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

Mechanistic Models of Protein Aggregation Across Length-Scales and Time-Scales: From the Test Tube to Neurodegenerative Disease.

DOI: http://doi.org/10.3389/fnins.2022.909861
Journal: Front Neurosci
E-pub date: 1 Aug 2022
Authors: G Meisl, TPJ Knowles, 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