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Disease Transcriptomics

We have a long-term interest in the systems-level transcriptional regulation underlying mammalian cell specification, often perturbed in disease. In particular, we are studying the mechanisms responsible for the association between aberrant splicing and pathologies like cancer and neurodegenerative disorders. We employ computational biology approaches for the analysis of next-generation sequencing data to find disease-specific transcriptomic signatures, aiming to understand how the regulation of alternative splicing is affected in different pathologies and thereby to identify molecular targets for functional exploration in vitro and in vivo.

We also combine molecular and clinical information for the unveiling of novel candidate prognostic factors and therapeutic targets.

Research Team

Joel Indi
PhD Student
joel.indi@medicina.ulisboa.pt

Mariana Ascensão Ferreira
PhD Student
marianaascferreira@medicina.ulisboa.pt

Marie Bordone
PhD Student
marie.bordone@medicina.ulisboa.pt

Marta Bica
Lab Technician
ana.bica@medicina.ulisboa.pt

Nuno Agostinho
PhD Student
nunoagostinho@medicina.ulisboa.pt

Research Areas

  • Cancer
  • Neurodegenerative disease
  • Evolution and regulation of alternative splicing
  • Transcriptomics
  • Bioinformatics

Ongoing Research Projects

2015/2017(9) "Transcriptomic landscapes of cancer: studying the transcriptional etiology of metastization and its implications on personalized therapeutics", EMBO Installation Grant

2015/2019 "RNA regulation in cancer: defining the transcriptional etiology of metastasis and its implications on personalized therapeutics", FCT Investigator Starting Grant

2017/2018 "Alternative splicing during neuronal development", AstraZeneca Foundation Innovate Grant - Translational Research

2016/2017 "RNA regulation in colorectal cancer: transcriptomic landscapes of metastasis and their clinical implications", iMM Directors' Exploratory Project

2011/2014 "Survey of tissue-specific alternative splicing in vertebrates by high-throughput sequencing: finding the elements of an evolutionary splicing predictor", Marie Curie International Outgoing Fellowship

Awards

  • AstraZeneca Innovate Competition - Translational Research (2017-) [Mariana Ferreira]
  • EMBO (European Molecular Biology Organization) Installation Grant (2015-)
  • FCT Investigator Starting Grant (2015-)
  • Marie Curie International Outgoing Fellowship (2011-2014)
  • Canadian Institutes for Health Research (CIHR) Postdoctoral Fellowship (2010-2012)

Selected Publications

  • Gallego-Paez LM, Bordone MC, Leote AC, Saraiva-Agostinho N, Ascensão-Ferreira M, Barbosa-Morais NL. "Alternative splicing: the pledge, the turn, and the prestige : The key role of alternative splicing in human biological systems". Hum Genet, 2017 Apr 3. doi: 10.1007/s00439-017-1790-y. Review.
  • Rijo-Ferreira F, Pinto-Neves D, Barbosa-Morais NL, Takahashi JS, Figueiredo LM. "Trypanosoma brucei metabolism is under circadian control". Nat Microbiol, 2017 Mar 13;2:17032.
  • Liu Y, Noon AP, Cabeza EA, Shen J, Kuk C, Ilczynski C, Ni R, Sukhu B, Chan K, Barbosa-Morais NL, Hermanns T, Blencowe BJ, Azad A, van der Kwast TH, Catto JWF, Zlotta AR, Wrana JL. "Next generation RNA sequencing of archival formalin fixed paraffin embedded urothelial bladder cancer". European Urology, 2014 Dec;66(6):982-6.
  • Braunschweig U, Barbosa-Morais NL, Pan Q, Nachman EN, Alipahani B, Gonatopoulos-Pournatzis T, Frey B, Irimia M, Blencowe BJ. "Widespread intron retention in mammals functionally tunes transcriptomes". Genome Res, 2014 Nov;24(11):1774-86.
  • Pena AC, Pimentel MR, Manso H, Vaz-Drago R, Neves D, Aresta-Branco F, Ferreira FR, Guegan F, Coelho LP, Carmo-Fonseca M, Barbosa-Morais NL, Figueiredo LM. "Trypanosoma brucei histone H1 inhibits RNA polymerase I transcription and is important for parasite fitness in vivo". Mol Microbiol, 2014 Aug;93(4):645-63.
  • Han H, Irimia M, Ross PJ, Sung HK, Alipanahi B, David L, Golipour A, Gabut M, Michael IP, Nachman EN, Wang E, Trcka D, Thompson T, O'Hanlon D, Slobodeniuc V, Barbosa-Morais NL, Burge CB, Moffat J, Frey BJ, Nagy A, Ellis J, Wrana JL, Blencowe BJ. "MBNL proteins repress ES-cell-specific alternative splicing and reprogramming". Nature, 2013 Jun 13;498(7453):241-5.
  • Barbosa-Morais NL, Irimia M, Pan Q, Xiong HY, Gueroussov S, Lee LJ, Slobodeniuc V, Kutter C, Watt S, Colak R, Kim T, Misquitta-Ali CM, Wilson MD, Kim PM, Odom DT, Frey BJ, Blencowe BJ. "The evolutionary landscape of alternative splicing in vertebrate species". Science, 2012 Dec 21;338(6114):1587-93.
  • Barbosa-Morais NL+, Dunning MJ, Samarajiwa SA, Darot JFJ, Ritchie ME, Lynch AG, Tavaré S. "A re-annotation pipeline for Illumina BeadArrays: improving the interpretation of gene expression data". Nucleic Acids Research, 2010 Jan 1;38(3):e17. (+ corresponding author)
  • Wilson MD*, Barbosa-Morais NL*, Schmidt D, Conboy CM, Vanes L, Tybulewicz VLJ, Fisher EMC, Tavaré S, Odom DT. "Species-specific transcription in mice carrying human chromosome 21". Science, 2008 Oct 17;322(5900):434-8. (* equal contributions)
  • Barbosa-Morais NL, Carmo-Fonseca M, Aparicio S. "Systematic genome-wide annotation of spliceosomal proteins reveals differential gene family expansion", Genome Res, 2006 Jan, 16(1):66-77.

group leader :
Nuno Barbosa Morais