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Full NameProfessor Elisabeth Vandenberghe
Organisation:Trinity College Dublin
- genetics, genomics and molecular biology
- Clinical Trials
My research interest in lymphoid malignancies is based on clinical trial involvement and translating molecular diagnostics into precision medicine pathways. I direct the Cancer Trials Unit (CTU) at St James Hospital (SJH) and am PI of 17 Phase II/III trials(5 open/12 completed) leading to 7 publications. I collaborate internationally with the European Mantle Cell Lymphoma (MCL) network and am on the lymphoma sub-group of the European Blood and Marrow Transplant (EBMT) and have co-authored 7 registry publications.
I direct the Cancer Molecular Diagnostic (CMD) laboratory at SJH which provides a national diagnostic service focussing on
(1) MCL including association with t(11;14) and treatment pathway incorporating transplantation, targeted therapy with ibrutinib and MRD-based treatment.
(2) Chronic lymphocytic leukaemia (CLL):I opened the only national multi-institutional phase II molecular and clinical trial, (published 2017). I collaborate with the European Research Initiative in CLL ‘big data’ project (submitting 140 genetically characterised cases). I am PI of a recruiting multi-institutional molecular epidemiology study of CLL.
(3) T lymphoid malignancies: the molecular diagnosis of T-large granular lymphocytic leukaemia and molecular analysis-based risk of coeliac disease transformation to lymphoma
I collaborate with Dr McElligott from Trinity Translational Medicine Institute (TTMI) who investigates cellular mechanisms of leukaemogenesis and new drug therapies and Professor Bracken (TCD) who leads an SFI-funded project ‘Understanding the role of EZH2 deregulation in B-Cell Lymphomas’.
Translational research in germinal centre lymphomas:
- I collaborate with Professor Adrian Bracken, Smurfit Institute of Genetics, TCD and Prof J Fitzgibbon, Barts Cancer Institute, on the role of EZH2 in germinal centre lymphomagenesis and will co-supervise a PhD student on that project in the next year working on a small biobank of available samples. The next phase of this study will require the identification and genetic characterization by NGS of different types of germinal centre lymphomas which can then be studied epigenetically. EZH2 inhibitors are clinically active, however their therapeutic activity does not co-segregate with mutation status and further analysis with the NGS based lymphoma chip which we can access through a current collaborator is likely to elucidate genetic pathways relevant to epigenetic disruption. EZH2 inhibitors are currently in phase 1 clinical trials and I would hope to open a relevant clinical trial for my lymphoma cohort. This project would suit a clinician scientist by providing clinical trial experience, translational experience by deep sequencing characterization of lymphomas in TTMI and finally functional epigenetic analysis in the Institute of Genetics.
CART therapy with axicabtagene ciloleuce (Gilead) and tisagenlecleucel (Novartis) may cure patients with otherwise refractory B-lymphoid malignancies and is undergoing EMEA review. CART therapy is delivered through allogeneic Stem Cell Transplant units such as the national SJH unit, because it is complex, toxic and expensive. We will collaborate with scientists in the TCD School of Immunology, to dissect the immunologically driven, idiosyncratic toxicities of CART therapy in vitro and this collaboration will have an international element also.
Regulation of chronic lymphocytic leukaemia cell homing and trafficking:
- Inhibition of the B cell receptor (BCR) signalling pathway has shown remarkable clinical activity in chronic lymphocytic leukaemia (CLL). In collaboration with Dr Tony McElligott in the TTMI, we have shown that the transcription factor STAT3 is a downstream target of BCR signalling and has a key role in regulating both cell survival and expression of L-selection, a key adhesion molecular homing and trafficking of CLL cells to lymph node microenvironments. We wish to further investigate the cross-talk between the BCR and the JAK/STAT3 signalling pathways and investigate novel therapeutic strategies for patients who do not respond well to BCR inhibitor therapy.