Dr Rui Monteiro

Dr Rui Monteiro

Institute of Cancer and Genomic Sciences
Birmingham Fellow

Contact details

Address
IBR West
Institute of Cancer and Genomic Sciences
University of Birmingham
Edgbaston
Birmingham
B15 2TT

Rui Monteiro is a Birmingham Fellow at the Institute of Cancer and Genomic Sciences (ICGS), University of Birmingham. His lab is interested in haematopoietic stem cells (HSCs) and how they emerge during embryonic development from a special type of endothelium, the haemogenic endothelium. Rui’s group studies the extrinsic signalling and intrinsic transcriptional regulators that allow endothelial cells to become haematopoietic, 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.

The group is also interested in studying tissue-specific regulatory regions (enhancers) that are required in specific tissues to drive expression of critical haematopoietic genes during development and in disease. We hope that understanding the mechanisms underlying gene regulation in normal development will help find strategies to correct those mechanisms in disease.

Qualifications

  • 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.

Postgraduate supervision

Rui has supervised three undergraduate and three PhD students and is interested in supervising doctoral research in the following areas:

  • The role of transcriptional and epigenetic regulators in endothelial and haematopoietic development
  • High throughput screening of endothelial and haemogenic-specific cis-regulatory elements in zebrafish
  • 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

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, transcriptional and epigenetic profiling and screening by transient transgenesis. Their current research interests are: 

  1. The role of TGFb 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. 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. Here, Rui’s group is developing a zebrafish model for gata2 haploinsufficiency syndromes such as Emberger’s or MonoMAC syndrome, for which there are no curative therapies beyond allogeneic stem cell transplants.
  3. Cis-regulatory elements that drive cell fate specification in endothelium and in blood stem cells. We are interesting in identifying key tissue-specific enhancers that drive gene expression during the haematopoietic process. Profiling their activity in vivo will help to dissect the tissue-specific functions of particular transcription factors and how it impinges in the development of the embryonic cardiovascular and haematopoietic systems. 

Postdoctoral researchers:

Other activities

  • Member of the British Society of Developmental Biology
  • Member of the Biochemical Society
  • Member of the EuFishBioMed Society
  • Member of the Zebrafish Disease Models Society 
  • Reviewer for scientific journals, including Nature, Developmental Cell, Cell Stem Cell, Cell Reports, Stem Cell Reports, PLoS journals, Development, Advances in Haematology, Haematologica, Blood and EMBO Journal. Rui also reviews national grant proposals (MRC, BBSRC, KKLF). 
  • Member of the Radcliffe Department of Medicine Sponsored Nursery Places Panel. 2015-2017
  • Member of the Clinical Medicine Animal Welfare and Ethical Review Body (University of Oxford) 2007-2017

Publications

  1. Tomasz Dobrzycki*, Monika Krecsmarik*, Florian Bonkhofer, Roger Patient and Rui Monteiro (2018) An optimized pipeline for parallel image-based quantification of gene expression and genotyping after in situ hybridization. Biology Open, 7: bio031096 doi: 10.1242/bio.031096 Published 9 April 2018.
  2. Lopes Susana S.*, Distel Martin*, Linker Claudia*, Fior Rita*,Monteiro Rui*, Bianco Isaac H.*, Portugues Ruben*, Strähle Uwe, and Saúde Leonor. Zebrafish. September 2016, ahead of print. doi:10.1089/zeb.2016.1364. (*equal contribution)
  3. Rui Monteiro*,#, Philip Pinheiro, Nicola Joseph, Tessa Peterkin, Jana Koth, Nicola Joseph, Arif Kirmizitas and Roger Patient* (2016). Transforming Growth Factor b drives haemogenic endothelium programming and the transition to haematopoietic stem cells. Developmental Cell. 38 (4), 358-370. (*corresponding author; #lead author)
  4. Mihaela Crisan, Parham Solaimani Kartalaei, Alex Neagu, Sofia Karkanpouna, Tomoko Yamada-Inagawa, Caterina Purini, Chris S. Vink, Reinier van der Linden, Wilfred van Ijcken, Susana M. Chuva de Sousa Lopes, Rui Monteiro, Christine Mummery, Elaine Dzierzak (2016). BMP and Hedgehog Regulate Distinct AGM Hematopoietic Stem Cells Ex Vivo. Stem Cell Reports. 6 (3):383-395. 
  5. Mihaela Crisan, Parham Solaimani Kartalaei, Chris Vink, Tomoko Yamada-Inagawa, Karine Bollerot, Wilfred van IJcken, Reinier van der Linden, Susana M Chuva de Sousa Lopes, Rui Monteiro, Christine Mummery, Elaine Dzierzak (2015). BMP signalling differentially regulates distinct haematopoietic stem cell types. Nat Comms. Aug 18;6:8040. doi: 10.1038/ncomms9040.
  6. Gu W, Monteiro R, Zuo J, Simões FC, Martella A, Andrieu-Soler C, Grosveld F, Sauka-Spengler T, Patient R. (2015). A Novel TGFβ Modulator that Uncouples R-Smad/I-Smad-Mediated Negative Feedback from R-Smad/Ligand-Driven Positive Feedback. PLoS Biol. 2015 Feb 09; 13(2) e1002051.
  7. Ciau-Uitz A, Monteiro R, Kirmizitas A, Patient R (2014). Developmental hematopoiesis: ontogeny, genetic programming and conservation. Exp Hematol. 42(8):669-83. Review.
  8. Gorsi B, Liu F, Ma X, Chico TJ, v A, Kramer KL, Bridges E, Monteiro R, Harris AL, Patient R, Stringer SE. The heparan sulfate editing enzyme Sulf1 plays a novel role in zebrafish VegfA mediated arterial venous identity (2014). Angiogenesis. 17(1):77-91.
  9. Natalia Sacilotto, Rui Monteiro, et al (2013) Analysis of Dll4 regulation reveals a novel combinatorial role for Sox and Notch in arterial development. PNAS. 110 (29), 11893-11898.
  10. Leung A, Ciau-Uitz A, Pinheiro P, Monteiro R, Zuo J, Vyas P, Patient R, Porcher C. (2013) Uncoupling VEGFA Functions in Arteriogenesis and Hematopoietic Stem Cell Specification. Dev Cell. 24, 144-158.
  11. Sountoulidis, A, Stavropoulos, A, Giaglis, S, Apostolou, E, Monteiro, R, de Sousa Lopes, SMC, Chen, H, Stripp, BR, Mummery, C, and Andreakos, E. (2012). Activation of the Canonical Bone Morphogenetic Protein (BMP) Pathway during Lung Morphogenesis and Adult Lung Tissue Repair. PloS one 7, e41460.
  12. Bridge G, Monteiro R, Henderson S, Emuss V, Lagos D, Georgopoulou D, Patient R, Boshoff C. (2012). The microRNA-30 family targets DLL4 to modulate endothelial cell behavior during angiogenesis. Blood. 120(25):5063-72.
  13. Boet van Riel, Tibor Pakozdi, Rutger Brouwer, Rui Monteiro, Kapil Tuladhar, Vedran Franke, Jan Christian Bryne, Ruud Jorna, Erik-Jan Rijkers, Wilfred van IJcken, Charlotte Andrieu-Soler, Jeroen Demmers, Roger Patient, Eric Soler, Boris Lenhard and Frank Grosveld (2012) A novel complex, RUNX1- MYEF2, represses hematopoietic genes in erythroid cells. Mol. Cell. Biol. 32(19):3814-22.
  14. Monteiro R, Pouget C, Patient R (2011). The gata1/pu.1 lineage fate paradigm varies between blood populations and is modulated by tif1γ.EMBO J. 30(6):1093-103. Epub 2011 Feb 18.* (*highlighted in Xu J, Orkin, SH (2011). The erythroid/myeloid lineage fate paradigm takes a new player.EMBO J. 30(6):983-5.)
  15. Beqqali A, Monshouwer-Kloots J, Monteiro R, Welling M, Bakkers J, Ehler E, Verkleij A, Mummery C, Passier R (2010). CHAP is a newly identified Z-disc protein essential for heart and skeletal muscle function. J Cell Sci;123(7):1141-50. Epub 2010 Mar 9.
  16. Rui M. Monteiro*, Susana M. Chuva de Sousa Lopes*, Monika Bialecka, Sophie de Boer, An Zwijsen and Christine L. Mummery(2008). Real time monitoring of BMP Smads transcriptional activity during mouse development. Genesis, 46(7):335-46.
  17. Rui Monteiro, Maarten van Dinther, Jeroen Bakkers, Robert Wilkinson, Roger Patient, Peter ten Dijke and Christine Mummery (2008). Two novel Type II receptors mediate BMP signalling and are required to establish left-right asymmetry in zebrafish. Dev Biol ;315(1):55-71.
  18. Colak D, Mori T, Brill MS, Pfeifer A, Falk S, Deng C, Monteiro R, Mummery C, Sommer L, Götz M. (2008). Adult neurogenesis requires Smad4-mediated bone morphogenic protein signaling in stem cells. J Neurosci ; 28(2):434-46
  19. Rutger L van Bezooijen , Marco C Deruiter , Nathalie Vilain , Rui M Monteiro , Annemieke Visser , Lianne van der Wee-Pals , Conny J van Munsteren , Pancras C W Hogendoorn , Michel Aguet , Christine L Mummery , Socrates E Papapoulos , Peter Ten Dijke , Clemens W G M Löwik (2007).SOST expression is restricted to the great arteries during embryonic and neonatal cardiovascular development. Dev Dyn. 236(2):606-12.
  20. Yang L, Cai CL, Lin L, Qyang Y, Chung C,  Monteiro RM, Mummery CL, Fishman GI, Cogen A, Evans S. (2006). Isl1Cre reveals a common Bmp pathway in heart and limb development. Development. 133(8):1575-85. 
  21. AN Fatehi, R van den Hurk, B Colenbrander, AJJM Daemen, HTA van Tol, RM Monteiro, BAJ Roelenand MM Bevers (2005). Expression of Bone Morphogenetic Protein2 (BMP2), BMP4 and BMP receptors in the bovine ovary but absence of effects of BMP2 and BMP4 during IVM on bovine oocyte nuclear maturation and subsequent embryo development. Theriogenology, 63, 872-889.
  22. Chuva de Sousa Lopes, S, Roelen, BA, Monteiro, RM, Emmens, R, Lin, HY, Li, E, Lawson, KA and Mummery, CL(2004). BMP signaling mediated by ALK2 in the visceral endoderm is necessary for the generation of primordial germ cells in the embryo. Genes Dev. 18(15):1838-49.
  23. *Rui M Monteiro, Susana M Chuva de Sousa Lopes,Olexander Korchynskyi, Peter ten Dijke and Christine L Mummery (2004). Spatio-temporal activitation of Smad1 and Smad5 in vivo: monitoring transcriptional activity of Smad proteins. J. Cell Sci. 117:4653-63. (

    *This publication has been awarded the “Best paper of the Year 2004” from Journal of Cell Science.)

View all publications in research portal