Dr Rui Monteiro

Supervisor Details

Contact Details

Institute of Cancer and Genomic Sciences, University of Birmingham

Scientific Background

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.

Research Groups

Institute of Cancer and Genomic Sciences

Birmingham Centre for Genome Biology

Genome Structure and Regulation

Supervision Style

In three words or phrases: Supportive, goal-driven, collaborative.

Provision of Training

It depends on the trainer's expertise; for some methods the training will be provided by myself. For methods where other lab members have more expertise, training will be provided by them instead. Training in any new methods that are not within the lab's expertise will be done through interactions with collaborators. My expectation is that PhD students become increasingly independent in performing different techniques.

Progression Monitoring and Management

I expect the PhD student to progressively take more ownership of their project as it progresses, so that they become the expert in that area. I like to have a weekly catch up meeting, but I'm always available for a chat/troubleshooting session/brainstorming session.

Communication

The team has a WhatsApp group chat with which we regularly communicate during the week (rarely at weekends); I do send emails out of hours but there is no expectation that my team do the same.

PhD Students can expect scheduled meetings with me:

In a group meeting

At least once per week

In year 1 of PhD study

At least once per week

In year 2 of PhD study

At least once per week

In year 3 of PhD study

At least once per week

The meetings will be face to face and I am usually contactable for an instant response (if required) on every working day.

Working Pattern

Certain tasks in my lab need to occur at set times, and students need to be able to commit to a rota/timetable shared with other members of the team.

Notice Period for Feedback

I need at least 1 week’s notice to provide feedback on written work of up to 5000 words.

MIBTP Project Details

Current Projects (2025-26)

Primary supervisor for:

Epigenetic regulation of cell fate by non-canonical histone deacetylases

See the PhD Opportunities section to see if this project is currently open for applications via MIBTP.

Please Note: The main page lists projects via BBSRC Research Theme(s) quoted and then relevant Topic(s).

Epigenetic regulation of cell fate by non-canonical histone deacetylases

Secondary Supervisor(s): Professor Shaun Cowley

University of Registration: University of Birmingham

BBSRC Research Themes: Understanding the Rules of Life (Stem Cells, Systems Biology)

Project Outline

Haematopoietic stem cells (HSCs) are generated during embryonic development and are responsible for the production and maintenance of all the blood lineages throughout adult life. This is a stepwise process that requires the differentiation of early embryonic cells towards a mesoderm fate, followed by another round of differentiation that specifies arterial and then haemogenic endothelial cells (HECs) that will give rise to the HSCs (Ciau-Uitz, Monteiro et al. 2014). Establishing precise cell identities is critical for normal development of the vasculature and emergence of the HSCs. This stepwise lineage commitment requires orchestration of gene expression programmes by transcriptional regulators. Class IIa Histone deacetylases (HDACs) include HDAC4, 5, 7 and 9 and form part of multiprotein complexes that regulate gene expression (Park and Kim 2020). By using selective HDAC inhibitors in an embryonic stem cell (ESC) model of haematopoietic differentiation (Goode et al, 2016), we identified a role for Class IIa HDACs at two key developmental stages: formation of mesoderm and emergence of HSCs from HECs. We propose to examine the novel mechanism of class IIa HDACs in HSC development.

Objectives

To investigate the role of different class IIa HDACs in cell fate determination during HSC formation. We will use CRISPR/Cas9 genome editing, in vitro differentiation of mESC, proteomics and zebrafish genetics to address two questions:

1. Which Class IIa HDACs orchestrate transcriptional and epigenetic programmes that dictate mesodermal and haematopoietic cell fates?

Expression data shows HDAC4 and HDAC5 are highly expressed in mESCs, whereas HDAC7 is highly expressed in HECs (Goode et al, 2016), suggesting that HDAC4/5 are important for their initial differentiation, whereas HDAC7 might plays a role in the transition from HECs to HSCs. The student will introduce a degradation tag (dTAG, Nabet et al., 2018) to HDAC4, HDAC5 and HDAC7 in mESCs using established CRISPR/Cas9 gene-editing methodology in the Cowley lab. This allows PROTAC mediated degradation of the POI in as little as an hour. Inducing degradation of each HDAC-dTAG at different timepoints during in vitro differentiation of mESCs towards haematopoietic cells (Monteiro Lab) will enable us to identify which class IIa HDACs play key roles in the stepwise differentiation towards the HSC cell fate. Further transcriptomics and genome-wide accessibility assays (e.g., RNA-seq, ATAC-seq, etc.) will help to pinpoint the molecular mechanism underlying class IIa HDAC function.

In addition, the student will use the HDAC-dTAGs mESC lines to pull down HDAC complexes from HECs/HSCs and perform mass spectrometry to identify class IIa HDAC-bound proteins that may play a role in HSC formation (Monteiro and Cowley labs).

2. Are class IIa functions conserved in vivo? To investigate this, the student will perform a mini CRISPR/Cas9 screen to knockout the relevant class IIa HDACs and the co-regulators identified in Aim 1 and assess their roles in HSC formation and differentiation in the zebrafish. This will be achieved by investigating expression of haematopoietic markers of HSCs (e.g. runx1, cmyb) and their differentiated lineages (e.g. mpx, rag1) throughout embryonic development by in situ hybridization combined with live imaging of transgenic zebrafish lines labelling specific haematopoietic lineages (Monteiro Lab). These approaches will be complemented by genome-wise analysis of chromatin accessibility and/or transcriptomics in zebrafish HECs/HSCs where appropriate.

Timeliness and promise

By using these complimentary experimental approaches, we will be the first to explore the mechanism of class IIa HDACs in HSC development. The approaches described here are being used daily in the Monteiro and Cowley labs. The student will benefit from expert guidance from existing postdocs and students, leading to successful outcomes of these aims.