My research group works on molecular pathology, genetics and progression of leukaemia and lymphomas, aiming to improve on current diagnostic, prognostic and treatment strategies.
Follicular lymphoma. Nat Rev Dis Primers (2019) 5(1):83. Review. PMID: 31831752
Recurrent mTORC1-activating RRAGC mutations in follicular lymphoma. Nat Genet (2016) 48(2):183-8. PMID: 26691987
Disease evolution and outcomes in familial AML with germline CEBPA mutations. Blood (2015) 126(10):1214-23. PMID: 26162409
Integrated genomic analysis identifies recurrent mutations and evolution patterns driving the initiation and progression of follicular lymphoma. Nat Genet (2014) 46(2):176-81. PMID: 24362818
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.
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)
The Biological Basis of Histologic Transformation Kumar EA, Okosun J, Fitzgibbon J Hematology/Oncology Clinics of North America (2020) 34(7) 771-784
A frameshift variant in the specificity protein 1 triggers superactivation of SP1-mediated transcription in familial bone marrow failure. Dokal I, Tummala H, Vulliamy T et al. Proceedings of the National Academy of Sciences of USA (2020) (1)
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) 105(7) E318-E321
Mesenchymal niche remodeling impairs hematopoiesis via stanniocalcin 1 in acute myeloid leukemia Waclawiczek A, Hamilton A, Rouault-Pierre K et al. Journal of Clinical Investigation (2020) 130(7) 3038-3050
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
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
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
Follicular lymphoma Carbone A, Roulland S, Gloghini A et al. Nature Reviews Disease Primers (2019) 5(7)
Evaluation of the m7-FLIPI in Patients with Follicular Lymphoma Treated within the Gallium Trial: EZH2 mutation Status May be a Predictive Marker for Differential Efficacy of Chemotherapy Jurinovic V, Passerini V, Oestergaard MZ et al. Blood (2019) 134(10) 122-122For additional publications, please click here
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.