Blood Builder Lab – Epigenetics of blood formation
Introduction
We are interested in regulation of cell identity. We investigate epigenetic and transcriptional regulation of normal and leukaemia blood cells, with a particular focus on the generation and maintenance of cell heterogeneity through variability of transcriptional activity, also known as transcriptional noise. We harness mechanisms of cell specification and maintenance of cell identity, to generate physiologically relevant 3D in vitro models of blood formation and study initiation of developmental leukaemias.
Funding
ERC Synergy Grant 2025
In the UK
C3Rs
CCLG/Little Princess Trust
Collaboration partners
- Gerald de Haan (Sanquin)
- Anna Bigas (HMRIB)
- Cecilia Sahlgren (Abo Akademi; TU/Eindhoven)
- Victor Hernandez, Sabrina Tosi and Alessandro Esposito (Brunel University)
- Stefaan Verbruggen (QMUL)
- Jordi Garcia-Ojalvo and Alfonso Martinez Arias (UPF).
Research lines
- Gastruloid models of blood development
- Cellular origin of infant leukaemia
- Transcriptional variability and epigenetic control of blood formation
- Gene regulatory networks of blood stem cell emergence
Key publications
Ragusa et al, Dissecting infant leukemia developmental origins with a hemogenic gastruloid model. eLife 2025; abstract
Pina, Contributions of transcriptional noise to leukaemia evolution. Phil. Trans. R. Soc. B.2024; 379: 20230052. abstract
Ragusa et al, Engineered model of t(7;12)(q36:p13) AML recapitulates patient-specific features and gene expression profiles. Oncogenesis 2022; 11:50. abstract
Gupta et al, Transcriptional variability accelerates pre-leukaemia by cell diversification and perturbation of protein synthesis. Sci Adv 2022; 8: eabn4886. abstract
Domingues et al, Loss of Kat2a enhances transcriptional noise and depletes acute myeloid leukemia stem-like cells. eLife 2020. 9: e51754. abstract
Pina et al, Ddit3 is a nodal regulator of erythron-myeloid lineage specification. Cell Rep 2015. abstract
Pina et al, Inferring rules of lineage commitment in haematopoiesis. Nat Cell Biol 2012. 14: 287-294. abstract
Group members working in the UK
Ayona Johns – PhD candidate
Denise Ragusa – post-doc
Holly Davison – PhD candidate
Alba Cedillo Anether – PhD candidate
Emily Johnson - MPhil candidate
