195 7110, USA
    Expert Opin Ther Targets 10:505-13. 2006
    ....
  33. pmc Familial dementia with Lewy bodies with an atypical clinical presentation
    Lauren T Bonner
    Department of Veterans Affairs Northwest Network Mental Illness Research, Education, and Clinical Center, University of Washington, Seattle 98108, USA
    J Geriatr Psychiatry Neurol 16:59-64. 2003
    ..Family history revealed 7 relatives with a history of dementia including 4 with possible or probable DLB. This case is unique because of the FTLD-like presentation, positive family history of dementia, and autopsy confirmation of DLB...
  34. ncbi request reprint Targeting toxic proteins for turnover
    Albert R La Spada
    Nat Med 11:1052-3. 2005
  35. ncbi request reprint Purkinje cell degeneration (pcd) phenotypes caused by mutations in the axotomy-induced gene, Nna1
    Angeles Fernandez-Gonzalez
    Department of Developmental Neurobiology, St Jude Children s Research Hospital, Memphis, TN 38105, USA
    Science 295:1904-6. 2002
    ..The present study suggests an unexpected molecular link between neuronal degeneration and regeneration, and its results have potential implications for neurodegenerative diseases and male infertility...
  36. pmc Polyglutamine-expanded ataxin-7 inhibits STAGA histone acetyltransferase activity to produce retinal degeneration
    Vikas B Palhan
    Laboratories of Biochemistry and Molecular Biology and Mass Spectrometry and Gaseous Ion Chemistry, The Rockefeller University, New York, NY 10021, USA
    Proc Natl Acad Sci U S A 102:8472-7. 2005
    ....
  37. ncbi request reprint Ataxin-7 can export from the nucleus via a conserved exportin-dependent signal
    Jillian Taylor
    Department of Biochemistry and Biomedical Sciences, McMaster University, HSC4H45 Hamilton, Ontario L8N3Z5 Canada
    J Biol Chem 281:2730-9. 2006
    ..Our results add ataxin-7 to a growing list of polyglutamine disease proteins that are capable of nuclear shuttling, and we define an activity of ataxin-7 in the STAGA complex of trafficking between the nucleus and cytoplasm...
  38. ncbi request reprint Proteolytic cleavage of ataxin-7 by caspase-7 modulates cellular toxicity and transcriptional dysregulation
    Jessica E Young
    Buck Institute for Age Research, Novato, California, 94945, USA
    J Biol Chem 282:30150-60. 2007
    ..Our results, thus, suggest that proteolytic processing of ataxin-7 by caspase-7 may contribute to SCA7 disease pathogenesis...
  39. ncbi request reprint Polyglutamine and transcription: gene expression changes shared by DRPLA and Huntington's disease mouse models reveal context-independent effects
    Ruth Luthi-Carter
    Center for Aging, Genetics and Neurodegeneration, Massachusetts General Hospital, Charlestown, MA 02129 4404, USA
    Hum Mol Genet 11:1927-37. 2002
    ..These results demonstrate that some of the gene expression effects of expanded polyglutamine proteins occur independently of protein context...
  40. ncbi request reprint Interference of Crx-dependent transcription by ataxin-7 involves interaction between the glutamine regions and requires the ataxin-7 carboxy-terminal region for nuclear localization
    Shiming Chen
    Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St Louis, MO 63110, USA
    Hum Mol Genet 13:53-67. 2004
    ..The results suggest that one mechanism of SCA7 disease pathogenesis is transcription dysregulation, and that Crx transcription interference is a predominant factor in SCA7 cone-rod dystrophy retinal degeneration...
  41. ncbi request reprint Akt blocks ligand binding and protects against expanded polyglutamine androgen receptor toxicity
    Isabella Palazzolo
    Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, 35 Convent Drive, Bethesda, MD 20892, USA
    Hum Mol Genet 16:1593-603. 2007
    ..IGF-1 rescue of AR toxicity is diminished by alanine substitutions at the Akt consensus sites. These results highlight potential targets for therapeutic intervention in SBMA...
  42. ncbi request reprint Polyglutamines stop traffic: axonal transport as a common target in neurodegenerative diseases
    Mel B Feany
    Department of Pathology, Division of Neuropathology, Brigham and Women s Hospital, Harvard Medical School, 221 Longwood Avenue, Boston, MA 02115, USA
    Neuron 40:1-2. 2003
    ..Szebenyi and colleagues find that polyQ proteins directly inhibit fast axonal transport using axoplasm from the squid giant axon and suggest that axonal transport defects may be a common feature of polyQ disease pathogenesis...

Research Grants1

  1. CCCTC-binding factor (CTCF) in trinucleotide repeat instability and disease
    Albert La Spada; Fiscal Year: 2007
    ..Finally, we will attempt to validate the function of the antisense non-coding RNA in vivo. ..