Research groups
Websites
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MRC Molecular Haematology Unit
Research Unit
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MRC Weatherall Institute of Molecular Medicine
Research Institute
DPHIL OPPORTUNITIES AVAILABLE
Claus Nerlov
Ph.D.
Professor of Stem Cell Biology
Single cell biology and genetics to understand hematopoiesis, leukemogenesis and ageing
The hematopoietic stem cell is capable of maintaining the output of >10 cellular lineage for the entire lifespan of the organism. This is made possible by the presence of structures (niches) dedicated to long-term maintenance of the multi-potent stem cell state, as well as mechanisms for the generation and subsequent lineage specification of stem cell progeny lacking long-term self-renewal capacity.
We use genetic methods, combined with genome-wide gene expression and chromatin profiling, to address the complexity of the hematopoietic stem cell population, the niches that maintain them, and the changes hematopoietic stem cells and niches undergo during aging. We investigate the regulators (transcription factors, signaling molecules) that control the lineage commitment of multi-potent hematopoietic progenitors, as well as the cellular pathways that they specify. Finally, we model how mutations affecting the normal transcriptional control of myelopoiesis result in acute myeloid leukemia, and address how the leukemic stem cells responsible for the disease are maintained.
The final goal is to understand the molecular basis for and spatial organization of normal, aging and malignant hematopoiesis, and to use this knowledge to devise cell based and molecular therapies that can be used to treat hematopoietic insufficiencies and malignancies.
Key publications
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Micro-environmental sensing by bone marrow stroma identifies IL-6 and TGFβ1 as regulators of hematopoietic ageing.
Journal article
Valletta S. et al, (2020), Nat Commun, 11
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C/EBPα and GATA-2 Mutations Induce Bilineage Acute Erythroid Leukemia through Transformation of a Neomorphic Neutrophil-Erythroid Progenitor.
Journal article
Di Genua C. et al, (2020), Cancer Cell, 37, 690 - 704.e8
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Identification of two distinct pathways of human myelopoiesis.
Journal article
Drissen R. et al, (2019), Sci Immunol, 4
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Hierarchically related lineage-restricted fates of multipotent haematopoietic stem cells.
Journal article
Carrelha J. et al, (2018), Nature, 554, 106 - 111
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Bi-directional signaling by membrane-bound KitL induces proliferation and coordinates thymic endothelial cell and thymocyte expansion.
Journal article
Buono M. et al, (2018), Nat Commun, 9
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Distinct myeloid progenitor-differentiation pathways identified through single-cell RNA sequencing.
Journal article
Drissen R. et al, (2016), Nat Immunol, 17, 666 - 676
Recent publications
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Author Correction: Myeloid lineage enhancers drive oncogene synergy in CEBPA/CSF3R mutant acute myeloid leukemia.
Journal article
Braun TP. et al, (2022), Nat Commun, 13
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To Bi or not to Bi: Acute Erythroid Leukemias and hematopoietic lineage choice.
Journal article
di Genua C. and Nerlov C., (2021), Exp Hematol
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Micro-environmental sensing by bone marrow stroma identifies IL-6 and TGFβ1 as regulators of hematopoietic ageing.
Journal article
Valletta S. et al, (2020), Nat Commun, 11
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Liver haploinsufficiency of RuvBL1 causes hepatic insulin resistance and enhances hepatocellular carcinoma progression.
Journal article
Mello T. et al, (2020), Int J Cancer, 146, 3410 - 3422
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C/EBPα and GATA-2 Mutations Induce Bilineage Acute Erythroid Leukemia through Transformation of a Neomorphic Neutrophil-Erythroid Progenitor.
Journal article
Di Genua C. et al, (2020), Cancer Cell, 37, 690 - 704.e8
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CD34 and EPCR coordinately enrich functional murine hematopoietic stem cells under normal and inflammatory conditions.
Journal article
Rabe JL. et al, (2020), Exp Hematol, 81, 1 - 15.e6