Head of Centre for Experimental Medicine & Rheumatology
Costantino Pitzalis is Professor of Experimental Medicine and Rheumatology and Head of the Centre for Experimental Medicine and Rheumatology. His clinical interests encompass general rheumatology with a focus on immune/inflammatory rheumatic diseases, including rheumatoid and psoriatic arthritis.
His major research interests focus on the cellular and molecular mechanisms of inflammation and autoimmunity in chronic arthritis with particular emphasis on translational research and biomarkers discovery. He leads a Research Team of over 35 Researchers (Clinicians and Scientists) with more than £11million research income. He has produced research of international standing captured in over 140 publications (over 50 in journals with impact factor >5) in the field of inflammation, immunity and arthritis.
Professor Pitzalis serves on the EULAR Scientific Committee and the Heberden Committee, British Society for Rheumatology. He is a member of the Research Grant Committee Arthritis Research UK and several other national and international committees. He serves on the Editorial Board of Annals of Rheumatic Diseases and Arthritis Research & Therapy.
Summary of Research
The 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 osteo arthritis.
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:
Breach of Tolerance & Autoimmunity
In this area our effort 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).
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.
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.
Patients stratification to understand pathogenesis of disease evolution and response to therapy
(Kelly/Humby/Barnes/Bombardieri/Sassieni/Pitzalis). 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 utilized 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 and is a recipient of two PhD programmes: a) an Oliver Bird Rheumatism Nuffield Foundation Programme and b) an Arthritis Research UK Clinical PhD Programme.
Through these 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.
Members of the Group
Senior staff: Professor Francesco Dell'Accio; Dr Michele Bombardieri; Dr Mohey El Shikh; Dr Frances Humby; Dr Stephen Kelly
Research Staff: Dr Rebecca Hands; Dr William Murray-Brown; Dr Giovanna Nalesso; Dr Jo Sherwood; Mrs Sudeh Riahi; Dr Vidalba Rocher; Dr Emanuela Carlotti; Dr Elisa Corsiero; Dr Yvonne Kam; Dr Sofia Grigoriadou; Dr Alessandra Nerviani; Dr Arti Mahto; Dr Maria Di Cicco; Mrs Celia Breston; Miss Victoria Katsande; Miss Audrey Davidson; Mrs Sandra Martins; Miss Suzanne Eldridge; Mr Mathieu Ferarri; Mr Davide Lucchesi; Dr Botan Nury; Miss Bethan Thomas
Support staff: Mrs Janice Haycocks; Mr Vladan Petrovic; Miss Laura White; Dr James Floyd; Dr Lu Zou; Mr Richard Meader, Miss Lauren Coombes; Mr Shannon Hyde.
Targeted delivery of cytokine therapy to rheumatoid tissue by a synovial targeting peptide. Wythe SE, Dicara D, Taher TE, Finucane CM, Jones R, Bombardieri M, Man YK, Nissim A, Mather SJ, Chernajovsky Y, Pitzalis C. Ann Rheum Dis. 2012 Jul 27. PMID: 22843486
Kamperidis P, Kamalati T, Ferrari M, Jones M, Garrood T, Smith MD, Diez-Posada S, Hughes C, Finucane C, Mather S, Nissim A, George AJ, Pitzalis C. Development of a novel recombinant biotherapeutic with applications in targeted therapy of human arthritis. Arthritis Rheum. 2011 Dec;63(12):3758-67. doi: 10.1002/art.30650. PMID: 21953304
Bombardieri M, Kam NW, Brentano F, Choi K, Filer A, Kyburz D, McInnes IB, Gay S, Buckley C, Pitzalis C. A BAFF/APRIL-dependent TLR3-stimulated pathway enhances the capacity of rheumatoid synovial fibroblasts to induce AID expression and Ig class-switching in B cells. Ann Rheum Dis. 2011 Oct;70(10):1857-65. Epub 2011 Jul 27. PMID: 21798884
Nalesso G, Sherwood J, Bertrand J, Pap T, Ramachandran M, De Bari C, Pitzalis C, Dell'accio F. WNT-3A modulates articular chondrocyte phenotype by activating both canonical and noncanonical pathways. J Cell Biol. 2011 May 2; 193 (3):551-64.
Manzo A, Bombardieri M, Humby F, Pitzalis C. Secondary and ectopic lymphoid tissue responses in rheumatoid arthritis: from inflammation to autoimmunity and tissue damage/remodeling. Immunol Rev. 2010 Jan;233(1):267-85. Review. PMID: 20193005
Humby F, Bombardieri M, Manzo A, Kelly S, Blades M ,Kirkham B, Spencer J and Pitzalis C. Ectopic lymphoid structures support ongoing production of class-switched autoantibodies in rheumatoid synovium. PLoS Med. 2009 Jan 13;6(1) PMID: 19143467
Barone F, Bombardieri M, Rosado M M, Morgan P R, Challacombe S J , De Vita S, Carsetti R, Spencer J, Valesini G and Pitzalis C. CXCL13, CCL21 and CXCL12 expression in salivary glands of patients with Sjogren’s Syndrome and MALT lymphoma: association with reactive and malignant areas of lymphoid organization. J Immunol. 2008 Apr 1;180(7):5130-40
Manzo A, Bugatti S, Caporali R, Prevo R, Jackson D.G, Uguccioni M, Buckley C.D, Montecucco C, Pitzalis C. CCL21 expression pattern of human secondary lymphoid organ stroma is conserved in inflammatory lesions with lymphoid neogenesis. Am J Pathol. Am J Pathol. 2007 Nov;171(5):1549-62.
Bombardieri M, Barone F, Humby F, Kelly S, McGurk M, Morgan P, Valesini V, Challacombe S, Spencer J and Pitzalis C. Activation-induced cytidine deaminase expression in germinal centers and large interfollicular B cells supports functionality of ectopic lymphoid neogenesis in reactive and neoplastic salivary glands of Sjogren’s syndrome. J Immunol. 2007 Oct 1;179(7):4929-4938).
Pitzalis C, Garrood T. From ubiquitous antigens to joint-specific inflammation: could local vascular permeability be the missing link? Trends Immunol. 2006 Jul;27(7):299-302.
Serena Bugatti, Roberto Caporali, Antonio Manzo, Barbara Vitolo, Costantino Pitzalis Carlomaurizio Montecucco. Subchondral bone marrow inflammatory involvement in rheumatoid arthritis: lymphoid neogenesis and in situ relationship with subchondral bone marrow osteoclasts. Arthritis Rheum. 2005 Nov;52(11):3448-59
Andrew JT George, Lewis Lee and Costantino Pitzalis. Isolating ligands specific for human vasculature using in vivo phage selection. Trends in Biotechnology 2003 21 (5) 199-203.
L. Lee, C. Buckley, M.C. Blades, G. Panayi, A. George and C. Pitzalis. Identification of synovial specific homing peptides by in vivo phage display selection. Arthritis & Rheumatism, (2002) 46: 2109-2120
MC Blades, F Ingegnoli, A Manzo, SK Wheller, G Panayi, DO Haskard, M Perretti, and C Pitzalis. Stromal cell derived factor-1 (CXCL12) induces cell migration into lymph nodes transplanted into SCID mice. J Immunol (2002) 168: 4308-4317
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Costantino Pitzalis, MD, PhD, FRCP
Professor of Experimental Medicine & Rheumatology Centre for Experimental Medicine & Rheumatology
William Harvey Research Institute
Barts and The London, Queen Mary's School of Medicine and Dentistry
2nd Floor John Vane Science Building
London, EC1M 6BQ
T: +44 (0) 20 7882 8191