Head of Centre for Experimental Medicine & Rheumatology / Deputy Director WHRI
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 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:
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).
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 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 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 Myles Lewis; Dr Frances Humby; Dr Stephen Kelly.
Research Staff: Dr Elisa Astorri, Mr Pedro Alves, Mrs Celia Breston, Dr Elisa Corsiero, Dr Suzanne Eldridge, Dr Magdalena B. Flak, Dr Sofia Grigoriadou, Dr Rebecca Hands, Dr Georgina Thorborn, Dr Lucas Jagemann, Dr Liliane Fossati-Jimack, Mr Davide Lucchesi, Dr Valentina Pucino, Dr Edoardo Prediletto , Dr Sudip Purkayastha, Mrs Sudeh Riahi, Dr Felice Rivellese, Dr Alessandra Nerviani, Dr Riham El Sayed, Dr Gina Tan, Dr Bethan Thomas
Support staff: Fabiola Bene, Emma Cutting, Victoria Hammond, Janice Haycocks, Hayley Noble, Jo Peel, Vladan Petrovic, Elin Rees, Katriona Goldmann, Louise Warren, Laura White, Christopher John, Sam Heenan
For a full list of publist publications click here
Ferrari M, Onuoha SC, Pitzalis C. Going with the flow: harnessing the power of the vasculature for targeted therapy in rheumatoid arthritis. Drug Discov Today. 2015 Oct 30. pii: S1359-6446(15)00391-8. doi: 10.1016/j.drudis.2015.10.014. [Epub ahead of print] Review. PMID: 26523772
Oni C, Mitchell S, James K, Ng WF, Griffiths B, Hindmarsh V, Price E, Pease CT, Emery P, Lanyon P, Jones A, Bombardieri M, Sutcliffe N, Pitzalis C, Hunter J, Gupta M, McLaren J, Cooper A, Regan M, Giles I, Isenberg D, Saravanan V, Coady D, Dasgupta B, McHugh N, Young-Min S, Moots R, Gendi N, Akil M, Barone F, Fisher B, Rauz S, Richards A, Bowman SJ; UK Primary Sjögren’s Syndrome Registry*. Eligibility for clinical trials in primary Sjögren's syndrome: lessons from the UK Primary Sjögren's Syndrome Registry. Rheumatology (Oxford). 2015 Oct 27. pii: kev373. [Epub ahead of print] PMID: 26510429
Jones GW, Bombardieri M, Greenhill CJ, McLeod L, Nerviani A, Rocher-Ros V, Cardus A, Williams AS, Pitzalis C, Jenkins BJ, Jones SA. Interleukin-27 inhibits ectopic lymphoid-like structure development in early inflammatory arthritis. J Exp Med. 2015 Oct 19;212(11):1793-802. doi: 10.1084/jem.20132307. Epub 2015 Sep 28. PMID: 26417004
Eldridge S, Nalesso G, Ismail H, Vicente-Greco K, Kabouridis P, Ramachandran M, Niemeier A, Herz J, Pitzalis C, Perretti M, Dell'Accio F. Agrin mediates chondrocyte homeostasis and requires both LRP4 and α-dystroglycan to enhance cartilage formation in vitro and in vivo. Ann Rheum Dis. 2015 Aug 19. pii: annrheumdis-2015-207316. doi: 10.1136/annrheumdis-2015-207316. [Epub ahead of print] PMID: 26290588
Barone F, Nayar S, Campos J, Cloake T, Withers DR, Toellner KM, Zhang Y, Fouser L, Fisher B, Bowman S, Rangel-Moreno J, Garcia-Hernandez ML, Randall TD, Lucchesi D, Bombardieri M, Pitzalis C, Luther SA, Buckley CD. IL-22 regulates lymphoid chemokine production and assembly of tertiary lymphoid organs. Proc Natl Acad Sci U S A. 2015 Aug 18. pii: 201503315. [Epub ahead of print] PMID: 26286991
Haas R, Smith J, Rocher-Ros V, Nadkarni S, Montero-Melendez T, D'Acquisto F, Bland EJ, Bombardieri M, Pitzalis C, Perretti M, Marelli-Berg FM, Mauro C. Lactate Regulates Metabolic and Pro-inflammatory Circuits in Control of T Cell Migration and Effector Functions. PLoS Biol. 2015 Jul 16;13(7):e1002202. doi: 10.1371/journal.pbio.1002202. eCollection 2015 Jul. PMID: 26181372
Onuoha SC, Ferrari M, Sblattero D, Pitzalis C. Rational design of anti-rheumatic pro-drugs specific for inflammatory sites. Arthritis Rheumatol. 2015 Jun 19. doi: 10.1002/art.39232. [Epub ahead of print] PMID: 26097196
Komarowska I, Coe D, Wang G, Haas R, Mauro C, Kishore M, Cooper D, Nadkarni S, Fu H, Steinbruchel DA, Pitzalis C, Anderson G, Bucy P, Lombardi G, Breckenridge R, Marelli-Berg FM. Hepatocyte Growth Factor Receptor c-Met Instructs T Cell Cardiotropism and Promotes T Cell Migration to the Heart via Autocrine Chemokine Release. Immunity. 2015 Jun 16;42(6):1087-99. doi: 10.1016/j.immuni.2015.05.014. Epub 2015 Jun 9. PMID: 26070483
Ferrari M, Onuoha SC, Pitzalis C. Trojan horses and guided missiles: targeted therapies in the war on arthritis. Nat Rev Rheumatol. 2015 Jun;11(6):328-337. doi: 10.1038/nrrheum.2015.17. Epub 2015 Mar 3. Review PMID: 25734971
Astorri E, Nerviani A, Bombardieri M, Pitzalis C. Towards a stratified targeted approach with biologic treatments in rheumatoid arthritis: role of synovial pathobiology. Curr Pharm Des. 2015;21(17):2216-24. PMID: 25760296
Kelly S, Humby F, Filer A, Ng N, Di Cicco M, Hands RE, et al. Ultrasound-guided synovial biopsy: a safe, well-tolerated and reliable technique for obtaining high-quality synovial tissue from both large and small joints in early arthritis patients. Annals of the rheumatic diseases. 2015 Mar;74(3):611-7. doi: 10.1136/annrheumdis-2013-204603. Epub 2013 Dec 13. PMID: 24336336
Humby F, Kelly S S, Hands R, Rocher V, DiCicco M, Ng N, Zou L, Bugatti S, Manzo A, Caporali R, Montecucco C, Bombardieri M, Pitzalis C. Evaluating the histopathological response to RA therapy using ultrasound guided small joint biopsy: Recommendations for application to clinical trials. Arthritis Rheumatol. 2015 Jun 19. doi: 10.1002/art.39235. [Epub ahead of print] PMID: 26097225
Pitzalis C, Jones GW, Bombardieri M, Jones SA. Ectopic lymphoid-like structures in infection, cancer and autoimmunity. Nat Rev Immunol. 2014 Jul;14(7):447-62. doi: 10.1038/nri3700. Epub 2014 Jun 20. Review. PMID: 24948366 [PubMed - indexed for MEDLINE]
Croia C, Astorri E, Murray-Brown W, Willis A, Brokstad KA, Sutcliffe N, Piper K, Jonsson R, Tappuni AR, Pitzalis C, Bombardieri M. Implication of Epstein-Barr virus infection in disease-specific autoreactive B cell activation in ectopic lymphoid structures of Sjögren's syndrome. Arthritis Rheumatol. 2014 Sep;66(9):2545-57. doi: 10.1002/art.38726. PMID: 24891330 [PubMed - indexed for MEDLINE]
Pitzalis C. Pathogenesis of rheumatoid arthritis: from systemic autoimmunity to localised joint disease. Drug Discov Today. 2014 Aug;19(8):1152-4. doi: 10.1016/j.drudis.2014.05.009. Epub 2014 May 21. No abstract available. PMID: 24859017 [PubMed - in process]
Kelly S, Humby F, Filer A, Ng N, Di Cicco M, Hands RE, Rocher V, Bombardieri M, D'Agostino MA, McInnes IB, Buckley CD, Taylor PC, Pitzalis C. Ultrasound-guided synovial biopsy: a safe, well-tolerated and reliable technique for obtaining high-quality synovial tissue from both large and small joints in early arthritis patients. Ann Rheum Dis. 2013 Dec 13. doi: 10.1136/annrheumdis-2013-204603. [Epub ahead of print] PMID: 24336336
Pitzalis C, Kelly S, Humby F. New learnings on the pathophysiology of RA from synovial biopsies. Curr Opin Rheumatol. 2013 May;25(3):334-44. doi: 10.1097/BOR.0b013e32835fd8eb. PMID: 23492740 [PubMed - in process]
Croia C, Serafini B, Bombardieri M, Kelly S, Humby F, Severa M, Rizzo F, Coccia EM, Migliorini P, Aloisi F, Pitzalis C. Epstein-Barr virus persistence and infection of autoreactive plasma cells in synovial lymphoid structures in rheumatoid arthritis.. Ann Rheum Dis. 2012 Dec 25. PMID: 23268369
Seymour MW, Kelly S, Beals CR, Malice MP, Bolognese JA, Dardzinski BJ, Cheng AS, Cummings CE, Smugar SS, McClinton C, Fox A, Dooley W, Pitzalis C, Taylor PC. Ultrasound of metacarpophalangeal joints is a sensitive and reliable endpoint for drug therapies in rheumatoid arthritis: Results of a randomized, two-centre, placebo-controlled study. Arthritis Res Ther. 2012 Sep 12;14(5):R198. [Epub ahead of print] PMID: 22972032
Wythe SE, Dicara D, Taher TE, Finucane CM, Jones R, Bombardieri M, Man YK, Nissim A, Mather SJ, Chernajovsky Y, Pitzalis C. Targeted delivery of cytokine therapy to rheumatoid tissue by a synovial targeting peptide. Ann Rheum Dis. 2012 Jul 27. [Epub ahead of print] 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. PMID: 21536751
Astorri E, Bombardieri M, Gabba S, Peakman M, Pozzilli P, Pitzalis C. Evolution of Ectopic Lymphoid Neogenesis and In Situ Autoantibody Production in Autoimmune Nonobese Diabetic Mice: Cellular and Molecular Characterization of Tertiary Lymphoid Structures in Pancreatic. Journal Immunology Immunol. 2010 Sep 15;185(6):3359-68. Epub 2010 Aug 16. PMID: 20713891
Ciccia F, Bombardieri M, Rizzo A, Principato A, Giardina AR, Raiata F, Peralta S, Ferrante A, Drago S, Cottone M, Pitzalis C, Triolo G. Over-expression of paneth cell-derived anti-microbial peptides in the gut of patients with ankylosing spondylitis and subclinical intestinal inflammation. Rheumatology (Oxford). 2010 Nov;49(11):2076-83. Epub 2010 Aug 5. PMID: 20688803
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) (Impact Factor 13.5) PMID: 19143467