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The William Harvey Research Institute - Barts and The London

Professor Costantino Pitzalis, MD, PhD, FRCP

Costantino

Versus Arthritis Professor of Rheumatology, Deputy Director of the William Harvey Research Institute, Director Versus Arthritis Experimental Arthritis Treatment Centre, and Head of Centre for Experimental Medicine and Rheumatology

Centre: Experimental Medicine and Rheumatology

Email: c.pitzalis@qmul.ac.uk
Telephone: +44(0) 20 7882 8191

Profile

ORCID iD: https://orcid.org/0000-0003-1326-5051

Costantino Pitzalis is Versus Arthritis Professor of Rheumatology at the William Harvey Research Institute, Barts and The London School of Medicine and Dentistry Queen Mary University of London.

He is Deputy Director of the William Harvey Research Institute and Chair of the NIHR Musculoskeletal Translational Research Collaboration (NIHR MSK TRC). He is also Head of the Centre for Experimental Medicine and Rheumatology, leading a Research Team of approximately 50 Researchers (Clinicians and Scientists) and 10 clinical trials staff. He has published over 290 peer-reviewed papers in the field of inflammation, immunity, and arthritis. 

His research interests focus on the cellular and molecular mechanisms of inflammation and autoimmunity in chronic rheumatic conditions particularly rheumatoid arthritis (RA). He was the Chief Investigator of the first 2 stratified, biopsy­driven, multicentre, randomised clinical trials in rheumatoid arthritis (RA) which were funded by the NIHR and MRC/VA (R4RA and STRAP). The results of the R4RA trial were published in The Lancet in January 2021.   These RCTs are the first worldwide biopsy-driven trials that span the disease course from early to late RA and are synchronised for drug exposure. This programme has led to the definition of specific pathobiological phenotypes linked to clinical and treatment response endotypes, as recently published in Cell Reports (August 2019) for early RA. The ultimate goal of the programme is the delineation of synovial specific signatures able to define a new taxonomy of disease integrating clinical and molecular pathology algorithms to more accurately predict prognosis and treatment response prior to initiation of potentially toxic and expensive therapies, in order to give the right drug to the right patients first time: towards precision medicine.

He is also currently a Chief Investigator and lead of the RA working group within 3TR, a public-private research initiative which aims to provide new insights into the mechanisms of response and non-response to treatment within and across seven different immune-mediated diseases.

 

Research

Group members: Centre for Experimental Medicine and Rheumatology

Deputy Centre Lead: Professor Michele Bombardieri

Senior Staff: Professor Francesco Dell'Accio, Dr Mohey El Shikh, Dr Frances Humby, Dr Myles LewisProfessor Alberto Mantovani, Professor Dylan Morrissey

Laboratory Manager: Dr Rebecca Hands

Research Staff: Dr Marie-Astrid Boutet, Dr Sara Caxaria, Dr Federico Colombo, Dr Elisa Corsiero, Dr Francesca Delvecchio, Dr Suzanne Eldridge, Dr Sofia Grigoriadou, Dr Magdalena Kaneva, Dr Lucas Jagemann, Dr Davide Lucchesi, Dr Elena Pontarini, Dr Edoardo Prediletto, Dr Shafaq Sikandar, Dr Georgina Thorborn, Dr Anne-Sophie Thorup, Sabah Bharde, Melody Deniz, Aida Barawi, Jacob Wilson, Rachel Coleby, Farzana Chowdhury, Mattia Caliste, Mareike Werle, Aseel Ismail, Giulia Ghirardi, Sara Pagani, Dr Riham El Sayed, Dr Ilaria Esposito

Clinical Staff: Dr Felice Rivellese, Dr Alessandra Nerviani, Dr Amy MacBrayne, Dr Chiara Giacomassi, Dr Susan Wang, Dr Mikalena Xenophontos, Mary Githinji, Fatima Bibi, Victoria Amosun, Ishraat Miah

Bioinformatician/Statisticians: Cankut Cubuk, Anna Surace, Elisabetta Sciacca, Katriona Goldman, Giovanni Giorli 

Clinical Trials Staff: Dr Liliane Fossati – Jimack, Joanna Peel, Louise Warren, Laura Basely

Centre Administration/IT: Grace Ma, Amani Lahmami, Vladan Petrovic

Biobank/Technical Staff: Dr Georgina Thorborn, Manzoor Ahmed, Edyta Jaworska

Summary

The Centre for Experimental Medicine and Rheumatology’s mission is to better understand disease pathogenesis in order to develop novel therapeutics and maximise therapeutic utility of existing therapies. The ultimate goal is to find a cure for rheumatoid and osteoarthritis.

To achieve this goal the Centre focuses on a strong basic science programme in the field of immunology & inflammation linked to a clinical translational programme in the following 4 research areas:

  1. Breach of Tolerance & Autoimmunity

    In this area our efforts focus on:

    a) Investigating development of T/B cell autoimmunity in secondary- vs tertiary-lymphoid-structures and in early vs established RA (Bombardieri / Pitzalis); b) Role of FDCs and RASF in auto-antigen retention and breach of B cell tolerance (ElShikh / Pitzalis) and c) analysis of the antigenic specificities of lesional T and B cells (Bombardieri / Pitzalis).

  2. Development and resolution of inflammation & Mechanisms of Tissue Damage and Repair

    In this area our effort focus on: a) Mechanisms of T and B cell recruitment and retention using in vivo models (eg. RA/SCID/)(Bombardieri/Pitzalis); b) Resolution-of-inflammation through endogenous anti-inflammatory pathway. This area is investigated/developed through a long-standing collaboration with Prof Perretti and c) Mechanisms of Tissue Damage and Repair with particular emphasis on cartilage homeostasis. This research area is particular competence of Professor Dell’Accio.

  3. Developing new therapies through understanding of pathogenesis

    The Centre is actively involved in the development of novel therapeutics both through its own drug development programme (e.g. developing single chain (sc)Fv antibodies, identified by phage display technology, to specifically target joint tissues) and, in collaboration with industry, via the progression of the pharma pipeline. The Centre has been awarded an ARUK Experimental Arthritis Treatment Centres and is part of the National Institute for Health Research Translational Research Partnership.

  4. Patients stratification to understand pathogenesis of disease evolution and response to therapy

    The Centre builds on an existing large biomarker discovery and clinical trial programme to identify specific synovial tissue-driven bio-variables and blood correlates of clinical evolution and response to therapy. These include MRC/PEAC, MRC/ABPI and NIHR-EME initiatives. In addition, the ability of targeted biologics (TNF/IL6R/B-cell blockade) to modulate the panoply of RA-associated immune abnormalities will be utilised to better understand and dissect the complex immunological networks in the disease tissue in patients with RA.

Training

To ensure the next generation of Doctors and Scientists is available to translate scientific discoveries into medicine for patient benefit, the Centre provides high-quality research training in musculoskeletal basic and translational sciences. The Centre has a highly successful training record with over 30 PhD/MD successfully completing on time.

Through high-profile translational programmes the Centre provides academic training for Specialist Registrars over and above excellent clinical training to include the use of musculoskeletal ultrasound (US) in the management of rheumatic conditions. In addition, as part of the MRC-funded Pathobiology of Early Arthritis Cohort (PEAC), the Centre provides national/international training in US-guided, minimally invasive, synovial biopsy. The Centre has pioneered the use of this procedure in the UK, which has made possible to incorporate synovial pathobiology in MRC and NIHR clinical trials based on tissue-driven patient stratification.  

Key Publications

For a full list of publications click here


Selected (2019-21) PUBLICATIONS (Total 297 – Source PubMed)  
  • Ferrari M, Onuoha SC, Fossati-Jimack L, Nerviani A, Alves PL, Pagani S, Deantonio C, Colombo F, Santoro C, Sblattero D, Pitzalis C. Novel Bispecific Antibody for Synovial-Specific Target Delivery of Anti-TNF Therapy in Rheumatoid Arthritis. Front Immunol. 2021 Feb 19;12:640070. doi: 10.3389/fimmu.2021.640070. eCollection 2021. PMID: 33679801
  • Fanelli G, Romano M, Nova-Lamperti E, Werner Sunderland M, Nerviani A, Scottà C, Bombardieri M, Quezada SA, Sacks SH, Noelle RJ, Pitzalis C, Lechler RI, Lombardi G, Becker PD. PD-L1 signaling on human memory CD4+ T cells induces a regulatory phenotype. PLoS Biol. 2021 Apr 26;19(4):e3001199. doi: 10.1371/journal.pbio.3001199. eCollection 2021 Apr. PMID: 33901179
  • 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 PC, Edwards CJ, Isaacs J, Sasieni P, Choy E, Pitzalis C; R4RA collaborative group. Rituximab versus tocilizumab in anti-TNF inadequate responder patients with rheumatoid arthritis (R4RA): 16-week outcomes of a stratified, biopsy-driven, multicentre, open-label, phase 4 randomised controlled trial. 2021 Jan 23;397(10271):305-317. doi: 10.1016/S0140-6736(20)32341-2. PMID: 33485455
  • Nerviani A, Boutet MA, Tan WSG, Goldmann K, Purkayastha N, Lajtos TA, Hands R, Lewis M, 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. 2020 Nov 26:annrheumdis-2020-218186. PMID: 33243781
  • Gomez EA, Colas RA, Souza PR, Hands R, Lewis MJ, Bessant C, Pitzalis C, Dalli J. Blood pro-resolving mediators are linked with synovial pathology and are predictive of DMARD responsiveness in rheumatoid arthritis. Nat Commun. 2020 Oct 27;11(1):5420. doi: 10.1038/s41467-020-19176-z. PMID: 33110080
  • Thorup AS, Strachan D, Caxaria S, Poulet B, Thomas BL, Eldridge SE, Nalesso G, Whiteford JR, Pitzalis C, Aigner T, Corder R, Bertrand J, Dell'Accio F. ROR2 blockade as a therapy for osteoarthritis. Sci Transl Med. 2020 Sep 16;12(561):eaax3063. doi: 10.1126/scitranslmed.aax3063. PMID: 32938794
  • Pitzalis C, Choy EHS, Buch MH. Transforming clinical trials in rheumatology: towards patient-centric precision medicine. Nat Rev Rheumatol. 2020 Oct;16(10):590-599. PMID: 32887976
  • 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 Jul 30:annrheumdis-2020-217204. doi: 10.1136/annrheumdis-2020-217204. Online ahead of print. PMID: 32732242
  • Alivernini S, MacDonald L, Elmesmari A, Finlay S, Tolusso B, Gigante MR, Petricca L, Di Mario C, Bui L, Perniola S, Attar M, Gessi M, Fedele AL, Chilaka S, Somma D, Sansom SN, Filer A, McSharry C, Millar NL, Kirschner K, Nerviani A, Lewis MJ, Pitzalis C, Clark AR, Ferraccioli G, Udalova I, Buckley CD, Gremese E, McInnes IB, Otto TD, Kurowska-Stolarska M. Distinct synovial tissue macrophage subsets regulate inflammation and remission in rheumatoid arthritis. Nat Med. 2020 Aug;26(8):1295-1306. doi: 10.1038/s41591-020-0939-8. Epub 2020 Jun 29. PMID: 32601335
  • Mattiola I, Tomay F, De Pizzol M, Silva-Gomes R, Savino B, Gulic T, Doni A, Lonardi S, Astrid Boutet M, Nerviani A, Carriero R, Molgora M, Stravalaci M, Morone D, Shalova IN, Lee Y, Biswas SK, Mantovani G, Sironi M, Pitzalis C, Vermi W, Bottazzi B, Mantovani A, Locati M. The macrophage tetraspan MS4A4A enhances dectin-1-dependent NK cell-mediated resistance to metastasis. Nat Immunol. 2019 Aug;20(8):1012-1022. doi: 10.1038/s41590-019-0417-y. Epub 2019 Jul 1. PMID: 31263276
  • Zhang F, Wei K, Slowikowski K, Fonseka CY, Rao DA, Kelly S, Goodman SM, Tabechian D, Hughes LB, Salomon-Escoto K, Watts GFM, Jonsson AH, Rangel-Moreno J, Meednu N, Rozo C, Apruzzese W, Eisenhaure TM, Lieb DJ, Boyle DL, Mandelin AM 2nd; Accelerating Medicines Partnership Rheumatoid Arthritis and Systemic Lupus Erythematosus (AMP RA/SLE) Consortium, Boyce BF, DiCarlo E, Gravallese EM, Gregersen PK, Moreland L, Firestein GS, Hacohen N, Nusbaum C, Lederer JA, Perlman H, Pitzalis C, Filer A, Holers VM, Bykerk VP, Donlin LT, Anolik JH, Brenner MB, Raychaudhuri S. Defining inflammatory cell states in rheumatoid arthritis joint synovial tissues by integrating single-cell transcriptomics and mass cytometry. Nat Immunol. 2019 Jul;20(7):928-942. doi: 10.1038/s41590-019-0378-1. Epub 2019 May 6
  • Humby F, Lewis M, Ramamoorthi N, Hackney JA, Barnes MR, Bombardieri M, Setiadi AF, Kelly S, Bene F, DiCicco M, Riahi S, Rocher V, Ng N, Lazarou I, Hands R, van der Heijde D, Landewé RBM, van der Helm-van Mil A, Cauli A, McInnes I, Buckley CD, Choy EH, Taylor PC, Townsend MJ, Pitzalis C. Synovial cellular and molecular signatures stratify clinical response to csDMARD therapy and predict radiographic progression in early rheumatoid arthritis patients. Ann Rheum Dis. 2019 Jun;78(6):761-772. doi: 10.1136/annrheumdis-2018-214539. Epub 2019 Mar 16. PMID: 30878974
  • Twohig JP, Cardus Figueras A, Andrews R, Wiede F, Cossins BC, Derrac Soria A, Lewis MJ, Townsend MJ, Millrine D, Li J, Hill DG, 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 Apr;20(4):458-470. doi: 10.1038/s41590-019-0350-0. Epub 2019 Mar 19. PMID: 30890796
  • Lliso-Ribera G, Humby F, Lewis M, Nerviani A, Mauro D, Rivellese F, Kelly S, Hands R, Bene F, Ramamoorthi N, Hackney JA, Cauli A, Choy EH, Filer A, Taylor PC, McInnes I, Townsend MJ, Pitzalis C. Synovial tissue signatures enhance clinical classification and prognostic/treatment response algorithms in early inflammatory arthritis and predict requirement for subsequent biological therapy: results from the pathobiology of early arthritis cohort (PEAC). Ann Rheum Dis. 2019 Dec;78(12):1642-1652. doi: 10.1136/annrheumdis-2019-215751. Epub 2019 Oct 2. PMID: 31582377
  • Lewis MJ, Barnes MR, Blighe K, Goldmann K, Rana S, Hackney JA, Ramamoorthi N, John CR, Watson DS, Kummerfeld SK, Hands R, 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 PC, Townsend MJ, Pitzalis C. Molecular Portraits of Early Rheumatoid Arthritis Identify Clinical and Treatment Response Phenotypes. Cell Rep. 2019 Aug 27;28(9):2455-2470.e5. doi: 10.1016/j.celrep.2019.07.091.PMID: 31461658

Collaborators

Internal

External

  • Professor Anne Barton
  • Professor Simon Jones
  • Professor Chris Buckley
  • Professor Iain McInnes
  • Professor Peter Taylor
  • Professor Marta Alarcón Riquelme
  • Professor Maya Buch
  • Dr Juan Cañete
  • Professor Eduardo Collantes
  • Professor Patrick Durez
  • Professor Alberto Cauli
  • Professor Ronald Van Vollenhoven
  • Professor João E Fonseca
  • Professor Pier Paolo Sainaghi