Nuno Morais Lab

Disease Transcriptomics

We apply mostly computational approaches, particularly those involving the analysis of high-throughput genomic and transcriptomic data, to fundamental questions in biomedical research.

We have a long-term interest in the systems-level transcriptional regulation underlying mammalian cell specification, often perturbed in disease. We aim to understand how RNA-level (transcription initiation, splicing, etc) changes in (mostly) human tissues increase proneness to diseases, namely cancer, neurodegenerative disorders and other ageing-related pathologies. We thereby aim 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.

Along the way, we develop some tools for assisting non-computational scientists in their analyses of transcriptomic data.

Research Team

Research Areas

RNA (de)regulation in disease contexts:

• Alternative transcription of CELF2 in colorectal cancer progression and therapeutics
• Alternative splicing during oncogene-induced senescence
• The role of tumour-infiltrating myeloid cells in breast cancer at the single-cell level
• The role of centrosome abnormalities in cancer
• Unravelling targetable systemic and cell-type-specific molecular phenotypes of Alzheimer’s and Parkinson’s brains
• Dynamics of transposable elements during neurodevelopment and in neurodevelopmental diseases

Bioinformatics tools for the analysis of RNA-seq data:

• Graphical applications for alternative splicing quantification and analysis
• Beta distribution-based differential splicing analysis
• Identification of candidate causal perturbations from differential gene expression data
• Graphical exploration of age-related gene expression alterations in human tissues

Ongoing Research Projects

2020/2026 Unveiling tissue-specific transcriptional signatures of human ageing for therapeutic targeting. Coordinator: Nuno Morais. Funding Agency: Fundação para a Ciência e a Tecnologia Scientific Employment Stimulus.

2015/2021 Transcriptomic landscapes of cancer: studying the transcriptional etiology of metastization and its implications on personalized therapeutics. Coordinator: Nuno Morais. Funding Agency: EMBO Installation Grant

Awards

2020-2026 FCT Scientific Employment Stimulus – Assistant Researcher.

2019 1^st prize, Young ICSA Poster Award, International Cell Senescence Association conference 2019 (Athens, Greece) [Mariana Ferreira].

2017 AstraZeneca Innovate Competition - Translational Research [Mariana Ferreira].

2015-2021 EMBO (European Molecular Biology Organization) Installation Grant.

2015-2019 FCT Investigator Starting Grant.

2011-2014 Marie Curie International Outgoing Fellowship.

2010-2012 Canadian Institutes for Health Research (CIHR) Postdoctoral Fellowship.

Selected Publications

Bordone MC, Barbosa-Morais NL (2020). Unraveling Targetable Systemic and Cell-Type-Specific Molecular Phenotypes of Alzheimer's and Parkinson's Brains with Digital Cytometry. Frontiers in Neuroscience 14:607215.

Saraiva-Agostinho N, Barbosa-Morais NL. "Interactive Alternative Splicing Analysis of Human Stem Cells Using psichomics." Methods in Molecular Biology, 2020;2117:179-205.

Godinho-Silva C, Domingues RG, Rendas M, Raposo B, Ribeiro H, da Silva JA, Vieira A, Costa RM, Barbosa-Morais NL, Carvalho T, Veiga-Fernandes H. "Light-entrained and brain-tuned circadian circuits regulate ILC3s and gut homeostasis." Nature, 2019 Oct;574(7777):254-258.

Munkley J, Li L, Krishnan SRG, Hysenaj G, Scott E, Dalgliesh C, Oo HZ, Maia TM, Cheung K, Ehrmann I, Livermore KE, Zielinska H, Thompson O, Knight B, McCullagh P, McGrath J, Crundwell M, Harries LW, Daugaard M, Cockell S, Barbosa-Morais NL+, Oltean S +, Elliott DJ +. "Androgen-regulated transcription of ESRP2 drives alternative splicing patterns in prostate cancer." eLife, 2019 Sep 3;8:e47678. (+ corresponding author)

de Almeida BP, Vieira AF, Paredes J, Bettencourt-Dias M, Barbosa-Morais NL. "Pan-cancer association of a centrosome amplification gene expression signature with genomic alterations and clinical outcome." PLoS Computational Biology, 2019 Mar 11;15(3):e1006832.

Saraiva-Agostinho N, Barbosa-Morais NL. "psichomics: graphical application for alternative splicing quantification and analysis." Nucleic Acids Research, 2019 Jan 25;47(2):e7.

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". Human Genetics, 2017 Sep;136(9):1015-1042. Review.

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 Research, 2014 Nov;24(11):1774-86.

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 Research, 2006 Jan, 16(1):66-77.

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