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Contact

Dr. Álvaro Rada-Iglesias

Lab 01.08

Phone: (+34) 942 203932 /
Fax:
(+34) 942 266399
Email: alvaro.rada@unican.es
Mailing address: IBBTEC. C/ Albert Einstein 22, PCTCAN, 39011 Santander

Transcriptional regulation in development and congenital disease


AlvaroRada.jpg

Principal Investigator

Dr. Álvaro Rada-Iglesias, STAR2 Investigator


Team

  • María Mariner Fauli, predoctoral
  • Sarah Robert, predoctoral
  • Víctor Sánchez Gaya, predoctoral

 

Research Interest

The major interest of our laboratory is to uncover the main genetic and epigenetic factors that allow the deployment of specific gene expression profiles as vertebrate developmental programs unroll. Our goal is to provide a deep mechanistic understanding of the non-coding genomic space that is dynamically and specifically used during mammalian embryogenesis, which is fundamental to reveal the molecular basis of human congenital diseases. More specifically, by functionally and mechanistically characterizing developmental enhancers, my laboratory aims at:

  • Uncovering transcriptional regulatory principles orchestrating mammalian embryogenesis.
  • Elucidating the genetic and epigenetic basis of human congenital diseases.

 

Funding

  • "Transcriptional Regulation during vertebrate Embryonic Patterning: from genomics to mechanism" – STAR2 Programme (Universidad de Cantabria; Banco Santander) - 2018/2023 – IP: Alvaro Rada Iglesias
  • "Embo Young Investigator Program (YIP)" – EMBO – 2018/2020 – IP: Alvaro Rada Iglesias
  • "Mechanistic characterization of poised enhancer function during the induction of major anterior neural regulatory loci" - German Research Foundation (DFG) - 2017/2020 – IP: Alvaro Rada Iglesias
  • "Identification and characterization of major stem cell regulators within the epidermis" - German Research Foundation (DFG) – 2017/2021 – IP: Alvaro Rada Iglesias
  • "A novel etiological mechanism for Branchio-Oculo-Facial Syndrome (BOFS) with implications for the current understanding of human neurocristopathies" - Else Kroner Fresenius Foundation - 2017/2019 - IP: Alvaro Rada Iglesias
  • "Functional and mechanistic characterization of Foxd3 during mouse peri-implantation transitions" – German Research Foundation (DFG) - 2016/2019 – IP: Alvaro Rada Iglesias
  • "A systems biology approach to characterize non-coding genetic variants associated with human disease" – University of Cologne Excellence Program – 2014/2017 - IP: Alvaro Rada Iglesias
  • "Bioinformatic and molecular characterization of non-coding genetic variants associated with craniofacial abnormalities" - Fritz Thyssen Foundation – 2014/2015 - IP: Alvaro Rada Iglesias
  • "Molecular mechanisms and functional relevance of poised developmental enhancers during embryonic stem cell differentiation" - German Research Foundation (DFG) – 2013/2016 – IP: Alvaro Rada Iglesias

 

Publications (last 10 years)

  1. Bleckwehl T, Rada-Iglesias A#. Transcriptional and epigenetic control of germline competence and specification. Curr Opin Cell Biol. 2019 Jun 21;61:1-8. PMID: 31233905.

  2. Matheus F, Rusha E, Rehimi R, Molitor L, Pertek A, Modic M, Feederle R, Flatley A, Kremmer E, Geerlof A, Rishko V, Rada-Iglesias A, Drukker M. Pathological ASXL1 Mutations and Protein Variants Impair Neural Crest Development. Stem Cell Reports. 2019 May 14;12(5):861-868. PMID: 31006630

  3. Laugsch M, Bartusel M, Rehimi R, Alirzayeva H, Karaolidou A, Crispatzu G, Zentis P, Nikolic M, Bleckwehl T, Kolovos P, van Ijcken, W.F.J., Šarić T, Köhler K, Frommolt P, Lachlan K, Baptista J#, Rada-Iglesias, A#. Modelling the pathological long-range regulatory effects of human structural variation with patient-specific hiPSCs. Cell Stem Cell, 2019 May 2;24(5):736-752.

  4. Irmak D, Fatima A, Gutiérrez-Garcia R, Rinschen MM, Wagle P, Altmüller J, Arrigoni L, Hummel B, Klein C, Frese CK, Sawarkar R, Rada-Iglesias A, Vilchez D. Mechanism suppressing H3K9 trimethylation in pluripotent stem cells and its demise by polyQ-expanded huntingtin mutations. Hum Mol Genet. 2018 Dec 1;27(23):4117-4134. PMID: 30452683

  5. Frank S, Ahuja G, Bartsch D, Russ N, Yao W, Kuo JC, Derks JP, Akhade VS, Kargapolova Y, Georgomanolis T, Messling JE, Gramm M, Brant L, Rehimi R, Vargas NE, Kuroczik A, Yang TP, Sahito RGA, Franzen J, Hescheler J, Sachinidis A, Peifer M, Rada-Iglesias A, Kanduri M, Costa IG, Kanduri C, Papantonis A, Kurian L. yylncT Defines a Class of Divergently Transcribed lncRNAs and Safeguards the T-mediated Mesodermal Commitment of Human PSCs. Cell Stem Cell. 2018 Nov 21. pii: S1934-5909(18)30541-1. doi: 10.1016/j.stem.2018.11.005. PMID: 30554961

  6. Rada-Iglesias A#. Pioneering of Enhancer Landscapes during Pluripotent State Transitions. Cell Stem Cell. 2018 Aug 2;23(2):149-151. PMID: 30075122

  7. Rada-Iglesias A#, Grosveld FG, Papantonis A#. Forces driving the three-dimensional folding of eukaryotic genomes. Mol Syst Biol. 2018 Jun 1;14(6):e8214. PMID: 29858282
  8. Fueyo R, Iacobucci S, Pappa S, Estarás C, Lois S, Vicioso-Mantis M, Navarro C, Cruz-Molina S, Reyes JC, Rada-Iglesias A#, de la Cruz X, Martínez-Balbás MA. Lineage specific transcription factors and epigenetic regulators mediate TGFβ-dependent enhancer activation. Nucleic Acids Res. 2018 Feb 9. PMID:29438503
  9. Rada-Iglesias A#. Is H3K4me1 at enhancers correlative or causative. Nat Genet. 2018 Jan;50(1):4-5. PMID:29273804
  10. Rada-Iglesias A#. Ready, Set… Poised: polycomb target genes are bound by poised RNA polymerase II throughout differentiation. Mol Syst Biol, 2017 Oct 23;13(10):950. PMID:29061670
  11. Rehimi R, Bartusel M, Solinas F, Altmüller J, Rada-Iglesias A#. Chromatin Immunoprecipitation (ChIP) Protocol for Low-abundance Embryonic Samples. J Vis Exp. 2017 Aug 29;(126). PMID: 28872116
  12. Cruz-Molina S, Respuela P, Tebartz C, Kolovos P, Nikolic M, Fueyo R, van Ijcken W.F.J, Grosveld F, Frommolt P, Bazzi H, Rada-Iglesias A#. PRC2 facilitates the regulatory topology required for poised enhancer function during pluripotent stem cell differentiation. Cell Stem Cell. 2017 May 4;20(5):689-705. PMID:28285903.
  13. Ludwig KU, Böhmer AC, Bowes J, Nikolić M, Ishorst N, Wyatt N, Hammond NL, Gölz L, Thieme F, Barth S, Schuenke H, Klamt J, Spielmann M, Aldhorae K, Rojas-Martinez A, Nöthen MM, Rada-Iglesias A, Dixon MJ, Knapp M, Mangold E. Imputation of Orofacial Clefting Data Identifies Novel Risk Loci and Sheds Light on the Genetic Background of Cleft Lip ± Cleft Palate and Cleft Palate Only. Hum Mol Genet. 2017 Feb 15;26(4):829-842. PMID:28087736.
  14. Nikolić M, Papantonis A, Rada-Iglesias A#. GARLIC: A Bioinformatic Toolkit for Etiologically Connecting Diseases and Cell Type-Specific Regulatory Maps. Hum Mol Genet. 2017 Feb 15;26(4):742-752. PMID:28007912.
  15. Rehimi R, Nikolic M, Cruz-Molina S, Tebartz C, Frommolt P, Mahabir E, Clément-Ziza M, Rada-Iglesias A#. Epigenomics-Based Identification of Major Cell Identity Regulators within Heterogeneous Cell Populations. Cell Rep. 2016 Dec 13;17(11):3062-3076.
  16. Respuela P and Rada-Iglesias A#. Enhancer Remodeling During Early Mammalian Embryogenesis:Lessons for Somatic Reprogramming, Rejuvenation, and Aging. Curr Stem Cell Rep. 2016 May 2:263–272
  17. Respuela P, Nikolic P, Tan M, Frommolt P, Zhao Y, Wysocka J and Rada-Iglesias A#. Foxd3 promotes exit from naïve pluripotency through enhancer decommissioning and inhibits germline specification. Cell Stem Cell. 2016 Jan 7;18(1):118-133. PMID:26748758
  18. Rada-Iglesias A#. Genetic variation within transcriptional regulatory elements and its implications for human disease. Biol Chem. 2014 Dec 1;395(12):1453-60. PMID:25205712
  19. Rada-Iglesias A, Prescott SL, and Wysocka, J. Human genetic variation within    neural crest enhancers: molecular and phenotypic implications. Philos. Trans. R. Soc. Lond. B. Biol. Sci. 2013 May 368, 20120360. PMID:23650634
  20. Rada-Iglesias A#. Pioneering barren land: mitotic bookmarking by transcription factors. Dev Cell. 2013 Feb 25;24(4):342-4. PMID:2344970
  21. Rada-Iglesias A*, Bajpai R*, Prescott R, Brugmann S, Swigut T and Wysocka J. Epigenomic mapping annotates human neural crest enhancers and predicts a new role for nuclear receptors NR2F1/2. Cell Stem Cell 2012 Nov 2;11(5):633-48. PMID: 22981823
  22. Valdés AE, Overnäs E, Johansson H, Rada-Iglesias A, Engström P. The homeodomain-leucine zipper (HD-Zip) class I transcription factors ATHB7 and ATHB12 modulate abscisic acid signalling by regulating protein phosphatase 2C and abscisic acid receptor gene activities. Plant Mol Biol. 2012 Nov;80(4-5):405-18. doi: 10.1007/s11103-012-9956-4.
  23. Enroth S, Rada-Iglesias A, Andersson R, Wallerman O, Wanders A, Påhlman L, Komorowski J, Wadelius C. Cancer associated epigenetic transitions identified by genome-wide histone methylation binding profiles in human colorectal cancer samples and paired normal mucosa. BMC Cancer. 2011 Oct 19; 11:450. PMID:22011431
  24. Rada-Iglesias A, Wysocka J. Epigenomics of human embryonic stem cells and induced pluripotent stem cells: insights into pluripotency and implications for disease. Genome Med. 2011 Jun 7;3(6):36. PMID:21658297
  25. Ma Z, Swigut T, Valouev A, Rada-Iglesias A, Wysocka J . Sequence-specific regulator Prdm14 safeguards mouse ESCs from entering extraembryonic endoderm fates. Nat Struct Mol Biol. 2011 Feb;18(2):120-7. PMID:21183938
  26. Rada-Iglesias A, Bajpai R, Swigut T, Brugmann SA, Flynn RA, Wysocka J. A unique chromatin signature uncovers early developmental enhancers in humans. Nature. 2011 Feb 10;470(7333):279-83. PMID:21160473
  27. Sandgren J, Andersson R, Rada-Iglesias A, Enroth S, Akerstrom G, Dumanski JP, Komorowski J, Westin G, Wadelius C Integrative epigenomic and genomic analysis of malignant pheochromocytoma. Exp Mol Med. 2010 Jul 31;42(7):484-502. PMID:20534969
  28. Bajpai R, Chen DA, Rada-Iglesias A, Zhang J, Xiong Y, Helms J, Chang CP, Zhao Y, Swigut T, Wysocka J. CHD7 cooperates with PBAF to control multipotent neural crest formation. Nature. 2010 Feb 18;463(7283):958-62. PMID:20130577
  29. Andersson R*, Enroth S*, Rada-Iglesias A*, Wadelius C, Komorowski J.. Nucleosomes are well positioned in exons and carry characteristic histone modifications. Genome Res. 2009 Oct;19(10):1732-41. PMID:19687145
  30. Motallebipour M, Rada-Iglesias A, Westin G, Wadelius C. Two polypyrimidine tracts in the nitric oxide synthase 2 gene: similar regulatory sequences with different properties. Mol Biol Rep. 2010 Apr;37(4):2021-30. PMID:19669598
  31. Ameur A*, Rada-Iglesias A*, Komorowski J, Wadelius C. Identification of candidate regulatory SNPs by combination of transcription-factor-binding site prediction, SNP genotyping and haploChIP. Nucleic Acids Res. 2009 Jul;37(12):e85. PMID:19451166
  32. Rada-Iglesias A, Enroth S, Andersson R, Wanders A, Påhlman L, Komorowski J, Wadelius C. Histone H3 lysine 27 trimethylation in adult differentiated colon associated to cancer DNA hypermethylation. Epigenetics. 2009 Feb 16;4(2):107-13. PMID:19276669
  33. Patricia Respuela, Marcela Ferella, Alvaro Rada-Iglesias and Lena Åslund, Histone acetylation at bidirectional promoters of divergent polycistronic gene clusters in Trypanosoma cruzi. J Biol Chem, 2008 Jun 6;283(23):15884-92. PMID:18400752
  34. Alvaro Rada-Iglesias*, Adam Ameur*, Philipp Kapranov, Stefan Enroth, Jan Komorowski, Thomas R. Gingeras, Claes Wadelius. Whole-genome maps of USF1 and USF2 binding and histone H3 acetylation reveal new aspects of promoter structure and candidate genes for common human disorders. Genome Research, 2008 Mar;18(3):380-92. PMID:18230803
  35. Michael  Draminski, Alvaro Rada-Iglesias, Stefan Enroth, Claes Wadelius, Jacek Koronacki, Jan Komorowski, Monte Carlo feature selection for supervised classification. Bioinformatics, 2008 Jan 1;24(1):110-7. PMID:18048398

# Corresponding Author

*Equal Contribution