Dr Damian Crowther University positionDirector R&D, AstraZeneca Neuroscience IMED DepartmentsDepartment of Genetics and Department of Medicine InstitutesAstraZeneca Neuroscience IMED Home pagehttps://www.linkedin.com/pub/dam... (personal home page) Research ThemesInterestsThe neuroscience group at AstraZeneca has particular interests in neurodegeneration, neuropsychiatry and pain. We are a highly collaborative group and keen to work productively with the Cambridge neuroscience community. More details at: www.azneuro.com Research Focus
EquipmentBehavioural analysis Biophysical analysis of protein aggregation Cell culture Enzyme assays FPLC/HPLC Microscopy Protein purification Recombinant protein expression Transgenic fly models of neurodegeneration Collaborators
Associated News Items
Key publicationsSperetta E, Jahn TR, Tartaglia GG, Favrin G, Barros TP, Imarisio S, Lomas DA, Luheshi LM, Crowther DC, Dobson CM (2012), “Expression in drosophila of tandem amyloid β peptides provides insights into links between aggregation and neurotoxicity.” J Biol Chem 287(24):20748-54 Details Jahn TR, Kohlhoff KJ, Scott M, Tartaglia GG, Lomas DA, Dobson CM, Vendruscolo M, Crowther DC (2011), “Detection of early locomotor abnormalities in a Drosophila model of Alzheimer's disease.” J Neurosci Methods 197(1):186-9 Details Brorsson AC, Bolognesi B, Tartaglia GG, Shammas SL, Favrin G, Watson I, Lomas DA, Chiti F, Vendruscolo M, Dobson CM, Crowther DC, Luheshi LM (2010), “Intrinsic determinants of neurotoxic aggregate formation by the amyloid beta peptide.” Biophys J 98(8):1677-84 Details Moloney A, Sattelle DB, Lomas DA, Crowther DC (2010), “Alzheimer's disease: insights from Drosophila melanogaster models.” Trends Biochem Sci 35(4):228-35 Details Rival, T, Page, R, Chandraratna, D, Sendall, TJ, Ryder, E, Liu, B, Lewis, H, Rosahl, T, Hider, R, Camargo, LM, Shearman, MS, Crowther, DC, Lomas, DA (2009), “Fenton chemistry and oxidative stress mediate the toxicity of the β-amyloid peptide in a Drosophila model of Alzheimer’s disease. ” Eur. J. Neurosci. 29: 1335-1347 Luheshi LM, Tartaglia GG, Brorsson AC, Pawar AP, Watson IE, Chiti F, Vendruscolo M, Lomas DA, Dobson CM, Crowther DC (2007), “Systematic In Vivo Analysis of the Intrinsic Determinants of Amyloid beta Pathogenicity” PLoS Biol 5(11):e290 Details Crowther DC, Kinghorn KJ, Miranda E, Page R, Curry JA, Duthie FA, Gubb DC, Lomas DA (2005), “Intraneuronal Aβ, non-amyloid aggregates and neurodegeneration in a Drosophila model of Alzheimer's disease” Neuroscience 132:123-35 Details Publications2014Acerra N, Kad NM, Griffith DA, Ott S, Crowther DC, Mason JM (2014), “Retro-inversal of intracellular selected β-amyloid-interacting peptides: implications for a novel alzheimer's disease treatment.” Biochemistry 53(13):2101-11 Details Chen KF, Crowther DC (2014), “Insights into amyloid disease from fly models.” Essays Biochem 56:69-83 Details Chen KF, Possidente B, Lomas DA, Crowther DC (2014), “The central molecular clock is robust in the face of behavioural arrhythmia in a Drosophila model of Alzheimer's disease.” Dis Model Mech 7(4):445-58 Details Khabirova E, Moloney A, Marciniak SJ, Williams J, Lomas DA, Oliver SG, Favrin G, Sattelle DB, Crowther DC (2014), “The TRiC/CCT chaperone is implicated in Alzheimer's disease based on patient GWAS and an RNAi screen in Aβ-expressing Caenorhabditis elegans.” PLoS One 9(7):e102985 Details Wacker J, Rönicke R, Westermann M, Wulff M, Reymann KG, Dobson CM, Horn U, Crowther DC, Luheshi LM, Fändrich M (2014), “Oligomer-targeting with a conformational antibody fragment promotes toxicity in Aβ-expressing flies.” Acta Neuropathol Commun 2:43 Details 2013Favrin G, Bean DM, Bilsland E, Boyer H, Fischer BE, Russell S, Crowther DC, Baylis HA, Oliver SG, Giannakou ME (2013), “Identification of novel modifiers of Aβ toxicity by transcriptomic analysis in the fruitfly.” Sci Rep 3:3512 Details Kruppa AJ, Ott S, Chandraratna DS, Irving JA, Page RM, Speretta E, Seto T, Camargo LM, Marciniak SJ, Lomas DA, Crowther DC (2013), “Suppression of Aβ toxicity by puromycin-sensitive aminopeptidase is independent of its proteolytic activity.” Biochim Biophys Acta 1832(12):2115-26 Details Malzer E, Szajewska-Skuta M, Dalton LE, Thomas SE, Hu N, Skaer H, Lomas DA, Crowther DC, Marciniak SJ (2013), “Coordinate regulation of eIF2α phosphorylation by PPP1R15 and GCN2 is required during Drosophila development.” J Cell Sci 126(Pt 6):1406-15 Details Roussel BD, Kruppa AJ, Miranda E, Crowther DC, Lomas DA, Marciniak SJ (2013), “Endoplasmic reticulum dysfunction in neurological disease.” Lancet Neurol 12(1):105-18 Details Roussel BD, Newton TM, Malzer E, Simecek N, Haq I, Thomas SE, Burr ML, Lehner PJ, Crowther DC, Marciniak SJ, Lomas DA (2013), “Sterol metabolism regulates neuroserpin polymer degradation in the absence of the unfolded protein response in the dementia FENIB.” Hum Mol Genet 22(22):4616-26 Details Thomas SE, Malzer E, Ordóñez A, Dalton LE, van 't Wout EF, Liniker E, Crowther DC, Lomas DA, Marciniak SJ (2013), “p53 and translation attenuation regulate distinct cell cycle checkpoints during endoplasmic reticulum (ER) stress.” J Biol Chem 288(11):7606-17 Details 2012Chen KF, Crowther DC (2012), “Functional genomics in Drosophila models of human disease.” Brief Funct Genomics Details Kumita JR, Helmfors L, Williams J, Luheshi LM, Menzer L, Dumoulin M, Lomas DA, Crowther DC, Dobson CM, Brorsson AC (2012), “Disease-related amyloidogenic variants of human lysozyme trigger the unfolded protein response and disturb eye development in Drosophila melanogaster.” FASEB J 26(1):192-202 Details Murakami T, Yang SP, Xie L, Kawano T, Fu D, Mukai A, Bohm C, Chen F, Robertson J, Suzuki H, Tartaglia GG, Vendruscolo M, Kaminski Schierle GS, Chan FT, Moloney A, Crowther D, Kaminski CF, Zhen M, St George-Hyslop P (2012), “ALS mutations in FUS cause neuronal dysfunction and death in Caenorhabditis elegans by a dominant gain-of-function mechanism.” Hum Mol Genet 21(1):1-9 Details Thackray AM, Muhammad F, Zhang C, Denyer M, Spiropoulos J, Crowther DC, Bujdoso R (2012), “Prion-induced toxicity in PrP transgenic Drosophila.” Exp Mol Pathol 92(2):194-201 Details Thackray AM, Muhammad F, Zhang C, Di Y, Jahn TR, Landgraf M, Crowther DC, Evers JF, Bujdoso R (2012), “Ovine PrP transgenic Drosophila show reduced locomotor activity and decreased survival.” Biochem J 444(3):487-95 Details 2011Belorgey D, Irving JA, Ekeowa UI, Freeke J, Roussel BD, Miranda E, Pérez J, Robinson CV, Marciniak SJ, Crowther DC, Michel CH, Lomas DA (2011), “Characterisation of serpin polymers in vitro and in vivo.” Methods 53(3):255-66 Details Costa R, Speretta E, Crowther DC, Cardoso I (2011), “Testing the therapeutic potential of doxycycline in a Drosophila melanogaster model of Alzheimer disease.” J Biol Chem 286(48):41647-55 Details Jahn TR, Malzer E, Roote J, Vishnivetskaya A, Imarisio S, Giannakou M, Panser K, Marciniak S, Crowther DC (2011), “Modeling serpin conformational diseases in Drosophila melanogaster.” Methods Enzymol 499:227-58 Details Kohlhoff KJ, Jahn TR, Lomas DA, Dobson CM, Crowther DC, Vendruscolo M (2011), “The iFly tracking system for an automated locomotor and behavioural analysis of Drosophila melanogaster.” Integr Biol (Camb) 3(7):755-60 Details Liu B, Moloney A, Meehan S, Morris K, Thomas SE, Serpell LC, Hider R, Marciniak SJ, Lomas DA, Crowther DC (2011), “Iron promotes the toxicity of amyloid beta peptide by impeding its ordered aggregation.” J Biol Chem 286(6):4248-56 Details Roussel BD, Irving JA, Ekeowa UI, Belorgey D, Haq I, Ordóñez A, Kruppa AJ, Duvoix A, Rashid ST, Crowther DC, Marciniak SJ, Lomas DA (2011), “Unravelling the twists and turns of the serpinopathies.” FEBS J 278(20):3859-67 Details 2010Bolognesi B, Kumita JR, Barros TP, Esbjorner EK, Luheshi LM, Crowther DC, Wilson MR, Dobson CM, Favrin G, Yerbury JJ (2010), “ANS binding reveals common features of cytotoxic amyloid species.” ACS Chem Biol 5(8):735-40 Details Brorsson AC, Kumita JR, MacLeod I, Bolognesi B, Speretta E, Luheshi LM, Knowles TP, Dobson CM, Crowther DC (2010), “Methods and models in neurodegenerative and systemic protein aggregation diseases.” Front Biosci 15:373-96 Details Luheshi LM, Hoyer W, de Barros TP, van Dijk Härd I, Brorsson AC, Macao B, Persson C, Crowther DC, Lomas DA, Ståhl S, Dobson CM, Härd T (2010), “Sequestration of the Abeta peptide prevents toxicity and promotes degradation in vivo.” PLoS Biol 8(3):e1000334 Details Malzer E, Daly ML, Moloney A, Sendall TJ, Thomas SE, Ryder E, Ryoo HD, Crowther DC, Lomas DA, Marciniak SJ (2010), “Impaired tissue growth is mediated by checkpoint kinase 1 (CHK1) in the integrated stress response.” J Cell Sci 123(Pt 17):2892-900 Details 2009Kroeger H, Miranda E, MacLeod I, Pérez J, Crowther DC, Marciniak SJ, Lomas DA (2009), “Endoplasmic reticulum-associated degradation (ERAD) and autophagy cooperate to degrade polymerogenic mutant serpins.” J Biol Chem 284(34):22793-802 Details Nerelius, C, Sandegren, A, Sargsyan, A, Raunak, Leijonmarck, H, Chatterjee, U, Fisahn, A, Imarisio, S, Lomas, DA, Crowther, DC, Stromberg, R, Johansson, J (2009), “α-Helix-targeting reduces amyloid β-peptide toxicity. ” Proc Natl Acad Sci U S A 106: 9191-9196 Rival T, Page RM, Chandraratna DS, Sendall TJ, Ryder E, Liu B, Lewis H, Rosahl T, Hider R, Camargo LM, Shearman MS, Crowther DC, Lomas DA (2009), “Fenton chemistry and oxidative stress mediate the toxicity of the beta-amyloid peptide in a Drosophila model of Alzheimer's disease.” Eur J Neurosci 29(7):1335-47 Details 2008Crowther DC, Page R, Rival T, Chandraratna DS, Lomas DA (2008), “Using a Drosophila model of Alzheimer's disease.” SEB Exp Biol Ser 60:57-77 Details Luheshi LM, Crowther DC, Dobson CM (2008), “Protein misfolding and disease: from the test tube to the organism.” Curr Opin Chem Biol 12(1):25-31 Details Miranda E, MacLeod I, Davies MJ, Pérez J, Römisch K, Crowther DC, Lomas DA (2008), “The intracellular accumulation of polymeric neuroserpin explains the severity of the dementia FENIB.” Hum Mol Genet 17(11):1527-39 Details 2007Nielsen HM, Minthon L, Londos E, Blennow K, Miranda E, Perez J, Crowther DC, Lomas DA, Janciauskiene SM (2007), “Plasma and CSF serpins in Alzheimer disease and dementia with Lewy bodies.” Neurology 69(16):1569-79 Details 2006Crowther DC, Page R, Chandraratna D, Lomas DA (2006), “A Drosophila model of Alzheimer's disease.” Methods Enzymol 412:234-55 Details Kinghorn KJ, Crowther DC, Sharp LK, Nerelius C, Davis RL, Chang HT, Green C, Gubb DC, Johansson J, Lomas DA (2006), “Neuroserpin binds Abeta and is a neuroprotective component of amyloid plaques in Alzheimer disease.” J Biol Chem 281(39):29268-77 Details Sharp LK, Mallya M, Kinghorn KJ, Wang Z, Crowther DC, Huntington JA, Belorgey D, Lomas DA (2006), “Sugar and alcohol molecules provide a therapeutic strategy for the serpinopathies that cause dementia and cirrhosis.” FEBS J 273(11):2540-52 Details 2005Lomas DA, Belorgey D, Mallya M, Miranda E, Kinghorn KJ, Sharp LK, Phillips RL, Page R, Robertson AS, Crowther DC (2005), “Molecular mousetraps and the serpinopathies.” Biochem Soc Trans 33(Pt 2):321-30 Details 2004Belorgey D, Sharp LK, Crowther DC, Onda M, Johansson J, Lomas DA (2004), “Neuroserpin Portland (Ser52Arg) is trapped as an inactive intermediate that rapidly forms polymers: implications for the epilepsy seen in the dementia FENIB.” Eur J Biochem 271(16):3360-7 Details Crowther DC, Belorgey D, Miranda E, Kinghorn KJ, Sharp LK, Lomas DA (2004), “Practical genetics: alpha-1-antitrypsin deficiency and the serpinopathies.” Eur J Hum Genet 12(3):167-72 Details Crowther DC, Kinghorn KJ, Page R, Lomas DA (2004), “Therapeutic targets from a Drosophila model of Alzheimer's disease.” Curr Opin Pharmacol 4(5):513-6 Details Lomas DA, Belorgey D, Mallya M, Onda M, Kinghorn KJ, Sharp LK, Phillips RL, Page R, Crowther DC, Miranda E (2004), “Polymerisation underlies alpha1-antitrypsin deficiency, dementia and other serpinopathies.” Front Biosci 9:2873-91 Details 2003Crowther DC, Serpell LC, Dafforn TR, Gooptu B, Lomas DA (2003), “Nucleation of alpha 1-antichymotrypsin polymerization.” Biochemistry 42(8):2355-63 Details 2002Belorgey D, Crowther DC, Mahadeva R, Lomas DA (2002), “Mutant Neuroserpin (S49P) that causes familial encephalopathy with neuroserpin inclusion bodies is a poor proteinase inhibitor and readily forms polymers in vitro.” J Biol Chem 277(19):17367-73 Details |