Selected Publications
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The HUSH Complex and Chromatin biology
Seczynska M, Bloor S, Cuesta SM, Lehner PJ. Genome surveillance by HUSH- mediated silencing of intronless mobile elements. Nature. 2022
Jan;601(7893):440-445. doi: 10.1038/s41586-021-04228-1. Epub 2021 Nov 18. PMID:34794168; PMCID: PMC8770142.
Dupont L, Bloor S, Williamson JC, Cuesta SM, Shah R, Teixeira-Silva A, Naamati A, Greenwood EJD, Sarafianos SG, Matheson NJ, Lehner PJ. The SMC5/6 complex compacts and silences unintegrated HIV-1 DNA and is antagonized by Vpr. Cell Host Microbe. 2021 May 12;29(5):792-805.e6.
doi: 10.1016/j.chom.2021.03.001. Epub 2021 Apr 2. PMID: 33811831; PMCID: PMC8118623.
Prigozhin DM, Douse CH, Farleigh LE, Albecka A, Tchasovnikarova IA, Timms RT, Oda SI, Adolf F, Freund SMV, Maslen S, Lehner PJ, Modis Y. Periphilin self- association underpins epigenetic silencing by the HUSH complex.
Nucleic Acids Res. 2020 Oct 9;48(18):10313-10328. doi: 10.1093/nar/gkaa785. PMID: 32976585; PMCID: PMC7544229.
Douse CH, Tchasovnikarova IA, Timms RT, Protasio AV, Seczynska M, Prigozhin DM, Albecka A, Wagstaff J, Williamson JC, Freund SMV, Lehner PJ, Modis Y. TASOR is a pseudo-PARP that directs HUSH complex assembly and epigenetic transposon control. Nature Comms. 2020 Oct 2;11(1):4940. doi: 10.1038/s41467-020-18761-6.
PMID: 33009411; PMCID: PMC7532188.
Burr ML, Sparbier CE, Chan KL, Chan YC, Kersbergen A, Lam EYN, Azidis-Yates E, Vassiliadis D, Bell CC, Gilan O, Jackson S, Tan L, Wong SQ, Hollizeck S, Michalak EM, Siddle HV, McCabe MT, Prinjha RK, Guerra GR, Solomon BJ, Sandhu S, Dawson SJ, Beavis PA, Tothill RW, Cullinane C, Lehner PJ, Sutherland KD, Dawson MA. An Evolutionarily Conserved Function of Polycomb Silences the MHC Class I Antigen Presentation Pathway and Enables Immune Evasion in Cancer. Cancer Cell. 2019 Oct 14;36(4):385-401.e8. doi: 10.1016/j.ccell.2019.08.008. Epub 2019 Sep
26. PMID: 31564637; PMCID: PMC6876280.
Timms RT, Tchasovnikarova IA, Lehner PJ. Differential viral accessibility (DIVA) identifies alterations in chromatin architecture through large-scale mapping of lentiviral integration sites. Nature Protoc. 2019 Jan;14(1):153-170. doi: 10.1038/s41596-018-0087-5. PMID: 30518911.
Robbez-Masson L, Tie CHC, Conde L, Tunbak H, Husovsky C, Tchasovnikarova IA, Timms RT, Herrero J, Lehner PJ, Rowe HM. The HUSH complex cooperates with TRIM28 to repress young retrotransposons and new genes. Genome Research 2018 Jun;28(6):836-845. doi: 10.1101/gr.228171.117. Epub 2018 May 4. PMID: 29728366; PMCID: PMC5991525.
Douse CH, Bloor S, Liu Y, Shamin M, Tchasovnikarova IA, Timms RT, Lehner PJ, Modis Y. Neuropathic MORC2 mutations perturb GHKL ATPase dimerization dynamics and epigenetic silencing by multiple structural mechanisms. Nature Comms. 2018 Feb 13;9(1):651. doi: 10.1038/s41467-018-03045-x. PMID: 29440755; PMCID: PMC5811534.
Tchasovnikarova IA, Timms RT, Douse CH, Roberts RC, Dougan G, Kingston RE, Modis Y, Lehner PJ. Hyperactivation of HUSH complex function by Charcot-Marie- Tooth disease mutation in MORC2. Nature Genet. 2017 Jul;49(7):1035-1044. doi: 10.1038/ng.3878. Epub 2017 Jun 5. PMID: 28581500; PMCID: PMC5493197.
Timms RT, Tchasovnikarova IA, Antrobus R, Dougan G, Lehner PJ. ATF7IP-Mediated Stabilization of the Histone Methyltransferase SETDB1 Is Essential for Heterochromatin Formation by the HUSH Complex. Cell Rep. 2016 Oct
11;17(3):653-659. doi: 10.1016/j.celrep.2016.09.050. PMID: 27732843; PMCID: PMC5081395.
Timms RT, Tchasovnikarova IA, Lehner PJ. Position-effect variegation revisited: HUSHing up heterochromatin in human cells. Bioessays. 2016 Apr;38(4):333-43. doi: 10.1002/bies.201500184. Epub 2016 Feb 8. PMID: 26853531.
Tchasovnikarova IA, Timms RT, Matheson NJ, Wals K, Antrobus R, Göttgens B, Dougan G, Dawson MA, Lehner PJ. GENE SILENCING. Epigenetic silencing by the HUSH complex mediates position-effect variegation in human cells. Science. 2015 Jun26;348(6242):1481-1485. doi: 10.1126/science.aaa7227. Epub 2015 May 28. PMID: 26022416; PMCID: PMC4487827.
Proteomics
Weekes MP, Tan SYL, Poole E, Talbot S, Antrobus R, Smith DL, Montag C, Gygi SP, Sinclair JH, and Lehner PJ. Latency-associated degradation of the MRP1 drug transporter offers a therapeutic target for latent human cytomegalovirus (HCMV) infection. Science (2013) Apr 12;340(6129):199-202. PMID: 23580527 doi: 10.1126/science.1235047.
Weekes MP, Tomasec P, Huttling, EL Fielding CA, Nusinow D, Stanton RJ, Wang ECY, Aicheler R, Murrell I, Wilkinson GWG, Lehner PJ and Gygi SP. Quantitative temporal viromics: a new approach to investigate host-pathogen interaction. Cell (2014) Jun 5;157(6):1460-72. PMID: 24906157 doi: 10.1016/j.cell.2014.04.028.
Matheson NJ, Sumner J, Wals K, Rapiteanu R, Weekes MP, Vigan R, Weinelt J, Schindler M, Antrobus R, Costa ASH, Frezza C, Clish CB, Neil SJD, Lehner PJ. Cell Surface Proteomic Map of HIV Infection Reveals Antagonism of Amino Acid Metabolism by Vpu and Nef. Cell, Host and Microbe (2015) 18(4):409-23 PMID: 26439863 doi: 10.1016/j.chom.2015.09.003.
Greenwood EJD, Matheson NJ, Wals K, van den Boomen DJ, Antrobus R, Williamson JC, Lehner PJ. Temporal proteomic analysis of HIV infection reveals remodelling of the host phosphoproteome by lentiviral Vif variants. eLife (2016);5:e18296 PMID: 27690223 doi: 10.7554/eLife.18296.
Gabaev I, Williamson JC, Crozier TWM, Schulz TF, Lehner PJ. Quantitative proteomics analysis of lytic KSHV infection in human endothelial cells reveals novel targets of viral immune modulation. Cell Reports 2020 Oct 13;33(2):108249. PMID: 33053346 doi: 10.1016/108249
MHC-1
Duncan, LM, Piper, S, Dodd, RB, Saville, MK, Sanderson, CM, Luzio JP and Lehner PJ. Lysine-63 Linked Ubiquitination Is Required For Endolysosomal Degradation of Class I Molecules. EMBO Journal (2006) 25:1635-1645. PMID: 16601694 doi: 10.1038/sj.emboj.7601056
Boname JM, Thomas M, Stagg HR, Xu P, Peng J, Lehner PJ. Efficient Internalization of MHC I Requires Lysine-11 and Lysine-63 Mixed Linkage Polyubiquitin Chains. Traffic (2010) 210 – 220 PMID: 19948006 doi: 10.1111/j.1600-0854.2009.01011.x.
Stagg, HR, Thomas M, Van den Boomen D, Wiertz EH, Drabkin HA, Gemmill RM and Lehner PJ. The TRC8 E3 Ligase ubiquitinates MHC class I molecules before dislocation from the ER. Journal of Cell Biology (2009) 186(5):685-92 PMID: 19720873 doi: 10.1083/jcb.200906110.
Van den Boomen DJH, Timms RT, Grice G, Stagg HR Skødt HR, Dougan G, Nathan JA & Lehner PJ. TMEM129 is a Derlin-1 associated ERAD E3 ligase essential for virus-induced degradation of MHC-I. Proc Natl Acad Sci (2014) 11(31):11425-30 PMID: 25030448 doi: 10.1073/pnas.1409099111.
Burr ML, Cano F, Svobodova S, Boyle LH, Boname JM, Lehner PJ. HRD1 and UBE2J1 target misfolded MHC class I heavy chains for endoplasmic reticulum-associated degradation. Proc Natl Acad Sci (2011) 108:2034-9 PMID: 21245296. doi: 10.1073/pnas.1016229108.
Ubiquitin
Volkmar N, Gawden-Bone CM, Williamson JC, Nixon-Abell J, West JA, St George-Hyslop PH, Kaser A, Lehner PJ. Regulation of membrane fluidity by RNF145-triggered degradation of the lipid hydrolase ADIPOR2. EMBO J. 2022 Oct 4;41(19):e110777. doi: 10.15252/embj.2022110777. Epub 2022 Aug 22. PMID: 35993436; PMCID: PMC9531299.
van den Boomen DJH, Sienkiewicz A, Berlin I, Jongsma MLM, van Elsland DM, Luzio JP, Neefjes JJC, Lehner PJ. A trimeric Rab7 GEF controls NPC1-dependent lysosomal cholesterol export. Nat Commun. 2020 Nov 3;11(1):5559. doi: 10.1038/s41467-020-19032-0. PMID: 33144569; PMCID: PMC7642327.
van den Boomen DJH, Volkmar N, Lehner PJ. Ubiquitin-mediated regulation of sterol homeostasis. Curr Opin Cell Biol. 2020 Aug;65:103-111. doi: 10.1016/j.ceb.2020.04.010. Epub 2020 Jun 21. PMID: 32580085.
Menzies SA, Volkmar N, van den Boomen DJ, Timms RT, Dickson AS, Nathan JA,Lehner PJ. The sterol-responsive RNF145 E3 ubiquitin ligase mediates the degradation of HMG-CoA reductase together with gp78 and Hrd1. Elife. 2018 Dec 13;7:e40009. doi: 10.7554/eLife.40009. PMID: 30543180; PMCID: PMC6292692