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:
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
HNRNPA2B1 controls an unfolded protein response-related prognostic gene signature in prostate cancer Foster J, Gea E, Labiba M et al. (2022) (18)
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. (2022) (18)
Acquired somatic variants in inherited myeloid malignancies Armes H, Rio-Machin A, Krizsán S et al. Leukemia (2022) 36(7) 1377-1381
Targeting the lysine-specific demethylase 1 rewires kinase networks and primes leukemia cells for kinase inhibitor treatment Pedicona F, Casado P, Hijazi M et al. Science Signaling (2022) 15(7)
Splicing Factor Mutations and Disease Phenotype: Searching for a Needle in a Haystack Rouault-Pierre K HemaSphere (2021) 5(7) E587
Ectopic Humanized Mesenchymal Niche in Mice Enables Robust Engraftment of Myelodysplastic Stem Cells Mian SA, Abarrategi A, Kong KL et al. Cancer discovery (2021) 2(7) 135-145
ER stress and unfolded protein response in leukemia: Friend, foe, or both? Féral K, Jaud M, Philippe C et al. Biomolecules (2021) 11(7) 1-31
Loss of tRNA-modifying enzyme Elp3 activates a p53-dependent antitumor checkpoint in hematopoiesis Rosu A, Hachem NE, Rapino F et al. Journal of Experimental Medicine (2021) 218(7)
Integration of Deep Multi-Omics Profiling Veals New Insights into the Biology of Poor-Risk Acute Myeloid Leukemia Rio-Machin A, Casado-Izquierdo P, Miettinen J et al. Blood (2020) 136(10) 39-40For 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.