My main research interests are in haematopoietic stem cells and leukemic initiating cells. I seek to understand how intrinsic and extrinsic signals are integrated by normal and malignant stem cells.
Preclinical modeling of myelodysplastic syndromes. Leukemia (2017) 31(12):2702-2708. PMID: 28663577
Myelodysplastic synrome can propagate from the multipotent progenitor compartment. Haematologica (2016) 102(1):e7-e10. PMID: PMC5210239
SF3B1 mutant MDS initiating-cells may arise from the haematopoietic stem cell compartment. Nature Communications (2015) 6:10004. PMID: 26643973
HIF-2α Protects Human Hematopoietic Stem/Progenitors and Acute Myeloid Leukemic Cells from Apoptosis Induced by Endoplasmic Reticulum Stress. Cell Stem Cell (2013) 13(5):549-63. PMID: 24095676
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:
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) 1295-1296For additional publications, please click here
Dr Celine Philippe
Doriana Di Bella, Weiwei Tang
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.
In September 2017 I was awarded the Kay Kendall Leukaemia intermediate fellowship and joined the Barts Cancer Institute at the Centre for Haemato-Oncology led by Prof John Gribben.