Yr Athro Adrian Harwood
(e/fe)
PhD, FRSB
- Sylwebydd y cyfryngau
Timau a rolau for Adrian Harwood
Athro
Ysgol y Biowyddorau
Trosolwg
I am neuro-cell biologist based in the Neuroscience and Mental Health Research Institute (NMHRI), and School of Biosciences. I have extensive experience in molecular signalling systems and cell analysis in neuronal and model cell systems.
My current work focuses on the molecular and cellular interactions that underlie genetic risk for psychiatric conditions and dementia. Current projects focus on cell signalling, synaptic function, neurodevelopment and epigenetic mechanisms, and how they modulate neuronal and glial cell function and drug sensitivity. I am using human stem cell and CRISPR technologies to create new model systems for the study of neuropsychiatric disorders and their pharmacological analysis, and have developed human cell-based assays using Multi-Electrode Array techniques to monitor altered neuronal network activity arising from genetic mutation. In doing so, my work aims to both develop new therapeutic strategies and provide basic insight into the cellular mechanisms underlying mental health.
Cyhoeddiad
2026
- Westacott, L. J. et al. 2026. Polyunsaturated fatty acids and psychotic disorders: integrating mechanistic, genetic, and clinical evidence. Frontiers in Nutrition 13 1929742. (10.3389/fnut.2026.1929742)
- Singh, T. et al., 2026. Human induced pluripotent stem cell-derived microglia with 1q21.1 deletion and duplication exhibit aberrant inflammatory response. Genes & diseases 13 (4) 101923. (10.1016/j.gendis.2025.101923)
- Wilkinson, G. et al. 2026. CACNA1C genetic variants differentially affect neuronal networks through divergent pathways. Biological Psychiatry Global Open Science 100792. (10.1016/j.bpsgos.2026.100792)
- Alsaqati, M. et al. 2026. Effects of acute fluctuations of extracellular Zinc on network activity of human iPSC-derived neurons; impact of NMDA Receptor and L-Type Calcium Channel Activation. Neuropharmacology 292 110952. (10.1016/j.neuropharm.2026.110952)
2025
- Huremagic, B. et al., 2025. MINDDS-connect: a federated data platform integrating biobanks for meta cohort building and analysis. European Journal of Human Genetics 33 , pp.1539-1546. (10.1038/s41431-025-01927-5)
- McPhail, D. K. et al. 2025. Loss of tuberous sclerosis complex 2 confers inflammation via dysregulation of nuclear factor kappa-light-chain-enhancer of activated B cells. Journal of Inflammation 22 (1) 38. (10.1186/s12950-025-00464-8)
2023
- Harwood, A. J. et al. 2023. Editorial: Mental health: cell models to mechanisms. Frontiers in Cell and Developmental Biology 11 1244425. (10.3389/fcell.2023.1244425)
- Dec, K. et al. 2023. A high ratio of linoleic acid (n-6 PUFA) to alpha-linolenic acid (n-3 PUFA) adversely affects early stage of human neuronal differentiation and electrophysiological activity of glutamatergic neurons in vitro. Frontiers in Cell and Developmental Biology 11 1166808. (10.3389/fcell.2023.1166808)
- Polit, L. D. et al., 2023. Recommendations, guidelines, and best practice for the use of human induced pluripotent stem cells for neuropharmacological studies of neuropsychiatric disorders. Neuroscience Applied 2 101125. (10.1016/j.nsa.2023.101125)
2022
- Alsaqati, M. et al. 2022. NRSF/REST lies at the intersection between epigenetic regulation, miRNA-mediated gene control and neurodevelopmental pathways associated with Intellectual disability (ID) and Schizophrenia. Translational Psychiatry 12 438. (10.1038/s41398-022-02199-z)
- Robinson, J. et al., 2022. The association of neurodevelopmental abnormalities, congenital heart and renal defects in a Tuberous Sclerosis Complex patient cohort. BMC Medicine 20 123. (10.1186/s12916-022-02325-0)
- Chapman, G. et al. 2022. Using induced pluripotent stem cells to investigate human neuronal phenotypes in 1q21.1 deletion and duplication syndrome. Molecular Psychiatry 27 , pp.819-830. (10.1038/s41380-021-01182-2)
- Sanders, B. et al. 2022. Transcriptional programs regulating neuronal differentiation are disrupted in DLG2 knockout human embryonic stem cells and enriched for schizophrenia and related disorders risk variants. Nature Communications 13 (1) 27. (10.1038/s41467-021-27601-0)
- Stewart, B. et al., 2022. The genetic architecture underlying prey-dependent performance in a microbial predator. Nature Communications 13 (1) 319. (10.1038/s41467-021-27844-x)
2021
- Gruenheit, N. et al., 2021. Mutant resources for functional genomics in Dictyostelium discoideum using REMI-seq technology. BMC Biology 19 (1) 172. (10.1186/s12915-021-01108-y)
2020
- Oliva-Teles, N. et al., 2020. Rare pathogenic copy number variation in the 16p11.2 (BP4–BP5) region associated with neurodevelopmental and neuropsychiatric disorders: a review of the literature. International Journal of Environmental Research and Public Health 17 (24) 9253. (10.3390/ijerph17249253)
- Alsaqati, M. , Heine, V. M. and Harwood, A. J. 2020. Pharmacological intervention to restore connectivity deficits of neuronal networks derived from ASD patient iPSC with a TSC2 mutation. Molecular Autism 11 80. (10.1186/s13229-020-00391-w)
- Davis, B. et al. 2020. Impairments in sensory-motor gating and information processing in a mouse model of Ehmt1 haploinsufficiency. Brain and Neuroscience Advances 4 (10.1177/2398212820928647)
- Drakulic, D. et al., 2020. Copy number variants (CNVs): a powerful tool for iPSC-based modelling of ASD. Molecular Autism 11 (1) 42. (10.1186/s13229-020-00343-4)
- Perry, C. J. et al., 2020. A new mechanism for cannabidiol in regulating the one-carbon cycle and methionine levels in Dictyostelium and in mammalian epilepsy models. British Journal of Pharmacology 177 (4), pp.912-928. (10.1111/bph.14892)
2019
- Plumbly, W. et al. 2019. L-type voltage-gated calcium channel regulation of in vitro human cortical neuronal networks. Scientific Reports 9 13810. (10.1038/s41598-019-50226-9)
- Harwood, J. C. et al. 2019. Nucleosome dynamics of human iPSC during neural differentiation. EMBO reports 20 (6) e46960. (10.15252/embr.201846960)
- Nadadhur, A. G. et al., 2019. Neuron-glia interactions increase neuronal phenotypes in tuberous sclerosis complex patient iPSC-derived models. Stem Cell Reports 12 (1), pp.42-56. (10.1016/j.stemcr.2018.11.019)
2018
- Harwood, A. and Baldwin, A. 2018. Dictyostelium. In: Encyclopedia of Microbiology (Fourth Edition). Elsevier. , pp.18-27. (10.1016/B978-0-12-809633-8.13033-X)
- Cocorocchio, M. et al., 2018. Curcumin and derivatives function through protein phosphatase 2A and presenilin orthologues in Dictyostelium discoideum. Disease Models & Mechanisms 11 032375. (10.1242/dmm.032375)
2017
- Platt, J. L. et al., 2017. Regulation of nucleosome positioning by a CHD Type III chromatin remodeler and its relationship to developmental gene expression in Dictyostelium. Genome Research 27 , pp.591-600. (10.1101/gr.216309.116)
2016
- Falk, A. et al., 2016. Modeling psychiatric disorders: from genomic findings to cellular phenotypes. Molecular Psychiatry 21 (9), pp.1167-1179. (10.1038/mp.2016.89)
2015
- Tarrés, M. et al., 2015. Biological interaction of living cells with COSAN-based synthetic vesicles. Scientific Reports 5 7804. (10.1038/srep07804)
2014
- Tarrés, M. et al., 2014. Imaging in living cells using νB–H Raman spectroscopy: monitoring COSAN uptake. Chemical Communications 50 (25), pp.3370-3372. (10.1039/c3cc49658a)
2013
- Fox, M. et al., 2013. Phosphorylation of the Actin Binding Protein Drebrin at S647 Is Regulated by Neuronal Activity and PTEN. PLoS ONE 8 (8) e71957. (10.1371/journal.pone.0071957)
- Harwood, A. J. et al. 2013. Aberrant spindle dynamics and cytokinesis in Dictyostelium discoideum cells that lack glycogen synthase kinase 3. European Journal of Cell Biology 92 (6-7), pp.222-228. (10.1016/j.ejcb.2013.05.001)
- Platt, J. L. et al. 2013. Different CHD chromatin remodelers are required for expression of distinct gene sets and specific stages during development of Dictyostelium discoideum. Development 140 (24), pp.4926-4936. (10.1242/dev.099879)
2011
- Harwood, A. J. 2011. Prolyl oligopeptidase, inositol phosphate signalling and lithium sensitivity. CNS & Neurological Disorders - Drug Targets 10 (3), pp.333-339. (10.2174/187152711794653779)
- Perrins, R. D. et al. 2011. Doing more with less: a method for low total mass, affinity measurement using variable-length nanotethers. Analytical Chemistry 83 (23), pp.8900-8905. (10.1021/ac2012569)
2010
- King, J. et al. 2010. Genetic control of lithium sensitivity and regulation of inositol biosynthetic genes. PLoS ONE 5 (6) e11151. (10.1371/journal.pone.0011151)
- Rey, S. M. et al. 2010. Mutant and wild type cell chemotaxis in 3D and 4D with ultrahigh- resolution optical coherence tomography.. Presented at: Optical Coherence Tomography and Coherence Domain Optical Methods in Biomedicine XIV San Francisco, CA, USA 25-27 January 2010. Published in: Izatt, J. A. , Fujimoto, J. G. and Tuchin, V. V. eds. Optical Coherence Tomography and Coherence Domain Optical Methods in Biomedicine XIV. Proceedings of SPIE Vol. 7554. Bellingham, WA: SPIE. , pp.505-509. (10.1117/12.843244)
- Teo, R. M. M. et al. 2010. Glycogen synthase kinase-3 is required for efficient 'Dictyostelium' chemotaxis. Molecular Biology of the Cell 21 (15), pp.2788-2796. (10.1091/mbc.E09-10-0891)
2009
- Rey, S. M. et al. 2009. Three- and four-dimensional visualization of cell migration using optical coherence tomography. Journal of Biophotonics 2 (6-7), pp.370-379. (10.1002/jbio.200910027)
- Rey, S. M. et al. 2009. Visualization of 3D cell migration using high speed ultrahigh resolution optical coherence tomography. Presented at: Optics in tissue engineering and regenerative medicine III San Jose, CA, USA 24 January 2009. Published in: Kirkpatrick, S. J. and Wang, R. eds. Optics in Tissue Engineering and Regenerative Medicine III, 24 January 2009, San Jose, CA, USA. Proceedings of SPIE Vol. 7179. Bellingham, WA: SPIE - International Society for Optical Engineering. , pp.505-509. (10.1117/12.809178)
- Kasry, A. et al. 2009. Comparison of methods for generating planar DNA-modified surfaces for hybridization studies. ACS Applied Materials & Interfaces 1 (8), pp.1793-1798. (10.1021/am9003073)
- King, J. et al. 2009. The mood stabiliser lithium suppresses PIP3 signalling in 'Dictyostelium' and human cells. Disease Models & Mechanisms 2 (5-6), pp.306-312. (10.1242/dmm.001271)
- Peineau, S. et al., 2009. A systematic investigation of the protein kinases involved in NMDA receptor-dependent LTD: evidence for a role of GSK-3 but not other serine/threonine kinases. Molecular Brain 2 (1) 22. (10.1186/1756-6606-2-22)
- Shimshoni, J. A. et al., 2009. Evaluation of the effects of propylisopropylacetic acid (PIA) on neuronal growth cone morphology. Neuropharmacology 56 (4), pp.831-837. (10.1016/j.neuropharm.2009.01.014)
- Teo, R. M. M. et al. 2009. Ptdins (3,4,5)P-3 and inositol depletion as a cellular target of mood stabilizers. Biochemical Society Transactions 37 (5), pp.1110-1114. (10.1042/BST0371110)
2008
- Cho, J. et al., 2008. Dephosphorylation of 2,3-bisphosphoglycerate by MIPP expands the regulatory capacity of the Rapoport-Luebering glycolytic shunt. Proceedings of the National Academy of Sciences of the United States of America 105 (16), pp.5998-6003. (10.1073/pnas.0710980105)
- Dale, T. C. , Harwood, A. J. and Borri, P. 2008. Method of measuring the affinity of biomolecules. EP1949104A2[Patent]
- Harwood, A. J. 2008. Dictyostelium development: a prototypic Wnt pathway?. In: Vincan, E. ed. Wnt Signaling. Vol. 2, Methods in Molecular Biology Vol. 469.New York, NY: Humana Press. , pp.21-32. (10.1007/978-1-60327-469-2_2)
- Harwood, A. J. 2008. Monitoring patterns of gene expression in Dictyostelium by beta-galacotsidase staining. In: Vincan, E. ed. Wnt signaling- Pathway models. Vol. 2, Methods in Molecular Biology Vol. 469.Totowa, N.J.: Humana. , pp.33-37.
- Harwood, A. J. 2008. Use of the Dictyostelium stalk cell assay to monitor GSK-3 regulation. In: Vincan, E. ed. Wnt Signaling. Vol. 469, Methods in Molecular Biology Springer. , pp.39-43. (10.1007/978-1-60327-469-2_4)
2007
- Shaltiel, G. et al., 2007. Specificity of mood stabilizer action on neuronal growth cones. Bipolar Disorders 9 (3), pp.281-289. (10.1111/j.1399-5618.2007.00400.x)
- Strmecki, L. et al., 2007. Proteomic and microarray analyses of the Dictyostelium Zak1-GSK-3 signaling pathway reveal a role in early development. Eukaryotic Cell 6 (2), pp.245-252. (10.1128/EC.00204-06)
2006
- Shimshoni, J. A. et al., 2006. The effects of central nervous system-active valproic acid constitutional isomers, cyclopropyl analogs, and amide derivatives on neuronal growth cone behavior. Molecular Pharmacology 71 (3), pp.884-892. (10.1124/mol.106.030601)
2005
- Ryves, W. J. et al. 2005. GSK-3 activity in neocortical cells is inhibited by lithium but not carbamazepine or valproic acid. Bipolar Disorders , pp.260-265. (10.1111/j.1399-5618.2005.00194.x)
2004
- Schilde, C. et al., 2004. GSK-3 is a multi-functional regulator of Dictyostelium development. Development 131 (18), pp.4555-4565. (10.1242/dev.01330)
2002
- Harwood, A. J. , Kim, L. and Kimmel, A. 2002. Receptor-dependent and tyrosine phosphatase-mediated inhibition of GSK3 regulates cell fate choice. Developmental Cell , pp.523-532. (10.1016/S1534-5807(02)00269-1)
- Williams, R. S. B. et al., 2002. A common mechanism of action for three mood-stabilizing drugs. Nature 417 (6886), pp.292-295. (10.1038/417292a)
- Fraser, E. et al. 2002. Identification of the Axin and Frat binding region of glycogen synthase kinase-3. Journal of Biological Chemistry 277 (3), pp.2176-2185. (10.1074/jbc.M109462200)
Adrannau llyfrau
- Harwood, A. and Baldwin, A. 2018. Dictyostelium. In: Encyclopedia of Microbiology (Fourth Edition). Elsevier. , pp.18-27. (10.1016/B978-0-12-809633-8.13033-X)
- Harwood, A. J. 2008. Dictyostelium development: a prototypic Wnt pathway?. In: Vincan, E. ed. Wnt Signaling. Vol. 2, Methods in Molecular Biology Vol. 469.New York, NY: Humana Press. , pp.21-32. (10.1007/978-1-60327-469-2_2)
- Harwood, A. J. 2008. Monitoring patterns of gene expression in Dictyostelium by beta-galacotsidase staining. In: Vincan, E. ed. Wnt signaling- Pathway models. Vol. 2, Methods in Molecular Biology Vol. 469.Totowa, N.J.: Humana. , pp.33-37.
- Harwood, A. J. 2008. Use of the Dictyostelium stalk cell assay to monitor GSK-3 regulation. In: Vincan, E. ed. Wnt Signaling. Vol. 469, Methods in Molecular Biology Springer. , pp.39-43. (10.1007/978-1-60327-469-2_4)
Cynadleddau
- Rey, S. M. et al. 2010. Mutant and wild type cell chemotaxis in 3D and 4D with ultrahigh- resolution optical coherence tomography.. Presented at: Optical Coherence Tomography and Coherence Domain Optical Methods in Biomedicine XIV San Francisco, CA, USA 25-27 January 2010. Published in: Izatt, J. A. , Fujimoto, J. G. and Tuchin, V. V. eds. Optical Coherence Tomography and Coherence Domain Optical Methods in Biomedicine XIV. Proceedings of SPIE Vol. 7554. Bellingham, WA: SPIE. , pp.505-509. (10.1117/12.843244)
- Rey, S. M. et al. 2009. Visualization of 3D cell migration using high speed ultrahigh resolution optical coherence tomography. Presented at: Optics in tissue engineering and regenerative medicine III San Jose, CA, USA 24 January 2009. Published in: Kirkpatrick, S. J. and Wang, R. eds. Optics in Tissue Engineering and Regenerative Medicine III, 24 January 2009, San Jose, CA, USA. Proceedings of SPIE Vol. 7179. Bellingham, WA: SPIE - International Society for Optical Engineering. , pp.505-509. (10.1117/12.809178)
Erthyglau
- Westacott, L. J. et al. 2026. Polyunsaturated fatty acids and psychotic disorders: integrating mechanistic, genetic, and clinical evidence. Frontiers in Nutrition 13 1929742. (10.3389/fnut.2026.1929742)
- Singh, T. et al., 2026. Human induced pluripotent stem cell-derived microglia with 1q21.1 deletion and duplication exhibit aberrant inflammatory response. Genes & diseases 13 (4) 101923. (10.1016/j.gendis.2025.101923)
- Wilkinson, G. et al. 2026. CACNA1C genetic variants differentially affect neuronal networks through divergent pathways. Biological Psychiatry Global Open Science 100792. (10.1016/j.bpsgos.2026.100792)
- Alsaqati, M. et al. 2026. Effects of acute fluctuations of extracellular Zinc on network activity of human iPSC-derived neurons; impact of NMDA Receptor and L-Type Calcium Channel Activation. Neuropharmacology 292 110952. (10.1016/j.neuropharm.2026.110952)
- Huremagic, B. et al., 2025. MINDDS-connect: a federated data platform integrating biobanks for meta cohort building and analysis. European Journal of Human Genetics 33 , pp.1539-1546. (10.1038/s41431-025-01927-5)
- McPhail, D. K. et al. 2025. Loss of tuberous sclerosis complex 2 confers inflammation via dysregulation of nuclear factor kappa-light-chain-enhancer of activated B cells. Journal of Inflammation 22 (1) 38. (10.1186/s12950-025-00464-8)
- Harwood, A. J. et al. 2023. Editorial: Mental health: cell models to mechanisms. Frontiers in Cell and Developmental Biology 11 1244425. (10.3389/fcell.2023.1244425)
- Dec, K. et al. 2023. A high ratio of linoleic acid (n-6 PUFA) to alpha-linolenic acid (n-3 PUFA) adversely affects early stage of human neuronal differentiation and electrophysiological activity of glutamatergic neurons in vitro. Frontiers in Cell and Developmental Biology 11 1166808. (10.3389/fcell.2023.1166808)
- Polit, L. D. et al., 2023. Recommendations, guidelines, and best practice for the use of human induced pluripotent stem cells for neuropharmacological studies of neuropsychiatric disorders. Neuroscience Applied 2 101125. (10.1016/j.nsa.2023.101125)
- Alsaqati, M. et al. 2022. NRSF/REST lies at the intersection between epigenetic regulation, miRNA-mediated gene control and neurodevelopmental pathways associated with Intellectual disability (ID) and Schizophrenia. Translational Psychiatry 12 438. (10.1038/s41398-022-02199-z)
- Robinson, J. et al., 2022. The association of neurodevelopmental abnormalities, congenital heart and renal defects in a Tuberous Sclerosis Complex patient cohort. BMC Medicine 20 123. (10.1186/s12916-022-02325-0)
- Chapman, G. et al. 2022. Using induced pluripotent stem cells to investigate human neuronal phenotypes in 1q21.1 deletion and duplication syndrome. Molecular Psychiatry 27 , pp.819-830. (10.1038/s41380-021-01182-2)
- Sanders, B. et al. 2022. Transcriptional programs regulating neuronal differentiation are disrupted in DLG2 knockout human embryonic stem cells and enriched for schizophrenia and related disorders risk variants. Nature Communications 13 (1) 27. (10.1038/s41467-021-27601-0)
- Stewart, B. et al., 2022. The genetic architecture underlying prey-dependent performance in a microbial predator. Nature Communications 13 (1) 319. (10.1038/s41467-021-27844-x)
- Gruenheit, N. et al., 2021. Mutant resources for functional genomics in Dictyostelium discoideum using REMI-seq technology. BMC Biology 19 (1) 172. (10.1186/s12915-021-01108-y)
- Oliva-Teles, N. et al., 2020. Rare pathogenic copy number variation in the 16p11.2 (BP4–BP5) region associated with neurodevelopmental and neuropsychiatric disorders: a review of the literature. International Journal of Environmental Research and Public Health 17 (24) 9253. (10.3390/ijerph17249253)
- Alsaqati, M. , Heine, V. M. and Harwood, A. J. 2020. Pharmacological intervention to restore connectivity deficits of neuronal networks derived from ASD patient iPSC with a TSC2 mutation. Molecular Autism 11 80. (10.1186/s13229-020-00391-w)
- Davis, B. et al. 2020. Impairments in sensory-motor gating and information processing in a mouse model of Ehmt1 haploinsufficiency. Brain and Neuroscience Advances 4 (10.1177/2398212820928647)
- Drakulic, D. et al., 2020. Copy number variants (CNVs): a powerful tool for iPSC-based modelling of ASD. Molecular Autism 11 (1) 42. (10.1186/s13229-020-00343-4)
- Perry, C. J. et al., 2020. A new mechanism for cannabidiol in regulating the one-carbon cycle and methionine levels in Dictyostelium and in mammalian epilepsy models. British Journal of Pharmacology 177 (4), pp.912-928. (10.1111/bph.14892)
- Plumbly, W. et al. 2019. L-type voltage-gated calcium channel regulation of in vitro human cortical neuronal networks. Scientific Reports 9 13810. (10.1038/s41598-019-50226-9)
- Harwood, J. C. et al. 2019. Nucleosome dynamics of human iPSC during neural differentiation. EMBO reports 20 (6) e46960. (10.15252/embr.201846960)
- Nadadhur, A. G. et al., 2019. Neuron-glia interactions increase neuronal phenotypes in tuberous sclerosis complex patient iPSC-derived models. Stem Cell Reports 12 (1), pp.42-56. (10.1016/j.stemcr.2018.11.019)
- Cocorocchio, M. et al., 2018. Curcumin and derivatives function through protein phosphatase 2A and presenilin orthologues in Dictyostelium discoideum. Disease Models & Mechanisms 11 032375. (10.1242/dmm.032375)
- Platt, J. L. et al., 2017. Regulation of nucleosome positioning by a CHD Type III chromatin remodeler and its relationship to developmental gene expression in Dictyostelium. Genome Research 27 , pp.591-600. (10.1101/gr.216309.116)
- Falk, A. et al., 2016. Modeling psychiatric disorders: from genomic findings to cellular phenotypes. Molecular Psychiatry 21 (9), pp.1167-1179. (10.1038/mp.2016.89)
- Tarrés, M. et al., 2015. Biological interaction of living cells with COSAN-based synthetic vesicles. Scientific Reports 5 7804. (10.1038/srep07804)
- Tarrés, M. et al., 2014. Imaging in living cells using νB–H Raman spectroscopy: monitoring COSAN uptake. Chemical Communications 50 (25), pp.3370-3372. (10.1039/c3cc49658a)
- Fox, M. et al., 2013. Phosphorylation of the Actin Binding Protein Drebrin at S647 Is Regulated by Neuronal Activity and PTEN. PLoS ONE 8 (8) e71957. (10.1371/journal.pone.0071957)
- Harwood, A. J. et al. 2013. Aberrant spindle dynamics and cytokinesis in Dictyostelium discoideum cells that lack glycogen synthase kinase 3. European Journal of Cell Biology 92 (6-7), pp.222-228. (10.1016/j.ejcb.2013.05.001)
- Platt, J. L. et al. 2013. Different CHD chromatin remodelers are required for expression of distinct gene sets and specific stages during development of Dictyostelium discoideum. Development 140 (24), pp.4926-4936. (10.1242/dev.099879)
- Harwood, A. J. 2011. Prolyl oligopeptidase, inositol phosphate signalling and lithium sensitivity. CNS & Neurological Disorders - Drug Targets 10 (3), pp.333-339. (10.2174/187152711794653779)
- Perrins, R. D. et al. 2011. Doing more with less: a method for low total mass, affinity measurement using variable-length nanotethers. Analytical Chemistry 83 (23), pp.8900-8905. (10.1021/ac2012569)
- King, J. et al. 2010. Genetic control of lithium sensitivity and regulation of inositol biosynthetic genes. PLoS ONE 5 (6) e11151. (10.1371/journal.pone.0011151)
- Teo, R. M. M. et al. 2010. Glycogen synthase kinase-3 is required for efficient 'Dictyostelium' chemotaxis. Molecular Biology of the Cell 21 (15), pp.2788-2796. (10.1091/mbc.E09-10-0891)
- Rey, S. M. et al. 2009. Three- and four-dimensional visualization of cell migration using optical coherence tomography. Journal of Biophotonics 2 (6-7), pp.370-379. (10.1002/jbio.200910027)
- Kasry, A. et al. 2009. Comparison of methods for generating planar DNA-modified surfaces for hybridization studies. ACS Applied Materials & Interfaces 1 (8), pp.1793-1798. (10.1021/am9003073)
- King, J. et al. 2009. The mood stabiliser lithium suppresses PIP3 signalling in 'Dictyostelium' and human cells. Disease Models & Mechanisms 2 (5-6), pp.306-312. (10.1242/dmm.001271)
- Peineau, S. et al., 2009. A systematic investigation of the protein kinases involved in NMDA receptor-dependent LTD: evidence for a role of GSK-3 but not other serine/threonine kinases. Molecular Brain 2 (1) 22. (10.1186/1756-6606-2-22)
- Shimshoni, J. A. et al., 2009. Evaluation of the effects of propylisopropylacetic acid (PIA) on neuronal growth cone morphology. Neuropharmacology 56 (4), pp.831-837. (10.1016/j.neuropharm.2009.01.014)
- Teo, R. M. M. et al. 2009. Ptdins (3,4,5)P-3 and inositol depletion as a cellular target of mood stabilizers. Biochemical Society Transactions 37 (5), pp.1110-1114. (10.1042/BST0371110)
- Cho, J. et al., 2008. Dephosphorylation of 2,3-bisphosphoglycerate by MIPP expands the regulatory capacity of the Rapoport-Luebering glycolytic shunt. Proceedings of the National Academy of Sciences of the United States of America 105 (16), pp.5998-6003. (10.1073/pnas.0710980105)
- Shaltiel, G. et al., 2007. Specificity of mood stabilizer action on neuronal growth cones. Bipolar Disorders 9 (3), pp.281-289. (10.1111/j.1399-5618.2007.00400.x)
- Strmecki, L. et al., 2007. Proteomic and microarray analyses of the Dictyostelium Zak1-GSK-3 signaling pathway reveal a role in early development. Eukaryotic Cell 6 (2), pp.245-252. (10.1128/EC.00204-06)
- Shimshoni, J. A. et al., 2006. The effects of central nervous system-active valproic acid constitutional isomers, cyclopropyl analogs, and amide derivatives on neuronal growth cone behavior. Molecular Pharmacology 71 (3), pp.884-892. (10.1124/mol.106.030601)
- Ryves, W. J. et al. 2005. GSK-3 activity in neocortical cells is inhibited by lithium but not carbamazepine or valproic acid. Bipolar Disorders , pp.260-265. (10.1111/j.1399-5618.2005.00194.x)
- Schilde, C. et al., 2004. GSK-3 is a multi-functional regulator of Dictyostelium development. Development 131 (18), pp.4555-4565. (10.1242/dev.01330)
- Harwood, A. J. , Kim, L. and Kimmel, A. 2002. Receptor-dependent and tyrosine phosphatase-mediated inhibition of GSK3 regulates cell fate choice. Developmental Cell , pp.523-532. (10.1016/S1534-5807(02)00269-1)
- Williams, R. S. B. et al., 2002. A common mechanism of action for three mood-stabilizing drugs. Nature 417 (6886), pp.292-295. (10.1038/417292a)
- Fraser, E. et al. 2002. Identification of the Axin and Frat binding region of glycogen synthase kinase-3. Journal of Biological Chemistry 277 (3), pp.2176-2185. (10.1074/jbc.M109462200)
Patentau
- Dale, T. C. , Harwood, A. J. and Borri, P. 2008. Method of measuring the affinity of biomolecules. EP1949104A2[Patent]
Ymchwil
Mae anhwylderau niwrodatblygiadol (NDDs), fel sgitsoffrenia ac anhwylderau'r sbectrwm awtistiaeth (ASD) yn gyflyrau seiciatrig cronig cyffredin sy'n cyfrannu'n sylweddol at faich y clefyd byd-eang. Mae astudiaethau genetig bellach yn nodi cyfres o enynnau sy'n cynyddu'r risg o ddatblygu'r cyflyrau hyn. Ar ben hynny, mae risg genetig sylweddol hefyd yn bodoli ar gyfer prif gyflyrau anhwylder deubegynol a dementia. Mae fy ymchwil yn anelu: sefydlu'r ffenoteipiau niwrogellog sy'n deillio o'r newidiadau genetig hyn; deall y mecanweithiau sy'n sail i salwch meddwl tarddiad a datblygu strategaethau therapiwtig newydd. Mae prosiectau cyfredol yn canolbwyntio ar fecanweithiau epigenetig, niwro-ddatblygiadol a synaptig sy'n gysylltiedig ag etioleg clefydau a gweithredu cyffuriau.
Rydym yn ymchwilio i dri math o fecanwaith ar draws ystod o fathau o gelloedd sydd wedi'u gwahaniaethu oddi wrth fôn-gelloedd amlbwerus a achosir gan ddynol (iPSC). Mae nifer o fodiwlyddion epigenetig wedi bod yn gysylltiedig ag ASD, sgitsoffrenia ac epilepsi. Rydym yn astudio effeithiau EHMT1 a'r teulu CHD o broteinau ar niwrodatblygiad, rheoleiddio genynnau a synaptogenesis. Yn ogystal â phroses strwythurol a metabolig, mae rhai lipidau ac asidau brasterog yn hanfodol ar gyfer signalau celloedd. Rydym yn ymchwilio i ryngweithio lipidau a'r genyn risg deubegynol Fatty Acid Desaturase 2 (FADS2) a'u heffeithiau ar amlhau bôn-gelloedd, niwrodatblygiad a swyddogaeth synaptig.
Mae genynnau sy'n amgodio proteinau synaptig sy'n cyfryngu signalau glutamad a GABA yn gysylltiedig yn gryf ag anhwylderau niwroseiciatrig. Rydym yn defnyddio cyfuniadau o dechnoleg CRISPR, genomig ac Multi-Electrode Array (MEA) mewn bôn-gelloedd dynol i greu systemau model newydd ar gyfer astudio'r anhwylderau hyn ac ymyrraeth ffarmacolegol newydd.
Rwy'n gyd-sylfaenydd y cwmni spinpit MeOmics
Grantiau cyfredol
- Grant Rhaglen MRC: CONVERGE
- Sefydliad Waterloo: Datblygu Meddyliau
Cydweithrediadau
- Jeremy Hall, NMHRI, Prifysgol Caerdydd
- John Atack, Sefydliad Darganfod Meddyginiaethau (MDI), Prifysgol Caerdydd
- Dayne Baccano-Kelly, Canolfan Sefydliad Ymchwil Dementia y DU (DRI), Prifysgol Caerdydd
- Vivi Heine, Canolfan Feddygol Prifysgol VU, Amsterdam
Bywgraffiad
Ar ôl fy BA mewn Sŵoleg o Brifysgol Rhydychen, ymchwiliais i dargedu genynnau trwy ailgyfuniad homologaidd mitotig mewn celloedd mamaliaid diwylliedig ym Mhrifysgol Caeredin o dan oruchwyliaeth Chris Bostock, a dyfarnwyd PhD iddo ym 1988.
Canolbwyntiodd fy ymchwil pellach ar astudio prosesau trawsgludo signal yng nghyd-destun bioleg celloedd. I ddechrau, cefais Gymrodoriaethau Ymchwil yn Labordai Clare Hall ICRF (1988-1991) yng ngrŵp Jeff Williams. Yn ystod y cyfnod hwn, arloesais yn yr astudiaeth o protein kinase sy'n ddibynnol ar cAMP yn Dictyostelium, gan sefydlu rôl sylfaenol y kinase pwysig hwn mewn rheolaeth ofodol ac amserol yn ystod y datblygiad. Sefydlais hefyd nifer o dechnolegau allweddol ar gyfer ymchwil Dictyostelium , gan gynnwys defnyddio genynnau marciwr lacZ. Cefais Gymrodoriaeth Ôl-ddoethurol MRC yn Labordy Bioleg Moleciwlaidd MRC, Caergrawnt, (1992-1994) yng ngrŵp Rob Kay. Yma, cynhaliais y sgriniau mutagenesis REMI cyntaf y tu allan i'r Unol Daleithiau, gan arwain at ddarganfod rôl hanfodol GSK-3 mewn bioleg gelloedd a datblygiadol Dictyostelium.
Ym 1995 dyfarnwyd Cymrodoriaeth Biofeddygol Uwch Wellcome Trust i mi a sefydlais fy ngrŵp ymchwil fy hun yn Labordy MRC ar gyfer Bioleg Celloedd Moleciwlaidd (LMCB), gan ddal swydd staff yn yr Adran Bioleg yng Ngholeg Prifysgol Llundain. Cefais fy nyrchafu'n Reader yn 2001 ac yn gadair bersonol yn 2003. Yn ystod y cyfnod hwn, parheais i astudio signalau GSK-3 yn Dictyostelium a datblygais enw da rhyngwladol ym maes signalau Wnt. Darganfyddais y beta-catenin cyntaf a bodolaeth cyffyrdd adherens y tu allan i'r metazoa, a gyhoeddwyd yn Nature. Yn ogystal, roedd fy mhapur Cell ar GSK-3 yn gonglfaen i'r darganfyddiad bod lithiwm yn atal GSK-3. Rwyf wedi parhau i ymchwilio i rôl lithiwm ar lwybrau signalau cellog, gan ymchwilio i signalau ffosffad GSK-3 ac inositol mewn Dictyosteliuma niwronau. Mae fy mhapur Nature 2002 yn bapur arloesol ym maes seicopharmacoleg, sy'n dangos bod signalau ffosffad inositol yn darged cyffredin i'r mwyafrif o sefydlogwyr hwyliau.
Yn 2005, symudais i Ysgol y Biowyddorau ym Mhrifysgol Caerdydd, ac roeddwn yn gyd-sylfaenydd Sefydliad Ymchwil Niwrowyddoniaeth ac Iechyd Meddwl y Brifysgol (NMHRI). Rwyf wedi parhau i ddatblygu fy ymchwil ar sail niwrogellog anhwylderau seiciatrig a mecanwaith gweithredu sefydlogwyr hwyliau, gan adeiladu grŵp newydd sy'n canolbwyntio ar iPSC dynol.
Yn 2024, deuthum yn Athro Bioleg Celloedd Niwroseiciatrig Integreiddiol ym Mhrifysgol Maastricht yn yr Iseldiroedd, sy'n cael ei gynnal ar y cyd â fy Nghadair yng Nghaerdydd. Ym Maastricht, rwy'n aelod o'r Adran Genomeg Drosiadol (TGX) a'r Sefydliad Iechyd Meddwl a Niwrowyddoniaeth (MHeNs).
Aelodaethau proffesiynol
Rwy'n aelod o'r Collegium Internationale Niwro-Seicopharmacologicum (CINP), ac yn Gymrawd o'r Gymdeithas Frenhinol Bioleg (FRSB).
Safleoedd academaidd blaenorol
O fewn Ysgol y Biowyddorau, roeddwn yn Arweinydd Grŵp y Grŵp Ymchwil Bioleg Celloedd Moleciwlaidd (2005-2007) ac roedd Niwrowyddoniaeth (2011) yn Bennaeth Arloesi, Partneriaeth ac Ymgysylltu o 2009-2013. Ar hyn o bryd rwy'n gyd-Gyfarwyddwr Ymchwil, ac yn gyd-gyfarwyddwr NMHRI.
Roeddwn hefyd yn Gadeirydd Gweithredu Gweithredu Ewropeaidd COST CA16210 MINDDS.
Rwy'n aelod o Blatfform iPSCs yr ECNP ar gyfer Rhwydwaith Niwroseiciatrig
Pwyllgorau ac adolygu
Ar hyn o bryd rwy'n aelod panel sifftio a chyfweld ar gyfer rhaglen Cymrodoriaeth Arweinwyr y Dyfodol UKRI ac yn aelod o Grŵp Cynghori Rhwydwaith (NAG) rhwydweithiau Iechyd Meddwl UKRI-ESRC.
Rwy'n dyfarnu ceisiadau grant yn rheolaidd ar gyfer cyllidwyr y DU a rhyngwladol.
Meysydd goruchwyliaeth
Goruchwyliaeth gyfredol
Max Mitchell
News articles
Contact Details
+44 29206 88492
Adeilad Hadyn Ellis, Ystafell Room 3.33, Heol Maendy, Caerdydd, CF24 4HQ
Themâu ymchwil
Arbenigeddau
- Bioleg celloedd niwronau