Professor Derek Blake
Professor of Neuroscience, Division of Psychological Medicine and Clinical Neurosciences
- BlakeDJ@cardiff.ac.uk
- +44 29206 88468
- Hadyn Ellis Building, Room 2.52, Maindy Road, Cardiff, CF24 4HQ
- Media commentator
- Available for postgraduate supervision
Overview
My research is focussed on the molecular basis of a range of inherited disorders (eg. neurodevelopmental syndromes and muscular dystrophies) that affect the brain and striated muscle. I use a range of molecular biology techniques to determine the cellular function of proteins involved in the aforementioned disorders. I am particularly interested in the effects of mutations and polymorphisms on protein function since these studies can identify underlying pathologies and potential therapies. We also use functional genomics and proteomic techniques to study disease mechanisms in common, polygenic disorders including schizophrenia, Alzheimer's disease and Fuchs' endothelial corneal dystrophy (FECD).
Publication
2023
- Esapa, C. T. et al. 2023. Misfolding of fukutin-related protein (FKRP) variants in congenital and limb girdle muscular dystrophies. Frontiers in Molecular Biosciences 10 (10.3389/fmolb.2023.1279700)
2022
- Stathopoulou, K. et al. 2022. CMYA5 is a novel interaction partner of FHL2 in cardiac myocytes. FEBS Journal 289(15), pp. 4622-4645. (10.1111/febs.16402)
- 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), article number: 27. (10.1038/s41467-021-27601-0)
2021
- Nurm, K. et al. 2021. Isoform-specific reduction of the basic Helix-Loop-Helix transcription factor TCF4 levels in Huntington's disease. eNeuro 8(5), article number: 0197-21.2021. (10.1523/ENEURO.0197-21.2021)
2019
- Chapman, R. M. et al. 2019. Convergent evidence that ZNF804A is a regulator of pre-messenger RNA processing and gene expression. Schizophrenia Bulletin 45(6), pp. 1267-1278. (10.1093/schbul/sby183)
- Cameron, D., Blake, D. J., Bray, N. J. and Hill, M. J. 2019. Transcriptional changes following cellular knockdown of the schizophrenia risk gene SETD1A are enriched for common variant association with the disorder. Molecular Neuropsychiatry 5(2), pp. 109-114. (10.1159/000497181)
- Lamb, R. et al. 2019. A novel TBK1 mutation in a family with diverse frontotemporal dementia spectrum disorders. Molecular Case Studies 5(3), article number: a003913. (10.1101/mcs.a003913)
- Okumura, N. et al. 2019. Effect of trinucleotide repeat expansion on the expression of TCF4 mRNA in Fuchs' endothelial corneal dystrophy. Investigative Ophthalmology & Visual Science 60(2), pp. 779. (10.1167/iovs.18-25760)
2018
- Forrest, M. P., Hill, M. J., Kavanagh, D. H., Tansey, K. E., Waite, A. J. and Blake, D. J. 2018. The psychiatric risk gene transcription factor 4 (TCF4) regulates neurodevelopmental pathways associated with schizophrenia, autism, and intellectual disability. Schizophrenia Bulletin 44(5), pp. 1100-1110. (10.1093/schbul/sbx164)
- Gyöngyösi, M., Haller, P. M., Blake, D. J. and Martin Rendon, E. 2018. Meta-analysis of cell therapy studies in heart failure and acute myocardial infarction. Circulation Research 123(2), pp. 301-308. (10.1161/CIRCRESAHA.117.311302)
2017
- Benson, M. A. et al. 2017. Ryanodine receptors are part of the myospryn complex in cardiac muscle. Scientific Reports 7(1), article number: 6312. (10.1038/s41598-017-06395-6)
- Petit, E. I. et al. 2017. Dysregulation of specialized delay/interference-dependent working memory following loss of Dysbindin-1A in schizophrenia-related phenotypes. Neuropsychopharmacology 42(6), pp. 1349-1360. (10.1038/npp.2016.282)
- Harvey, E. et al. 2017. Potency of human cardiosphere-derived cells from patients with ischemic heart disease is associated with robust vascular supportive ability. Stem Cells Translational Medicine 6(5), pp. 1399-1411. (10.1002/sctm.16-0229)
- Xiao, J. et al. 2017. Role of major and brain-specific Sgce isoforms in the pathogenesis of myoclonus-dystonia syndrome. Neurobiology of Disease 98, pp. 52-65. (10.1016/j.nbd.2016.11.003)
- Grütz, K. et al. 2017. Faithful SGCE imprinting in iPSC-derived cortical neurons: an endogenous cellular model of myoclonus-dystonia. Scientific Reports 7, article number: 41156. (10.1038/srep41156)
2016
- Waite, A. J., Carlisle, F. A., Chan, Y. M. and Blake, D. J. 2016. Myoclonus dystonia and muscular dystrophy: ɛ-sarcoglycan is part of the dystrophin-associated protein complex in brain. Movement Disorders 31(11), pp. 1694-1703. (10.1002/mds.26738)
2015
- Koppers, M. et al. 2015. C9orf72 ablation in mice does not cause motor neuron degeneration or motor deficits. Annals of Neurology 78(3), pp. 426-438. (10.1002/ana.24453)
2014
- Peall, K. J. et al. 2014. SGCE and myoclonus dystonia: motor characteristics, diagnostic criteria and clinical predictors of genotype. Journal of Neurology 261(12), pp. 2296-2304. (10.1007/s00415-014-7488-3)
- Hill, M., Forrest, M. P., Martin-Rendon, E. and Blake, D. J. 2014. Association of Transcription Factor 4 (TCF4) variants with schizophrenia and intellectual disability. Current Behavioral Neuroscience Reports 1(4), pp. 206-214. (10.1007/s40473-014-0027-9)
- Peall, K. J. et al. 2014. SGCZ mutations are unlikely to be associated with myoclonus dystonia. Neuroscience 272, pp. 88-91. (10.1016/j.neuroscience.2014.04.034)
- Waite, A., Bäumer, D., East, S., Neal, J., Morris, H., Ansorge, O. and Blake, D. 2014. Reduced C9orf72 protein levels in frontal cortex of amyotrophic lateral sclerosis and frontotemporal degeneration brain with the C9ORF72 hexanucleotide repeat expansion. Neurobiology of Aging 35(7), pp. 1779.e5-1779.e13. (10.1016/j.neurobiolaging.2014.01.016)
- Forrest, M., Hill, M. J., Quantock, A. J., Martin-Rendon, E. and Blake, D. J. 2014. The emerging roles of TCF4 in disease and development. Trends in Molecular Medicine 20(6), pp. 322-331. (10.1016/j.molmed.2014.01.010)
2013
- Xu, L. et al. 2013. Adeno-associated virus 9 mediated FKRP gene therapy restores functional glycosylation of α-dystroglycan and improves muscle functions. Molecular Therapy 21(10), pp. 1832-40. (10.1038/mt.2013.156)
- Forrest, M., Waite, A. J., Martin-Rendon, E. and Blake, D. J. 2013. Knockdown of human TCF4 affects multiple signaling pathways involved in cell survival, epithelial to mesenchymal transition and neuronal differentiation. PLoS ONE 8(8), pp. e73169. (10.1371/journal.pone.0073169)
- Peall, K. J. et al. 2013. SGCE mutations cause psychiatric disorders: clinical and genetic characterization. Brain 136(1), pp. 294-303. (10.1093/brain/aws308)
2012
- Forrest, M., Chapman, R. M., Doyle, A. M., Tinsley, C. L., Waite, A. J. and Blake, D. J. 2012. Functional analysis of TCF4 missense mutations that cause Pitt-Hopkins syndrome. Human Mutation 33(12), pp. 1676-1686. (10.1002/humu.22160)
- Waite, A. J., Brown, S. C. and Blake, D. J. 2012. The dystrophin-glycoprotein complex in brain development and disease [Review]. Trends in Neurosciences 35(8), pp. 487-496. (10.1016/j.tins.2012.04.004)
- Peall, K. J. et al. 2012. Myoclonus dystonia syndrome: SGCE mutations and psychiatric disease [Abstract]. Journal of Neurology 259, pp. S30-S30.
- Morris, H. R., Waite, A. J., Williams, N. M., Neal, J. W. and Blake, D. J. 2012. Recent advances in the genetics of the ALS-FTLD complex. Current Neurology and Neuroscience Reports 12(3), pp. 243-250. (10.1007/s11910-012-0268-5)
- Chapman, R. M., Tinsley, C. L., Doyle, A. M., O'Donovan, M. C. and Blake, D. J. 2012. Inducible over-expression and siRNA mediated knock-down of the schizophrenia susceptibility gene ZNF804A: Detection of altered gene expression and splicing using whole genome exon arrays. International Journal of Developmental Neuroscience 30(8), pp. 673-673. (10.1016/j.ijdevneu.2012.10.011)
2011
- Waite, A. J., De Rosa, M. C., Brancaccio, A. and Blake, D. J. 2011. A gain-of-glycosylation mutation associated with myoclonus-dystonia syndrome affects trafficking and processing of mouse ε-sarcoglycan in the late secretory pathway. Human Mutation 32(11), pp. 1246-1258. (10.1002/humu.21561)
- Renton, A. et al. 2011. A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-linked ALS-FTD. Neuron 72(2), pp. 257-268. (10.1016/j.neuron.2011.09.010)
- Talbot, K., Louneva, N., Cohen, J. W., Kazi, H., Blake, D. J. and Arnold, S. E. 2011. Synaptic dysbindin-1 reductions in schizophrenia occur in an isoform-specific manner indicating their subsynaptic location. PLoS ONE 6(3), article number: e16886. (10.1371/journal.pone.0016886)
- Peall, K. J., Waite, A. J., Blake, D. J., Owen, M. J. and Morris, H. R. 2011. Psychiatric disorders, myoclonus dystonia, and the epsilon-sarcoglycan gene: a systematic review. Movement Disorders 26(10), pp. 1939-1942. (10.1002/mds.23791)
2010
- Lu, P. J. et al. 2010. Mutations alter secretion of fukutin-related protein. Biochimica et Biophysica Acta - Molecular Basis of Disease 1802(2), pp. 253-258. (10.1016/j.bbadis.2009.10.016)
- Chan, Y. M. et al. 2010. Fukutin-related protein is essential for mouse muscle, brain and eye development and mutation recapitulates the wide clinical spectrums of dystroglycanopathies. Human Molecular Genetics 19(20), pp. 3995-4006. (10.1093/hmg/ddq314)
2009
- Borg, K. et al. 2009. Intragenic deletion of TRIM32 in compound heterozygotes with sarcotubular myopathy/LGMD2H. Human Mutation 30(10), pp. E831-E844. (10.1002/humu.21063)
- Locke, M., Tinsley, C. L., Benson, M. A. and Blake, D. J. 2009. TRIM32 is an E3 ubiquitin ligase for dysbindin. Human Molecular Genetics 18(13), pp. 2344-2358. (10.1093/hmg/ddp167)
- Waite, A. J., Tinsley, C. L., Locke, M. and Blake, D. J. 2009. The neurobiology of the dystrophin-associated glycoprotein complex. Annals of Medicine 41(5), pp. 344-359. (10.1080/07853890802668522)
- Tang, J. et al. 2009. Dysbindin-1 in dorsolateral prefrontal cortex of schizophrenia cases is reduced in an isoform-specific manner unrelated to dysbindin-1 mRNA expression. Human Molecular Genetics 18(20), pp. 3851-3863. (10.1093/hmg/ddp329)
2008
- Hjermind, L. E. et al. 2008. No muscle involvement in myoclonus-dystonia caused by ɛ-sarcoglycan gene mutations. European Journal of Neurology 15(5), pp. 525-529. (10.1111/j.1468-1331.2008.02116.x)
2007
- Keramaris-Vrantsis, E. et al. 2007. Fukutin-related protein localizes to the Golgi apparatus and mutations lead to mislocalization in muscle in vivo. Muscle & Nerve 36(4), pp. 455-465. (10.1002/mus.20833)
- Schröder, J. E. et al. 2007. Dystroglycan regulates structure, proliferation and differentiation of neuroepithelial cells in the developing vertebrate CNS. Developmental Biology 307(1), pp. 62-78. (10.1016/j.ydbio.2007.04.020)
- Blake, D. J. 2007. Dysbindin-1 is a synaptic and microtubular protein that binds brain snapin.. Schizophrenia bulletin 33(2), pp. 255-255.
- Esapa, C. T. et al. 2007. SGCE missense mutations that cause myoclonus-dystonia syndrome impair epsilon-sarcoglycan trafficking to the plasma membrane: modulation by ubiquitination and torsinA. Human Molecular Genetics 16(3), pp. 327-342. (10.1093/hmg/ddl472)
- Martin-Rendon, E. and Blake, D. J. 2007. Patenting human genes and stem cells. Recent Patents on DNA and Gene Sequences 1(1), pp. 25-34.
2006
- Talbot, K. et al. 2006. Dysbindin-1 is a synaptic and microtubular protein that binds brain snapin. Human Molecular Genetics 15(20), pp. 3041-3054. (10.1093/hmg/ddl246)
2005
- Blake, D. J., Esapa, C. T. and McIlhinney, R. A. 2005. Fukutin-related protein mutations that cause congenital muscular dystrophy result in ER-retention of the mutant protein in cultured cells. Human Molecular Genetics 14(2), pp. 295-305. (10.1093/hmg/ddi026)
- Blake, D. J., Esapa, C. T., Martin-Rendon, E. and McIlhinney, R. A. 2005. Glycosylation defects and muscular dystrophy. Advances in Experimental Medicine and Biology 564, pp. 97-98. (10.1007/0-387-25515-X_15)
2004
- Lien, C. F., Vlachouli, C., Blake, D. J., Simons, J. P. and Górecki, D. C. 2004. Differential spatio-temporal expression of alpha-dystrobrevin-1 during mouse development. Gene Expression Patterns 4(5), pp. 583-593. (10.1016/j.modgep.2004.01.015)
- Benson, M. A., Sillitoe, R. V. and Blake, D. J. 2004. Schizophrenia genetics: dysbindin under the microscope. Trends in Neurosciences 27(9), pp. 516-519. (10.1016/j.tins.2004.06.004)
- Talbot, K. et al. 2004. Dysbindin-1 is reduced in intrinsic, glutamatergic terminals of the hippocampal formation in schizophrenia. The Journal of Clinical Investigation 113(9), pp. 1353-1363. (10.1172/JCI200420425)
- Talbot, K. et al. 2004. Dysbindin-1 is reduced in intrinsic, glutamatergic terminals of the hippocampal formation in schizophrenia. The Journal of Clinical Investigation 113(9), pp. 1353-1363. (10.1172/JCI200420425)
- Benson, M. A., Tinsley, C. L. and Blake, D. J. 2004. Myospryn is a novel binding partner for dysbindin in muscle. Journal of Biological Chemistry 279(11), pp. 10450-10458. (10.1074/jbc.M312664200)
2003
- Esapa, C. T., Bentham, G. R. B., Schröder, J. E., Kröger, S. and Blake, D. J. 2003. The effects of post-translational processing on dystroglycan synthesis and trafficking. FEBS Letters 555(2), pp. 209-216. (10.1016/S0014-5793(03)01230-4)
- Burgueno, J. et al. 2003. The adenosine A2A receptor interacts with the actin-binding protein α-actinin. Journal of Biological Chemistry 278(39), pp. 37545-37552. (10.1074/jbc.M302809200)
- Li, W. et al. 2003. Hermansky-Pudlak syndrome type 7 (HPS-7) results from mutant dysbindin, a member of the biogenesis of lysosome-related organelles complex 1 (BLOC-1) [Letter]. Nature Genetics 35(1), pp. 84-89. (10.1038/ng1229)
- Muntoni, F. et al. 2003. 114th ENMC International Workshop on Congenital Muscular Dystrophy (CMD) 17?19 January 2003, Naarden, The Netherlands: (8th Workshop of the International Consortium on CMD; 3rd Workshop of the MYO-CLUSTER project GENRE). Neuromuscular Disorders 13(7-8), pp. 579-588. (10.1016/S0960-8966(03)00072-5)
- Sillitoe, R. V., Benson, M. A., Blake, D. J. and Hawkes, R. 2003. Abnormal dysbindin expression in cerebellar mossy fiber synapses in the mdx mouse model of Duchenne muscular dystrophy. Journal of Neuroscience 23(16), pp. 6576-6585.
- Sillitoe, R., Benson, M., Blake, D. J. and Hawkes, R. 2003. Abnormal dysbindin expression in cerebellar mossy fiber synapses in the mdx mouse model of Duchenne muscular dystrophy.. Journal of Neuroscience 23(16), pp. 6576-6585.
- Mercuri, E. et al. 2003. Phenotypic spectrum associated with mutations in the fukutin-related protein gene. Annals of Neurology 53(4), pp. 537-542. (10.1002/ana.10559)
- Martin-Rendon, E. and Blake, D. J. 2003. Protein glycosylation in disease: new insights into the congenital muscular dystrophies. Trends in Pharmacological Sciences 24(4), pp. 178-183. (10.1016/S0165-6147(03)00050-6)
- Topaloglu, H. et al. 2003. FKRP gene mutations cause congenital muscular dystrophy, mental retardation, and cerebellar cysts. Neurology 60(6), pp. 988-992. (10.1212/01.WNL.0000052996.14099.DC)
2002
- Blake, D. J., Martin-Rendon, E., Schroder, J. E. and Benson, M. A. 2002. Functional requirements for fukutin-related protein in the Golgi apparatus. Human Molecular Genetics 11(26), pp. 3319-3331. (10.1093/hmg/11.26.3319)
- Muntoni, F., Brockington, M., Blake, D. J., Torelli, S. and Brown, S. C. 2002. Defective glycosylation in muscular dystrophy. The Lancet 360(9343), pp. 1419-1421. (10.1016/S0140-6736(02)11397-3)
- Blake, D. J. 2002. Dystrobrevin dynamics in muscle-cell signalling: a possible target for therapeutic intervention in Duchenne muscular dystrophy?. Neuromuscular Disorders 12, pp. S110. (10.1016/S0960-8966(02)00091-3)
- Blake, D. J. and Martin-Rendon, E. 2002. Intermediate filaments and the function of the dystrophin-protein complex. Trends in Cardiovascular Medicine 12(5), pp. 224-228. (10.1016/S1050-1738(02)00166-4)
- Blank, M., Blake, D. J. and Kröger, S. 2002. Molecular diversity of the dystrophin-like protein complex in the developing and adult avian retina. Neuroscience 111(2), pp. 259-273. (10.1016/S0306-4522(02)00032-5)
- Blake, D. J., Weir, A., Newey, S. E. and Davies, K. E. 2002. Function and genetics of dystrophin and dystrophin-related proteins in muscle. Physiological Reviews 82(2), pp. 291-329. (10.1152/physrev.00028.2001)
- Brockington, M., Blake, D. J., Brown, S. C. and Muntoni, F. 2002. The gene for a novel glycosyltransferase is mutated in congenital muscular dystrophy MDC1C and limb girdle muscular dystrophy 2I [Editorial]. Neuromuscular Disorders 12(3), pp. 233-234. (10.1016/S0960-8966(01)00325-X)
2001
- Marangi, P. A. et al. 2001. Acetylcholine receptors are required for agrin-induced clustering of postsynaptic proteins. The EMBO Journal 20(24), pp. 7060-7073. (10.1093/emboj/20.24.7060)
- Brockington, M. et al. 2001. Mutations in the fukutin-related protein gene (FKRP) cause a form of congenital muscular dystrophy with secondary laminin 2 deficiency and abnormal glycosylation of -dystroglycan. American Journal of Human Genetics 69(6), pp. 1198-1209. (10.1086/324412)
- , . 2001. Mutations in the fukutin-related protein gene (FKRP) identify limb girdle muscular dystrophy 2I as a milder allelic variant of congenital muscular dystrophy MDC1C. Human Molecular Genetics 10(25), pp. 2851-2859. (10.1093/hmg/10.25.2851)
- Blake, D. J., Brockington, M., Muntoni, F. and Benson, M. A. 2001. Golgi-localisation of fukutin and fukutin-related protein: implications for muscular dystrophy. Molecular Biology of the Cell 12, pp. 85A-85A.
- Loh, N. Y., Nebenius-Oosthuizen, D., Blake, D. J., Smith, A. J. H. and Davies, K. E. 2001. Role of β-dystrobrevin in nonmuscle dystrophin-associated protein complex-like complexes in kidney and liver. Molecular and Cellular Biology 21(21), pp. 7442-7448. (10.1128/MCB.21.21.7442-7448.2001)
- Brickington, M. et al. 2001. A novel glycosyltransferase is mutated in a form of congenital muscular dystrophy with secondary laminin alpha 2 deficiency and abnormal glycosylation of alpha-dystroglycan. American Journal of Human Genetics 69(4), pp. 229-229.
- Brockington, M., Prandini, P., Brown, S. C., Sewry, C. A., Blake, D. J. and Muntoni, F. 2001. A new gene encoding a fukutin-like protein and its analysis in patients with congenital muscular dystrophy [Abstract]. Neuromuscular Disorders 11(6-7), pp. 635-635.
- Benson, M. A., Newey, S. E., Martin-Rendon, E., Hawkes, R. and Blake, D. J. 2001. Dysbindin, a novel coiled-coil-containing protein that interacts with the dystrobrevins in muscle and brain. Journal of Biological Chemistry 276(26), pp. 24232-24241. (10.1074/jbc.M010418200)
- Newey, S. E. et al. 2001. Syncoilin, a novel member of the intermediate filament superfamily that interacts with α-dystrobrevin in skeletal muscle. Journal of Biological Chemistry 276(9), pp. 6645-6655. (10.1074/jbc.M008305200)
- Newey, S. E. et al. 2001. Syncoilin, a novel member of the intermediate filament superfamily that interacts with alpha-dystrobrevin in skeletal muscle. Journal of Biological Chemistry 276(9), pp. 6645-6655. (10.1074/jbc.M008305200)
- Newey, S. E., Gramolini, A. O., Wu, J., Holzfeind, P., Jasmin, B. J., Davies, K. E. and Blake, D. J. 2001. A novel mechanism for modulating synaptic gene expression: differential localization of alpha-dystrobrevin transcripts in skeletal muscle. Molecular and Cellular Neuroscience 17(1), pp. 127-140. (10.1212/01.wnl.0000302174.08951.cf.)
- Newey, S. E., Gramolini, A. O., Wu, J., Holzfiend, P., Jasmin, B. J., Davies, K. E. and Blake, D. J. 2001. A novel mechanism for modulating synaptic gene expression: differential localization of α-dystrobrevin transcripts in skeletal muscle. Molecular and Cellular Neuroscience 17(1), pp. 127-140. (10.1006/mcne.2000.0918)
2000
- Newey, S. E., Benson, M. A., Ponting, C. P., Davies, K. E. and Blake, D. J. 2000. Alternative splicing of dystrobrevin regulates the stoichiometry of syntrophin binding to the dystrophin protein complex. Current Biology 10(20), pp. 1295-1298. (10.1016/S0960-9822(00)00760-0)
- Loh, N. Y., Newey, S. E., Davies, K. E. and Blake, D. J. 2000. Assembly of multiple dystrobrevin-containing complexes in the kidney. Journal of Cell Science 113(15), pp. 2715-2724.
- Blake, D. J. and Kröger, S. 2000. The neurobiology of Duchenne muscular dystrophy: learning lessons from muscle?. Trends in Neurosciences 23(3), pp. 92-99. (10.1016/S0166-2236(99)01510-6)
1999
- Blake, D. J., Hawkes, R., Benson, M. A. and Beesley, P. W. 1999. Different dystrophin-like complexes are expressed in neurons and glia. Journal of Cell Biology 147(3), pp. 645-658. (10.1083/jcb.147.3.645)
- Blank, M., Koulen, P., Blake, D. J. and Kröger, S. 1999. Dystrophin and beta-dystroglycan in photoreceptor terminals from normal and mdx3Cv mouse retinae. European Journal of Neuroscience 11(6), pp. 2121-2133. (10.1046/j.1460-9568.1999.00636.x)
- Holzfeind, P. J., Ambrose, H. J., Newey, S. E., Nawrotzki, R. A., Blake, D. J. and Davies, K. E. 1999. Tissue-selective Expression of alpha-Dystrobrevin is Determined by Multiple Promoters. Journal of Biological Chemistry 274(10), pp. 6250-6258. (10.1074/jbc.274.10.6250)
- Blake, D. J., Benson, M. A., Hawkes, R. and Beesley, P. W. 1999. Dystrophin-binding proteins in the brain. Journal of Neurochemistry 73, pp. S93-S93.
1998
- Loh, N. Y., Ambrose, H. J., Guay-Woodford, L. M., DasGupta, S., Nawrotzki, R. A., Blake, D. J. and Davies, K. E. 1998. Genomic organization and refined mapping of the mouse beta-dystrobrevin gene. Mammalian Genome 9(11), pp. 857-862.
- Loh, N. Y., Ambrose, H. J., Guay-Woodford, L. M., DasGupta, S., Nawrotzki, R. A., Blake, D. J. and Davies, K. E. 1998. Genomic organization and refined mapping of the mouse β-dystrobrevin gene. Mammalian Genome 9(11), pp. 857-862. (10.1007/s003359900883)
- Nawrotzki, R., Loh, N. Y., Ruegg, M. A., Davies, K. E. and Blake, D. J. 1998. Characterisation of alpha-dystrobrevin in muscle. Journal of Cell Science 111(17), pp. 2595-2605.
- Vater, R. et al. 1998. Utrophin mRNA expression in muscle is not restricted to the neuromuscular junction. Molecular and Cellular Neuroscience 10(5-6), pp. 229-242. (10.1006/mcne.1998.0661)
- Blake, D. J., Nawrotzki, R., Loh, N. Y., Gorecki, D. C. and Davies, K. E. 1998. β-dystrobrevin, a member of the dystrophin-related protein family. Proceedings of the National Academy of Sciences of the United States of America 95(1), pp. 241-246.
- Blake, D. J., Nawrotzki, R., Loh, N. Y., Gorecki, D. C. and Davies, K. E. 1998. beta-dystrobrevin, a member of the dystrophin-related protein family. Proceedings of the National Academy of Sciences of the United States of America 95(1), pp. 241-246. (10.1073/pnas.95.1.241)
1997
- Blake, D. J., Loh, N. Y., Beesley, P. and Davies, K. E. 1997. The function dystrophin-related and -associated proteins in the brain. Journal of Neurochemistry 69(S), pp. S123-S123.
- Blake, D. J., Nawrotzki, R., Loh, N. Y. and Davies, K. E. 1997. A novel dystrophin-associated protein in brain. American Journal of Human Genetics 61(4), pp. A8-A8.
- Loh, N. Y., Blake, D. J., Nawrotzki, R., Ambrose, H. J. and Davies, K. E. 1997. Beta-dystrobrevin; a new member of the dystrophin-related protein family. American Journal of Human Genetics 61(4), pp. A177-A177.
- Metzinger, L. et al. 1997. Dystrobrevin deficiency at the sarcolemma of patients with muscular dystrophy. Human Molecular Genetics 6(7), pp. 1185-1191. (10.1093/hmg/6.7.1185)
- Ponting, C. P., Phillips, C., Davies, K. E. and Blake, D. J. 1997. PDZ domains: targeting signalling molecules to sub-membranous sites. Bioessays 19(6), pp. 469-479. (10.1002/bies.950190606)
- Ambrose, H. J., Blake, D. J., Nawrotzki, R. A. and Davies, K. E. 1997. Genomic organization of the mouse dystrobrevin gene: comparative analysis with the dystrophin gene. Genomics 39(3), pp. 359-369. (10.1006/geno.1996.4515)
1996
- Picketts, D. J., Higgs, D. R., Bachoo, S., Blake, D. J., Quarrel, O. W. J. and Gibbons, R. J. 1996. ATRX encodes a novel member of the SNF2 family of proteins: mutations point to a common mechanism underlying the ATR-X syndrome. Human Molecular Genetics 5(12), pp. 1899-1907. (10.1093/hmg/5.12.1899)
- Morrison, K. E. et al. 1996. Novel transcribed sequences represented in the complex genomic region 5q13. Acta Biochimica et Biophysica 1308(2), pp. 97-102. (10.1016/0167-4781(96)00097-8)
- Nawrotzki, R., Blake, D. J. and Davies, K. E. 1996. The genetic basis of neuromuscular disorders. Trends in Genetics 12(8), pp. 294-298. (10.1016/0168-9525(96)10033-0)
- Theodosiou, A. M. et al. 1996. A member of the MAP kinase phosphatase gene family in mouse containing a complex trinucleotide repeat in the coding region. Human Molecular Genetics 5(5), pp. 675-684. (10.1093/hmg/5.5.675)
- Blake, D. J., Nawrotzki, R. A., Peters, M. F., Froehner, S. C. and Davies, K. E. 1996. Isoform diversity of dystrobrevin, the murine 87-kDa postsynaptic protein. Journal of Biological Chemistry 271(13), pp. 7802-7810. (10.1074/jbc.271.13.7802)
- Zuelling, R. A., Blake, D. J., Tinsley, J. M. and Davies, K. E. 1996. Cloning of the rat utrophin and characterization of an alternate transcript. Journal of Muscle Research and Cell Motility 17(1), pp. 110-110.
- Zuellig, R. A., Blake, D. J., Tinsley, J. M. and Davies, K. E. 1996. Cloning of the rat utrophin and characterization of an alternate transcript. Journal of Muscle Research and Cell Motility 17(1), pp. 110-110.
- Blake, D. J., Tinsley, J. M. and Davies, K. E. 1996. Utrophin: a structural and functional comparison to dystrophin. Brain Pathology 6(1), pp. 37-47. (10.1111/j.1750-3639.1996.tb00781.x)
- Ponting, C. P., Blake, D. J., Davies, K. E., Kendrick-Jones, J. and Winder, S. J. 1996. ZZ and TAZ: new putative zinc fingers in dystrophin and other proteins. Trends in Biochemical Sciences 21(1), pp. 11-13. (10.1016/S0968-0004(06)80020-4)
1995
- Millwood, I. Y., Blake, D. J., Gauguier, D. and Monaco, A. P. 1995. Two polymorphic dinucleotide repeats in the rat dystrophin gene, including the conserved 3' UTR repeat. Mammalian Genome 6(9), pp. 668-669.
- Davies, K. E., Tinsley, J. M. and Blake, D. J. 1995. Molecular analysis of Duchenne muscular dystrophy: past, present, and future. Annals of the New York Academy of Sciences 758, pp. 287-296. (10.1111/j.1749-6632.1995.tb24834.x)
- Blake, D. J. et al. 1995. G-Utrophin, the autosomal homologue of dystrophin Dp116, is expressed in sensory ganglia and brain. Proceedings of the National Academy of Sciences of the United States of America 92(9), pp. 3697-3701. (10.1073/pnas.92.9.3697)
- Blake, D. J., Tinsley, J. M., Davies, K. E., Knight, A. E., Winder, S. J. and Kendrick-Jones, J. 1995. Coiled-coil regions in the carboxy-terminal domains of dystrophin and related proteins: potentials for protein-protein interactions. Trends in Biochemical Sciences 20(4), pp. 133-135. (10.1016/S0968-0004(00)88986-0)
- Pasquini, F., Guerin, C., Blake, D. J., Davies, K., Karpati, G. and Holland, P. 1995. The effect of glucocorticoids on the accumulation of utrophin by cultured normal and dystrophic human skeletal muscle satellite cells. Neuromuscular Disorders 5(2), pp. 105-114. (10.1016/0960-8966(94)00042-8)
1994
- Brookes, A. J., Slorach, E. M., Morrison, K. E., Qureshi, S. J., Blake, D. J., Davies, K. and Porteous, D. J. 1994. Cloning the shared components of complex DNA resources. Human Molecular Genetics 3(11), pp. 2011-2017. (10.1093/hmg/3.11.2011)
- Tinsley, J. M., Blake, D. J., Zuellig, R. A. and Davies, K. E. 1994. Increasing complexity of the dystrophin-associated protein complex. Proceedings of the National Academy of Sciences of the United States of America 91(18), pp. 8307-8313.
- Schofield, J. N., Blake, D. J., Simmons, C., Morris, G. E., Tinsley, J. M., Davies, K. E. and Edwards, Y. H. 1994. Apo-dystrophin-1 and apo-dystrophin-2, products of the Duchenne muscular dystrophy locus: expression during mouse embryogenesis and in cultured cell lines. Human Molecular Genetics 3(8), pp. 1309-1316. (10.1093/hmg/3.8.1309)
- Davies, K., Tinsley, J., Blake, D. J., Pearce, M., Deconick, A. and Dennis, C. 1994. Possible roles for utrophin in gene-therapy of duchenne muscular-dystrophy. Journal of Cellular Biochemistry 1994(18A), pp. 188-188.
- Blake, D. J., Tinsley, J. M. and Davies, K. E. 1994. The emerging family of dystrophin-related proteins. Trends in Cell Biology 4(1), pp. 19-23. (10.1016/0962-8924(94)90034-5)
1993
- Pearce, M., Blake, D. J., Tinsley, J. M., Byth, B. C., Campbell, L., Monaco, A. P. and Davies, K. E. 1993. The utrophin and dystrophin genes share similarities in genomic structure. Human Molecular Genetics 2(11), pp. 1765-1772. (10.1093/hmg/2.11.1765)
- Tinsley, J. M., Blake, D. J., Pearce, M., Knight, A. E., Kendrick-Jones, J. and Davies, K. E. 1993. Dystrophin and related proteins. Current Opinion in Genetics & Development 3(3), pp. 484-490. (10.1016/0959-437X(93)90124-8)
- Tinsley, J. M., Blake, D. J. and Davies, K. E. 1993. Apo-dystrophin-3: a 2.2kb transcript from the DMD locus encoding the dystrophin glycoprotein binding site. Human Molecular Genetics 2(5), pp. 521-524. (10.1093/hmg/2.5.521)
- Blake, D. 1993. Dystrophin and dystrophin-related proteins: a review of protein and RNA studies. Neuromuscular Disorders 3(1), pp. 5-21. (10.1016/0960-8966(93)90037-K)
1992
- Blake, D. J. et al. 1992. Characterization of a 4.8kb transcript from the Duchenne muscular dystrophy locus expressed in Schwannoma cells. Human Molecular Genetics 1(2), pp. 103-109. (10.1093/hmg/1.2.103)
- Tinsley, J. M. et al. 1992. Primary structure of dystrophin-related protein. Nature 360(6404), pp. 591-593. (10.1038/360591a0)
- thi Man, N., Thanh, L., Blake, D. J., Davies, K. . and Morris, G. E. 1992. Utrophin, the autosomal homologue of dystrophin, is widely-expressed and membrane-associated in cultured cell lines. FEBS Letters 313(1), pp. 19-22. (10.1016/0014-5793(92)81174-K)
1991
- Coleman, M. P. et al. 1991. Genetic and physical mapping around the properdin P gene. Genomics 11(4), pp. 991-996. (10.1016/0888-7543(91)90024-9)
- Sellar, G. C., Blake, D. J. and Reid, K. B. 1991. Characterization and organization of the genes encoding the A-, B- and C-chains of human complement subcomponent C1q. The complete derived amino acid sequence of human C1q. Biochemical Journal 274(2), pp. 481-490.
- Sellar, G. C., Blake, D. J. and Reid, K. B. 1991. Characterization and organization of the genes encoding the A-, B- and C-chains of human complement subcomponent C1q. The complete derived amino acid sequence of human C1q. Biochemical Journal 274(2), pp. 481-490. (10.1042/bj2740481)
1989
- Knott, V., Blake, D. J. and Brownlee, G. G. 1989. Completion of the detailed restriction map of the E.coli genome by the isolation of overlapping cosmid clones. Nucleic Acids Research 17(15), pp. 5901-5912. (10.1093/nar/17.15.5901)
- Blake, D. J. and Brownlee, G. G. 1989. Deletion of the MCF.2 transforming gene in 2 Hemophilia-B inhibitor patients [Abstract]. Cytogenetics and Cell Genetics 51(1-4), pp. 963.
- Blake, D. J. and Brownlee, G. 1989. Deletion of the mcf.2 transforming gene in 2 hemophilia-b inhibitor patients. Cytogenetics and Cell Genetics 51(1-4), pp. 963-963.
1988
- Anson, D. S., Blake, D. J., Winship, P. R., Birnbaum, D. and Brownlee, G. G. 1988. Nullisomic deletion of the mcf.2 transforming gene in two haemophilia B patients. EMBO Journal 7(9), pp. 2795-2799.
- Anson, D., Blake, D. J., Winship, P., Birnbaum, D. and Brownlee, G. 1988. Nullisomic deletion of the mcf.2 transforming gene in two haemophilia B patients.. EMBO Journal 7(9), pp. 2795-2799.
1987
- Blake, D. J., Knott, V. and Brownlee, G. 1987. A random cosmid contig approach to gene-mapping [Abstract]. Cytogenetics and Cell Genetics 46(1-4), pp. 581. (10.1159/000316989)
- Blake, D. J., Knott, V. and Brownlee, G. 1987. A random cosmid contig approach to gene-mapping. Cytogenetics and Cell Genetics 46(1), pp. 581-581.
Articles
- Esapa, C. T. et al. 2023. Misfolding of fukutin-related protein (FKRP) variants in congenital and limb girdle muscular dystrophies. Frontiers in Molecular Biosciences 10 (10.3389/fmolb.2023.1279700)
- Stathopoulou, K. et al. 2022. CMYA5 is a novel interaction partner of FHL2 in cardiac myocytes. FEBS Journal 289(15), pp. 4622-4645. (10.1111/febs.16402)
- 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), article number: 27. (10.1038/s41467-021-27601-0)
- Nurm, K. et al. 2021. Isoform-specific reduction of the basic Helix-Loop-Helix transcription factor TCF4 levels in Huntington's disease. eNeuro 8(5), article number: 0197-21.2021. (10.1523/ENEURO.0197-21.2021)
- Chapman, R. M. et al. 2019. Convergent evidence that ZNF804A is a regulator of pre-messenger RNA processing and gene expression. Schizophrenia Bulletin 45(6), pp. 1267-1278. (10.1093/schbul/sby183)
- Cameron, D., Blake, D. J., Bray, N. J. and Hill, M. J. 2019. Transcriptional changes following cellular knockdown of the schizophrenia risk gene SETD1A are enriched for common variant association with the disorder. Molecular Neuropsychiatry 5(2), pp. 109-114. (10.1159/000497181)
- Lamb, R. et al. 2019. A novel TBK1 mutation in a family with diverse frontotemporal dementia spectrum disorders. Molecular Case Studies 5(3), article number: a003913. (10.1101/mcs.a003913)
- Okumura, N. et al. 2019. Effect of trinucleotide repeat expansion on the expression of TCF4 mRNA in Fuchs' endothelial corneal dystrophy. Investigative Ophthalmology & Visual Science 60(2), pp. 779. (10.1167/iovs.18-25760)
- Forrest, M. P., Hill, M. J., Kavanagh, D. H., Tansey, K. E., Waite, A. J. and Blake, D. J. 2018. The psychiatric risk gene transcription factor 4 (TCF4) regulates neurodevelopmental pathways associated with schizophrenia, autism, and intellectual disability. Schizophrenia Bulletin 44(5), pp. 1100-1110. (10.1093/schbul/sbx164)
- Gyöngyösi, M., Haller, P. M., Blake, D. J. and Martin Rendon, E. 2018. Meta-analysis of cell therapy studies in heart failure and acute myocardial infarction. Circulation Research 123(2), pp. 301-308. (10.1161/CIRCRESAHA.117.311302)
- Benson, M. A. et al. 2017. Ryanodine receptors are part of the myospryn complex in cardiac muscle. Scientific Reports 7(1), article number: 6312. (10.1038/s41598-017-06395-6)
- Petit, E. I. et al. 2017. Dysregulation of specialized delay/interference-dependent working memory following loss of Dysbindin-1A in schizophrenia-related phenotypes. Neuropsychopharmacology 42(6), pp. 1349-1360. (10.1038/npp.2016.282)
- Harvey, E. et al. 2017. Potency of human cardiosphere-derived cells from patients with ischemic heart disease is associated with robust vascular supportive ability. Stem Cells Translational Medicine 6(5), pp. 1399-1411. (10.1002/sctm.16-0229)
- Xiao, J. et al. 2017. Role of major and brain-specific Sgce isoforms in the pathogenesis of myoclonus-dystonia syndrome. Neurobiology of Disease 98, pp. 52-65. (10.1016/j.nbd.2016.11.003)
- Grütz, K. et al. 2017. Faithful SGCE imprinting in iPSC-derived cortical neurons: an endogenous cellular model of myoclonus-dystonia. Scientific Reports 7, article number: 41156. (10.1038/srep41156)
- Waite, A. J., Carlisle, F. A., Chan, Y. M. and Blake, D. J. 2016. Myoclonus dystonia and muscular dystrophy: ɛ-sarcoglycan is part of the dystrophin-associated protein complex in brain. Movement Disorders 31(11), pp. 1694-1703. (10.1002/mds.26738)
- Koppers, M. et al. 2015. C9orf72 ablation in mice does not cause motor neuron degeneration or motor deficits. Annals of Neurology 78(3), pp. 426-438. (10.1002/ana.24453)
- Peall, K. J. et al. 2014. SGCE and myoclonus dystonia: motor characteristics, diagnostic criteria and clinical predictors of genotype. Journal of Neurology 261(12), pp. 2296-2304. (10.1007/s00415-014-7488-3)
- Hill, M., Forrest, M. P., Martin-Rendon, E. and Blake, D. J. 2014. Association of Transcription Factor 4 (TCF4) variants with schizophrenia and intellectual disability. Current Behavioral Neuroscience Reports 1(4), pp. 206-214. (10.1007/s40473-014-0027-9)
- Peall, K. J. et al. 2014. SGCZ mutations are unlikely to be associated with myoclonus dystonia. Neuroscience 272, pp. 88-91. (10.1016/j.neuroscience.2014.04.034)
- Waite, A., Bäumer, D., East, S., Neal, J., Morris, H., Ansorge, O. and Blake, D. 2014. Reduced C9orf72 protein levels in frontal cortex of amyotrophic lateral sclerosis and frontotemporal degeneration brain with the C9ORF72 hexanucleotide repeat expansion. Neurobiology of Aging 35(7), pp. 1779.e5-1779.e13. (10.1016/j.neurobiolaging.2014.01.016)
- Forrest, M., Hill, M. J., Quantock, A. J., Martin-Rendon, E. and Blake, D. J. 2014. The emerging roles of TCF4 in disease and development. Trends in Molecular Medicine 20(6), pp. 322-331. (10.1016/j.molmed.2014.01.010)
- Xu, L. et al. 2013. Adeno-associated virus 9 mediated FKRP gene therapy restores functional glycosylation of α-dystroglycan and improves muscle functions. Molecular Therapy 21(10), pp. 1832-40. (10.1038/mt.2013.156)
- Forrest, M., Waite, A. J., Martin-Rendon, E. and Blake, D. J. 2013. Knockdown of human TCF4 affects multiple signaling pathways involved in cell survival, epithelial to mesenchymal transition and neuronal differentiation. PLoS ONE 8(8), pp. e73169. (10.1371/journal.pone.0073169)
- Peall, K. J. et al. 2013. SGCE mutations cause psychiatric disorders: clinical and genetic characterization. Brain 136(1), pp. 294-303. (10.1093/brain/aws308)
- Forrest, M., Chapman, R. M., Doyle, A. M., Tinsley, C. L., Waite, A. J. and Blake, D. J. 2012. Functional analysis of TCF4 missense mutations that cause Pitt-Hopkins syndrome. Human Mutation 33(12), pp. 1676-1686. (10.1002/humu.22160)
- Waite, A. J., Brown, S. C. and Blake, D. J. 2012. The dystrophin-glycoprotein complex in brain development and disease [Review]. Trends in Neurosciences 35(8), pp. 487-496. (10.1016/j.tins.2012.04.004)
- Peall, K. J. et al. 2012. Myoclonus dystonia syndrome: SGCE mutations and psychiatric disease [Abstract]. Journal of Neurology 259, pp. S30-S30.
- Morris, H. R., Waite, A. J., Williams, N. M., Neal, J. W. and Blake, D. J. 2012. Recent advances in the genetics of the ALS-FTLD complex. Current Neurology and Neuroscience Reports 12(3), pp. 243-250. (10.1007/s11910-012-0268-5)
- Chapman, R. M., Tinsley, C. L., Doyle, A. M., O'Donovan, M. C. and Blake, D. J. 2012. Inducible over-expression and siRNA mediated knock-down of the schizophrenia susceptibility gene ZNF804A: Detection of altered gene expression and splicing using whole genome exon arrays. International Journal of Developmental Neuroscience 30(8), pp. 673-673. (10.1016/j.ijdevneu.2012.10.011)
- Waite, A. J., De Rosa, M. C., Brancaccio, A. and Blake, D. J. 2011. A gain-of-glycosylation mutation associated with myoclonus-dystonia syndrome affects trafficking and processing of mouse ε-sarcoglycan in the late secretory pathway. Human Mutation 32(11), pp. 1246-1258. (10.1002/humu.21561)
- Renton, A. et al. 2011. A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-linked ALS-FTD. Neuron 72(2), pp. 257-268. (10.1016/j.neuron.2011.09.010)
- Talbot, K., Louneva, N., Cohen, J. W., Kazi, H., Blake, D. J. and Arnold, S. E. 2011. Synaptic dysbindin-1 reductions in schizophrenia occur in an isoform-specific manner indicating their subsynaptic location. PLoS ONE 6(3), article number: e16886. (10.1371/journal.pone.0016886)
- Peall, K. J., Waite, A. J., Blake, D. J., Owen, M. J. and Morris, H. R. 2011. Psychiatric disorders, myoclonus dystonia, and the epsilon-sarcoglycan gene: a systematic review. Movement Disorders 26(10), pp. 1939-1942. (10.1002/mds.23791)
- Lu, P. J. et al. 2010. Mutations alter secretion of fukutin-related protein. Biochimica et Biophysica Acta - Molecular Basis of Disease 1802(2), pp. 253-258. (10.1016/j.bbadis.2009.10.016)
- Chan, Y. M. et al. 2010. Fukutin-related protein is essential for mouse muscle, brain and eye development and mutation recapitulates the wide clinical spectrums of dystroglycanopathies. Human Molecular Genetics 19(20), pp. 3995-4006. (10.1093/hmg/ddq314)
- Borg, K. et al. 2009. Intragenic deletion of TRIM32 in compound heterozygotes with sarcotubular myopathy/LGMD2H. Human Mutation 30(10), pp. E831-E844. (10.1002/humu.21063)
- Locke, M., Tinsley, C. L., Benson, M. A. and Blake, D. J. 2009. TRIM32 is an E3 ubiquitin ligase for dysbindin. Human Molecular Genetics 18(13), pp. 2344-2358. (10.1093/hmg/ddp167)
- Waite, A. J., Tinsley, C. L., Locke, M. and Blake, D. J. 2009. The neurobiology of the dystrophin-associated glycoprotein complex. Annals of Medicine 41(5), pp. 344-359. (10.1080/07853890802668522)
- Tang, J. et al. 2009. Dysbindin-1 in dorsolateral prefrontal cortex of schizophrenia cases is reduced in an isoform-specific manner unrelated to dysbindin-1 mRNA expression. Human Molecular Genetics 18(20), pp. 3851-3863. (10.1093/hmg/ddp329)
- Hjermind, L. E. et al. 2008. No muscle involvement in myoclonus-dystonia caused by ɛ-sarcoglycan gene mutations. European Journal of Neurology 15(5), pp. 525-529. (10.1111/j.1468-1331.2008.02116.x)
- Keramaris-Vrantsis, E. et al. 2007. Fukutin-related protein localizes to the Golgi apparatus and mutations lead to mislocalization in muscle in vivo. Muscle & Nerve 36(4), pp. 455-465. (10.1002/mus.20833)
- Schröder, J. E. et al. 2007. Dystroglycan regulates structure, proliferation and differentiation of neuroepithelial cells in the developing vertebrate CNS. Developmental Biology 307(1), pp. 62-78. (10.1016/j.ydbio.2007.04.020)
- Blake, D. J. 2007. Dysbindin-1 is a synaptic and microtubular protein that binds brain snapin.. Schizophrenia bulletin 33(2), pp. 255-255.
- Esapa, C. T. et al. 2007. SGCE missense mutations that cause myoclonus-dystonia syndrome impair epsilon-sarcoglycan trafficking to the plasma membrane: modulation by ubiquitination and torsinA. Human Molecular Genetics 16(3), pp. 327-342. (10.1093/hmg/ddl472)
- Martin-Rendon, E. and Blake, D. J. 2007. Patenting human genes and stem cells. Recent Patents on DNA and Gene Sequences 1(1), pp. 25-34.
- Talbot, K. et al. 2006. Dysbindin-1 is a synaptic and microtubular protein that binds brain snapin. Human Molecular Genetics 15(20), pp. 3041-3054. (10.1093/hmg/ddl246)
- Blake, D. J., Esapa, C. T. and McIlhinney, R. A. 2005. Fukutin-related protein mutations that cause congenital muscular dystrophy result in ER-retention of the mutant protein in cultured cells. Human Molecular Genetics 14(2), pp. 295-305. (10.1093/hmg/ddi026)
- Blake, D. J., Esapa, C. T., Martin-Rendon, E. and McIlhinney, R. A. 2005. Glycosylation defects and muscular dystrophy. Advances in Experimental Medicine and Biology 564, pp. 97-98. (10.1007/0-387-25515-X_15)
- Lien, C. F., Vlachouli, C., Blake, D. J., Simons, J. P. and Górecki, D. C. 2004. Differential spatio-temporal expression of alpha-dystrobrevin-1 during mouse development. Gene Expression Patterns 4(5), pp. 583-593. (10.1016/j.modgep.2004.01.015)
- Benson, M. A., Sillitoe, R. V. and Blake, D. J. 2004. Schizophrenia genetics: dysbindin under the microscope. Trends in Neurosciences 27(9), pp. 516-519. (10.1016/j.tins.2004.06.004)
- Talbot, K. et al. 2004. Dysbindin-1 is reduced in intrinsic, glutamatergic terminals of the hippocampal formation in schizophrenia. The Journal of Clinical Investigation 113(9), pp. 1353-1363. (10.1172/JCI200420425)
- Talbot, K. et al. 2004. Dysbindin-1 is reduced in intrinsic, glutamatergic terminals of the hippocampal formation in schizophrenia. The Journal of Clinical Investigation 113(9), pp. 1353-1363. (10.1172/JCI200420425)
- Benson, M. A., Tinsley, C. L. and Blake, D. J. 2004. Myospryn is a novel binding partner for dysbindin in muscle. Journal of Biological Chemistry 279(11), pp. 10450-10458. (10.1074/jbc.M312664200)
- Esapa, C. T., Bentham, G. R. B., Schröder, J. E., Kröger, S. and Blake, D. J. 2003. The effects of post-translational processing on dystroglycan synthesis and trafficking. FEBS Letters 555(2), pp. 209-216. (10.1016/S0014-5793(03)01230-4)
- Burgueno, J. et al. 2003. The adenosine A2A receptor interacts with the actin-binding protein α-actinin. Journal of Biological Chemistry 278(39), pp. 37545-37552. (10.1074/jbc.M302809200)
- Li, W. et al. 2003. Hermansky-Pudlak syndrome type 7 (HPS-7) results from mutant dysbindin, a member of the biogenesis of lysosome-related organelles complex 1 (BLOC-1) [Letter]. Nature Genetics 35(1), pp. 84-89. (10.1038/ng1229)
- Muntoni, F. et al. 2003. 114th ENMC International Workshop on Congenital Muscular Dystrophy (CMD) 17?19 January 2003, Naarden, The Netherlands: (8th Workshop of the International Consortium on CMD; 3rd Workshop of the MYO-CLUSTER project GENRE). Neuromuscular Disorders 13(7-8), pp. 579-588. (10.1016/S0960-8966(03)00072-5)
- Sillitoe, R. V., Benson, M. A., Blake, D. J. and Hawkes, R. 2003. Abnormal dysbindin expression in cerebellar mossy fiber synapses in the mdx mouse model of Duchenne muscular dystrophy. Journal of Neuroscience 23(16), pp. 6576-6585.
- Sillitoe, R., Benson, M., Blake, D. J. and Hawkes, R. 2003. Abnormal dysbindin expression in cerebellar mossy fiber synapses in the mdx mouse model of Duchenne muscular dystrophy.. Journal of Neuroscience 23(16), pp. 6576-6585.
- Mercuri, E. et al. 2003. Phenotypic spectrum associated with mutations in the fukutin-related protein gene. Annals of Neurology 53(4), pp. 537-542. (10.1002/ana.10559)
- Martin-Rendon, E. and Blake, D. J. 2003. Protein glycosylation in disease: new insights into the congenital muscular dystrophies. Trends in Pharmacological Sciences 24(4), pp. 178-183. (10.1016/S0165-6147(03)00050-6)
- Topaloglu, H. et al. 2003. FKRP gene mutations cause congenital muscular dystrophy, mental retardation, and cerebellar cysts. Neurology 60(6), pp. 988-992. (10.1212/01.WNL.0000052996.14099.DC)
- Blake, D. J., Martin-Rendon, E., Schroder, J. E. and Benson, M. A. 2002. Functional requirements for fukutin-related protein in the Golgi apparatus. Human Molecular Genetics 11(26), pp. 3319-3331. (10.1093/hmg/11.26.3319)
- Muntoni, F., Brockington, M., Blake, D. J., Torelli, S. and Brown, S. C. 2002. Defective glycosylation in muscular dystrophy. The Lancet 360(9343), pp. 1419-1421. (10.1016/S0140-6736(02)11397-3)
- Blake, D. J. 2002. Dystrobrevin dynamics in muscle-cell signalling: a possible target for therapeutic intervention in Duchenne muscular dystrophy?. Neuromuscular Disorders 12, pp. S110. (10.1016/S0960-8966(02)00091-3)
- Blake, D. J. and Martin-Rendon, E. 2002. Intermediate filaments and the function of the dystrophin-protein complex. Trends in Cardiovascular Medicine 12(5), pp. 224-228. (10.1016/S1050-1738(02)00166-4)
- Blank, M., Blake, D. J. and Kröger, S. 2002. Molecular diversity of the dystrophin-like protein complex in the developing and adult avian retina. Neuroscience 111(2), pp. 259-273. (10.1016/S0306-4522(02)00032-5)
- Blake, D. J., Weir, A., Newey, S. E. and Davies, K. E. 2002. Function and genetics of dystrophin and dystrophin-related proteins in muscle. Physiological Reviews 82(2), pp. 291-329. (10.1152/physrev.00028.2001)
- Brockington, M., Blake, D. J., Brown, S. C. and Muntoni, F. 2002. The gene for a novel glycosyltransferase is mutated in congenital muscular dystrophy MDC1C and limb girdle muscular dystrophy 2I [Editorial]. Neuromuscular Disorders 12(3), pp. 233-234. (10.1016/S0960-8966(01)00325-X)
- Marangi, P. A. et al. 2001. Acetylcholine receptors are required for agrin-induced clustering of postsynaptic proteins. The EMBO Journal 20(24), pp. 7060-7073. (10.1093/emboj/20.24.7060)
- Brockington, M. et al. 2001. Mutations in the fukutin-related protein gene (FKRP) cause a form of congenital muscular dystrophy with secondary laminin 2 deficiency and abnormal glycosylation of -dystroglycan. American Journal of Human Genetics 69(6), pp. 1198-1209. (10.1086/324412)
- , . 2001. Mutations in the fukutin-related protein gene (FKRP) identify limb girdle muscular dystrophy 2I as a milder allelic variant of congenital muscular dystrophy MDC1C. Human Molecular Genetics 10(25), pp. 2851-2859. (10.1093/hmg/10.25.2851)
- Blake, D. J., Brockington, M., Muntoni, F. and Benson, M. A. 2001. Golgi-localisation of fukutin and fukutin-related protein: implications for muscular dystrophy. Molecular Biology of the Cell 12, pp. 85A-85A.
- Loh, N. Y., Nebenius-Oosthuizen, D., Blake, D. J., Smith, A. J. H. and Davies, K. E. 2001. Role of β-dystrobrevin in nonmuscle dystrophin-associated protein complex-like complexes in kidney and liver. Molecular and Cellular Biology 21(21), pp. 7442-7448. (10.1128/MCB.21.21.7442-7448.2001)
- Brickington, M. et al. 2001. A novel glycosyltransferase is mutated in a form of congenital muscular dystrophy with secondary laminin alpha 2 deficiency and abnormal glycosylation of alpha-dystroglycan. American Journal of Human Genetics 69(4), pp. 229-229.
- Brockington, M., Prandini, P., Brown, S. C., Sewry, C. A., Blake, D. J. and Muntoni, F. 2001. A new gene encoding a fukutin-like protein and its analysis in patients with congenital muscular dystrophy [Abstract]. Neuromuscular Disorders 11(6-7), pp. 635-635.
- Benson, M. A., Newey, S. E., Martin-Rendon, E., Hawkes, R. and Blake, D. J. 2001. Dysbindin, a novel coiled-coil-containing protein that interacts with the dystrobrevins in muscle and brain. Journal of Biological Chemistry 276(26), pp. 24232-24241. (10.1074/jbc.M010418200)
- Newey, S. E. et al. 2001. Syncoilin, a novel member of the intermediate filament superfamily that interacts with α-dystrobrevin in skeletal muscle. Journal of Biological Chemistry 276(9), pp. 6645-6655. (10.1074/jbc.M008305200)
- Newey, S. E. et al. 2001. Syncoilin, a novel member of the intermediate filament superfamily that interacts with alpha-dystrobrevin in skeletal muscle. Journal of Biological Chemistry 276(9), pp. 6645-6655. (10.1074/jbc.M008305200)
- Newey, S. E., Gramolini, A. O., Wu, J., Holzfeind, P., Jasmin, B. J., Davies, K. E. and Blake, D. J. 2001. A novel mechanism for modulating synaptic gene expression: differential localization of alpha-dystrobrevin transcripts in skeletal muscle. Molecular and Cellular Neuroscience 17(1), pp. 127-140. (10.1212/01.wnl.0000302174.08951.cf.)
- Newey, S. E., Gramolini, A. O., Wu, J., Holzfiend, P., Jasmin, B. J., Davies, K. E. and Blake, D. J. 2001. A novel mechanism for modulating synaptic gene expression: differential localization of α-dystrobrevin transcripts in skeletal muscle. Molecular and Cellular Neuroscience 17(1), pp. 127-140. (10.1006/mcne.2000.0918)
- Newey, S. E., Benson, M. A., Ponting, C. P., Davies, K. E. and Blake, D. J. 2000. Alternative splicing of dystrobrevin regulates the stoichiometry of syntrophin binding to the dystrophin protein complex. Current Biology 10(20), pp. 1295-1298. (10.1016/S0960-9822(00)00760-0)
- Loh, N. Y., Newey, S. E., Davies, K. E. and Blake, D. J. 2000. Assembly of multiple dystrobrevin-containing complexes in the kidney. Journal of Cell Science 113(15), pp. 2715-2724.
- Blake, D. J. and Kröger, S. 2000. The neurobiology of Duchenne muscular dystrophy: learning lessons from muscle?. Trends in Neurosciences 23(3), pp. 92-99. (10.1016/S0166-2236(99)01510-6)
- Blake, D. J., Hawkes, R., Benson, M. A. and Beesley, P. W. 1999. Different dystrophin-like complexes are expressed in neurons and glia. Journal of Cell Biology 147(3), pp. 645-658. (10.1083/jcb.147.3.645)
- Blank, M., Koulen, P., Blake, D. J. and Kröger, S. 1999. Dystrophin and beta-dystroglycan in photoreceptor terminals from normal and mdx3Cv mouse retinae. European Journal of Neuroscience 11(6), pp. 2121-2133. (10.1046/j.1460-9568.1999.00636.x)
- Holzfeind, P. J., Ambrose, H. J., Newey, S. E., Nawrotzki, R. A., Blake, D. J. and Davies, K. E. 1999. Tissue-selective Expression of alpha-Dystrobrevin is Determined by Multiple Promoters. Journal of Biological Chemistry 274(10), pp. 6250-6258. (10.1074/jbc.274.10.6250)
- Blake, D. J., Benson, M. A., Hawkes, R. and Beesley, P. W. 1999. Dystrophin-binding proteins in the brain. Journal of Neurochemistry 73, pp. S93-S93.
- Loh, N. Y., Ambrose, H. J., Guay-Woodford, L. M., DasGupta, S., Nawrotzki, R. A., Blake, D. J. and Davies, K. E. 1998. Genomic organization and refined mapping of the mouse beta-dystrobrevin gene. Mammalian Genome 9(11), pp. 857-862.
- Loh, N. Y., Ambrose, H. J., Guay-Woodford, L. M., DasGupta, S., Nawrotzki, R. A., Blake, D. J. and Davies, K. E. 1998. Genomic organization and refined mapping of the mouse β-dystrobrevin gene. Mammalian Genome 9(11), pp. 857-862. (10.1007/s003359900883)
- Nawrotzki, R., Loh, N. Y., Ruegg, M. A., Davies, K. E. and Blake, D. J. 1998. Characterisation of alpha-dystrobrevin in muscle. Journal of Cell Science 111(17), pp. 2595-2605.
- Vater, R. et al. 1998. Utrophin mRNA expression in muscle is not restricted to the neuromuscular junction. Molecular and Cellular Neuroscience 10(5-6), pp. 229-242. (10.1006/mcne.1998.0661)
- Blake, D. J., Nawrotzki, R., Loh, N. Y., Gorecki, D. C. and Davies, K. E. 1998. β-dystrobrevin, a member of the dystrophin-related protein family. Proceedings of the National Academy of Sciences of the United States of America 95(1), pp. 241-246.
- Blake, D. J., Nawrotzki, R., Loh, N. Y., Gorecki, D. C. and Davies, K. E. 1998. beta-dystrobrevin, a member of the dystrophin-related protein family. Proceedings of the National Academy of Sciences of the United States of America 95(1), pp. 241-246. (10.1073/pnas.95.1.241)
- Blake, D. J., Loh, N. Y., Beesley, P. and Davies, K. E. 1997. The function dystrophin-related and -associated proteins in the brain. Journal of Neurochemistry 69(S), pp. S123-S123.
- Blake, D. J., Nawrotzki, R., Loh, N. Y. and Davies, K. E. 1997. A novel dystrophin-associated protein in brain. American Journal of Human Genetics 61(4), pp. A8-A8.
- Loh, N. Y., Blake, D. J., Nawrotzki, R., Ambrose, H. J. and Davies, K. E. 1997. Beta-dystrobrevin; a new member of the dystrophin-related protein family. American Journal of Human Genetics 61(4), pp. A177-A177.
- Metzinger, L. et al. 1997. Dystrobrevin deficiency at the sarcolemma of patients with muscular dystrophy. Human Molecular Genetics 6(7), pp. 1185-1191. (10.1093/hmg/6.7.1185)
- Ponting, C. P., Phillips, C., Davies, K. E. and Blake, D. J. 1997. PDZ domains: targeting signalling molecules to sub-membranous sites. Bioessays 19(6), pp. 469-479. (10.1002/bies.950190606)
- Ambrose, H. J., Blake, D. J., Nawrotzki, R. A. and Davies, K. E. 1997. Genomic organization of the mouse dystrobrevin gene: comparative analysis with the dystrophin gene. Genomics 39(3), pp. 359-369. (10.1006/geno.1996.4515)
- Picketts, D. J., Higgs, D. R., Bachoo, S., Blake, D. J., Quarrel, O. W. J. and Gibbons, R. J. 1996. ATRX encodes a novel member of the SNF2 family of proteins: mutations point to a common mechanism underlying the ATR-X syndrome. Human Molecular Genetics 5(12), pp. 1899-1907. (10.1093/hmg/5.12.1899)
- Morrison, K. E. et al. 1996. Novel transcribed sequences represented in the complex genomic region 5q13. Acta Biochimica et Biophysica 1308(2), pp. 97-102. (10.1016/0167-4781(96)00097-8)
- Nawrotzki, R., Blake, D. J. and Davies, K. E. 1996. The genetic basis of neuromuscular disorders. Trends in Genetics 12(8), pp. 294-298. (10.1016/0168-9525(96)10033-0)
- Theodosiou, A. M. et al. 1996. A member of the MAP kinase phosphatase gene family in mouse containing a complex trinucleotide repeat in the coding region. Human Molecular Genetics 5(5), pp. 675-684. (10.1093/hmg/5.5.675)
- Blake, D. J., Nawrotzki, R. A., Peters, M. F., Froehner, S. C. and Davies, K. E. 1996. Isoform diversity of dystrobrevin, the murine 87-kDa postsynaptic protein. Journal of Biological Chemistry 271(13), pp. 7802-7810. (10.1074/jbc.271.13.7802)
- Zuelling, R. A., Blake, D. J., Tinsley, J. M. and Davies, K. E. 1996. Cloning of the rat utrophin and characterization of an alternate transcript. Journal of Muscle Research and Cell Motility 17(1), pp. 110-110.
- Zuellig, R. A., Blake, D. J., Tinsley, J. M. and Davies, K. E. 1996. Cloning of the rat utrophin and characterization of an alternate transcript. Journal of Muscle Research and Cell Motility 17(1), pp. 110-110.
- Blake, D. J., Tinsley, J. M. and Davies, K. E. 1996. Utrophin: a structural and functional comparison to dystrophin. Brain Pathology 6(1), pp. 37-47. (10.1111/j.1750-3639.1996.tb00781.x)
- Ponting, C. P., Blake, D. J., Davies, K. E., Kendrick-Jones, J. and Winder, S. J. 1996. ZZ and TAZ: new putative zinc fingers in dystrophin and other proteins. Trends in Biochemical Sciences 21(1), pp. 11-13. (10.1016/S0968-0004(06)80020-4)
- Millwood, I. Y., Blake, D. J., Gauguier, D. and Monaco, A. P. 1995. Two polymorphic dinucleotide repeats in the rat dystrophin gene, including the conserved 3' UTR repeat. Mammalian Genome 6(9), pp. 668-669.
- Davies, K. E., Tinsley, J. M. and Blake, D. J. 1995. Molecular analysis of Duchenne muscular dystrophy: past, present, and future. Annals of the New York Academy of Sciences 758, pp. 287-296. (10.1111/j.1749-6632.1995.tb24834.x)
- Blake, D. J. et al. 1995. G-Utrophin, the autosomal homologue of dystrophin Dp116, is expressed in sensory ganglia and brain. Proceedings of the National Academy of Sciences of the United States of America 92(9), pp. 3697-3701. (10.1073/pnas.92.9.3697)
- Blake, D. J., Tinsley, J. M., Davies, K. E., Knight, A. E., Winder, S. J. and Kendrick-Jones, J. 1995. Coiled-coil regions in the carboxy-terminal domains of dystrophin and related proteins: potentials for protein-protein interactions. Trends in Biochemical Sciences 20(4), pp. 133-135. (10.1016/S0968-0004(00)88986-0)
- Pasquini, F., Guerin, C., Blake, D. J., Davies, K., Karpati, G. and Holland, P. 1995. The effect of glucocorticoids on the accumulation of utrophin by cultured normal and dystrophic human skeletal muscle satellite cells. Neuromuscular Disorders 5(2), pp. 105-114. (10.1016/0960-8966(94)00042-8)
- Brookes, A. J., Slorach, E. M., Morrison, K. E., Qureshi, S. J., Blake, D. J., Davies, K. and Porteous, D. J. 1994. Cloning the shared components of complex DNA resources. Human Molecular Genetics 3(11), pp. 2011-2017. (10.1093/hmg/3.11.2011)
- Tinsley, J. M., Blake, D. J., Zuellig, R. A. and Davies, K. E. 1994. Increasing complexity of the dystrophin-associated protein complex. Proceedings of the National Academy of Sciences of the United States of America 91(18), pp. 8307-8313.
- Schofield, J. N., Blake, D. J., Simmons, C., Morris, G. E., Tinsley, J. M., Davies, K. E. and Edwards, Y. H. 1994. Apo-dystrophin-1 and apo-dystrophin-2, products of the Duchenne muscular dystrophy locus: expression during mouse embryogenesis and in cultured cell lines. Human Molecular Genetics 3(8), pp. 1309-1316. (10.1093/hmg/3.8.1309)
- Davies, K., Tinsley, J., Blake, D. J., Pearce, M., Deconick, A. and Dennis, C. 1994. Possible roles for utrophin in gene-therapy of duchenne muscular-dystrophy. Journal of Cellular Biochemistry 1994(18A), pp. 188-188.
- Blake, D. J., Tinsley, J. M. and Davies, K. E. 1994. The emerging family of dystrophin-related proteins. Trends in Cell Biology 4(1), pp. 19-23. (10.1016/0962-8924(94)90034-5)
- Pearce, M., Blake, D. J., Tinsley, J. M., Byth, B. C., Campbell, L., Monaco, A. P. and Davies, K. E. 1993. The utrophin and dystrophin genes share similarities in genomic structure. Human Molecular Genetics 2(11), pp. 1765-1772. (10.1093/hmg/2.11.1765)
- Tinsley, J. M., Blake, D. J., Pearce, M., Knight, A. E., Kendrick-Jones, J. and Davies, K. E. 1993. Dystrophin and related proteins. Current Opinion in Genetics & Development 3(3), pp. 484-490. (10.1016/0959-437X(93)90124-8)
- Tinsley, J. M., Blake, D. J. and Davies, K. E. 1993. Apo-dystrophin-3: a 2.2kb transcript from the DMD locus encoding the dystrophin glycoprotein binding site. Human Molecular Genetics 2(5), pp. 521-524. (10.1093/hmg/2.5.521)
- Blake, D. 1993. Dystrophin and dystrophin-related proteins: a review of protein and RNA studies. Neuromuscular Disorders 3(1), pp. 5-21. (10.1016/0960-8966(93)90037-K)
- Blake, D. J. et al. 1992. Characterization of a 4.8kb transcript from the Duchenne muscular dystrophy locus expressed in Schwannoma cells. Human Molecular Genetics 1(2), pp. 103-109. (10.1093/hmg/1.2.103)
- Tinsley, J. M. et al. 1992. Primary structure of dystrophin-related protein. Nature 360(6404), pp. 591-593. (10.1038/360591a0)
- thi Man, N., Thanh, L., Blake, D. J., Davies, K. . and Morris, G. E. 1992. Utrophin, the autosomal homologue of dystrophin, is widely-expressed and membrane-associated in cultured cell lines. FEBS Letters 313(1), pp. 19-22. (10.1016/0014-5793(92)81174-K)
- Coleman, M. P. et al. 1991. Genetic and physical mapping around the properdin P gene. Genomics 11(4), pp. 991-996. (10.1016/0888-7543(91)90024-9)
- Sellar, G. C., Blake, D. J. and Reid, K. B. 1991. Characterization and organization of the genes encoding the A-, B- and C-chains of human complement subcomponent C1q. The complete derived amino acid sequence of human C1q. Biochemical Journal 274(2), pp. 481-490.
- Sellar, G. C., Blake, D. J. and Reid, K. B. 1991. Characterization and organization of the genes encoding the A-, B- and C-chains of human complement subcomponent C1q. The complete derived amino acid sequence of human C1q. Biochemical Journal 274(2), pp. 481-490. (10.1042/bj2740481)
- Knott, V., Blake, D. J. and Brownlee, G. G. 1989. Completion of the detailed restriction map of the E.coli genome by the isolation of overlapping cosmid clones. Nucleic Acids Research 17(15), pp. 5901-5912. (10.1093/nar/17.15.5901)
- Blake, D. J. and Brownlee, G. G. 1989. Deletion of the MCF.2 transforming gene in 2 Hemophilia-B inhibitor patients [Abstract]. Cytogenetics and Cell Genetics 51(1-4), pp. 963.
- Blake, D. J. and Brownlee, G. 1989. Deletion of the mcf.2 transforming gene in 2 hemophilia-b inhibitor patients. Cytogenetics and Cell Genetics 51(1-4), pp. 963-963.
- Anson, D. S., Blake, D. J., Winship, P. R., Birnbaum, D. and Brownlee, G. G. 1988. Nullisomic deletion of the mcf.2 transforming gene in two haemophilia B patients. EMBO Journal 7(9), pp. 2795-2799.
- Anson, D., Blake, D. J., Winship, P., Birnbaum, D. and Brownlee, G. 1988. Nullisomic deletion of the mcf.2 transforming gene in two haemophilia B patients.. EMBO Journal 7(9), pp. 2795-2799.
- Blake, D. J., Knott, V. and Brownlee, G. 1987. A random cosmid contig approach to gene-mapping [Abstract]. Cytogenetics and Cell Genetics 46(1-4), pp. 581. (10.1159/000316989)
- Blake, D. J., Knott, V. and Brownlee, G. 1987. A random cosmid contig approach to gene-mapping. Cytogenetics and Cell Genetics 46(1), pp. 581-581.
Research
Transcription factors in neurodevelopmental disorders
Recent advances in neuropsychiatric genetics have identified biological processes and risk variants that are regulated by key schizophrenia-associated transcription factors (TFs) and chromatin writers (collectively transcriptional regulators) that are also causally implicated in a range of neurodevelopmental disorders through rare, exonic mutations. For many common disorders, altered binding of transcriptional regulators to non-coding variants can directly mediate disease risk, modulate gene expression and ultimately shape phenotypes. The major aim of this project is to define the genomic targets for selected schizophrenia-associated transcriptional regulators such as TCF4 (Transcription Factor 4) in cell models and tissue two differentiated human using chromatin-immunoprecipitation and next generation sequencing (ChIP-seq). In collaboration with Dr Matt Hill (https://www.cardiff.ac.uk/people/view/62738-hill-matt), we have used the near base-pair resolution of ChIP-seq to discover regulatory binding sites in genomic loci associated with schizophrenia and other common neurodevelopmental disorders and derive binding-site motifs for each TF where appropriate (https://orca.cf.ac.uk/107566/1/sbx164.pdf). We are also interested in Pitt-Hopkins Syndrome (PTHS) - a rare neurodevelopmental disorder caused by heterozygous TCF4 mutations. We are currently trying to determine the role of PTHS-associated mutations on the function of TCF4 in a range of model systems.
TCF4 in Fuchs' endothelial corneal dystrophy (FECD)
The cornea, the clear window at the front of the eye, is one of the most transplanted tissues worldwide with nearly 50,000 corneal grafts performed in 2015 in the USA alone. FECD affects approximately 4% of people over the age of 40 and is the most common indication for corneal graft surgery in the USA. Over time, cell loss and painful blistering cause changes in the transparency of the cornea and progressive loss of vision leading to blindness in the most severe cases. FECD is an inherited condition with approximately 80% of cases being associated with trinucleotide repeat expansion in an intron of the TCF4 gene. As described above, TCF4 has a regulatory function and can act as a molecular switch to turn other genes on and off by binding to specific sites in the genome. In collaboration with Prof Andrew Quantock (https://www.cardiff.ac.uk/people/view/38248-quantock-andrew) and Dr Matt Hill, we have shown that small alterations in the levels of TCF4 can have dramatic effects on cell function and cell survival. To improve our understanding of the molecular basis for FECD and to find new drug targets to treat this disorder, we are using the latest genetic techniques and cell models to identity the genes and processes that are controlled by TCF4 in corneal endothelial cells.
Microglial biology
The majority of risk genes for Alzheimer’s Disease (AD) are highly expressed in microglia - a specialized population of resident macrophage-like cells found in brain. Genetic risk for AD is concentrated in specific macrophage and microglial transcriptional networks that are regulated by a handful of transcription factors (TFs) including PU.1 and MEF2C. In collaboration with Dr Matt Hill (https://www.cardiff.ac.uk/people/view/62738-hill-matt), we are studying how these TFs regulate gene expression and AD risk using proteomic and genomic techniques. We are also using proximity-labelling proteomics to study the function of selected genes that form part of the AD-risk network in microglia. These projects will provide mechanistic insights into the molecular process involved in AD pathogenesis and will be used to find new drug targets to treat this disorder.
Organisation of the junctional sarcoplasmic reticulum (jSR) in striated muscle
The jSR is a specialised region of the sarcoplasmic reticulum of muscle cells that concentrates resident and peripheral proteins to regulate calcium release and excitation-contraction coupling. To understand how the jSR is assembled we used immunoaffinity purification and mass spectrometry to identify proteins complexes that are targeted to the jSR in cardiac and skeletal muscle. We found that the myospryn complex interacts with ryanodine receptors (the major calcium release channel of the SR) and other components of the jSR in cardiac muscle (https://www.nature.com/articles/s41598-017-06395-6). We are currently using a range of molecular tools to understand the role of the myospryn complex during the assembly of jSR and how these processes are altered in heart disease.
Teaching
Bioinformatics (MSc) - Introduction to Bioinformatics
Medicine (MBBCh) - Case Based Learning (CBL) Facilitator
Medicine (MBBCh) - Platform for Clinical Sciences Tutor
Medical Pharmacology (BSc) and Biological Sciences (BSc) - Profession Training Year (PTY) supervisor