Menu

Research Focus

Keywords

  • Fluorescence Microscopy
  • Tau Pathology
  • Amyloid Beta
  • Clinical Conditions

  • Alzheimer's disease
  • Parkinson's disease
  • Progressive supranuclear palsy
  • Equipment & Techniques

  • Fluorescence microscopy
  • Back

    Professor David Klenerman

    University Position
    Professor

    Interests

    Small soluble protein aggregates are thought to play a key role in the initial development of neurodegenerative diseases, such as Alzheimer's and Parkinson's disease, but are difficult to study using conventional methods due to their low concentration and dynamic and heterogeneous nature. We have developed single molecule fluorescence based methods to detect and analyse the protein oligomers formed during an aggregation reaction, with time, and to study how these oligomers interact with the membrane of live neuronal cells and initiate and spread cellular damage.

    Key Publications

    Structure-specific amyloid precipitation in biofluids.

    DOI: http://doi.org/10.1038/s41557-022-00976-3
    Journal: Nat Chem
    E-pub date: 1 Sep 2022
    Authors: M Rodrigues, P Bhattacharjee, A Brinkmalm, DT Do, CM Pearson, S De, A Ponjavic, JA Varela, K Kulenkampff, I Baudrexel, D Emin, FS Ruggeri, JE Lee, AR Carr, TPJ Knowles, H Zetterberg, TN Snaddon, S Gandhi, SF Lee, D Klenerman

    Imaging protein aggregates in the serum and cerebrospinal fluid in Parkinson’s disease.

    DOI: http://doi.org/10.1093/brain/awab306
    Journal: Brain
    E-pub date: 18 Apr 2022
    Authors: E Lobanova, D Whiten, FS Ruggeri, CG Taylor, A Kouli, Z Xia, D Emin, YP Zhang, JYL Lam, CH Williams-Gray, D Klenerman

    Phase Separation of FUS is Modulated by Methylation State of Cation-π Interactions and Interaction with TNPO1

    DOI: http://doi.org/10.1016/j.cell.2018.03.056
    Journal: Cell
    E-pub date: 19 Apr 2018
    Authors: PH St George-Hyslop, S Qamar, G Wang, SJ Randle, FS Ruggeri, J Varela, CF Kaminski, GS Kaminski, M Vendruscolo, TPJ Knowles, D Klenerman, CE Holt, Q Lin, W meadows

    Direct observation of the interconversion of normal and toxic forms of α-synuclein.

    DOI: http://doi.org/10.1016/j.cell.2012.03.037
    Journal: Cell
    E-pub date: 25 May 2012
    Authors: N Cremades, SIA Cohen, E Deas, AY Abramov, AY Chen, A Orte, M Sandal, RW Clarke, P Dunne, FA Aprile, CW Bertoncini, NW Wood, TPJ Knowles, CM Dobson, D Klenerman

    Publications

    Imaging Protein Aggregates in Parkinson’s Disease Serum Using Aptamer-Assisted Single-Molecule Pull-Down.

    DOI: http://doi.org/10.1021/acs.analchem.3c02515
    Journal: Anal Chem
    E-pub date: 17 Oct 2023
    Authors: YP Zhang, E Lobanova, D Emin, SV Lobanov, A Kouli, CH Williams-Gray, D Klenerman

    An antibody scanning method for the detection of α-synuclein oligomers in the serum of Parkinson’s disease patients.

    DOI: http://doi.org/10.1039/d2sc00066k
    Journal: Chem Sci
    E-pub date: 30 Nov 2022
    Authors: K Kulenkampff, D Emin, R Staats, YP Zhang, L Sakhnini, A Kouli, O Rimon, E Lobanova, CH Williams-Gray, FA Aprile, P Sormanni, D Klenerman, M Vendruscolo

    Small soluble α-synuclein aggregates are the toxic species in Parkinson’s disease

    DOI: http://doi.org/10.1038/s41467-022-33252-6
    Journal: Nat Commun
    E-pub date: 20 Sep 2022
    Authors: D Emin, YP Zhang, E Lobanova, A Miller, X Li, Z Xia, H Dakin, DI Sideris, JYL Lam, RT Ranasinghe, A Kouli, Y Zhao, S De, TPJ Knowles, M Vendruscolo, FS Ruggeri, FI Aigbirhio, CH Williams-Gray, D Klenerman

    Rate‐limiting processes of tau aggregate accumulation in Alzheimer’s disease

    DOI: http://doi.org/10.1002/alz.051680
    Journal: Alzheimer's & Dementia
    E-pub date: 1 Dec 2021
    Authors: G Meisl, Y Zuo, K Allinson, T Rittman, SL DeVos, JS Sanchez, CK Xu, KE Duff, KA Johnson, JB Rowe, BT Hyman, T Knowles, D Klenerman

    In vivo rate-determining steps of tau seed accumulation in Alzheimer’s disease.

    DOI: http://doi.org/10.1126/sciadv.abh1448
    Journal: Sci Adv
    E-pub date: 29 Oct 2021
    Authors: G Meisl, E Hidari, K Allinson, T Rittman, SL DeVos, JS Sanchez, CK Xu, KE Duff, KA Johnson, JB Rowe, BT Hyman, TPJ Knowles, D Klenerman

    Wild-type sTREM2 blocks Aβ aggregation and neurotoxicity, but the Alzheimer’s R47H mutant increases Aβ aggregation.

    DOI: http://doi.org/10.1016/j.jbc.2021.100631
    Journal: J Biol Chem
    E-pub date: 1 Aug 2021
    Authors: A Vilalta, Y Zhou, J Sevalle, JK Griffin, K Satoh, DH Allendorf, S De, M Puigdellívol, A Bruzas, MA Burguillos, RB Dodd, F Chen, Y Zhang, P Flagmeier, L-M Needham, M Enomoto, S Qamar, J Henderson, J Walter, PE Fraser, D Klenerman, SF Lee, P St George-Hyslop, GC Brown

    Single-Molecule Characterization of the Interactions between Extracellular Chaperones and Toxic α-Synuclein Oligomers.

    DOI: http://doi.org/10.1016/j.celrep.2018.05.074
    Journal: Cell Rep
    E-pub date: 19 Jun 2018
    Authors: DR Whiten, D Cox, MH Horrocks, CG Taylor, S De, P Flagmeier, L Tosatto, JR Kumita, H Ecroyd, CM Dobson, D Klenerman, MR Wilson

    The small heat shock protein Hsp27 binds α-synuclein fibrils, preventing elongation and cytotoxicity.

    DOI: http://doi.org/10.1074/jbc.M117.813865
    Journal: J Biol Chem
    E-pub date: 23 Mar 2018
    Authors: D Cox, DR Whiten, JWP Brown, MH Horrocks, R San Gil, CM Dobson, D Klenerman, AM van Oijen, H Ecroyd