Research

Myelodysplastic Syndromes (MDS) and Acute myeloid leukaemia (AML) are both clonal diseases that harbour MDS stem cells (MDS-SC) and pre-leukemic cells, respectively. Various studies have demonstrated that acquired mutations in haematopoietic cells' genes can lead to clonal fitness and eventually to propagation of the disease. Understanding the switch between clonal haematopoiesis and clonal disease is one of the major challenges of the scientific community, which highlights the need to unravel how epigenetic/spliceosome stresses are integrated by stem cells and dictate their clonal fate.

In the lab we develop in-vitro and in-vivo modelling of MDS and AML diseases. Using primary human samples and multi-omics approaches including RNAseq (Bulk & single cell), Proteomics, Phosphoproteomics, Metabolomics and drug screening, we challenge normal and malignant haematopoiesis to unveil new therapeutic targets in myeloid malignancies.

Key words: Stem cells, patient samples, AML, MDS, splicing, RNA biology, metabolism and translation regulation.

Prizes from the group for Poster and Oral communications:

• September 2021: Oral presentation by Doriana Di Bella (PhD student) at the Barts Cancer Institute PhD Day, Won the Prize for the best oral presentation (AML & Microenvironment)
• October 2021: Oral presentation by Celine Philippe (Postdoctoral Fellow) at the annual conference of Hematology and Oncology, France. Won the Prize for the best presentation (Splicing & MDS)
• October 2021: Poster presentation (KRP) at the Endoplasmic Reticulum Symposium, France. Poster Prize.

Other Activities

• Member of the British Society of Haematology
• Member of the European Haematology Association
• Member of the Société Française d'Hématologie

Major Funding

• 2022-2025- Barts Charity, Project Grant, £237,000
• 2022-2023- British Society of Haematology, Early Stage Research grants support, £20,000
• 2021-2022- Lady Tata Memorial Trust awarded to Celine Philippe (Postdoctoral Fellow), £40,000
• 2019-2022- Academy of Medical Sciences Springboard Award, £100,000
• 2017-2022- Kay Kendall Leukaemia Fund, £292,000

Recent Publications

Integrative phosphoproteomics defines two biologically distinct groups of KMT2A rearranged acute myeloid leukaemia with different drug response phenotypes Casado P, Rio-Machin A, Miettinen JJ et al. Signal Transduction and Targeted Therapy (2023) 8(7)

Mannose metabolism inhibition sensitizes acute myeloid leukaemia cells to therapy by driving ferroptotic cell death Woodley K, Dillingh LS, Giotopoulos G et al. Nature Communications (2023) 14(7)

O20 TARGETING THE DEFECTIVE COA PATHWAY TO IMPROVE ERYTHROPOIESIS IN SF3B1-MUTANT MDS-RS PATIENTS Philippe C, Mian S, Maniati E et al. Leukemia Research (2023) 128(10) 107133

Vitamin B5 and succinyl-CoA improve ineffective erythropoiesis in SF3B1-mutated myelodysplasia Mian SA, Philippe C, Maniati E et al. Science Translational Medicine (2023) 15(7)

Germline ERCC excision repair 6 like 2 (ERCC6L2) mutations lead to impaired erythropoiesis and reshaping of the bone marrow microenvironment Armes H, Bewicke-Copley F, Rio-Machin A et al. British Journal of Haematology (2022) 199(7) 754-764

The transcription factor DDIT3 is a potential driver of dyserythropoiesis in myelodysplastic syndromes Berastegui N, Ainciburu M, Romero JP et al. Nature Communications (2022) 13(7)

Deep Multi-Omics Profiling in Cytogenetically Poor-Risk AML Rio-Machin A, Bewicke-Copley F, Zheng J et al. Blood (2022) 140(10) 1030-1032

Inhibition of Stearoyl-CoA Desaturase Has Anti-Leukemic Properties in Acute Myeloid Leukemia Dembitz V, Lawson H, Philippe C et al. Blood (2022) 140(10) 3058-3060

A dual role for the RNA helicase DHX34 in NMD and pre-mRNA splicing and its function in hematopoietic differentiation Hug N, Aitken S, Longman D et al. RNA (2022) 28(7) 1224-1238

P1411: DUAL EPIGENETIC AND GENETIC EDITING OF PRIMARY HUMAN HAEMATOPOIETIC STEM AND PROGENITOR CELLS Saunderson E, Encabo H, Rouault-Pierre K et al. HemaSphere (2022) 6(10) 1295-1296

Team

Posdoctoral Researchers
Dr Celine Philippe

PhD students
Doriana Di Bella, Weiwei Tang

Biography

I have been developing my expertise on haematopoietic stem cells and multiple cancer fields throughout my career and have beneficiated in particular of the Francis Crick Institute’s world-class environment, with one of the world leaders in the haematology and stem cell field, Dr Dominique Bonnet. The work conducted in Dr Bonnet’s group in collaboration with Prof Mufti from King’s College Hospital has significantly contributed to providing me with the tools and knowledge for the project I am developing.