Michael R Hayden

Summary

Affiliation: University of British Columbia
Country: Canada

Publications

  1. pmc Perceptions of genetic discrimination among people at risk for Huntington's disease: a cross sectional survey
    Yvonne Bombard
    Department of Medical Genetics, University of British Columbia, Vancouver, BC, V5Z 4H4, Canada
    BMJ 338:b2175. 2009
  2. pmc Islet cholesterol accumulation due to loss of ABCA1 leads to impaired exocytosis of insulin granules
    Janine K Kruit
    Departments of Medical Genetics, Centre for Molecular Medicine, and Therapeutics, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada
    Diabetes 60:3186-96. 2011
  3. pmc Loss of both ABCA1 and ABCG1 results in increased disturbances in islet sterol homeostasis, inflammation, and impaired β-cell function
    Janine K Kruit
    Department of Medical Genetics, Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, British Columbia, Canada
    Diabetes 61:659-64. 2012
  4. pmc miR-33a modulates ABCA1 expression, cholesterol accumulation, and insulin secretion in pancreatic islets
    Nadeeja Wijesekara
    Department of Medical Genetics, Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada
    Diabetes 61:653-8. 2012
  5. pmc Low levels of human HIP14 are sufficient to rescue neuropathological, behavioural, and enzymatic defects due to loss of murine HIP14 in Hip14-/- mice
    Fiona B Young
    Department of Medical Genetics and Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada
    PLoS ONE 7:e36315. 2012
  6. pmc Identification of binding sites in Huntingtin for the Huntingtin Interacting Proteins HIP14 and HIP14L
    Shaun S Sanders
    Department of Medical Genetics and Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada
    PLoS ONE 9:e90669. 2014
  7. pmc Segregation of LIPG, CETP, and GALNT2 mutations in Caucasian families with extremely high HDL cholesterol
    Ian Tietjen
    Xenon Pharmaceuticals Inc, Burnaby, Canada
    PLoS ONE 7:e37437. 2012
  8. pmc A quantitative method for the specific assessment of caspase-6 activity in cell culture
    Dagmar E Ehrnhoefer
    Centre for Molecular Medicine and Therapeutics CMMT, Department of Medical Genetics, CFRI, University of British Columbia, Vancouver, British Columbia, Canada
    PLoS ONE 6:e27680. 2011
  9. pmc Hunting human disease genes: lessons from the past, challenges for the future
    Liam R Brunham
    Department of Medicine, Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, Vancouver, Canada
    Hum Genet 132:603-17. 2013
  10. doi request reprint Pharmacogenomic prediction of anthracycline-induced cardiotoxicity in children
    Henk Visscher
    University of British Columbia, Vancouver, British Columbia
    J Clin Oncol 30:1422-8. 2012

Detail Information

Publications135 found, 100 shown here

  1. pmc Perceptions of genetic discrimination among people at risk for Huntington's disease: a cross sectional survey
    Yvonne Bombard
    Department of Medical Genetics, University of British Columbia, Vancouver, BC, V5Z 4H4, Canada
    BMJ 338:b2175. 2009
    ..To assess the nature and prevalence of genetic discrimination experienced by people at risk for Huntington's disease who had undergone genetic testing or remained untested...
  2. pmc Islet cholesterol accumulation due to loss of ABCA1 leads to impaired exocytosis of insulin granules
    Janine K Kruit
    Departments of Medical Genetics, Centre for Molecular Medicine, and Therapeutics, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada
    Diabetes 60:3186-96. 2011
    ..The ATP-binding cassette transporter A1 (ABCA1) is essential for normal insulin secretion from β-cells. The aim of this study was to elucidate the mechanisms underlying the impaired insulin secretion in islets lacking β-cell ABCA1...
  3. pmc Loss of both ABCA1 and ABCG1 results in increased disturbances in islet sterol homeostasis, inflammation, and impaired β-cell function
    Janine K Kruit
    Department of Medical Genetics, Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, British Columbia, Canada
    Diabetes 61:659-64. 2012
    ..These data suggest that ABCA1 and ABCG1 each make complimentary and important contributions to β-cell function by maintaining islet cholesterol homeostasis in vivo...
  4. pmc miR-33a modulates ABCA1 expression, cholesterol accumulation, and insulin secretion in pancreatic islets
    Nadeeja Wijesekara
    Department of Medical Genetics, Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada
    Diabetes 61:653-8. 2012
    ..These findings confirm the critical role of β-cell ABCA1 in islet cholesterol homeostasis and β-cell function and highlight modulation of β-cell miR-33a expression as a means to influence insulin secretion...
  5. pmc Low levels of human HIP14 are sufficient to rescue neuropathological, behavioural, and enzymatic defects due to loss of murine HIP14 in Hip14-/- mice
    Fiona B Young
    Department of Medical Genetics and Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada
    PLoS ONE 7:e36315. 2012
    ..Our findings yield important insights into HIP14 function in vivo...
  6. pmc Identification of binding sites in Huntingtin for the Huntingtin Interacting Proteins HIP14 and HIP14L
    Shaun S Sanders
    Department of Medical Genetics and Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada
    PLoS ONE 9:e90669. 2014
    ..Both enzymes showed reduced but not abolished interaction with 15Q HTT 1-548Δ257-315. This suggests that two potential binding domains exist, one around residues 224 and the other around 427, for the PAT enzymes HIP14 and HIP14L. ..
  7. pmc Segregation of LIPG, CETP, and GALNT2 mutations in Caucasian families with extremely high HDL cholesterol
    Ian Tietjen
    Xenon Pharmaceuticals Inc, Burnaby, Canada
    PLoS ONE 7:e37437. 2012
    ..Moreover, LIPG mutations do not overcome low HDLc in individuals with ABCA1 and possibly LCAT and LPL mutations, indicating that LIPG affects HDLc levels downstream of these proteins...
  8. pmc A quantitative method for the specific assessment of caspase-6 activity in cell culture
    Dagmar E Ehrnhoefer
    Centre for Molecular Medicine and Therapeutics CMMT, Department of Medical Genetics, CFRI, University of British Columbia, Vancouver, British Columbia, Canada
    PLoS ONE 6:e27680. 2011
    ..This method should be useful to screen for and characterize caspase-6 inhibitor compounds and other interventions to decrease intracellular caspase-6 activity for applications in neurodegenerative disorders...
  9. pmc Hunting human disease genes: lessons from the past, challenges for the future
    Liam R Brunham
    Department of Medicine, Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, Vancouver, Canada
    Hum Genet 132:603-17. 2013
    ..We review progress in mapping and identifying human disease genes and discuss future challenges and opportunities for the field...
  10. doi request reprint Pharmacogenomic prediction of anthracycline-induced cardiotoxicity in children
    Henk Visscher
    University of British Columbia, Vancouver, British Columbia
    J Clin Oncol 30:1422-8. 2012
    ..Our aim was to identify genetic variants associated with ACT in patients treated for childhood cancer...
  11. pmc Genome-wide significance for a modifier of age at neurological onset in Huntington's disease at 6q23-24: the HD MAPS study
    Jian Liang Li
    Department of Neurology, Boston University School of Medicine, Boston, MA, USA
    BMC Med Genet 7:71. 2006
    ....
  12. pmc CAG-encoded polyglutamine length polymorphism in the human genome
    Stefanie L Butland
    UBC Bioinformatics Centre, Michael Smith Laboratories, University of British Columbia, Vancouver, Canada
    BMC Genomics 8:126. 2007
    ....
  13. ncbi request reprint Cholesterol efflux regulatory protein, Tangier disease and familial high-density lipoprotein deficiency
    M R Hayden
    Centre for Molecular Medicine and Therapeutics, Department of Medical Genetics, University of British Columbia, Vancouver, Canada
    Curr Opin Lipidol 11:117-22. 2000
    ....
  14. ncbi request reprint Predictive testing for Huntington's disease: a universal model?
    Michael R Hayden
    Centre for Molecular Medicine and Therapeutics, University of British Columbia, 950 West 28th Avenue, V5Z 4H4, Vancouver, BC, Canada
    Lancet Neurol 2:141-2. 2003
  15. ncbi request reprint Efflux and atherosclerosis: the clinical and biochemical impact of variations in the ABCA1 gene
    Roshni R Singaraja
    Centre for Molecular Medicine and Therapeutics, University of British Columbia, and Children s and Women s Hospital, Vancouver, BC, Canada
    Arterioscler Thromb Vasc Biol 23:1322-32. 2003
    ..In this study we review how genetic variation at the ABCA1 locus affects its role in the maintenance of lipid homeostasis and the natural progression of atherosclerosis...
  16. pmc Mice lacking caspase-2 are protected from behavioral changes, but not pathology, in the YAC128 model of Huntington disease
    Jeffrey B Carroll
    Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, Department of Medical Genetics, University of British Columbia, Vancouver, V5Z 4H4, Canada
    Mol Neurodegener 6:59. 2011
    ..abstract:..
  17. pmc Palmitoylation of huntingtin by HIP14 is essential for its trafficking and function
    Anat Yanai
    Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, British Columbia V5Z 4H4, Canada
    Nat Neurosci 9:824-31. 2006
    ..These results suggest that the expansion of the polyglutamine tract in htt results in decreased palmitoylation, which contributes to the formation of inclusion bodies and enhanced neuronal toxicity...
  18. ncbi request reprint Levels of mutant huntingtin influence the phenotypic severity of Huntington disease in YAC128 mouse models
    Rona K Graham
    Centre for Molecular Medicine and Therapeutics, Department of Medical Genetics, University of British Columbia, 980 West 28th Avenue, Vancouver, BC, Canada V5Z 4H4
    Neurobiol Dis 21:444-55. 2006
    ..These results provide clear evidence in vivo supporting a more severe phenotype associated with increased levels of mutant huntingtin as seen in homozygotes for HD...
  19. doi request reprint Palmitoylation of ATP-binding cassette transporter A1 is essential for its trafficking and function
    Roshni R Singaraja
    950 West 28th Ave, Vancouver, BC, V5Z 4H4, Canada
    Circ Res 105:138-47. 2009
    ..Thus, palmitoylation regulates ABCA1 localization at the plasma membrane, and regulates its lipid efflux ability...
  20. doi request reprint Polyglutamine-modulated striatal calpain activity in YAC transgenic huntington disease mouse model: impact on NMDA receptor function and toxicity
    Catherine M Cowan
    Department of Psychiatry, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z3
    J Neurosci 28:12725-35. 2008
    ..Thus, the cumulative effect of increasing huntingtin polyglutamine length is to enhance MSN sensitivity to excitotoxicity at least in part by calpain-mediated cell death signaling...
  21. ncbi request reprint Phenotypic abnormalities in the YAC128 mouse model of Huntington disease are penetrant on multiple genetic backgrounds and modulated by strain
    Jeremy M Van Raamsdonk
    Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada V6T 1Z3
    Neurobiol Dis 26:189-200. 2007
    ..Importantly, the demonstration of penetrance across all three strains permits examining the effect of specific genes on the phenotypic severity in YAC128 mice without necessarily backcrossing onto the FVB/N strain background...
  22. ncbi request reprint Cleavage at the caspase-6 site is required for neuronal dysfunction and degeneration due to mutant huntingtin
    Rona K Graham
    Department of Medical Genetics, Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, BC V5Z 4H4, Canada
    Cell 125:1179-91. 2006
    ....
  23. pmc Despite antiatherogenic metabolic characteristics, SCD1-deficient mice have increased inflammation and atherosclerosis
    Marcia L E MacDonald
    Centre for Molecular Medicine and Therapeutics, Department of Medical Genetics, University of British Columbia, and Child and Family Research Institute, 980 West 28th Avenue, Vancouver, BC, Canada V5Z 4H4
    Arterioscler Thromb Vasc Biol 29:341-7. 2009
    ..The aim of this study was to determine the effect of SCD1 deficiency on atherosclerosis...
  24. doi request reprint Hip14l-deficient mice develop neuropathological and behavioural features of Huntington disease
    Liza M Sutton
    Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, British Columbia V5Z 4H4, Canada
    Hum Mol Genet 22:452-65. 2013
    ..Thus, both HIP14 and HIP14L may be dysfunctional in the disease...
  25. ncbi request reprint Tissue-specific roles of ABCA1 influence susceptibility to atherosclerosis
    Liam R Brunham
    Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, Vancouver, BC, Canada
    Arterioscler Thromb Vasc Biol 29:548-54. 2009
    ..The ATP-binding cassette transporter, subfamily A, member 1 (ABCA1) plays a key role in HDL cholesterol metabolism. However, the role of ABCA1 in modulating susceptibility to atherosclerosis is controversial...
  26. doi request reprint Phosphorylation of huntingtin at Ser421 in YAC128 neurons is associated with protection of YAC128 neurons from NMDA-mediated excitotoxicity and is modulated by PP1 and PP2A
    Martina Metzler
    Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia V5Z 4H4, Canada
    J Neurosci 30:14318-29. 2010
    ....
  27. doi request reprint Regulation of ABCA1 protein expression and function in hepatic and pancreatic islet cells by miR-145
    Martin H Kang
    From the Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, BC, Canada
    Arterioscler Thromb Vasc Biol 33:2724-32. 2013
    ..In the liver, ABCA1 is crucial for high-density lipoprotein biogenesis, and in the pancreas ABCA1 can regulate insulin secretion. In this study, our aim was to identify novel microRNAs that regulate ABCA1 expression in these tissues...
  28. pmc Specific loss of brain ABCA1 increases brain cholesterol uptake and influences neuronal structure and function
    Joanna M Karasinska
    Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, British Columbia, V5Z 4H4 Canada
    J Neurosci 29:3579-89. 2009
    ..Moreover, our findings also demonstrate that specific changes in brain cholesterol metabolism can lead to alterations in cholesterol uptake from plasma to brain...
  29. pmc Altered palmitoylation and neuropathological deficits in mice lacking HIP14
    Roshni R Singaraja
    Centre for Molecular Medicine and Therapeutics and Child and Family Research Institute, Vancouver, BC, Canada
    Hum Mol Genet 20:3899-909. 2011
    ..Hip14 is dysfunctional in the presence of mutant htt in the YAC128 mouse model of HD, suggesting that altered palmitoylation mediated by HIP14 may contribute to HD...
  30. pmc Wild-type huntingtin ameliorates striatal neuronal atrophy but does not prevent other abnormalities in the YAC128 mouse model of Huntington disease
    Jeremy M Van Raamsdonk
    Department of Medical Genetics and Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, Vancouver, V5Z 4H4, BC, Canada
    BMC Neurosci 7:80. 2006
    ....
  31. ncbi request reprint Complete functional rescue of the ABCA1-/- mouse by human BAC transgenesis
    Jonathan M Coutinho
    Centre for Molecular Medicine and Therapeutics, Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia V5Z 4H4, Canada
    J Lipid Res 46:1113-23. 2005
    ..Our humanized ABCA1 mice can serve as a useful model system for functional analysis of the human ABCA1 gene in vivo and can be used for the generation of potential new therapeutics that target HDL metabolism...
  32. doi request reprint ABCA1 influences neuroinflammation and neuronal death
    Joanna M Karasinska
    Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, British Columbia, Canada
    Neurobiol Dis 54:445-55. 2013
    ..Our findings suggest that coordinated ABCA1 activity across neurons and glial cells influences neuroinflammation and neurodegeneration...
  33. ncbi request reprint Physiologically regulated transgenic ABCA1 does not reduce amyloid burden or amyloid-beta peptide levels in vivo
    Veronica Hirsch-Reinshagen
    Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada
    J Lipid Res 48:914-23. 2007
    ..These data suggest that an induction of ABCA1 expression may be associated with late-stage Alzheimer's neuropathology...
  34. pmc Differential susceptibility to excitotoxic stress in YAC128 mouse models of Huntington disease between initiation and progression of disease
    Rona K Graham
    Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada V5Z 4H4
    J Neurosci 29:2193-204. 2009
    ..These data highlight the dynamic nature of the mutant htt-mediated excitotoxic phenotype and suggests that therapeutic approaches to HD may need to be altered, depending on the stage and development of the disease...
  35. ncbi request reprint NMDA receptor function and NMDA receptor-dependent phosphorylation of huntingtin is altered by the endocytic protein HIP1
    Martina Metzler
    Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada V5Z 4H4
    J Neurosci 27:2298-308. 2007
    ..These findings may provide novel insights into the cellular mechanisms underlying enhanced NMDA-induced excitotoxicity in Huntington's disease...
  36. ncbi request reprint Body weight is modulated by levels of full-length huntingtin
    Jeremy M Van Raamsdonk
    Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada V6T 1Z3
    Hum Mol Genet 15:1513-23. 2006
    ..Overall, we demonstrate that increased levels of both wild-type and mutant full-length htt are associated with increased body weight...
  37. ncbi request reprint Elevated plasma triglyceride levels precede amyloid deposition in Alzheimer's disease mouse models with abundant A beta in plasma
    Braydon L Burgess
    Department of Pathology and Laboratory Medicine, University of British Columbia, 980 West 28th Avenue, Vancouver, BC, Canada V5Z 4H4
    Neurobiol Dis 24:114-27. 2006
    ..Our results suggest that the presence of A beta in plasma may affect peripheral lipid metabolism early in AD pathogenesis...
  38. ncbi request reprint The absence of ABCA1 decreases soluble ApoE levels but does not diminish amyloid deposition in two murine models of Alzheimer disease
    Veronica Hirsch-Reinshagen
    Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia V4Z 5H5, Canada
    J Biol Chem 280:43243-56. 2005
    ..These data suggested that ABCA1-mediated effects on apoE levels and lipidation influenced amyloidogenesis in vivo...
  39. doi request reprint Phosphorylation of huntingtin reduces the accumulation of its nuclear fragments
    Simon C Warby
    Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia V5Z4H4, Canada
    Mol Cell Neurosci 40:121-7. 2009
    ....
  40. doi request reprint The Canadian Pharmacogenomics Network for Drug Safety: a model for safety pharmacology
    Colin J D Ross
    Department of Medical Genetics, Faculty of Medicine, Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, Canada
    Thyroid 20:681-7. 2010
    ....
  41. pmc Absence of behavioral abnormalities and neurodegeneration in vivo despite widespread neuronal huntingtin inclusions
    Elizabeth J Slow
    Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, BC, Canada V5Z 4H4
    Proc Natl Acad Sci U S A 102:11402-7. 2005
    ....
  42. pmc Cleavage at the 586 amino acid caspase-6 site in mutant huntingtin influences caspase-6 activation in vivo
    Rona K Graham
    Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, Department of Medical Genetics, Brain Research Centre, University of British Columbia, Vancouver, British Columbia, Canada V5Z 4H4
    J Neurosci 30:15019-29. 2010
    ....
  43. ncbi request reprint HIP14, a novel ankyrin domain-containing protein, links huntingtin to intracellular trafficking and endocytosis
    Roshni R Singaraja
    Centre for Molecular Medicine and Therapeutics, Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada V5Z 4H4
    Hum Mol Genet 11:2815-28. 2002
    ..Our findings suggest that decreased interaction between htt and HIP14 could contribute to the neuronal dysfunction in HD by perturbing normal intracellular transport pathways in neurons...
  44. doi request reprint Natural history of disease in the YAC128 mouse reveals a discrete signature of pathology in Huntington disease
    Jeffrey B Carroll
    Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, Vancouver, Canada V5Z 4H4
    Neurobiol Dis 43:257-65. 2011
    ..The use of mice furthermore enables us to address questions difficult to address in humans, including the sequential changes of HD from baseline and the relation between MRI and stereological measures...
  45. ncbi request reprint Beta-cell ABCA1 influences insulin secretion, glucose homeostasis and response to thiazolidinedione treatment
    Liam R Brunham
    Department of Medical Genetics, Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, 950 West 28th Avenue, Vancouver, British Columbia V5Z 4H4, Canada
    Nat Med 13:340-7. 2007
    ..These experiments establish a new role for Abca1 in beta-cell cholesterol homeostasis and insulin secretion, and suggest that cholesterol accumulation may contribute to beta-cell dysfunction in type 2 diabetes...
  46. pmc Neuronal palmitoyl acyl transferases exhibit distinct substrate specificity
    Kun Huang
    Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, BC V5Z 4H4, Canada
    FASEB J 23:2605-15. 2009
    ..Taken together, this study indicates that individual PATs have specific substrate preference, determined by regulatory domains outside the DHHC domain of the enzymes...
  47. ncbi request reprint Huntingtin-interacting protein HIP14 is a palmitoyl transferase involved in palmitoylation and trafficking of multiple neuronal proteins
    Kun Huang
    Department of Psychiatry, Brain Research Centre, University of British Columbia, Vancouver, British Columbia, Canada
    Neuron 44:977-86. 2004
    ..These findings define HIP14 as a mammalian palmitoyl transferase involved in the palmitoylation and trafficking of multiple neuronal proteins...
  48. pmc Wild-type HTT modulates the enzymatic activity of the neuronal palmitoyl transferase HIP14
    Kun Huang
    Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, British Columbia, Canada V5Z 4H4
    Hum Mol Genet 20:3356-65. 2011
    ..This study describes an important biochemical function for wild-type HTT modulation of HIP14 palmitoylation and its enzymatic activity...
  49. pmc Potent and selective antisense oligonucleotides targeting single-nucleotide polymorphisms in the Huntington disease gene / allele-specific silencing of mutant huntingtin
    Jeffrey B Carroll
    Program in Neuroscience, Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada
    Mol Ther 19:2178-85. 2011
    ..We demonstrate that potent and selective allele-specific knockdown of the mHTT protein can be achieved at therapeutically relevant SNP sites using ASOs in vitro and in vivo...
  50. doi request reprint Prevention of depressive behaviour in the YAC128 mouse model of Huntington disease by mutation at residue 586 of huntingtin
    Mahmoud A Pouladi
    Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, V6T 1Z3 Canada
    Brain 132:919-32. 2009
    ..In conclusion, our study provides strong support for a primary neurobiological basis for depression in Huntington disease...
  51. ncbi request reprint Wild-type huntingtin protects neurons from excitotoxicity
    Blair R Leavitt
    Centre for Molecular Medicine and Therapeutics, British Colombia Research Institute for Children s and Women s Health, Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada
    J Neurochem 96:1121-9. 2006
    ....
  52. ncbi request reprint Specific mutations in ABCA1 have discrete effects on ABCA1 function and lipid phenotypes both in vivo and in vitro
    Roshni R Singaraja
    Center for Molecular Medicine and Therapeutics, University of British Columbia and Child and Family Research Institute, Vancouver, British Columbia, Canada
    Circ Res 99:389-97. 2006
    ....
  53. ncbi request reprint Alterations of plasma lipids in mice via adenoviral-mediated hepatic overexpression of human ABCA1
    Cheryl L Wellington
    Centre for Molecular Medicine and Therapeutics, British Columbia Children s and Women s Hospital, University of British Columbia, Vancouver, BC, Canada
    J Lipid Res 44:1470-80. 2003
    ..Our results suggest that appropriate regulation of ABCA1 is critical for a selective increase in HDL cholesterol levels...
  54. doi request reprint Activated caspase-6 and caspase-6-cleaved fragments of huntingtin specifically colocalize in the nucleus
    Simon C Warby
    Centre for Molecular Medicine and Therapeutics, University of British Columbia, 980 West 28th Avenue, Vancouver, British Columbia, Canada
    Hum Mol Genet 17:2390-404. 2008
    ..The different cellular itineraries of endogenously generated caspase products of huntingtin may provide an explanation for the selective toxicity of huntingtin fragments cleaved at amino acid 586...
  55. ncbi request reprint Testicular degeneration in Huntington disease
    Jeremy M Van Raamsdonk
    Department of Medical Genetics, Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, 950 West 28th Ave, Vancouver, BC, Canada V5Z 4H4
    Neurobiol Dis 26:512-20. 2007
    ..Understanding the pathogenesis of HD in the testis may reveal common critical pathways which lead to degeneration in both the brain and testis...
  56. ncbi request reprint Both hepatic and extrahepatic ABCA1 have discrete and essential functions in the maintenance of plasma high-density lipoprotein cholesterol levels in vivo
    Roshni R Singaraja
    Center for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, British Columbia, Canada
    Circulation 114:1301-9. 2006
    ..Recent studies, however, including both overexpression and deletion of ABCA1 selectively in the liver, have highlighted the primary role of the liver in the maintenance of HDL levels in vivo...
  57. pmc Transcriptional changes in Huntington disease identified using genome-wide expression profiling and cross-platform analysis
    Kristina Becanovic
    Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada V5Z 4H4
    Hum Mol Genet 19:1438-52. 2010
    ..Further study of these genes may unravel novel pathways contributing to HD pathogenesis. DDBJ/EMBL/GenBank accession no: GSE19677...
  58. doi request reprint Interaction of postsynaptic density protein-95 with NMDA receptors influences excitotoxicity in the yeast artificial chromosome mouse model of Huntington's disease
    Jing Fan
    Graduate Program in Neuroscience, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada
    J Neurosci 29:10928-38. 2009
    ..Our results elucidate further the mechanisms underlying enhanced excitotoxicity in HD...
  59. pmc Bidirectional Control of Postsynaptic Density-95 (PSD-95) Clustering by Huntingtin
    Matthew P Parsons
    From the Department of Psychiatry and Brain Research Centre, University of British Columbia, Vancouver, British Columbia V6T 1Z3 and
    J Biol Chem 289:3518-28. 2014
    ..In all, our results demonstrate that nonpathogenic HTT can indeed influence synaptic protein localization and uncover a novel role of HTT in PSD-95 distribution. ..
  60. pmc Memory and synaptic deficits in Hip14/DHHC17 knockout mice
    Austen J Milnerwood
    Department of Psychiatry and Brain Research Centre, University of British Columbia, Vancouver, BC, Canada V6T 1Z3
    Proc Natl Acad Sci U S A 110:20296-301. 2013
    ..Moreover, an improved understanding of the role of PATs in synaptic modification and maintenance highlights a potential strategy for intervention against early cognitive impairments in neurodegenerative disease. ..
  61. ncbi request reprint Huntingtin phosphorylation on serine 421 is significantly reduced in the striatum and by polyglutamine expansion in vivo
    Simon C Warby
    Centre for Molecular Medicine and Therapeutics CMMT, British Columbia Children s and Women s Hospital, University of British Columbia, 980 West 28th Avenue, Vancouver, British Columbia V5Z 4H4, Canada
    Hum Mol Genet 14:1569-77. 2005
    ..The presence and pattern of significant htt phosphorylation in the brain indicates that this dynamic post-translational modification is important for the regulation of htt and may contribute to the selective neurodegeneration seen in HD...
  62. ncbi request reprint Cognitive dysfunction precedes neuropathology and motor abnormalities in the YAC128 mouse model of Huntington's disease
    Jeremy M Van Raamsdonk
    Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, V6T 1Z3 Canada
    J Neurosci 25:4169-80. 2005
    ....
  63. ncbi request reprint Caspase cleavage of mutant huntingtin precedes neurodegeneration in Huntington's disease
    Cheryl L Wellington
    Centre for Molecular Medicine and Therapeutics, British Columbia Children s and Women s Hospital, Vancouver, British Columbia, Canada
    J Neurosci 22:7862-72. 2002
    ....
  64. ncbi request reprint Striatal neuronal apoptosis is preferentially enhanced by NMDA receptor activation in YAC transgenic mouse model of Huntington disease
    Jacqueline Shehadeh
    Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada
    Neurobiol Dis 21:392-403. 2006
    ..Our results suggest that increased NMDAR signaling plays a major role in enhanced excitotoxic MSN death in this HD mouse model...
  65. ncbi request reprint Correction of feline lipoprotein lipase deficiency with adeno-associated virus serotype 1-mediated gene transfer of the lipoprotein lipase S447X beneficial mutation
    Colin J D Ross
    Department of Medical Genetics, University of British Columbia, and Centre for Molecular Medicine and Therapeutics, Vancouver, BC, Canada V5Z 4H4
    Hum Gene Ther 17:487-99. 2006
    ..We conclude that AAV1-mediated delivery of LPL(S447X) in muscle is an effective means to correct the hypertriglyceridemia associated with feline LPL deficiency...
  66. ncbi request reprint The metabolic phenotype of SCD1-deficient mice is independent of melanin-concentrating hormone
    Melissa B Glier
    Department of Medical Genetics, Child and Family Research Institute, University of British Columbia, Canada
    Peptides 31:123-9. 2010
    ..We conclude that the increased food intake and increased energy expenditure of Scd1-/- mice are independent of the neuropeptide melanin-concentrating hormone...
  67. ncbi request reprint Mitochondrial sensitivity and altered calcium handling underlie enhanced NMDA-induced apoptosis in YAC128 model of Huntington's disease
    Herman B Fernandes
    Department of Psychiatry and Brain Research Centre, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z3
    J Neurosci 27:13614-23. 2007
    ..These results suggest that the CAG repeat length influences the mechanism by which mHtt enhances NMDAR-mediated excitotoxicity...
  68. ncbi request reprint Ethyl-EPA treatment improves motor dysfunction, but not neurodegeneration in the YAC128 mouse model of Huntington disease
    Jeremy M Van Raamsdonk
    Department of Medical Genetics and Centre for Molecular Medicine and Therapeutics, British Columbia Research Institute for Children s and Women s Health, University of British Columbia, 980 West 28th Avenue, Vancouver, BC, Canada V5Z 4H4
    Exp Neurol 196:266-72. 2005
    ..Overall, this work demonstrates the feasibility of experimental therapeutics in the YAC128 mouse model and suggests that experiments in these mice may be predictive for future human clinical trials...
  69. pmc HTT haplotypes contribute to differences in Huntington disease prevalence between Europe and East Asia
    Simon C Warby
    Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, Vancouver, BC, Canada
    Eur J Hum Genet 19:561-6. 2011
    ..Instead, the expansion bias may be because of genetic cis-elements within the haplotype that influence CAG instability in HTT, possibly through different mutational mechanisms for the different haplogroups...
  70. pmc Full-length huntingtin levels modulate body weight by influencing insulin-like growth factor 1 expression
    Mahmoud A Pouladi
    Department of Medical Genetics, Centre for Molecular Medicine and Therapeutics, University of British Columbia, and Child and Family Research Institute, Vancouver, BC, Canada V5Z 4H4
    Hum Mol Genet 19:1528-38. 2010
    ..We demonstrate that the levels of FL htt influence IGF-1 expression in striatal tissues. Our data identify a novel function for FL htt in influencing IGF-1 expression...
  71. ncbi request reprint Deficiency of ABCA1 impairs apolipoprotein E metabolism in brain
    Veronica Hirsch-Reinshagen
    Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver V5Z 4H4, Canada
    J Biol Chem 279:41197-207. 2004
    ..Additionally, the effect of ABCA1 on apoE is selective, as apoJ levels are unchanged in brains of ABCA1-/- mice. Taken together, these results show that glial ABCA1 is a key influence on apoE metabolism in the CNS...
  72. pmc A fully humanized transgenic mouse model of Huntington disease
    Amber L Southwell
    Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, Vancouver, BC, Canada V5Z 4H4
    Hum Mol Genet 22:18-34. 2013
    ..This mouse line will be useful for gaining additional insights into the disease mechanisms of HD as well as for testing genetic therapies targeting human HTT...
  73. pmc Intestinal ABCA1 directly contributes to HDL biogenesis in vivo
    Liam R Brunham
    Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada
    J Clin Invest 116:1052-62. 2006
    ..These data establish a critical role for intestinal ABCA1 in plasma HDL biogenesis in vivo...
  74. pmc Factors associated with experiences of genetic discrimination among individuals at risk for Huntington disease
    Yvonne Bombard
    Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada
    Am J Med Genet B Neuropsychiatr Genet 156:19-27. 2011
    ..Overall, highly educated individuals were also more likely to report discrimination. These results provide direction for clinical and family discussions, counseling practice, and policy aimed at mitigating experiences of GD...
  75. ncbi request reprint Alternate transcripts expressed in response to diet reflect tissue-specific regulation of ABCA1
    Roshni R Singaraja
    Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, Canada
    J Lipid Res 46:2061-71. 2005
    ..Our data indicate that specific transcripts in different tissues play key roles in alterations of ABCA1-mediated changes in HDL levels and atherosclerosis in response to environmental stimuli...
  76. ncbi request reprint Complete rescue of lipoprotein lipase-deficient mice by somatic gene transfer of the naturally occurring LPLS447X beneficial mutation
    Colin J D Ross
    Department of Medical Genetics, University of British Columbia, Centre for Molecular Medicine and Therapeutics, Vancouver, Canada
    Arterioscler Thromb Vasc Biol 25:2143-50. 2005
    ..9-fold higher than LPLWT (P<0.01). These data provide in vivo evidence that the increased catalytic activity of LPLS447X improves plasma TG clearance and increases the HDL cholesterol pool compared with LPLWT...
  77. ncbi request reprint Cystamine treatment is neuroprotective in the YAC128 mouse model of Huntington disease
    Jeremy M Van Raamsdonk
    Centre for Molecular Medicine and Therapeutics, Department of Medical Genetics and British Columbia Research Institute for Women and Children s Health, University of British Columbia, Vancouver, British Columbia, Canada
    J Neurochem 95:210-20. 2005
    ..While the exact mechanism responsible for the beneficial effects of cystamine in YAC128 mice is uncertain, our findings suggest that cystamine is neuroprotective and may be beneficial in the treatment of HD...
  78. pmc CAG expansion in the Huntington disease gene is associated with a specific and targetable predisposing haplogroup
    Simon C Warby
    Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, BC, Canada
    Am J Hum Genet 84:351-66. 2009
    ....
  79. ncbi request reprint Protective up-regulation of CK2 by mutant huntingtin in cells co-expressing NMDA receptors
    Mannie M Y Fan
    Graduate Program in Neuroscience, University of British Columbia, British Columbia, Canada
    J Neurochem 104:790-805. 2008
    ....
  80. ncbi request reprint Hepatic ATP-binding cassette transporter A1 is a key molecule in high-density lipoprotein cholesteryl ester metabolism in mice
    Roshni R Singaraja
    University of British Columbia, Vancouver, Canada
    Arterioscler Thromb Vasc Biol 26:1821-7. 2006
    ..However, the role of ABCA1 in the liver for HDL apolipoprotein and cholesteryl ester (CE) catabolism in vivo is unknown...
  81. ncbi request reprint Tissue-specific induction of intestinal ABCA1 expression with a liver X receptor agonist raises plasma HDL cholesterol levels
    Liam R Brunham
    Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada
    Circ Res 99:672-4. 2006
    ..These data indicate that intestinal ABCA1 may be an attractive therapeutic target for raising HDL levels while avoiding the hepatic lipogenesis and hypertriglyceridemia typical of systemic LXR activation...
  82. ncbi request reprint Enhanced striatal NR2B-containing N-methyl-D-aspartate receptor-mediated synaptic currents in a mouse model of Huntington disease
    Lijun Li
    Kinsmen Laboratory, Department of Psychiatry, University of British Columbia, 4N3 2255 Wesbrook Mall, Vancouver, BC V6T 1Z3, Canada
    J Neurophysiol 92:2738-46. 2004
    ..Together with previous results, our data suggest that enhanced activity of NR2B-containing NMDARs is one of the earliest changes leading to neuronal degeneration in HD...
  83. doi request reprint Early increase in extrasynaptic NMDA receptor signaling and expression contributes to phenotype onset in Huntington's disease mice
    Austen J Milnerwood
    Department of Psychiatry, University of British Columbia, Vancouver, BC V6T 1Z3, Canada
    Neuron 65:178-90. 2010
    ..We provide a candidate mechanism linking several pathways previously implicated in HD pathogenesis and demonstrate successful early therapeutic intervention in mice...
  84. ncbi request reprint Selective striatal neuronal loss in a YAC128 mouse model of Huntington disease
    Elizabeth J Slow
    Centre for Molecular Medicine and Therapeutics, Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada V5Z 4H4
    Hum Mol Genet 12:1555-67. 2003
    ....
  85. ncbi request reprint Selective degeneration and nuclear localization of mutant huntingtin in the YAC128 mouse model of Huntington disease
    Jeremy M Van Raamsdonk
    Department of Medical Genetics, University of British Columbia, and Centre for Molecular Medicine and Thrapeutics, British Columbia Research Institute for Children s and Women s Health, Vancouver, Canada
    Hum Mol Genet 14:3823-35. 2005
    ....
  86. ncbi request reprint Role of NR2B-type NMDA receptors in selective neurodegeneration in Huntington disease
    Lijun Li
    Kinsmen Laboratories, Department of Psychiatry, University of British Columbia, 4N3 2255 Westbrook Mall, BC, Vancouver, Canada V6T 1Z3
    Neurobiol Aging 24:1113-21. 2003
    ..Potentiation of NR2B-containing NMDAR current in striatal MSNs expressing mutant huntingtin may help explain the exquisite vulnerability of these neurons to degeneration in HD...
  87. pmc Small changes, big impact: posttranslational modifications and function of huntingtin in Huntington disease
    Dagmar E Ehrnhoefer
    Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, Vancouver, BC, Canada
    Neuroscientist 17:475-92. 2011
    ..Identifying and testing specific modulators of PTMs now constitute the next big challenges in order to further validate these targets and proceed towards the goal of a mechanism-based treatment for HD...
  88. ncbi request reprint Increased huntingtin protein length reduces the number of polyglutamine-induced gene expression changes in mouse models of Huntington's disease
    Edmond Y W Chan
    Center for Molecular Medicine and Therapeutics, Department of Medical Genetics, Children s and Women s Hospital, University of British Columbia, Vancouver, British Columbia, Canada, V5H 4H4
    Hum Mol Genet 11:1939-51. 2002
    ..Furthermore, our findings suggest that short N-terminal fragments of mutant htt might be responsible for the gene expression alterations observed in human HD brain...
  89. ncbi request reprint Selective degeneration in YAC mouse models of Huntington disease
    Jeremy M Van Raamsdonk
    Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada
    Brain Res Bull 72:124-31. 2007
    ..Overall, YAC mice recapitulate the region specific damage that occurs in HD and provide a suitable model for examining the mechanisms underlying of selective degeneration...
  90. ncbi request reprint Loss of wild-type huntingtin influences motor dysfunction and survival in the YAC128 mouse model of Huntington disease
    Jeremy M Van Raamsdonk
    Department of Medical Genetics, University of British Columbia, Vancouver, Canada
    Hum Mol Genet 14:1379-92. 2005
    ....
  91. ncbi request reprint Potentiation of NMDA receptor-mediated excitotoxicity linked with intrinsic apoptotic pathway in YAC transgenic mouse model of Huntington's disease
    Melinda M Zeron
    Kinsmen Laboratory of Neurological Research, Department of Psychiatry, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z3
    Mol Cell Neurosci 25:469-79. 2004
    ..Agents that improve mitochondrial function or inhibit the permeability transition may eliminate increased caspase activation and cell death associated with enhanced NMDAR activity in HD...
  92. ncbi request reprint Targeted disruption of Huntingtin-associated protein-1 (Hap1) results in postnatal death due to depressed feeding behavior
    Edmond Y W Chan
    Center for Molecular Medicine and Therapeutics, Department of Medical Genetics, Children s and Women s Hospital, University of British Columbia, Vancouver, British Columbia, Canada
    Hum Mol Genet 11:945-59. 2002
    ..HAP-1 is particularly enriched in the hypothalamus, which is well documented to regulate feeding behavior. Our results demonstrate that HAP-1 plays an essential role in regulating postnatal feeding...
  93. pmc Mouse models of Huntington disease: variations on a theme
    Dagmar E Ehrnhoefer
    Centre for Molecular Medicine and Therapeutics, Department of Medical Genetics, Child and Family Research Institute, University of British Columbia, Vancouver, Canada
    Dis Model Mech 2:123-9. 2009
    ..These differences in phenotypic expression may be attributable to the influences of protein context, mouse strain and a difference in regulatory sequences between the mouse Htt and human HTT genes...
  94. ncbi request reprint Cross-species characterization of the ALS2 gene and analysis of its pattern of expression in development and adulthood
    Rebecca S Devon
    Centre for Molecular Medicine and Therapeutics, Department of Medical Genetics, University of British Columbia, and Children and Women s Hospital, 980 West 28th Avenue, Vancouver, BC, Canada V5Z 4H4
    Neurobiol Dis 18:243-57. 2005
    ..Additionally, the product of a second, widely expressed gene, ALS2 C-terminal like (ALS2CL), may subserve or modulate some of the functions of alsin as an activator of Rab and Rho GTPases...
  95. pmc Increased ABCA1 activity protects against atherosclerosis
    Roshni R Singaraja
    Centre for Molecular Medicine and Therapeutics, Children s and Women s Hospital, University of British Columbia, 950 West 28th Avenue, Vancouver, British Columbia V5Z 4H4, Canada
    J Clin Invest 110:35-42. 2002
    ..Lipid analysis of HDL particles from BAC(+)ApoE(-/-) mice revealed an increase in phospholipid levels, which was correlated significantly with their ability to enhance cholesterol efflux...
  96. ncbi request reprint To be or not to be toxic: aggregations in Huntington and Alzheimer disease
    Elizabeth J Slow
    Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, Department of Medical Genetics, University of British Columbia, Vancouver V5Z 4H4, BC, Canada
    Trends Genet 22:408-11. 2006
    ..Furthermore, aggregates can exist in the absence of disease pathology in mice or symptoms in humans. Recent research suggests that soluble protein fragments, not insoluble aggregated proteins, are the toxic species in these disorders...
  97. pmc Accurate prediction of the functional significance of single nucleotide polymorphisms and mutations in the ABCA1 gene
    Liam R Brunham
    Centre for Molecular Medicine and Therapeutics, Department of Medical Genetics, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia
    PLoS Genet 1:e83. 2005
    ....
  98. ncbi request reprint Altered NMDA receptor trafficking in a yeast artificial chromosome transgenic mouse model of Huntington's disease
    Mannie M Y Fan
    Graduate Program in Neuroscience, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z3
    J Neurosci 27:3768-79. 2007
    ..This polyQ length-dependent, neuronal-specific change in NMDAR activity induced by mhtt may contribute to selective neuronal degeneration in HD...
  99. ncbi request reprint Psychosocial effects of predictive testing for Huntington's disease
    Michael R Hayden
    Department of Medical Genetics, Centrefor Molecular Medicine and Therapeutics, Children s and Women s Health Centre of British Columbia, University of British Columbia, Vancouver, Canada
    Adv Neurol 96:226-39. 2005
  100. ncbi request reprint Mutations in the ABC1 gene in familial HDL deficiency with defective cholesterol efflux
    M Marcil
    Xenon Bioresearch Inc, NRC Innovation Centre, Vancouver, British Columbia, Canada
    Lancet 354:1341-6. 1999
    ..This gene codes for the cholesterol-efflux regulatory protein (CERP). We investigated the presence of mutations in this gene in patients with familial HDL deficiency...
  101. pmc Age and residual cholesterol efflux affect HDL cholesterol levels and coronary artery disease in ABCA1 heterozygotes
    S M Clee
    Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, British Columbia, Canada
    J Clin Invest 106:1263-70. 2000
    ..These data provide direct evidence that impairment of cholesterol efflux and consequently reverse cholesterol transport is associated with reduced plasma HDL-C levels and increased risk of CAD...