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Dr Gaynor Smith
Uwch Ddarlithydd, Sefydliad Ymchwil Dementia
- Ar gael fel goruchwyliwr ôl-raddedig
Trosolwyg
Mecanweithiau moleciwlaidd o niwrofioleg, bioleg mitocondrial a chlefyd niwroddirywiol
Mae anhwylderau niwroddirywiol fel Alzheimer, Parkinson's a chlefyd Huntington yn gyflyrau anwelladwy a gwanychol sy'n arwain at ddirywiad cynyddol poblogaethau niwronau gwahanol. Mae camweithrediad mitochondrial, agregu protein ac ymatebion glial wedi'u newid yn uno nodweddion ar draws y clefydau hyn a hyd yn oed yn amlwg mewn cyfnodau prodromal. Mae gan fy labordy ddiddordeb mewn deall y mecanweithiau moleciwlaidd a cellog a warchodir sy'n sail i'r prosesau niwrobiolegol sylfaenol hyn, o Drosophila i bobl.
Nodau Ymchwil
- I ddarganfod genynnau newydd sy'n rheoli cynnal a chadw mitochondria mewn niwronau gan ddefnyddio dull genetig diduedd in vivo .
- Ymchwilio i sut mae genynnau newydd a ddarganfuwyd o ddulliau GWAS yn cyfrannu at fecanweithiau patholegol clefyd Alzheimer.
- Penderfynu sut mae newid homeostasis rhydocs yn effeithio ar ddatblygiad clefyd Alzheimer a Huntington.
Cyhoeddiad
2024
- Kors, S. et al. 2024. New insights into the functions of ACBD4/5-like proteins using a combined phylogenetic and experimental approach across model organisms. Biochimica et Biophysica Acta (BBA) - Molecular Cell Research 1871, article number: 119843. (10.1016/j.bbamcr.2024.119843)
2023
- Townsend, L. N. et al. 2023. Cdk12 maintains the integrity of adult axons by suppressing actin remodeling. Cell Death Discovery 9(1), article number: 348. (10.1038/s41420-023-01642-4)
- Rees, D. et al. 2023. Acyl-ghrelin attenuates neurochemical and motor deficits in the 6-OHDA model of Parkinson’s Disease. Cellular and Molecular Neurobiology 43, pp. 2377-2384. (10.1007/s10571-022-01282-9)
- Smith, G., Sweeney, S. T., O’Kane, C. J. and Prokop, A. 2023. How neurons maintain their axons long-term: an integrated view of axon biology and pathology. Frontiers in Neuroscience 17, article number: 1236815. (10.3389/fnins.2023.1236815)
- Maddison, D. C., Malik, B., Amadio, L., Bis-Brewer, D. M., Züchner, S., Peters, O. M. and Smith, G. A. 2023. COPI-regulated mitochondria-ER contact site formation maintains axonal integrity. Cell Reports 42(8), article number: 112883. (10.1016/j.celrep.2023.112883)
- Mattedi, F., Maddison, D., Smith, G. A. and Vagnoni, A. 2023. Live imaging of mitochondria in the intact fly wing. Cold Spring Harbor Protocol 2023(2), article number: 108052. (10.1101/pdb.prot108052)
- Maddison, D., Mattedi, F., Vagnoni, A. and Smith, G. A. 2023. Analysis of mitochondrial dynamics in adult drosophila axons. Cold Spring Harbor Protocol 2023(2), article number: 107819. (10.1101/pdb.top107819)
- Maddison, D., Mattedi, F., Vagnoni, A. and Smith, G. A. 2023. Clonal imaging of mitochondria in the dissected fly wing. Cold Spring Harbor Protocol 2023(2), article number: 108051. (10.1101/pdb.prot108051)
2021
- Peters, O. M. et al. 2021. Genetic diversity of axon degenerative mechanisms in models of Parkinson's disease. Neurobiology of Disease 155, article number: 105368. (10.1016/j.nbd.2021.105368)
- Lin, T. et al. 2021. TSG101 negatively regulates mitochondrial biogenesis in axons. Proceedings of the National Academy of Sciences 118(20), article number: e2018770118. (10.1073/pnas.2018770118)
2020
- Precious, S. V. et al. 2020. Dopaminergic progenitors derived from epiblast stem cells function similarly to primary VM-derived progenitors when transplanted into a Parkinson’s disease model. Frontiers in Neuroscience 14, article number: 312. (10.3389/fnins.2020.00312)
2019
- Malik, B. R., Maddison, D. C., Smith, G. A. and Peters, O. M. 2019. Autophagic and endo-lysosomal dysfunction in neurodegenerative disease. Molecular Brain 12(1), article number: 100. (10.1186/s13041-019-0504-x)
- Smith, G. A. et al. 2019. Glutathione-S-transferase regulates mitochondrial populations in axons through increased glutathione oxidation. Neuron 103(1), pp. 52-65.e6. (10.1016/j.neuron.2019.04.017)
2017
- Breger, L. S., Kienle, K., Smith, G. A., Dunnett, S. B. and Lane, E. L. 2017. Influence of chronic L-DOPA treatment on immune response following allogeneic and xenogeneic graft in a rat model of Parkinson's disease. Brain, Behavior, and Immunity 61, pp. 155-164. (10.1016/j.bbi.2016.11.014)
2016
- Smith, G. A., Jansson, J., Rocha, E. M., Osborn, T., Hallett, P. J. and Isacson, O. 2016. Fibroblast biomarkers of sporadic Parkinson's Disease and LRRK2 kinase inhibition. Molecular Neurobiology 53(8), pp. 5161-5177. (10.1007/s12035-015-9435-4)
- Lewis, E. A. and Smith, G. A. 2016. Using Drosophila models of Huntington's disease as a translatable tool. Journal of Neuroscience Methods 265, pp. 89-98. (10.1016/j.jneumeth.2015.07.026)
2015
- Rocha, E. M. et al. 2015. Glucocerebrosidase gene therapy prevents α-synucleinopathy of midbrain dopamine neurons. Neurobiology of Disease 82, pp. 495-503. (10.1016/j.nbd.2015.09.009)
- Rocha, E. M. et al. 2015. Sustained systemic glucocerebrosidase inhibition induces brain α-Synuclein aggregation, microglia and complement C1q activation in mice. Antioxidants and Redox Signaling 23(6), pp. 550-564. (10.1089/ars.2015.6307)
- Rocha, E. M., Smith, G. A., Park, E., Cao, H., Brown, E., Hallett, P. and Isacson, O. 2015. Progressive decline of glucocerebrosidase in aging and Parkinson's disease. Annals of Clinical and Translational Neurology 2(4), pp. 433-438. (10.1002/acn3.177)
- Smith, G. A. et al. 2015. A nurr1 agonist causes neuroprotection in a Parkinson's Disease lesion model primed with the toll-like receptor 3 dsRNA inflammatory stimulant poly(I:C). PLoS ONE 10(3), article number: e0121072. (10.1371/journal.pone.0121072)
- Hallett, P. et al. 2015. Successful function of Autologous iPSC-derived dopamine neurons following transplantation in a non-human primate model of Parkinson's disease. Cell Stem Cell 16(3), pp. 269-274. (10.1016/j.stem.2015.01.018)
2014
- McLean, J. R. et al. 2014. ALS-associated peripherin spliced transcripts form distinct protein inclusions that are neuroprotective against oxidative stress. Experimental Neurology 261, pp. 217-229. (10.1016/j.expneurol.2014.05.024)
- Smith, G. A., Rocha, E. M., McLean, J. R., Hayes, M. A., Izen, S. C., Isacson, O. and Hallett, P. J. 2014. Progressive axonal transport and synaptic protein changes correlate with behavioral and neuropathological abnormalities in the heterozygous Q175 KI mouse model of Huntington's disease. Human Molecular Genetics 23(17), pp. 4510-4527. (10.1093/hmg/ddu166)
- McLean, J. R., Smith, G. A., Rocha, E. M., Hayes, M. A., Beagan, J. A., Hallett, P. J. and Isacson, O. 2014. Widespread neuron-specific transgene expression in brain and spinal cord following synapsin promoter-driven AAV9 neonatal intracerebroventricular injection. Neuroscience Letters. 576, pp. 73-78. (10.1016/j.neulet.2014.05.044)
- Davies, S. E. et al. 2014. Enhanced ubiquitin-dependent degradation by Nedd4 protects against α-synuclein accumulation and toxicity in animal models of Parkinson's disease. Neurobiology of Disease 64, pp. 79-87. (10.1016/j.nbd.2013.12.011)
2013
- Smith, G. A. and Snyder, E. Y. 2013. Two cells are better than one: optimizing stem cell survival by co-grafting “helper” cells that offer regulated trophic support. Experimental Neurology 247, pp. 751-754. (10.1016/j.expneurol.2013.07.003)
- Peters, O. M. et al. 2013. Chronic administration of dimebon does not ameliorate amyloid-β pathology in 5xFAD transgenic mice. Journal of Alzheimer's Disease 36(3), pp. 589-596. (10.3233/JAD-130071)
- Heuer, A., Smith, G. A. and Dunnett, S. B. 2013. Comparison of 6-hydroxydopamine lesions of the substantia nigra and the medial forebrain bundle on a lateralised choice reaction time task in mice. European Journal of Neuroscience 37(2), pp. 294-302. (10.1111/ejn.12036)
- Sundberg, M. et al. 2013. Improved cell therapy protocols for Parkinson's disease based on differentiation efficiency and safety of hESC-, hiPSC-, and non-human primate iPSC-derived dopaminergic neurons. Stem Cells 31(8), pp. 1548-152. (10.1002/stem.1415)
2012
- Smith, G. A., Breger, L. S., Lane, E. L. and Dunnett, S. B. 2012. Pharmacological modulation of amphetamine-induced dyskinesia in transplanted hemi-parkinsonian rats. Neuropharmacology 63(5), pp. 818-828. (10.1016/j.neuropharm.2012.06.011)
- Smith, G. A., Isacson, O. and Dunnett, S. B. 2012. The search for genetic mouse models of prodromal Parkinson's disease. Experimental Neurology 237(2), pp. 267-273. (10.1016/j.expneurol.2012.06.035)
- Smith, G. A., Dunnett, S. B. and Lane, E. L. 2012. Amphetamine-induced rotation in the transplanted hemi-parkinsonian rat - Response to pharmacological modulation. Behavioural Brain Research 232(2), pp. 411-415. (10.1016/j.bbr.2012.04.003)
- Heuer, A., Smith, G. A., Lelos, M. J., Lane, E. L. and Dunnett, S. B. 2012. Unilateral nigrostriatal 6-hydroxydopamine lesions in mice I: Motor impairments identify extent of dopamine depletion at three different lesion sites. Behavioural Brain Research 228(1), pp. 30-43. (10.1016/j.bbr.2011.11.027)
- Smith, G. A., Heuer, A., Dunnett, S. B. and Lane, E. L. 2012. Unilateral nigrostriatal 6-hydroxydopamine lesions in mice II: Predicting L-DOPA-induced dyskinesia. Behavioural Brain Research 226(1), pp. 281-292. (10.1016/j.bbr.2011.09.025)
- Smith, G. A., Heuer, A., Klein, A., Vinh, N., Dunnett, S. B. and Lane, E. 2012. Amphetamine-induced dyskinesia in the transplanted hemi-Parkinsonian mouse. Journal of Parkinson's Disease 2, pp. 107-113. (10.3233/JPD-2012-12102)
- Smith, G. A. et al. 2012. L-dopa and graft-induced dyskinesia in the 6-OHDA-lesioned mouse [Abstract]. Cell Transplantation 21(4), pp. 792-792.
2011
- Torres, E. M., Lane, E. L., Heuer, A., Smith, G. A., Murphy, E. M. and Dunnett, S. B. 2011. Increased efficacy of the 6-hydroxydopamine lesion of the median forebrain bundle in small rats, by modification of the stereotaxic coordinates. Journal of Neuroscience Methods 200(1), pp. 29-35. (10.1016/j.jneumeth.2011.06.012)
- Lane, E. L., Daly, C. S., Smith, G. A. and Dunnett, S. B. 2011. Context-driven changes in 1-DOPA-induced behaviours in the 6-OHDA lesioned rat. Neurobiology of Disease 42(1), pp. 99-107. (10.1016/j.nbd.2011.01.010)
- Smith, G. A., Breger, L. S., Dunnett, S. B. and Lane, E. L. 2011. Developments in Graft-Induced Dyskinesia [Abstract]. Cell Transplantation 20(4), pp. 584-585.
- Smith, G. A., Lane, E. L. and Dunnett, S. B. 2011. Graft-Induced Dyskinesia in Transplanted Hemiparkinsonian Mice and Rats: A Pharmacological Manipulation [Abstract]. Cell Transplantation 20(4), pp. 585-585.
- Smith, G. 2011. Optimisation and mechanistic insights of dyskinesia in rodent models of Parkinson’s disease. PhD Thesis, Cardiff University.
2010
- Lane, E. L. and Smith, G. A. 2010. Understanding graft-induced dyskinesia. Regenerative Medicine 5(5), pp. 787-797. (10.2217/rme.10.42)
Articles
- Kors, S. et al. 2024. New insights into the functions of ACBD4/5-like proteins using a combined phylogenetic and experimental approach across model organisms. Biochimica et Biophysica Acta (BBA) - Molecular Cell Research 1871, article number: 119843. (10.1016/j.bbamcr.2024.119843)
- Townsend, L. N. et al. 2023. Cdk12 maintains the integrity of adult axons by suppressing actin remodeling. Cell Death Discovery 9(1), article number: 348. (10.1038/s41420-023-01642-4)
- Rees, D. et al. 2023. Acyl-ghrelin attenuates neurochemical and motor deficits in the 6-OHDA model of Parkinson’s Disease. Cellular and Molecular Neurobiology 43, pp. 2377-2384. (10.1007/s10571-022-01282-9)
- Smith, G., Sweeney, S. T., O’Kane, C. J. and Prokop, A. 2023. How neurons maintain their axons long-term: an integrated view of axon biology and pathology. Frontiers in Neuroscience 17, article number: 1236815. (10.3389/fnins.2023.1236815)
- Maddison, D. C., Malik, B., Amadio, L., Bis-Brewer, D. M., Züchner, S., Peters, O. M. and Smith, G. A. 2023. COPI-regulated mitochondria-ER contact site formation maintains axonal integrity. Cell Reports 42(8), article number: 112883. (10.1016/j.celrep.2023.112883)
- Mattedi, F., Maddison, D., Smith, G. A. and Vagnoni, A. 2023. Live imaging of mitochondria in the intact fly wing. Cold Spring Harbor Protocol 2023(2), article number: 108052. (10.1101/pdb.prot108052)
- Maddison, D., Mattedi, F., Vagnoni, A. and Smith, G. A. 2023. Analysis of mitochondrial dynamics in adult drosophila axons. Cold Spring Harbor Protocol 2023(2), article number: 107819. (10.1101/pdb.top107819)
- Maddison, D., Mattedi, F., Vagnoni, A. and Smith, G. A. 2023. Clonal imaging of mitochondria in the dissected fly wing. Cold Spring Harbor Protocol 2023(2), article number: 108051. (10.1101/pdb.prot108051)
- Peters, O. M. et al. 2021. Genetic diversity of axon degenerative mechanisms in models of Parkinson's disease. Neurobiology of Disease 155, article number: 105368. (10.1016/j.nbd.2021.105368)
- Lin, T. et al. 2021. TSG101 negatively regulates mitochondrial biogenesis in axons. Proceedings of the National Academy of Sciences 118(20), article number: e2018770118. (10.1073/pnas.2018770118)
- Precious, S. V. et al. 2020. Dopaminergic progenitors derived from epiblast stem cells function similarly to primary VM-derived progenitors when transplanted into a Parkinson’s disease model. Frontiers in Neuroscience 14, article number: 312. (10.3389/fnins.2020.00312)
- Malik, B. R., Maddison, D. C., Smith, G. A. and Peters, O. M. 2019. Autophagic and endo-lysosomal dysfunction in neurodegenerative disease. Molecular Brain 12(1), article number: 100. (10.1186/s13041-019-0504-x)
- Smith, G. A. et al. 2019. Glutathione-S-transferase regulates mitochondrial populations in axons through increased glutathione oxidation. Neuron 103(1), pp. 52-65.e6. (10.1016/j.neuron.2019.04.017)
- Breger, L. S., Kienle, K., Smith, G. A., Dunnett, S. B. and Lane, E. L. 2017. Influence of chronic L-DOPA treatment on immune response following allogeneic and xenogeneic graft in a rat model of Parkinson's disease. Brain, Behavior, and Immunity 61, pp. 155-164. (10.1016/j.bbi.2016.11.014)
- Smith, G. A., Jansson, J., Rocha, E. M., Osborn, T., Hallett, P. J. and Isacson, O. 2016. Fibroblast biomarkers of sporadic Parkinson's Disease and LRRK2 kinase inhibition. Molecular Neurobiology 53(8), pp. 5161-5177. (10.1007/s12035-015-9435-4)
- Lewis, E. A. and Smith, G. A. 2016. Using Drosophila models of Huntington's disease as a translatable tool. Journal of Neuroscience Methods 265, pp. 89-98. (10.1016/j.jneumeth.2015.07.026)
- Rocha, E. M. et al. 2015. Glucocerebrosidase gene therapy prevents α-synucleinopathy of midbrain dopamine neurons. Neurobiology of Disease 82, pp. 495-503. (10.1016/j.nbd.2015.09.009)
- Rocha, E. M. et al. 2015. Sustained systemic glucocerebrosidase inhibition induces brain α-Synuclein aggregation, microglia and complement C1q activation in mice. Antioxidants and Redox Signaling 23(6), pp. 550-564. (10.1089/ars.2015.6307)
- Rocha, E. M., Smith, G. A., Park, E., Cao, H., Brown, E., Hallett, P. and Isacson, O. 2015. Progressive decline of glucocerebrosidase in aging and Parkinson's disease. Annals of Clinical and Translational Neurology 2(4), pp. 433-438. (10.1002/acn3.177)
- Smith, G. A. et al. 2015. A nurr1 agonist causes neuroprotection in a Parkinson's Disease lesion model primed with the toll-like receptor 3 dsRNA inflammatory stimulant poly(I:C). PLoS ONE 10(3), article number: e0121072. (10.1371/journal.pone.0121072)
- Hallett, P. et al. 2015. Successful function of Autologous iPSC-derived dopamine neurons following transplantation in a non-human primate model of Parkinson's disease. Cell Stem Cell 16(3), pp. 269-274. (10.1016/j.stem.2015.01.018)
- McLean, J. R. et al. 2014. ALS-associated peripherin spliced transcripts form distinct protein inclusions that are neuroprotective against oxidative stress. Experimental Neurology 261, pp. 217-229. (10.1016/j.expneurol.2014.05.024)
- Smith, G. A., Rocha, E. M., McLean, J. R., Hayes, M. A., Izen, S. C., Isacson, O. and Hallett, P. J. 2014. Progressive axonal transport and synaptic protein changes correlate with behavioral and neuropathological abnormalities in the heterozygous Q175 KI mouse model of Huntington's disease. Human Molecular Genetics 23(17), pp. 4510-4527. (10.1093/hmg/ddu166)
- McLean, J. R., Smith, G. A., Rocha, E. M., Hayes, M. A., Beagan, J. A., Hallett, P. J. and Isacson, O. 2014. Widespread neuron-specific transgene expression in brain and spinal cord following synapsin promoter-driven AAV9 neonatal intracerebroventricular injection. Neuroscience Letters. 576, pp. 73-78. (10.1016/j.neulet.2014.05.044)
- Davies, S. E. et al. 2014. Enhanced ubiquitin-dependent degradation by Nedd4 protects against α-synuclein accumulation and toxicity in animal models of Parkinson's disease. Neurobiology of Disease 64, pp. 79-87. (10.1016/j.nbd.2013.12.011)
- Smith, G. A. and Snyder, E. Y. 2013. Two cells are better than one: optimizing stem cell survival by co-grafting “helper” cells that offer regulated trophic support. Experimental Neurology 247, pp. 751-754. (10.1016/j.expneurol.2013.07.003)
- Peters, O. M. et al. 2013. Chronic administration of dimebon does not ameliorate amyloid-β pathology in 5xFAD transgenic mice. Journal of Alzheimer's Disease 36(3), pp. 589-596. (10.3233/JAD-130071)
- Heuer, A., Smith, G. A. and Dunnett, S. B. 2013. Comparison of 6-hydroxydopamine lesions of the substantia nigra and the medial forebrain bundle on a lateralised choice reaction time task in mice. European Journal of Neuroscience 37(2), pp. 294-302. (10.1111/ejn.12036)
- Sundberg, M. et al. 2013. Improved cell therapy protocols for Parkinson's disease based on differentiation efficiency and safety of hESC-, hiPSC-, and non-human primate iPSC-derived dopaminergic neurons. Stem Cells 31(8), pp. 1548-152. (10.1002/stem.1415)
- Smith, G. A., Breger, L. S., Lane, E. L. and Dunnett, S. B. 2012. Pharmacological modulation of amphetamine-induced dyskinesia in transplanted hemi-parkinsonian rats. Neuropharmacology 63(5), pp. 818-828. (10.1016/j.neuropharm.2012.06.011)
- Smith, G. A., Isacson, O. and Dunnett, S. B. 2012. The search for genetic mouse models of prodromal Parkinson's disease. Experimental Neurology 237(2), pp. 267-273. (10.1016/j.expneurol.2012.06.035)
- Smith, G. A., Dunnett, S. B. and Lane, E. L. 2012. Amphetamine-induced rotation in the transplanted hemi-parkinsonian rat - Response to pharmacological modulation. Behavioural Brain Research 232(2), pp. 411-415. (10.1016/j.bbr.2012.04.003)
- Heuer, A., Smith, G. A., Lelos, M. J., Lane, E. L. and Dunnett, S. B. 2012. Unilateral nigrostriatal 6-hydroxydopamine lesions in mice I: Motor impairments identify extent of dopamine depletion at three different lesion sites. Behavioural Brain Research 228(1), pp. 30-43. (10.1016/j.bbr.2011.11.027)
- Smith, G. A., Heuer, A., Dunnett, S. B. and Lane, E. L. 2012. Unilateral nigrostriatal 6-hydroxydopamine lesions in mice II: Predicting L-DOPA-induced dyskinesia. Behavioural Brain Research 226(1), pp. 281-292. (10.1016/j.bbr.2011.09.025)
- Smith, G. A., Heuer, A., Klein, A., Vinh, N., Dunnett, S. B. and Lane, E. 2012. Amphetamine-induced dyskinesia in the transplanted hemi-Parkinsonian mouse. Journal of Parkinson's Disease 2, pp. 107-113. (10.3233/JPD-2012-12102)
- Smith, G. A. et al. 2012. L-dopa and graft-induced dyskinesia in the 6-OHDA-lesioned mouse [Abstract]. Cell Transplantation 21(4), pp. 792-792.
- Torres, E. M., Lane, E. L., Heuer, A., Smith, G. A., Murphy, E. M. and Dunnett, S. B. 2011. Increased efficacy of the 6-hydroxydopamine lesion of the median forebrain bundle in small rats, by modification of the stereotaxic coordinates. Journal of Neuroscience Methods 200(1), pp. 29-35. (10.1016/j.jneumeth.2011.06.012)
- Lane, E. L., Daly, C. S., Smith, G. A. and Dunnett, S. B. 2011. Context-driven changes in 1-DOPA-induced behaviours in the 6-OHDA lesioned rat. Neurobiology of Disease 42(1), pp. 99-107. (10.1016/j.nbd.2011.01.010)
- Smith, G. A., Breger, L. S., Dunnett, S. B. and Lane, E. L. 2011. Developments in Graft-Induced Dyskinesia [Abstract]. Cell Transplantation 20(4), pp. 584-585.
- Smith, G. A., Lane, E. L. and Dunnett, S. B. 2011. Graft-Induced Dyskinesia in Transplanted Hemiparkinsonian Mice and Rats: A Pharmacological Manipulation [Abstract]. Cell Transplantation 20(4), pp. 585-585.
- Lane, E. L. and Smith, G. A. 2010. Understanding graft-induced dyskinesia. Regenerative Medicine 5(5), pp. 787-797. (10.2217/rme.10.42)
Thesis
- Smith, G. 2011. Optimisation and mechanistic insights of dyskinesia in rodent models of Parkinson’s disease. PhD Thesis, Cardiff University.
- Breger, L. S., Kienle, K., Smith, G. A., Dunnett, S. B. and Lane, E. L. 2017. Influence of chronic L-DOPA treatment on immune response following allogeneic and xenogeneic graft in a rat model of Parkinson's disease. Brain, Behavior, and Immunity 61, pp. 155-164. (10.1016/j.bbi.2016.11.014)
- Peters, O. M. et al. 2013. Chronic administration of dimebon does not ameliorate amyloid-β pathology in 5xFAD transgenic mice. Journal of Alzheimer's Disease 36(3), pp. 589-596. (10.3233/JAD-130071)
- Heuer, A., Smith, G. A. and Dunnett, S. B. 2013. Comparison of 6-hydroxydopamine lesions of the substantia nigra and the medial forebrain bundle on a lateralised choice reaction time task in mice. European Journal of Neuroscience 37(2), pp. 294-302. (10.1111/ejn.12036)
- Smith, G. A., Breger, L. S., Lane, E. L. and Dunnett, S. B. 2012. Pharmacological modulation of amphetamine-induced dyskinesia in transplanted hemi-parkinsonian rats. Neuropharmacology 63(5), pp. 818-828. (10.1016/j.neuropharm.2012.06.011)
- Smith, G. A., Isacson, O. and Dunnett, S. B. 2012. The search for genetic mouse models of prodromal Parkinson's disease. Experimental Neurology 237(2), pp. 267-273. (10.1016/j.expneurol.2012.06.035)
- Smith, G. A., Dunnett, S. B. and Lane, E. L. 2012. Amphetamine-induced rotation in the transplanted hemi-parkinsonian rat - Response to pharmacological modulation. Behavioural Brain Research 232(2), pp. 411-415. (10.1016/j.bbr.2012.04.003)
- Heuer, A., Smith, G. A., Lelos, M. J., Lane, E. L. and Dunnett, S. B. 2012. Unilateral nigrostriatal 6-hydroxydopamine lesions in mice I: Motor impairments identify extent of dopamine depletion at three different lesion sites. Behavioural Brain Research 228(1), pp. 30-43. (10.1016/j.bbr.2011.11.027)
- Smith, G. A., Heuer, A., Dunnett, S. B. and Lane, E. L. 2012. Unilateral nigrostriatal 6-hydroxydopamine lesions in mice II: Predicting L-DOPA-induced dyskinesia. Behavioural Brain Research 226(1), pp. 281-292. (10.1016/j.bbr.2011.09.025)
- Smith, G. A. et al. 2012. L-dopa and graft-induced dyskinesia in the 6-OHDA-lesioned mouse [Abstract]. Cell Transplantation 21(4), pp. 792-792.
- Torres, E. M., Lane, E. L., Heuer, A., Smith, G. A., Murphy, E. M. and Dunnett, S. B. 2011. Increased efficacy of the 6-hydroxydopamine lesion of the median forebrain bundle in small rats, by modification of the stereotaxic coordinates. Journal of Neuroscience Methods 200(1), pp. 29-35. (10.1016/j.jneumeth.2011.06.012)
- Lane, E. L., Daly, C. S., Smith, G. A. and Dunnett, S. B. 2011. Context-driven changes in 1-DOPA-induced behaviours in the 6-OHDA lesioned rat. Neurobiology of Disease 42(1), pp. 99-107. (10.1016/j.nbd.2011.01.010)
- Smith, G. A., Breger, L. S., Dunnett, S. B. and Lane, E. L. 2011. Developments in Graft-Induced Dyskinesia [Abstract]. Cell Transplantation 20(4), pp. 584-585.
- Smith, G. A., Lane, E. L. and Dunnett, S. B. 2011. Graft-Induced Dyskinesia in Transplanted Hemiparkinsonian Mice and Rats: A Pharmacological Manipulation [Abstract]. Cell Transplantation 20(4), pp. 585-585.
- Smith, G. 2011. Optimisation and mechanistic insights of dyskinesia in rodent models of Parkinson’s disease. PhD Thesis, Cardiff University.
- Lane, E. L. and Smith, G. A. 2010. Understanding graft-induced dyskinesia. Regenerative Medicine 5(5), pp. 787-797. (10.2217/rme.10.42)
Ymchwil
Nodau Ymchwil
I ddarganfod genynnau newydd sy'n rheoli cynnal a chadw mitochondria yn axons niwronau gan ddefnyddio dull genetig diduedd in vivo .
Ychydig iawn a wyddom am fioleg sylfaenol biogenesis mitochondrial, newidiadau morffolegol, trafnidiaeth, neu swyddogaeth mewn axons in vivo, ac eto mae annormaleddau mitochondrial yn y terfynellau wedi'u cysylltu'n gryf ag etioleg sawl anhwylder niwroddirywiol.
Mae iechyd niwronau yn cael ei gynnal gan y cydbwysedd rhwng diraddio cyson o mitocondria sydd wedi'i ddifrodi trwy mitophagy a deuogenesis. Mae'r llwybrau hyn yn cael eu cadw'n fawr gan bobl i infertebratau. Mae Mitophagy yn gofyn am weithred gydlynol PINK1 a Parkin a darganfuwyd rhyngweithiad genetig y ddau foleciwl hyn gan ddefnyddio Drosophila (Park et al., 2006).
Datgelodd gwaith gan Drosophila hefyd fod angen dau brotein allweddol, Miro a Milton, i gludo mitocondria a threfnu eu datgysylltu o'r cytoskeleton mewn ardaloedd o Ca 2+ uchel i wella byfferu (adolygwyd gan Tang,2016 ).
Mae Mitochondria hefyd yn ddeinamig iawn yn yr echelin ac yn cael ymasiad cyson ac ymholltiad i rannu neu osgoi cymysgu mtDNA a phroteinau yn dibynnu ar statws y niwroron. Hyd yn hyn mae OPA-1, Marf, Drp1 a Fis1 wedi'u darganfod fel prif reoleiddwyr cydbwysedd ymholltiad / ymasiad.
Mae fy labordy yn perfformio sgrinio genetig diduedd mewn pryfed ffrwythau i ddarganfod rheoleiddwyr mitochondrial newydd mewn axons, a allai fod yn berthnasol i glefyd niwroddirywiol ac yn nodweddu eu swyddogaeth. Mae diddordebau eraill yn cynnwys deall sut mae mitocondria yn "cyfathrebu" ag organelles eraill fel peroxisomes a reticulum endoplasmig i yrru prosesau metabolaidd.
Ymchwilio i sut mae genynnau newydd a ddarganfuwyd o ddulliau GWAS yn cyfrannu at fecanweithiau patholegol clefyd Alzheimer.
Rhagwelir y bydd nifer y bobl sy'n byw gyda dementia yn y DU yn cynyddu i oddeutu 1 miliwn erbyn 2025 a dros 2 filiwn erbyn 2051 (https://www.alzheimers.org.uk/) ac ar hyn o bryd nid oes triniaeth a all helpu i arafu datblygiad clefydau.
Nodweddion patholegol allweddol y clefyd yw rhyngweithiadau niwroimiwnedd sydd wedi'u rheoleiddio, newidiadau metabolaidd, newidiadau trawsgrifio a datblygu placiau amyloid. Gwnaed mewnwelediadau i darddiad genetig clefyd Alzheimer trwy Astudiaethau Cymdeithas Genom Gyfan (GWAS), lle mae Prifysgol Caerdydd wedi chwarae rhan bwysig, dan arweiniad yr Athro Julie Williams.
Bydd fy labordy, mewn cydweithrediad â Dr Owen Peters ac aelodau o'r Sefydliad Ymchwil Dementia (DRI) yn canolbwyntio ar ddeall geneteg y prosesau patholegol allweddol hyn sy'n cyfrannu at glefyd Alzheimer gan ddefnyddio Drosophila a gwybodaeth a gasglwyd trwy GWAS.
Penderfynu sut mae newid homeostasis rhydocs yn effeithio ar ddatblygiad clefyd Alzheimer a Huntington.
Gall radicalau rhydd a gynhyrchir gan mitocondria ddod yn niweidiol i niwronau oni bai eu bod yn cael eu diffodd gan wrthocsidyddion.
Mae gan fy labordy ddiddordeb mewn tanlinellu sut mae moleciwlau sy'n ymwneud â statws rhydocs yn cyfrannu at niwroddirywiad, gyda ffocws penodol ar peroxidases, trosglwyddiadau a reductases sy'n byw naill ai o fewn y mitocondria neu axoplasm.
Addysgu
MBBCh - SSC - Tiwtor Blwyddyn 1
MBBCh- ME2100 - Hwylusydd Dysgu Seiliedig ar Achos
MBBCh - Tiwtor Personol
ME3048 Ffarmacoleg feddygol - Goruchwyliwr
Prosiect blwyddyn olaf BI3001 - Goruchwyliwr
Prosiect ymchwil uwch BI4001 - Goruchwyliwr
PTY - Goruchwyliwr
Bywgraffiad
Enillais fy BSc mewn Ffisioleg o Brifysgol Caerdydd ac arhosais yno i gwblhau fy PhD yn labordy yr Athro Stephan Dunnett lle canolbwyntiais ar ddeall sut yr effeithiodd strategaethau triniaeth fel trawsblannu celloedd a therapi L-DOPA ganlyniad ffenoteipig modelau Parkinson.
Dechreuais fy hyfforddiant ôl-ddoethurol yn Ysgol Feddygol Harvard yn labordy yr Athro Ole Isacson lle nodweddais y diffygion histopatholegol ac ymddygiadol ym model llygoden Q175 o glefyd Huntington, a defnyddio stratagïau therapi genynnau a gweinyddu moleciwlau bach i liniaru ffenoteipiau mewn modelau cnofilod clefyd Parkinson. Astudiais sawl ffenoteip mitochondrial ymhellach yng nghlaf Parkinson a samplau meinwe rheoli a oedd yn agored i docsinau penodol mitochondrial. Gyrrodd hyn newidiadau gwahaniaethol mewn morffoleg mitochondrial, ffosfforeiddiad LRRK2, cynhyrchu rhywogaethau ocsigen adweithiol, potensial bilen mitochondrial a lefelau mitophagy .
Yn ystod fy ail swydd ôl-ddoethurol yn labordy yr Athro Marc Freeman, a leolir gyntaf ym Mhrifysgol Massachusetts yna symud i Brifysgol Iechyd a Gwyddoniaeth Oregon, parheais i astudio mitocondria yn Drosophila a sgrinio ar gyfer addaswyr newydd deinameg mitocondrial mewn niwronau.
Bydd fy ngrŵp ymchwil fy hun ym Mhrifysgol Caerdydd yn parhau i astudio deinameg mitochondrial mewn niwronau ac yn ymchwilio i addaswyr genetig clefyd Alzheimer a chlefyd Huntington.
Meysydd goruchwyliaeth
Mae gen i ddiddordeb mewn goruchwylio myfyrwyr PhD ym meysydd:
- Niwrowyddoniaeth
- Clefyd niwroddirywiol
- Bioleg Mitocondrial
- Bioleg axon
Ymgysylltu
I am a trained as a STEM ambassador. I am involved with ‘Brain Games’ events held at Cardiff Museum and also contribute to patient and career events run by local charities both within the University and externally. I also contribute to Pint of Science, with my lastest lecture centered on how we use fruit flies in research “Me, Myself and Fly”. I also also take part in the In2 Science mentor scheme, which offers small group sessions and a placement day for Year 12 high school students from disadvantaged backgrounds.
Contact Details
SmithGA@caerdydd.ac.uk
Adeilad Hadyn Ellis, Ystafell 1.03, Office F, Heol Maendy, Caerdydd, CF24 4HQ
Adeilad Hadyn Ellis, Ystafell 1.03, Office F, Heol Maendy, Caerdydd, CF24 4HQ
Themâu ymchwil
Arbenigeddau
- Mitocondria
- Drosophila
- Clefyd Alzheimer
- niwron