Dr Damian Crowther

Damian Crowther

University position

Group Leader, Alzheimer's Research Trust Senior Resarch Fellow

Departments

Department of Genetics and Department of Medicine

Institutes

MedImmune Ltd

Email

damian.crowther@azneuro.com

Home page

https://www.linkedin.com/pub/dam... (personal home page)

Research Themes

Cellular and Molecular Neuroscience

Clinical and Veterinary Neuroscience

Interests

We use a range of in vitro and in vivo techniques to understand how amyloid protein aggregates: i) mediate their toxic effects and ii) underpin the pathological progression of disorders such as Alzheimer's disease.

We are investigating the molecular basis for Alzheimer's related phenotypes such as circadian rhythm disruption using our fruit fly model systems. We are also interested in the role of neurotrophins in protecting neurones against amyloid-beta mediated toxicity. There is also a body of work investigating the prion-like spread of proteinopathies and how we might measure this.

Research Focus

Keywords

Alzheimer's Disease

dementia

animal model

protein aggregation

genetics

Clinical conditions

Alzheimer's disease

Cognitive impairment

Equipment

Behavioural analysis

Biophysical analysis of protein aggregation

Cell culture

Enzyme assays

FPLC/HPLC

Microscopy

Protein purification

Recombinant protein expression

Transgenic fly models of neurodegeneration

Collaborators

Cambridge

Florian Hollfelder

Stefan Marciniak

United Kingdom

David Sattelle Web: http://www.mrcfgu.ox.ac.uk/researc...

Associated News Items


Key publications

Speretta 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

Publications

2014

Acerra 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

2013

Favrin 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

2012

Chen 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

2011

Belorgey 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

2010

Bolognesi 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

2009

Kroeger 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

2008

Crowther 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

2007

Nielsen 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

2006

Crowther 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

2005

Lomas 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

2004

Belorgey 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

2003

Crowther DC, Serpell LC, Dafforn TR, Gooptu B, Lomas DA (2003), “Nucleation of alpha 1-antichymotrypsin polymerization.” Biochemistry 42(8):2355-63 Details

2002

Belorgey 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