Dr Rui Monteiro

Department of Cancer and Genomic Sciences
Associate Professor

Contact details

Telephone: +44 (0)121 414 7846
Email: r.monteiro@bham.ac.uk
Twitter: @LabMonteiro

Address: Department of Cancer and Genomic Sciences
University of Birmingham
Edgbaston
Birmingham
B15 2TT
UK

The Monteiro Lab studies the fundamental mechanisms underpinning haematopoiesis in development and homeostasis and how perturbations in these mechanisms lead to haematopoietic disease.

What factors direct cells of a particular lineage(endothelium) to de-differentiate and become a stem cell for a different tissue type (blood)? How do these stem cells maintain the balance between differentiation and self-renewal and what happens when that fails?

Haematopoietic stem cells (HSCs) arise during embryonic development and generate and maintain all the blood lineages throughout adult life. They arise from the haemogenic endothelium (HE), a specialized subset of endothelial cells located in the floor of the main embryonic artery, the dorsal aorta. Importantly, HSC ontogeny is conserved throughout vertebrate development, allowing the use of animal models like the zebrafish to gain fundamental insights into the molecular mechanisms that shape this process. We use a broad range of techniques like transgenesis and gene editing, genome-wide analysis of chromatin accessibility and epigenetic marks and single-cell transcriptional profiling.

The goal is to understand how extrinsic factors, transcriptional regulators and cis-regulatory regions (enhancers) interplay to carry out key lineage decisions that enable the emergence of HSCs and their self-renewal and differentiation to give rise to all haematopoietic lineages (e.g. erythrocytes, macrophages, T-cells). Understanding of how these factors interact to generate and maintain a healthy haematopoietic system in a whole organism is critical both to design new approaches to generating stem cells in vitro but also to help design effective interventions when haematopoiesis is perturbed in diseases such as leukaemias.

Qualifications

Fellow of the Higher Education Academy (2022 – present)
Postgraduate Certificate in Higher Education (2022)
PhD in Developmental Biology, Hubrecht Institute, University of Utrecht, The Netherlands (2005)
MSc (equivalent 5-year degree) in Biochemistry, University of Lisbon, Portugal (2000)

Biography

Rui started his research career as an undergraduate, studying Notch target genes in chick embryos at the Instituto de Histologia e Embriologia, University of Lisbon, Portugal. After graduating in 2000, he went on to pursue a PhD in Developmental Biology at the Hubrecht Institute, University of Utrecht, The Netherlands. He graduated in 2005, and during this period studied BMP signalling in mouse and in zebrafish. In 2006 he joined Prof Patient’s lab at the Weatherall Institute of Molecular Medicine, University of Oxford to do research on developmental haematopoiesis. In 2014, he was awarded a BHF Intermediate Basic Science Research Fellowship and became a Principal Investigator at the Radcliffe Department of Medicine, University of Oxford. He became a University Research Lecturer in 2016. Rui joined the University of Birmingham in 2018 as a Birmingham Fellow. In 2022 Rui became an Associate Professor.

Teaching

MBChB - Research Taster sessions, 1^st year students.
MBChB – SGT on Cancer metastasis and invasion, 2^nd year
Biomedical Sciences – 3^rd and 4^th year - SGT on TGFβ signalling for the ‘Cell communication in health and disease’ module.
MSc Genomic Medicine - Lecture on the use of zebrafish for genomics research for the ‘Fundamentals of Human Genetics and Genomics’ module.
MSc Genomic Medicine - Module lead for the Research Project and Literature Dissertation modules.

Postgraduate supervision

Rui supervises undergraduate and postgraduate Master (MSc, MRes) and PhD students in the following areas of research:

The role of transcriptional and epigenetic regulators in endothelial and haematopoietic development
The role of endothelial and haemogenic-specific cis-regulatory elements in zebrafish
Screening of modifiers of blood stem cell fitness, survival and differentiation
In vivo modelling of the genetic basis of human disease in zebrafish

If you are interested in studying any of these subject areas please contact Rui on the contact details above.

Research

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:

1. 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.

2. 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.

3. 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.

Other activities

Professional Body Memberships

2014 - Member of the British Society of Developmental Biology
2015 - Member of the Biochemical Society
2018 - Member of the Zebrafish Disease Models Society
2018 - Member of the International Society of Experimental Hematology
2017 - Member of the European Zebrafish Society

Institutional Responsibilities

2020 – present – Institute of Cancer and Genomic Sciences (ICGS) Early Career Researcher lead, University of Birmingham, UK
2020 – present – Member of the ICGS Postgraduate Research Committee, University of Birmingham, UK
2020 – present - Member of the ICGS Executive Committee, University of Birmingham, UK.

Reviewing and Editorial Activities

2022 – present – Review Editor, Frontiers in Hematology
2022 – 2023– Topic Editor, Frontiers in Cell and Developmental Biology
2014 – present – Peer reviewer for Developmental Cell, Nature communications, Blood, Haematologica, Stem Cell Reports, Development, others.
2014 – present – Grant reviewer for UK (MRC, BBSRC, KKLF, GOSH Charity, BHF, Leukaemia UK, Royal Society) and European research funders (KWF)

Publications

Recent publications

Article

Brix, A, Belleri, L, Pezzotta, A, Pettinato, E, Mazzola, M, Zoccolillo, M, Marozzi, A, Monteiro, R, Bene, FD, Mortellaro, A & Pistocchi, A 2024, 'ADA2 regulates inflammation and hematopoietic stem cell emergence via the A_2bR pathway in zebrafish', Communications Biology, vol. 7, no. 1, 615. https://doi.org/10.1038/s42003-024-06286-3

Mahony, C & Monteiro, R 2024, 'Protocol for the analysis of hematopoietic lineages in the whole kidney marrow of adult zebrafish', STAR Protocols, vol. 5, no. 1, 102810. https://doi.org/10.1016/j.xpro.2023.102810

Mahony, CB, Copper, L, Vrljicak, P, Noyvert, B, Constantinidou, C, Browne, S, Pan, Y, Palles, C, Ott, S, Higgs, MR & Monteiro, R 2023, 'Lineage skewing and genome instability underlie marrow failure in a zebrafish model of GATA2 deficiency', Cell Reports, vol. 42, no. 6, 112571. https://doi.org/10.1016/j.celrep.2023.112571

Gioacchino, E, Koyunlar, C, Zink, J, de Looper, H, de Jong, M, Dobrzycki, T, Mahony, CB, Hoogenboezem, R, Bosch, D, van Strien, PMH, van Royen, ME, French, PJ, Bindels, E, Gussinklo, KJ, Monteiro, R, Touw, IP & de Pater, E 2021, 'Essential role for Gata2 in modulating lineage output from hematopoietic stem cells in zebrafish', Blood Advances, vol. 5, no. 13, pp. 2687-2700. https://doi.org/10.1182/bloodadvances.2020002993

Mahony, CB, Cacialli, P, Pasche, C, Monteiro, R, Savvides, SN & Bertrand, JY 2021, 'Hapln1b, a central organizer of the ECM, modulates kit signaling to control developmental hematopoiesis in zebrafish', Blood Advances, vol. 5, no. 23, pp. 4935–4948. https://doi.org/10.1182/bloodadvances.2020001524

Dobrzycki, T, Mahony, CB, Krecsmarik, M, Koyunlar, C, Rispoli, R, Peulen-Zink, J, Gussinklo, K, Fedlaoui, B, de Pater, E, Patient, R & Monteiro, R 2020, 'Deletion of a conserved Gata2 enhancer impairs haemogenic endothelium programming and adult zebrafish haematopoiesis', Communications Biology, vol. 3, no. 1, 71. https://doi.org/10.1038/s42003-020-0798-3

Dobrzycki, T, Krecsmarik, M & Monteiro, R 2020, 'Genotyping and Quantification of In Situ Hybridization Staining in Zebrafish', Journal of Visualized Experiments , vol. 2020, no. 155, e59956. https://doi.org/10.3791/59956

Dobrzycki, T, Lalwani, M, Telfer, C, Monteiro, R & Patient, R 2020, 'The roles and controls of GATA factors in blood and cardiac development', IUBMB Life, vol. 72, no. 1, pp. 39-44. https://doi.org/10.1002/iub.2178

Bonkhofer, F, Rispoli, R, Pinheiro, P, Krecsmarik, M, Schneider-Swales, J, Tsang, IHC, Bruijn, MD, Monteiro, R, Peterkin, T & Patient, R 2019, 'Blood stem cell-forming haemogenic endothelium in zebrafish derives from arterial endothelium', Nature Communications, vol. 10, no. 1, 3577. https://doi.org/10.1038/s41467-019-11423-2

Dobrzycki, T, Krecsmarik, M, Bonkhofer, F, Patient, R & Monteiro, R 2018, 'An optimized pipeline for parallel image-based quantification of gene expression and genotyping after in situ hybridization', Biology Open, pp. bio.031096. https://doi.org/10.1242/bio.031096

Crisan, M, Solaimani Kartalaei, P, Neagu, A, Karkanpouna, S, Yamada-Inagawa, T, Purini, C, Vink, CS, Van Der Linden, R, Van Ijcken, W, Chuva De Sousa Lopes, SM, Monteiro, R, Mummery, C & Dzierzak, E 2016, 'BMP and Hedgehog Regulate Distinct AGM Hematopoietic Stem Cells Ex Vivo', Stem Cell Reports, vol. 6, no. 3, pp. 383-395. https://doi.org/10.1016/j.stemcr.2016.01.016