McEwan Lab plasmids at Addgene here
Pre-prints
Neurodegeneration emerges at a cellular tipping point between aggregate accumulation and removal.
Cotton MW, Venkatesan S, Beckwith JS, Böken D, Xu CK, Fertan E, Breiter JC, Berkowicz LE, Salazar LS, Von Schulze A, Andrzejewska EA, Brock EE, Han HL, Schneider MM, Sahtoe DD, Baker D, Rowe JB, Goriely A, McEwan WA, Knowles TPJ, Lee SF, Halfmann R, Klenerman D, Meisl G.
bioRxiv 2025 Oct 30:2025.09.08.674880. doi: 10.1101/2025.09.08.674880. PMID: 41040193; PMCID: PMC12485761.
Small tau aggregates exhibit disease-specific molecular profiles across tauopathies Dorothea Böken, Melissa Huang, Yunzhao Wu, Emre Fertan, Jeff Y.L. Lam, Georg Meisl, Shaan Baig, James Rowe, Colin Smith, Annelies Quaegebeur, Dezerae Cox, William A McEwan and David Klenerman
bioRxiv. posted 11 June 2025,10.1101/2025.06.10.658934
Antibody-dependent Intracellular neutralisation by TRIM21 is potentiated by HOIP and linear ubiquitin chains
Christopher Green, Konstanze F. Winklhofer, Adam J. Fletcher, Leo C. James, John Skidmore, James Duce, William A. McEwan
bioRxiv 2024.04.02.587719; doi: https://doi.org/10.1101/2024.04.02.587719
Peer-reviewed publications
2025
State-selective small molecule degraders that preferentially remove aggregates and oligomers.
Luptak J, Clift D, Mukadam A, Benn J, Rhinesmith T, McLaughlin SH, Dodds AC, Lapetaje JE, Sczaniecka-Clift M, France DJ, McEwan WA, James LC.
Nat Commun. 2025 Nov 25;16(1):10486. doi: 10.1038/s41467-025-65454-z. PMID: 41290659; PMCID: PMC12647892.
Novel blood-based proteomic signatures across multiple neurodegenerative diseases.
Durcan R, Heslegrave A, Swann P, Goddard J, Chouliaras L, Murley AG, Savulich G, Bevan-Jones WR, Swann O, Ashton NJ, Blennow K, McEwan W, Zetterberg H, Rowe JB, O’Brien JT, Malpetti M.
Alzheimers Dement. 2025 Mar;21(3):e70116. doi: 10.1002/alz.70116. PMID: 40145305;
Additive effect of distant Lewy bodies and tau seeds injections on nigral degeneration in macaques.
Darricau M, Kulifaj V, Arotcarena ML, Li Q, Katsinelos T, McEwan WA, Xilouri M, Dehay B, Bezard E, Planche V.
NPJ Parkinsons Dis. 2025 Apr 13;11(1):75. doi: 10.1038/s41531-025-00938-9. PMID: 40221462
Sensitive detection and propagation of brain-derived tau assemblies in HEK293-based wild-type tau seeding assays.
Huang M & McEwan WA
J Biol Chem. 2025 Jan 27;301(3):108245. doi: 10.1016/j.jbc.2025.108245. Epub ahead of print. PMID: 39880096.
SynPull: An advanced method for studying neurodegeneration-related aggregates in synaptosomes using super-resolution microscopy.
Kedia S, Fertan E, Wu Y, Zhang YP, Meisl G, Lam JYL, K Wiseman F, McEwan WA, Quaegebeur A, Spillantini MG, Danial JSH, Klenerman D.
Cell Chem Biol. 2025 Feb 20;32(2):338-351.e4. doi: 10.1016/j.chembiol.2025.01.001. Epub 2025 Jan 24. PMID: 39862866.
2024
Distinct regulation of Tau Monomer and aggregate uptake and intracellular accumulation in human neurons.
Marvian AT, Strauss T, Tang Q, Tuck BJ, Keeling S, Rüdiger D, Mirzazadeh Dizaji N, Mohammad-Beigi H, Nuscher B, Chakraborty P, Sutherland DS, McEwan WA, Köglsperger T, Zahler S, Zweckstetter M, Lichtenthaler SF, Wurst W, Schwarz S, Höglinger G.
Mol Neurodegener.2024 Dec 31;19(1):100. doi: 10.1186/s13024-024-00786-w. PMID: 39736627; PMCID: PMC11686972.
Carbonic anhydrase inhibition ameliorates tau toxicity via enhanced tau secretion.
Lopez A, Siddiqi FH, Villeneuve J, Ureshino RP, Jeon HY, Koulousakis P, Keeling S, McEwan WA, Fleming A, Rubinsztein DC.
Nat Chem Biol. 2024 Oct 31. doi: 10.1038/s41589-024-01762-7
Co-opting templated aggregation to degrade pathogenic tau assemblies and improve motor function.
Miller LVC, Papa G, Vaysburd M, Cheng S, Sweeney PW, Smith A, Franco C, Katsinelos T, Huang M, Sanford SAI, Benn J, Farnsworth J, Higginson K, Joyner H, McEwan WA, James LC.
Cell. 2024 Sep 10:S0092-8674(24)00912-7. doi: 10.1016/j.cell.2024.08.024.
Aggregate-selective removal of pathological tau by clustering-activated degraders.
Benn J, Cheng S, Keeling S, Smith AE, Vaysburd MJ, Böken D, Miller LVC, Katsinelos T, Franco C, Dupré E, Danis C, Landrieu I, Buée L, Klenerman D, James LC, McEwan WA.
Science. 2024 Aug 30;385(6712):1009-1016. doi: 10.1126/science.adp5186. Epub 2024 Aug 29.
[Open access version here]
Single-Molecule Characterization and Super-Resolution Imaging of Alzheimer’s Disease-Relevant Tau Aggregates in Human Samples.
Angew Chem Int Ed Engl. 2024 Mar 24:e202317756. doi: 10.1002/anie.202317756.
Sanford SAI, Miller LVC, Vaysburd M, Keeling S, Tuck BJ, Clark J, Neumann M, Syanda V, James LC, McEwan WA.
Alzheimers Dement. 2024 Feb;20(2):1013-1025. doi: 10.1002/alz.13493. Epub 2023 Oct 17.
2023
Super-resolution imaging unveils the self-replication of tau aggregates upon seeding
Eleni Dimou, Taxiarchis Katsinelos, Georg Meisl, Benjamin J Tuck, Sophie Keeling, Annabel E Smith, Eric Hidari, Jeff Y L Lam, Melanie Burke, Sofia Lövestam, Rohan T Ranasinghe, William A McEwan, David Klenerman
Cell Reports 2023 Jul 1;42(7):112725. doi: 10.1016/j.celrep.2023.112725
Perforin-2 is a pore-forming effector of endocytic escape in cross-presenting dendritic cells
Pablo Rodríguez-Silvestre , Marco Laub, Patrycja A Krawczyk, Alexandra K Davies, Julia P Schessner, Reejuana Parveen, Benjamin J Tuck, William A McEwan, Georg H H Borner, Patrycja Kozik
Science. 2023 23;380(6651):1258-1265. doi: 10.1126/science.adg8802
Cytosolic antibody receptor TRIM21 is required for effective tau immunotherapy in mouse models
2022
Tau seeds from patients induce progressive supranuclear palsy pathology and symptoms in primates.
Darricau M, Katsinelos T, Raschella F, Milekovic T, Crochemore L, Li Q, Courtine G, McEwan WA, Dehay B, Bezard E, Planche V
Brain. 2022 Nov doi:10.1093/brain/awac428
Type-I Interferons in Alzheimer’s Disease and Other Tauopathies
Sanford SAI & McEwan WA
Front Cell Neurosci 2022 July doi: 10.3389/fncel.2022.949340
Cholesterol determines the cytosolic entry and seeded aggregation of tau.
Cell Rep. 2022 May 3;39(5):110776. doi: 10.1016/j.celrep.2022.110776.
Antibodies in the intracellular domain. (Editorial)
Semin Cell Dev Biol. 2022 Jun;126:97-98. doi: 10.1016/j.semcdb.2022.02.020. Epub 2022 Feb 28.
Targeted protein degradation using intracellular antibodies and its application to neurodegenerative disease.
Semin Cell Dev Biol. 2022 Jun;126:138-149. doi: 10.1016/j.semcdb.2021.09.012.
2021
Microglia become hypofunctional and release metalloproteases and tau seeds when phagocytosing live neurons with P301S tau aggregates.
Brelstaff JH, Mason M, Katsinelos T, McEwan WA, Ghetti B, Tolkovsky AM, Spillantini MG.
Sci Adv. 2021 Oct doi: 10.1126/sciadv.abg4980.
Identification of cis-acting determinants mediating the unconventional secretion of tau
Katsinelos T, McEwan WA, Jahn TR, Nickel W.
Scientific Reports 2021 Jun 11:12946
Tau assemblies do not behave like independently acting prion-like particles in mouse neural tissue.
Miller LVC, Mukadam AS, Durrant CS, Vaysburd MJ, Katsinelos T, Tuck BJ, Sanford S, Sheppard O, Knox C, Cheng S, James LC, Coleman MP, McEwan WA.
Acta Neuropathol Commun. 2021 Mar 12;9(1):41. doi: 10.1186/s40478-021-01141-6.
Target-induced clustering activates Trim-Away of pathogens and proteins
Zeng J, Santos AF, Mukadam AS, Osswald M, Jacques DA, Dickson CF, McLaughlin SH, Johnson CM, Kiss L, Luptak J, Renner N, Vaysburd M, McEwan WA, Morais-de-Sá E, Clift D, James LC.
Nat Struct Mol Biol. 2021 Feb 25. doi: 10.1038/s41594-021-00560-2.
2020
Enhancing mitophagy as a therapeutic approach for neurodegenerative diseases
Aman Y, Ryan B, Torsetnes SB, Knapskog AB, Watne LO, McEwan WA, Fang EF.
Int Rev Neurobiol. 2020;155:169-202. doi: 10.1016/bs.irn.2020.02.008.
Disassembly of Tau fibrils by the human Hsp70 disaggregation machinery generates small seeding-competent species
Nachman E, Wentink AS, Madiona K, Bousset L, Katsinelos T, Allinson K, Kampinga H, McEwan WA, Jahn TR, Melki R, Mogk A, Bukau B, Nussbaum-Krammer C
J Biol Chem 2020 May 28. doi: 10.1074/jbc.RA120.013478
2019
The Role of Antibodies and Their Receptors in Protection Against Ordered Protein Assembly in Neurodegeneration
Katsinelos T, Tuck BJ, Mukadam AS, McEwan WA.
Frontiers in Immunology 2019 May 31. doi: 10.3389/fimmu.2019.01139
2018
Acute and rapid degradation of endogenous proteins by Trim-Away.
Clift D, So C, McEwan WA, James LC, Schuh M.
Nat Protoc. 2018 Sep 24. doi: 10.1038/s41596-018-0028-3.
IP6 is an HIV pocket factor that prevents capsid collapse and promotes DNA synthesis
Mallery DL, Márquez CL, McEwan WA, Dickson C, Jacques DA, Anandapadamanaban M, Bichel K, Towers GJ, Saiardi A, Böcking T, James LC
eLife 2018 Jun 7 e35335
Measurement of Tau Filament Fragmentation Provides Insights into Prion-like Spreading.
Kundel F, Hong L, Falcon B, McEwan WA, Michaels TCT, Meisl G, Esteras N, Abramov AY, Knowles TJP, Goedert M, Klenerman D.
ACS Chem Neurosci. 2018 Apr 8. doi: 10.1021/acschemneuro.8b00094.
Relevant papers before lab started in 2017
A Method for the Acute and Rapid Degradation of Endogenous Proteins
Clift D, McEwan WA, Labzin LI, Konieczny V, Mogessie B, James LC, Schuh M.
Cell 2017 Dec 171 1692-1706
Cytosolic Fc receptor TRIM21 inhibits seeded tau aggregation.
McEwan WA, Falcon B, Vaysburd M, Clift D, Oblak AL, Ghetti B, Goedert M, James LC.
Proc Natl Acad Sci U S A. 2017 Jan 114 574-579
Surveillance for Intracellular Antibody by Cytosolic Fc Receptor TRIM21.
McEwan WA.
Antibodies 2016 Nov 5 21-33
Intracellular antibody-bound pathogens stimulate immune signaling via the Fc receptor TRIM21
McEwan WA, Tam JCH, Watkinson RE, Bidgood SR, Mallery DL, James LC.
Nat Immunol 2013 Apr 14 327-36
Regulation of Virus Neutralization and the Persistent Fraction by TRIM21
McEwan WA, Hauler F, Williams CR, Bidgood SR, Mallery DL, Crowther RA, James LC.
J Virol 2012 Aug 86 8482-9
Antibodies mediate intracellular immunity through tripartite motif-containing 21 (TRIM21)
Mallery DL, McEwan WA, Bidgood SR, Towers GJ, Johnson CM, James LC.
Proc Natl Acad Sci U S A 2010 Nov 107 19985-90
Truncation of TRIM5 in the Feliformia explains the absence of retroviral restriction in cells of the domestic cat
McEwan WA, Schaller T, Ylinen LM, Hosie MJ, Towers GJ, Willett BJ.
J Virol 2009 Aug 83 8270-5.
McEwan Lab 