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The William Harvey Research Institute - Barts and The London

Dr Myles Lewis

Myles

Senior Clinical Lecturer and Consultant Rheumatologist

Centre: Experimental Medicine and Rheumatology

Email: myles.lewis@qmul.ac.uk
Telephone: +44(0) 20 7882 3305

Profile

ORCID iD: https://orcid.org/0000-0001-9365-5345 

Myles Lewis studied preclinical medicine at Cambridge University, and clinical medicine at Oxford University. During his Rheumatology clinical training at multiple London teaching hospitals, he has worked extensively on Systemic Lupus Erythematosus (SLE) and other connective tissue diseases. He was awarded a Clinical Research Fellowship from the Wellcome Trust in 2005, for his PhD at the Hammersmith Hospital/Imperial College London, focused on understanding the causes of accelerated heart disease in SLE. In 2011 for his ongoing lab research on the role of ubiquitination in SLE and autoimmune disease, he was awarded a Clinician Scientist Fellowship by Arthritis Research UK. In 2015 he was awarded the Lancet Prize for Clinician Scientists at the Academy of Medical Sciences for his research on ubiquitination genes in SLE.

Dr Lewis also heads up a bioinformatics/biostatistics group analysing and integrating multi-omic data across autoimmune rheumatic diseases (SLE, Sjogren’s syndrome and rheumatoid arthritis). He is a group leader within the biostatistics and bioinformatics analysis teams for several rheumatoid arthritis studies including the Pathobiology of Early Arthritis Cohort (PEAC), the R4RA biopsy-driven randomised clinical trial and the Stratification of Biologic Therapies for RA by Pathobiology study (STRAP). He is a member of the bioinformatic analysis team for several stratified medicine projects including MRC MATURA, MRC RA-MAP and IMID-Bio.

Research

Group members

Research staff (lab): Ilaria Esposito, Daniele Mauro, Sotiria Manou-Stathopoulou, Chiara Giacomassi Christopher Johns, Katriona Goldmann, Giovanni Giorli, Elisabetta Sciacca

Former group members: Felice Rivellese, Fabiola Bene, Lu Zou, Kevin Blighe, Sharmila Rana, Xiujuan Hou, Simon Vyse, Adrian Shields, Sebastian Boeltz

Summary 

Ubiquitination in autoimmune disease
My lab research involves understanding the effects of ubiquitination pathways on the immune system, and their impact on autoimmune rheumatic diseases especially SLE, rheumatoid arthritis and other connective tissue disorders. Ubiquitination is a post-translocational modification in which target proteins are labelled with the small protein ubiquitin. Different types of ubiquitin chains act as a critically important control system, which can either activate (switch on) or degrade (switch off) many proteins. Numerous genes identified in genome-wide association studies are key ubiquitination regulators, such as UBE2L3, which is associated with multiple autoimmune diseases including SLE, rheumatoid arthritis, juvenile idiopathic arthritis, coeliac disease, Crohn’s disease, ulcerative colitis and psoriasis. My research focuses on trying to understand how genetic variation in ubiquitination genes influences B cell differentiation and autoantibody production through regulation of the master transcription factor of inflammation, NF-kB, thus increasing susceptibility to lupus and autoimmune disease. Our work has important translational medical implications, since we aim to determine whether particular ubiquitination genes represent novel targets for new therapies to treat lupus and other autoimmune diseases.

Bioinformatics and machine learning in stratified medicine
Dr Lewis leads a bioinformatics and biostatistics team involved in analysing and integrating multi-omic data including bulk & single cell RNA-seq, genotype & eQTL analysis, Ig V gene repertoire analysis, CyTOF and protein microarray. Our group has interests in machine learning to predict clinical response for personalised/stratified medicine, data visualisation of big data and disseminating results through interactive data web portals. Our group developed an R/shiny app (https://peac.hpc.qmul.ac.uk/) to allow exploration of RNA-sequencing data on synovial biopsies from the Pathobiology of Early Arthritis Cohort (PEAC). This website allows researchers to directly compare synovium and blood genes and gene modules in early rheumatoid arthritis and see how gene expression correlates with clinical measures of disease activity and response to therapy, thus enabling in-depth interrogation of the data.

Key Publications

  • Lewis MJ, Barnes MR, Blighe K, Goldmann K, Rana S, Hackney J, Ramamoorthi N, John CR, Watson D, Kummerfeld S, Hands RE, Riahi S, Rocher-Ros V, Rivellese F, Humby F, Kelly S, Bombardieri M, Ng N, DiCicco M, van der Heijde D, Landewé R, van der Helm-van Mil A, Cauli A, McInnes IB, Buckley CD, Choy E, Taylor P, Townsend MJ, Pitzalis C. Molecular portraits of early rheumatoid arthritis identify clinical and treatment response phenotypes. Cell Reports 2019; 28(9): 2455-70. PMID: 31461658
  • Humby F, Lewis MJ,* Ramamoorthi N, Hackney J, Barnes M, Bombardieri M, Setiadi F, Kelly S, Bene F, di Cicco M, Riahi S, Rocher-Ros V, Ng N, Hands RE, van der Heijde D, Landewé R, van der Helm-van Mil S, Cauli A, McInnes IB, Buckley CD, Choy E, Taylor P, Townsend MJ, Pitzalis C. Synovial cellular and molecular signatures in early rheumatoid arthritis stratify clinical response to csDMARD therapy and predict radiographic progression. Ann Rheum Dis 2019; 78(6): 761-772. PMID: 30878974 *Joint first author
  • Twohig JP, Cardus Figueras A, Andrews R, Wiede F, Cossins BC, Derrac Soria A, Lewis MJ, Townsend MJ, Millrine D, Li J, Hill D, Uceda Fernandez J, Liu X, Szomolay B, Pepper CJ, Taylor PR, Pitzalis C, Tiganis T, Williams NM, Jones GW, Jones SA. Activation of naïve CD4+ T cells re-tunes STAT1 signaling to deliver unique cytokine responses in memory CD4+ T cells. Nat Immunol 2019; 20(4): 458-470. PMID: 30890796
  • John CR, Watson D, Barnes M, Pitzalis C, Lewis MJ. Spectrum: Fast density-aware spectral clustering for single and multi-omic data. Bioinformatics 2019; doi: 10.1093/bioinformatics/btz704 PMID: 31501851
  • Lliso-Ribera G, Humby F, Lewis MJ, Nerviani A, Mauro D, Rivellese F, Kelly S, Hands RE, Bene F, Ramamoorthi N, Hackney J, Cauli A, Choy E, Filer A, Taylor P, McInnes I, Townsend M, Pitzalis C. Synovial tissue signatures enhance clinical classification and prognostic/treatment response algorithms in early inflammatory arthritis and predict requirement for subsequent biologic therapy. Ann Rheum Dis (accepted)
  • Boutet MA, Nerviani A, Lliso-Ribera G, Lucchesi D, Goldmann K, Lewis MJ, Pitzalis C. Interleukin-36 family dysregulation drives joint inflammation and therapy response in Psoriatic Arthritis. Rheumatology DOI: 10.1093/rheumatology/kez358 PMID: 31504934
  • El Shikh ME, El Sayed R, Nerviani A, Goldmann K, John CR, Hands R, Fossati-Jimack L, Lewis MJ, Pitzalis C. Extracellular traps and PAD4 released by macrophages induce citrullination and auto-antibody production in autoimmune arthritis. J Autoimmun Epub doi: 10.1016/j.jaut.2019.06.008 PMID: 31277965
  • Hensor EMA, McKeigue P, Buch MH, Barrett JH, Nam JL, Freeston J, Colombo M, Spiliopoulou A, Agakov F, Kelly S, Lewis MJ, Ling SF, Viatte S, Verstappen SMM, Barton A, Pitzalis C, Emery P, IACON consortium, PEAC consortium, Conaghan PG, Morgan AW. Validity of a 2-component imaging-derived disease activity score (2C-DAS28) for improved assessment of synovitis in early rheumatoid arthritis. Rheumatology 2019; 58(8): 1400-9. PMID: 30824919
  • Bottini A, Wu D, Bartok B, Bombardieri M, Doody K, Zhang V, Sacchetti C, Zoccheddu M, Lonic, A, Boyle D, Hammker D, Meng TC, Corr M, Stanford S, Lewis MJ, Wang W, Firestein G, Pitzalis C, Bottini N. PTPN14 phosphatase and YAP promote TGFbeta signalling in rheumatoid synoviocytes. Ann Rheum Dis 2019; 78(5): 600-609. PMID: 30808624
  • Dorris ER, Tazzyman SJ, Moylett J, Ramamoorthi N, Hackney J, Townsend M, Muthana M, Lewis MJ, Pitzalis C, Wilson AG. The autoimmune susceptibility gene C5orf30 regulates macrophage-mediated resolution of inflammation. J Immunol 2019; 202(4):1069-1078. PMID: 30659109
  • RA-MAP Consortium. Novel methodology to discern predictors of remission and patterns of disease activity over time using rheumatoid arthritis clinical trials data. RMD Open 2018; 4(2): e000721. PMID: 30487994
  • Lewis MJ, Barnes MR. RNA sequencing and machine learning as molecular scalpels. Nat Rev Rheumatol 2018; 14: 388–390. PMID: 29752460
  • Lewis MJ, McAndrew MB, Wheeler C, Workman N, Agashe P, Koopmann J, Uddin E, Morris DL, Zou L, Stark R, Anson J, Cope AP, Vyse TJ. Autoantibodies targeting TLR and SMAD pathways define new subgroups in Systemic Lupus Erythematosus. J Autoimmun 2018; 91: 1-12. PMID: 29576246
  • RA-MAP Consortium. The RA-MAP Consortium: a working model for academia-industry collaboration. Nat Rev Rheumatol 2018; 14(1): 53-60. PMID: 29213124
  • Pullabhatla V, Roberts AL, Lewis MJ, Mauro D, Morris DL, Odhams CA, Tombleson P, Liljedahl U, Vyse S, Simpson MA, Sauer S, de Rinaldis E, Syvänen AC, Vyse TJ. De novo mutations implicate novel genes in Systemic Lupus Erythematosus. Hum Mol Genet 2018; 27(3): 421-9. PMID: 29177435
  • Ursini F, Leporini C, Bene F, D'Angelo S, Mauro D, Russo E, De Sarro G, Olivieri I, Pitzalis C, Lewis M, Grembiale RD. Anti-TNF-alpha agents and endothelial function in rheumatoid arthritis: a systematic review and meta-analysis. Sci Rep 2017; 7(1): 5346. PMID: 28706194
  • Bombardieri M, Lewis M, Pitzalis C. Ectopic lymphoid neogenesis in rheumatic autoimmune diseases. Nat Rev Rheumatol. 2017; 13(3): 141-154. PMID: 28202919
  • Lewis MJ, Jawad A. The effect of ethnicity and genetic ancestry on the epidemiology, clinical features and outcome of Systemic Lupus Erythematosus. Rheumatology 2017; 56: i67-i77. PMID: 27940583
  • Lewis MJ, Vyse S, Shields AM, Zou L, Khamashta M, Gordon PA, Pitzalis C, Vyse TJ, D’Cruz DP. Improved monitoring of clinical response in Systemic Lupus Erythematosus by longitudinal trend in soluble vascular cell adhesion molecule-1. Arthritis Res Ther 2016; 18: 5. PMID: 26746423
  • Lewis MJ, Vyse S, Shields AM, Boeltz S, Gordon PA, Spector TD, Lehner PJ, Walczak H, Vyse TJ. UBE2L3 polymorphism amplifies NF-kB activation and promotes plasma cell development linking linear ubiquitination to multiple autoimmune diseases. Am J Hum Genet 2015; 96(2): 221-34. PMID: 25640675
  • Lewis M, Vyse S, Shields A, Boeltz S, Gordon P, Spector T, Lehner P, Walczak H, Vyse T. Effect of UBE2L3 genotype on regulation of the linear ubiquitin chain assembly complex in systemic lupus erythematosus. The Lancet 2015; 385: S9. PMID: 26312912
  • Davies RJ, Sangle SR, Jordan NP, Aslam L, Lewis MJ, Wedgwood R, D’Cruz DP. Rituximab in the treatment of resistant lupus nephritis: therapy failure in rapidly progressive crescentic lupus nephritis. Lupus 2013; 22(6): 574-82. PMID: 23632989
  • Lewis MJ, Vyse TV. “Connective Tissue Disease” in Chapter “Genetics and the Environment” in Oxford Textbook of Rheumatology, 2013, 4th edition, Ed. Watts RA et al.
  • Lewis MJ, Malik TH, Fossati-Jimeck L, Carassiti D, Cook HT, Haskard DO, Botto M. Combining lupus and hyperlipidaemia in mice reveals distinct roles for complement in glomerulonephritis and atherosclerosis. Arthritis Rheum 2012; 64(8): 2707-18. PMID: 22392450
  • Lewis MJ, Malik TH, Ehrenstein MR, Boyle JJ, Botto M, Haskard DO. Immunoglobulin M is required for protection against atherosclerosis in low-density lipoprotein receptor-deficient mice. Circulation 2009; 120(5): 417-26. PMID: 19620499Lewis MJ, Botto M. Complement deficiencies in humans and animals: Links to autoimmunity. Autoimmunity 2006; 39(5): 367-78. PMID: 16923536