My research focuses on mouse and human hematopoiesis. The hematopoietic stem cell gives rise to all different blood cell types. In this process, intermediate progenitor cells derive from the stem cell that gradually loose lineage potential while differentiating towards one specific cell type. I am characterising various progenitors. This work leads towards improved models for hematopoietic hierarchies. These models are imperative for studying aspects of hematopoiesis, such as the mechanisms that are involved in lineage decisions and characterising cells of origin in hematopoietic malignancies. I am specifically interested in progenitors leading towards myeloid cell types, which consists of neutrophils, macrophages, eosinophils, basophils and mast cells. With single cell technologies, we have shown that these myeloid cell types are produced via two independent pathways. In particular the finding of a separate pathway that produces eosinophils, basophils and mast cells gives a unique opportunity to study myeloid malignancies that involve these cells, such as systemic mastocytosis and idiopathic eosinophilia.
Since my PhD at the Erasmus MC in Rotterdam, the Netherlands (1999-2005), followed by a first postdoc position at the WIMM (2005-2009), I have had an interest in the control and effect of transcription factors in hematopoiesis. My earlier work involved erythropoiesis, and shifted towards myelopoiesis when I started my position at the Centre for Regenerative Medicine in Edinburgh (2009-2012). Now back at the WIMM, I continue working on normal hematopoieisis, translating the findings in the mouse to human, with the goal to study malignant human myelopoiesis.
Epigenetic programming defines haematopoietic stem cell fate restriction.
Meng Y. et al, (2023), Nat Cell Biol
Micro-environmental sensing by bone marrow stroma identifies IL-6 and TGFβ1 as regulators of hematopoietic ageing.
Valletta S. et al, (2020), Nat Commun, 11
C/EBPα and GATA-2 Mutations Induce Bilineage Acute Erythroid Leukemia through Transformation of a Neomorphic Neutrophil-Erythroid Progenitor.
Di Genua C. et al, (2020), Cancer Cell, 37, 690 - 704.e8
Myeloid lineage enhancers drive oncogene synergy in CEBPA/CSF3R mutant acute myeloid leukemia.
Braun TP. et al, (2019), Nat Commun, 10
Cell-intrinsic depletion of Aml1-ETO-expressing pre-leukemic hematopoietic stem cells by K-Ras activating mutation.
Di Genua C. et al, (2019), Haematologica, 104, 2215 - 2224