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The William Harvey Research Institute - Faculty of Medicine and Dentistry

Dr Myles Lewis

Myles

Clinical Reader in Rheumatology

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, IMID-Bio and the EU Innovative Medicines Initiative (IMI) programme 3TR. He is a Fellow of the Turing Institute and an Academic Fellow of the Digital Environment Research Institute at Queen Mary.

 

Research

Group members

Bioinformatics and biostatistics team: Cankut Çubuk, Katriona Goldmann, Giovanni Giorli, Elisabetta Sciacca, Anna Surace

Research staff (wet lab): Ilaria Esposito, Sotiria Manou-Stathopoulou, Yoanna Kontra, Chiara Giacomassi, Susan Wang

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

Summary 

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-Sequencing (RNA-Seq), genotype & expression Quantitative Trait Loci (eQTL) analysis, immunoglobulin 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 a number of R/shiny apps (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. In the R4RA clinical trial, our analysis of RNA-Seq data from synovial biopsies from this cohort showed that patients with low levels of B cell signature genes were less likely to respond to the B cell depleting agent rituximab in comparison to the IL-6 receptor inhibitor tocilizumab. 

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 (lupus), rheumatoid arthritis (RA) and other connective tissue disorders. 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, RA and other autoimmune diseases.

 

Key Publications

For a full list of publications click here

  • ** Humby F, Durez P, Buch MH, Lewis MJ, Rizvi H, Rivellese F, Nerviani A, Giorli G, Mahto A, Montecucco C, Lauwerys B, Ng N, Ho P, Bombardieri M, Romão VC, Verschueren P, Kelly S, Sainaghi PP, Gendi N, Dasgupta B, Cauli A, Reynolds P, Cañete JD, Moots R, Taylor P, Edwards CJ, Isaacs J, Sasieni P, Choy E, Pitzalis C. Rituximab versus Tocilizumab in anti-TNF inadequate responder patients with Rheumatoid Arthritis (R4RA): a stratified, biopsy-driven, multi-centre, randomised, open label, controlled clinical trial – 16 week outcomes. The Lancet 2021; 397(10271): 305-17. PMID: 33485455
  • Nerviani A, Boutet MA, Tan WSG, Goldmann K, Purkayastha N, Lajtos T, Hands RE, Lewis MJ, Kelly S, Pitzalis C. IL-23 skin and joint profiling in psoriatic arthritis: novel perspectives in understanding clinical responses to IL-23 inhibitors. Ann Rheum Dis 2021; 80(5):591-597. PMID: 33243781
  • Rivellese F, Manou-Stathopoulou S, Mauro D, Goldmann K, Pyne D, Rajakariah R, Gordon PA, Schafer P, Bombardieri M, Pitzalis C, Lewis MJ. Effects of targeting the transcription factors Ikaros and Aiolos on B cell activation and differentiation in Systemic Lupus Erythematosus. Lupus Sci Med 2021; 8(1): e000445. PMID: 33727237
  • Gomez EA, Colas RA, Souza PR, Hands RE, Lewis MJ, Bessant C, Pitzalis C, Dalli J. Blood pro-resolving mediators are linked with synovial pathology and predictive of DMARD responsiveness in rheumatoid arthritis. Nature Communications 2020; 11(1): 5420. PMID: 33110080
  • Cherlin S, Lewis MJ, Plant D, Nair N, Goldmann K, Tzanis E, Barnes MR, McKeigue P, Barrett JH, Pitzalis C, Barton A, MATURA Consortium, Cordell HJ. Investigation of genetically-regulated gene expression and response to treatment in rheumatoid arthritis highlights an association between IL18RAP expression and treatment response. Ann Rheum Dis 2020; 79(11): 1446-52. PMID: 32732242
  • Alivernini S, MacDonald L, Elmesmari A, Finlay S, Tolusso B, Rita Gigante M, Petricca M, Di Mario C, Bui L, Perniola S, Attar M, Gessi M, Fedele AL, Filer A, McSharry C, Millar NL, Kirschner K, Nerviani A, Lewis MJ, Pitzalis C, Clark A, Ferraccioli G, Udalova I, Gremese E, McInnes IB, Otto TD, Kurowska-Stolarska M. Distinct tissue macrophage subsets provide a cellular and molecular mechanism for disease remission in rheumatoid arthritis. Nature Medicine 2020; 26(8):1295-1306. PMID: 32601335
  • Rivellese F, Humby F, Bugatti S, Fossati-Jimack L, Rizvi H, Lucchesi D, Lliso-Ribera G, Nerviani A, Hands RE, Giorli G, Frias B, Thornborn G, Jaworska E, John CR, Goldmann K, Lewis MJ, Manzo A, Bombardieri M, Pitzalis C. B cell synovitis and clinical phenotypes in rheumatoid arthritis: relationship to disease stages and drug exposure. Arthritis Rheumatol 2020; 72(5): 714-25. PMID: 31785084
  • John CR, Watson D, Russ R, Goldmann K, Ehrenstein M, Pitzalis C, Lewis MJ, Barnes M. M3C: Monte Carlo reference-based consensus clustering. Sci Rep 2020; 10(1): 1816. PMID: 32020004
  • ** 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
  • Pucino V, Certo M, Bulusu V, Cucchi D, Goldmann K, Pontarini E, Haas R, Smith J, Headland SE, Blighe K, Ruscica M, Humby F, Lewis MJ, Kamphorst JJ, Bombardieri M, Pitzalis C, Mauro C. Lactate Buildup at the Site of Chronic Inflammation Promotes Disease by Inducing CD4+ T Cell Metabolic Rewiring. Cell Metab 2019; 30(6): 1055-1074. PMID: 31708446
  • 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 2019; 78(12): 1642-52. PMID: 31582377
  • John CR, Watson D, Barnes M, Pitzalis C, Lewis MJ. Spectrum: Fast density-aware spectral clustering for single and multi-omic data. Bioinformatics 2020; 36(4): 1159-66. PMID: 31501851
  • 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
  • ** 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
  • 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
  • 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
  • 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 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: 19620499

Collaborators

Internal

Prof Costantino Pitzalis; Prof Michele Bombardieri; Prof Francesco Dell’Accio; Prof Michael Barnes; Dr Paul Pfeffer; Prof Jesmond Dalli; Dr Adam Brentnall; Prof Marta Korbonits; Prof Pedro Cutillas; Dr James Whiteford 

External

Prof Anne Barton (Manchester);Prof Paul McKeigue (Edinburgh); Prof Heather Cordell (Newcastle); Prof Iain McInnes (Glasgow); Prof Simon Jones (Cardiff); Prof Tim Vyse (KCL); Dr Francesca Capon (KCL); Prof James Wason (Newcastle); Dr Rachael Bashford-Rogers (Oxford)