Research

In lymphoma our focus is a B cell malignancy called follicular lymphoma and the (epi)genomic changes responsible for the onset and severity of the disease. Although these tumours are chemo-sensitive, the disease is incurable, with many patients experiencing several episodes of relapse before the disease becomes refractory to treatment. We have traced the genetic changes in these tumours over time and uncovered a highly complex pattern of tumour evolution, consistent with the existence of a common progenitor B cell (CPC) population from which each new episode of disease is thought to arise. Current studies are focusing on characterising this CPC population and the use of KDM5 inhibition as a means of subverting the effects of mutations in the histone methyltransferase, KMT2D, that arise in >70% of FL tumours.

In leukaemia we have a longstanding interest in the study of familial acute myeloid leukaemia (AML) and myelodysplasia. These studies are important both to the individual families and are providing new insights into the molecular evolution of AML, the patterns by which mutations arise and an explanation for the clinical heterogeneity that exists both within and between families. We also have a parallel programme in poor risk AML where outcomes have changed little over the past 40 years, and are following a multi-omic strategy to profile these AMLs and gain a deeper understanding of the disease in this group of patients.  

• Watch Professor Fitzgibbon’s interview with the MDS UK Patient Support Group at the UK MDS Education Forum.
• Watch below: European School of Haematology Video -  Meeting Highlights - Faculty Panel Discussion: What are the big discoveries in lymphoma pathogenesis over the last 5 years? Genetics and precision medicine

Other Activities

• Chair of the NCRI Lymphoma Science sub-group (2020-)
• Visiting Professor at the 1st Department of Pathology, Semmelweis University Budapest Hungary (2019-)
• Member of the Bloodwise Grant Committee (2017-)
• Member of the Associazione Italiana per la Ricerca sul Cancro (AIRC) international fellowship committee (2016 - )
• Member of the NCRI Lymphoma CSG (2018-)
• Advisory Board Lancet Haematology
• Editor Annals of Human Genetics
• External Examiner on the BMedSCi Course, Birmingham (2016-)

Major Funding

• 2018-2023- Cancer Research UK Accelerator Award, UK & Follicular Lymphoma lead (Jesus San Miguel (Spain) and Mario Cazzola (Italy), £1.6M to UK
• 2017-2022- Cancer Research UK Programme Award, Co-PI (Improving treatment in Poor Risk Acute Myeloid Leukemia), £1.9M
• 2015-2019- Bloodwise Programme Award, Co-PI (with Dokal and Vulliamy) Genetics of Familial Leukaemia, £1.4M
• 2013-2018- Cancer Research UK, Personalised Epidgenetic Therapy for Follicular Lymphoma, £542,566.63
• 2016-2018- Bloodwise, Precision medicine for aggressive lymphoma, £340,538.00

Recent Publications

The complex genetic landscape of familial MDS and AML reveals pathogenic germline variants Rio-Machin A, Vulliamy T, Hug N et al. Nature Communications (2020) 11(7)

Mesenchymal niche remodeling impairs hematopoiesis via stanniocalcin 1 in acute myeloid leukemia. Waclawiczek A, Hamilton A, Rouault-Pierre K et al. J Clin Invest (2020) (2)
https://www.ncbi.nlm.nih.gov/pubmed/32364536

Distinct genetic changes reveal evolutionary history and heterogeneous molecular grade of DLBCL with MYC/BCL2 double-hit Cucco F, Barrans S, Sha C et al. Leukemia (2020) 34(7) 1329-1341

Genetic heterogeneity highlighted by differential FDG-PET response in diffuse large B-cell lymphoma. Araf S, Korfi' K, Bewicke-Copley F et al. Haematologica (2020) (2)
https://www.ncbi.nlm.nih.gov/pubmed/32273479

An immunocompetent, spontaneous mouse model of DLBCL for studying the response to R-CHOP and identifying new treatment targets Maybury B, Fitzgibbon J, Calado D BRITISH JOURNAL OF HAEMATOLOGY (2020) 189(11) 110-111
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000528597400150&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=612ae0d773dcbdba3046f6df545e9f6a

AML through the prism of molecular genetics Charrot S, Armes H, Rio-Machin A et al. British Journal of Haematology (2020) 188(7) 49-62

The Biological Basis of Histologic Transformation Kumar EA, Okosun J, Fitzgibbon J Hematology/Oncology Clinics of North America (2020) (7)

Follicular lymphoma Carbone A, Roulland S, Gloghini A et al. Nature Reviews Disease Primers (2019) 5(7)

Oncogenic Rag GTPase signalling enhances B cell activation and drives follicular lymphoma sensitive to pharmacological inhibition of mTOR Ortega-Molina A, Deleyto-Seldas N, Carreras J et al. Nature Metabolism (2019) 1(7) 775-789

Correction: Genomic profiling reveals spatial intra-tumor heterogeneity in follicular lymphoma (Leukemia, (2018), 32, 5, (1261-1265), 10.1038/s41375-018-0043-y) Araf S, Wang J, Korfi K et al. Leukemia (2019) 33(7) 1540

Team

Postdoctoral Researchers in this group
Dr James Heward, Dr Ana Rio-Machin, Dr Findlay Copley, Dr Eve Coulter, Dr Hannah Armes 

PhD Students
Karina Close

Clinical Research Fellows
Emil Arjun Kumar

Research Assistant
Lily Hoa

Biography

I joined Barts and the London Medical School as a Research Fellow in Medical Oncology in 1997, becoming Senior Lecturer in 2004, Reader in 2009 and Professor in 2013. I received my BA degree in Genetics at Trinity College Dublin in 1989 before completing my PhD studies on the Genetics of Tuberous Sclerosis at University College London in 1993.