Research Interests

Zebrafish has become an important resource for biomedical research, helping to understand human disease and addressing critical questions in regenerative medicine. Because zebrafish share the same genes with other vertebrates, including humans, and angiogenesis and haematopoiesis are so well conserved, the lessons we learn from this model can be directly applied to other vertebrate systems and to human health. The Monteiro Lab are interested in learning how extrinsic signalling and intrinsic transcriptional regulators control lineage fate decisions and thus programme the embryonic endothelium towards a blood stem cell (HSC) fate. To this end, they use a mix of classical developmental biology approaches with novel cutting edge approaches like genome editing with CRISPR/Cas9, single cell transcriptional and epigenetic profiling and screening by transient transgenesis.

Current projects:

• The role of TGFβ signalling in the formation of HSCs and how that relates to its function in making blood vessels. Gaining insights into the role of TGFβ in vascular and blood stem cell biology in vivo is particularly relevant, given that the TGFβ pathway is an attractive therapeutic target in haematopoietic malignancies and cardiovascular disease.
• The interplay between epigenetic regulators and cis-regulatory elements that drive cell fate specification in endothelium and in blood stem cells. We are interested in identifying key tissue-specific drivers of gene expression and cellular fate during the haematopoietic process. Understanding their activity in vivo will help to dissect their contribution to the development of the embryonic cardiovascular and haematopoietic systems.
• To develop in vivo leukaemia models in zebrafish. Transcriptional regulators that are important for HSC formation in the embryo are frequently mutated or mis-expressed in haematopoietic malignancies. For example, the Monteiro lab has developed a zebrafish model for GATA2 deficiency and shown that disease progression is linked to defects in DNA damage repair pathways.