Rui Monteiro is a Birmingham Fellow at the Institute of Cancer and Genomic Sciences (ICGS), University of Birmingham. Rui’s group studies the formation of haematopoietic stem cells (HSCs) in the vertebrate embryo development, using zebrafish as a model system. They are interested in learning how extrinsic signalling and intrinsic transcriptional regulators control lineage fate decisions and thus programme the embryonic endothelium towards an HSC fate, with a particular emphasis on the Transforming Growth Factor β (TGFβ) pathway. Defects in TGFβ signalling lead to cardiovascular diseases such as Marfan syndrome and Hereditary Haemorrhagic Telangiectasia, but are also found in haematopoietic malignancies like leukaemia. Our approach includes classical genetic analyses, but also the use of Tol2-mediated transgenesis and genome editing tools (CRISPRs/TALENs), transcriptional profiling and epigenetic analysis. We use the zebrafish as a model and are developing tools to model human cardiovascular diseases induced by altered TGFβ signalling.

The group is also interested in studying tissue-specific regulatory regions (enhancers) that are used by the transcription factors to drive the expression of critical haematopoietic genes during development and in disease. Deletion of a conserved Gat2a enhancer leads to severe cytopenias in homozygous enhancer mutants, reminiscent of Gata2 deficiency syndromes in human. Our lab is currently exploring this mutant to gain critical insights into the progression of Gata2 deficiency. Understanding the mechanisms underlying gene regulation in normal development as well as in disease models is crucial to help find strategies to correct those mechanisms in disease.