Innovative Therapies

Functional Genomics and RNA-based Therapeutics

Functional Genomics

Cardiovascular Diseases

High-throughput/High-content Screening



Miguel Mano


Research lines

Identification and molecular characterization of novel RNA-based therapeutics for cardiac regeneration and repair

Development and application of high-throughput and high-content screening technologies using genome-wide siRNA, miRNA and CRISPR libraries


The research of the Functional Genomics and RNA-based Therapeutics laboratory is focused on two main areas: i) the identification and molecular characterization of novel cellular factors relevant to cardiac regeneration and repair, and the translation of this knowledge into effective RNA-based therapeutic strategies, and ii) the development and application of high-throughput and high-content screening technologies using genome-wide siRNA, miRNA and CRISPR libraries.

i) Novel RNA-based therapeutics for cardiac regeneration and repair

Cardiovascular diseases, including myocardial infarction, are the leading cause of death globally. The main area of research of the Functional Genomics and RNA-based Therapeutics laboratory is the identification and characterization of novel cellular factors that control regeneration and repair of cardiac tissue following injury. This is achieved through systematic and unbiased genome-wide experimental approaches such as functional high-throughput screening (HTS) and RNA-seq. Our ultimate goal is to exploit this knowledge to develop novel RNA-based therapeutic strategies able to induce heart regeneration.

ii) High-Throughput and High-Content Screening using genome-wide siRNA, miRNA and CRISPR libraries

An additional area of research of the Functional Genomics and RNA-based Therapeutics laboratory is the development of high-throughput screening (HTS) and high-content screening (HCS) technologies and their application to different areas of biomedical research (e.g. regenerative medicine, infection biology, intracellular signaling and cancer). The state-of-the-art high-throughput screening (HTS) platform hosted by the Functional Genomics and RNA-based Therapeutics laboratory at CNC is the first platform in Portugal equipped with the adequate instrumentation, libraries and expertise to perform arrayed human and mouse genome-wide siRNA, miRNA and CRISPR screenings.


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Information about journal articles, updated at 17-12-2023, from platform CIÊNCIAVITAE.

MiR-182-3p targets TRF2 and impairs tumor growth of triple-negative breast cancer

Dinami, R.; Pompili, L.; Petti, E.; Porru, M.; D'Angelo, C.; Di Vito, S.; Rizzo, A.; et al, 2023. EMBO Molecular Medicine. 1. 15. 2023. . 10.15252/emmm.202216033 . EMBO Molecular Medicine

Microscopy-based phenotypic profiling of infection by Staphylococcus aureus clinical isolates reveals intracellular lifestyle as a prevalent feature

Ines Rodrigues Lopes; Laura Maria Alcantara; Ricardo Jorge Silva; Jerome Josse; Elena Pedrero Vega; Ana Marina Cabrerizo; Melanie Bonhomme; et al, 2022. Nature Communications. 1. 13. 2022. . 10.1038/s41467-022-34790-9 . Nature Communications

Dysregulated endolysosomal trafficking in cells arrested in the G1 phase of the host cell cycle impairs Salmonella vacuolar replication

Clivia Lisowski; Jane Dias; Susana Costa; Ricardo Jorge Silva; Miguel Mano; Ana Eulalio, 2021. Autophagy. 2021. . 10.1080/15548627.2021.1999561 . Autophagy

Co-Exposure of Cardiomyocytes to IFN-¿ and TNF-a Induces Mitochondrial Dysfunction and Nitro-Oxidative Stress

João Paulo Silva Nunes; Pauline Andrieux; Pauline Brochet; Rafael Ribeiro Almeida; Eduardo Kitano; André Kenji Honda; Leo Kei Iwai; et al, 2021. Frontiers in Immunology. 12. 2021. . 10.3389/fimmu.2021.755862 . Frontiers in Immunology

Reprogramming of microRNA expression via E2F1 downregulation promotes Salmonella infection both in infected and bystander cells

Carmen Aguilar; Susana Costa; Claire Maudet; R. P. Vivek-Ananth; Sara Zaldívar-López; Juan J. Garrido; Areejit Samal; Miguel Mano; Ana Eulalio, 2021. Nature Communications. 2021. 10.1038/s41467-021-23593-z . Nature Communications

Che-1/AATF binds to RNA polymerase I machinery and sustains ribosomal RNA gene transcription

Sorino, C.; Catena, V.; Bruno, T.; De Nicola, F.; Scalera, S.; Bossi, G.; Fabretti, F.; et al, 2020. Nucleic Acids Research. 5891 - 5906. 11. 48. 2020. 10.1093/NAR/GKAA344 . Nucleic Acids Research

Functional screenings reveal different requirements for host microRNAs in Salmonella and Shigella infection

Aguilar, C.; Cruz, A.R.; Rodrigues Lopes, I.; Maudet, C.; Sunkavalli, U.; Silva, R.J.; Sharan, M.; et al, 2020. Nature Microbiology. 192 - 205. 1. 5. 2020. # co-last author . 10.1038/s41564-019-0614-3 . Nature Microbiology

Multifaceted roles of microRNAs in host-bacterial pathogen interaction

Aguilar, C.; Mano, M.; Eulalio, A., 2019. Microbiology Spectrum. 3. 7. 2019. 10.1128/microbiolspec.BAI-0002-2019 . Microbiology Spectrum

High-content screen in human pluripotent cells identifies miRNA-regulated pathways controlling pluripotency and differentiation

De Souza Lima, I.M.; Schiavinato, J.L.D.S.; Paulino Leite, S.B.; Sastre, D.; Bezerra, H.L.D.O.; Sangiorgi, B.; Corveloni, A.C.; et al, 2019. Stem Cell Research and Therapy. 1. 10. 2019. 10.1186/s13287-019-1318-6 . Stem Cell Research and Therapy

Cellular TRIM33 restrains HIV-1 infection by targeting viral integrase for proteasomal degradation

Ali, H.; Mano, M.; Braga, L.; Naseem, A.; Marini, B.; Vu, D.M.; Collesi, C.; et al, 2019. Nature Communications. 1. 10. 2019. 10.1038/s41467-019-08810-0 . Nature Communications

Common Regulatory Pathways Mediate Activity of MicroRNAs Inducing Cardiomyocyte Proliferation

Torrini, C.; Cubero, R.J.; Dirkx, E.; Braga, L.; Ali, H.; Prosdocimo, G.; Gutierrez, M.I.; et al, 2019. Cell Reports. 2759 - 2771.e5. 9. 27. 2019. 10.1016/j.celrep.2019.05.005 . Cell Reports

Shedding light on microRNA function via microscopy-based screening

Rodrigues Lopes, I.; Silva, R.J.; Caramelo, I.; Eulalio, A.; Mano, M., 2019. Methods. 55 - 64. 152. 2019. 10.1016/j.ymeth.2018.09.011 . Methods

MicroRNAs at the Host–Bacteria Interface: Host Defense or Bacterial Offense

Aguilar, C.; Mano, M.; Eulalio, A., 2019. Trends in Microbiology. 206 - 218. 3. 27. 2019. 10.1016/j.tim.2018.10.011 . Trends in Microbiology

Sterol regulatory element binding protein 1 couples mechanical cues and lipid metabolism

Bertolio, R.; Napoletano, F.; Mano, M.; Maurer-Stroh, S.; Fantuz, M.; Zannini, A.; Bicciato, S.; Sorrentino, G.; Del Sal, G., 2019. Nature Communications. 1. 10. 2019. 10.1038/s41467-019-09152-7 . Nature Communications

Cell-autonomous and cell non-autonomous downregulation of tumor suppressor DAB2IP by microRNA-149-3p promotes aggressiveness of cancer cells

Bellazzo, A.; Di Minin, G.; Valentino, E.; Sicari, D.; Torre, D.; Marchionni, L.; Serpi, F.; et al, 2018. Cell Death and Differentiation. 1224 - 1238. 7. 25. 2018. 10.1038/s41418-018-0088-5 . Cell Death and Differentiation

MiR-16 regulates the pro-tumorigenic potential of lung fibroblasts through the inhibition of HGF production in an FGFR-1- and MEK1-dependent manner

Andriani, F.; Majorini, M.T.; Mano, M.; Landoni, E.; Miceli, R.; Facchinetti, F.; Mensah, M.; et al, 2018. Journal of Hematology and Oncology. 1. 11. 2018. 10.1186/s13045-018-0594-4 . Journal of Hematology and Oncology

CIAP1 regulates the EGFR/Snai2 axis in triple-negative breast cancer cells

Majorini, M.T.; Manenti, G.; Mano, M.; De Cecco, L.; Conti, A.; Pinciroli, P.; Fontanella, E.; et al, 2018. Cell Death and Differentiation. 2147 - 2164. 12. 25. 2018. 10.1038/s41418-018-0100-0 . Cell Death and Differentiation

Stress-induced host membrane remodeling protects from infection by non-motile bacterial pathogens

Tawk, C.; Nigro, G.; Rodrigues Lopes, I.; Aguilar, C.; Lisowski, C.; Mano, M.; Sansonetti, P.; Vogel, J.; Eulalio, A., 2018. EMBO Journal. 23. 37. 2018. 10.15252/embj.201798529 . EMBO Journal

Mechanical cues control mutant p53 stability through a mevalonate-RhoA axis

Ingallina, E.; Sorrentino, G.; Bertolio, R.; Lisek, K.; Zannini, A.; Azzolin, L.; Severino, L.U.; et al, 2018. Nature Cell Biology. 28 - 35. 1. 20. 2018. 10.1038/s41556-017-0009-8 . Nature Cell Biology

Glucocorticoid receptor signalling activates YAP in breast cancer

Sorrentino, G.; Ruggeri, N.; Zannini, A.; Ingallina, E.; Bertolio, R.; Marotta, C.; Neri, C.; et al, 2017. Nature Communications. 8. 2017. 10.1038/ncomms14073 . Nature Communications

Id genes are essential for early heart formation

Cunningham, T.J.; Yu, M.S.; McKeithan, W.L.; Spiering, S.; Carrette, F.; Huang, C.-T.; Bushway, P.J.; et al, 2017. Genes and Development. 1325 - 1338. 13. 31. 2017. 10.1101/gad.300400.117 . Genes and Development

Analysis of host microRNA function uncovers a role for miR-29b-2-5p in Shigella capture by filopodia

Sunkavalli, U.; Aguilar, C.; Silva, R.J.; Sharan, M.; Cruz, A.R.; Tawk, C.; Maudet, C.; Mano, M.; Eulalio, A., 2017. PLoS Pathogens. 4. 13. 2017. 10.1371/journal.ppat.1006327 . PLoS Pathogens

Epigenetic silencing of miR-296 and miR-512 ensures hTERT dependent apoptosis protection and telomere maintenance in basal-type breast cancer cells

Dinami, R.; Buemi, V.; Sestito, R.; Zappone, A.; Ciani, Y.; Mano, M.; Petti, E.; et al, 2017. Oncotarget. 95674 - 95691. 56. 8. 2017. 10.18632/oncotarget.21180 . Oncotarget

High-throughput screening uncovers miRNAs enhancing glioblastoma cell susceptibility to tyrosine kinase inhibitors

Cunha, P.P.; Costa, P.M.; Morais, C.M.; Lopes, I.R.; Cardoso, A.M.; Cardoso, A.L.; Mano, M.; Jurado, A.S.; Pedroso De Lima, M.C.P., 2017. Human Molecular Genetics. 4375 - 4387. 22. 26. 2017. 10.1093/hmg/ddx323 . Human Molecular Genetics

Lemur tyrosine kinase 2 (LMTK2) is a determinant of cell sensitivity to apoptosis by regulating the levels of the BCL2 family members

Conti, A.; Majorini, M.T.; Fontanella, E.; Bardelli, A.; Giacca, M.; Delia, D.; Mano, M.; Lecis, D., 2017. Cancer Letters. 59 - 69. 389. 2017. 10.1016/j.canlet.2016.12.025 . Cancer Letters

Human MageB2 protein expression enhances E2F transcriptional activity, cell proliferation, and resistance to ribotoxic stress

Peche, L.Y.; Ladelfa, M.F.; Toledo, M.F.; Mano, M.; Laiseca, J.E.; Schneider, C.; Monte, M., 2015. Journal of Biological Chemistry. 29652 - 29662. 49. 290. 2015. 10.1074/jbc.M115.671982 . Journal of Biological Chemistry

Genome-wide RNAi screening identifies host restriction factors critical for in vivo AAV transduction

Mano, M.; Ippodrino, R.; Zentilin, L.; Zacchigna, S.; Giacca, M., 2015. Proceedings of the National Academy of Sciences of the United States of America. 11276 - 11281. 36. 112. 2015. # corresponding author . 10.1073/pnas.1503607112 . Proceedings of the National Academy of Sciences of the United States of America

MicroRNAs in glioblastoma: Role in pathogenesis and opportunities for targeted therapies

Costa, P.M.; Cardoso, A.L.; Mano, M.; de Lima, M.C.P., 2015. CNS and Neurological Disorders - Drug Targets. 222 - 238. 2. 14. 2015. 10.2174/1871527314666150116123610 . CNS and Neurological Disorders - Drug Targets

MicroRNA Screening and the Quest for Biologically Relevant Targets

Eulalio, A.; Mano, M., 2015. Journal of Biomolecular Screening. 1003 - 1017. 8. 20. 2015. 10.1177/1087057115578837 . Journal of Biomolecular Screening

MicroRNAs in the interaction between host and bacterial pathogens

Maudet, C.; Mano, M.; Eulalio, A., 2014. FEBS Letters. 4140 - 4147. 22. 588. 2014. 10.1016/j.febslet.2014.08.002 . FEBS Letters

Metabolic control of YAP and TAZ by the mevalonate pathway

Sorrentino, G.; Ruggeri, N.; Specchia, V.; Cordenonsi, M.; Mano, M.; Dupont, S.; Manfrin, A.; et al, 2014. Nature Cell Biology. 357 - 366. 4. 16. 2014. 10.1038/ncb2936 . Nature Cell Biology

Functional high-throughput screening identifies the miR-15 microRNA family as cellular restriction factors for Salmonella infection

Maudet, C.; Mano, M.; Sunkavalli, U.; Sharan, M.; Giacca, M.; Förstner, K.U.; Eulalio, A., 2014. Nature Communications. 5. 2014. 10.1038/ncomms5718 . Nature Communications

Reversible acetylation regulates vascular endothelial growth factor receptor-2 activity

Zecchin, A.; Pattarini, L.; Gutierrez, M.I.; Mano, M.; Mai, A.; Valente, S.; Myers, M.P.; Pantano, S.; Giacca, M., 2014. Journal of Molecular Cell Biology. 116 - 127. 2. 6. 2014. 10.1093/jmcb/mju010 . Journal of Molecular Cell Biology

Rotavirus increases levels of lipidated LC3 supporting accumulation of infectious progeny virus without inducing autophagosome formation

Arnoldi, F.; De Lorenzo, G.; Mano, M.; Schraner, E.M.; Wild, P.; Eichwald, C.; Burrone, O.R., 2014. PLoS ONE. 4. 9. 2014. 10.1371/journal.pone.0095197 . PLoS ONE

Specific mesothelial signature marks the heterogeneity of mesenchymal stem cells from high-grade serous ovarian cancer

Verardo, R.; Piazza, S.; Klaric, E.; Ciani, Y.; Bussadori, G.; Marzinotto, S.; Mariuzzi, L.; et al, 2014. Stem Cells. 2998 - 3011. 11. 32. 2014. 10.1002/stem.1791 . Stem Cells

Effect of class IV laser therapy on chemotherapy-induced oral mucositis: A clinical and experimental study

Ottaviani, G.; Gobbo, M.; Sturnega, M.; Martinelli, V.; Mano, M.; Zanconati, F.; Bussani, R.; et al, 2013. American Journal of Pathology. 1747 - 1757. 6. 183. 2013. 10.1016/j.ajpath.2013.09.003 . American Journal of Pathology

Neuropilin-1 identifies a subset of bone marrow Gr1-monocytes that can induce tumor vessel normalization and inhibit tumor growth

Carrer, A.; Moimas, S.; Zacchigna, S.; Pattarini, L.; Zentilin, L.; Ruozi, G.; Mano, M.; et al, 2012. Cancer Research. 6371 - 6381. 24. 72. 2012. 10.1158/0008-5472.CAN-12-0762 . Cancer Research

Functional screening identifies miRNAs inducing cardiac regeneration

Eulalio, A.; Mano, M.; Ferro, M.D.; Zentilin, L.; Sinagra, G.; Zacchigna, S.; Giacca, M., 2012. Nature. 376 - 381. 7429. 492. 2012. 10.1038/nature11739 . Nature

Terminal differentiation of cardiac and skeletal myocytes induces permissivity to AAV transduction by relieving inhibition imposed by DNA damage response proteins

Lovric, J.; Mano, M.; Zentilin, L.; Eulalio, A.; Zacchigna, S.; Giacca, M., 2012. Molecular Therapy. 2087 - 2097. 11. 20. 2012. 10.1038/mt.2012.144 . Molecular Therapy

Production of in vivo-biotinylated rotavirus particles

de Lorenzo, G.; Eichwald, C.; Schraner, E.M.; Nicolin, V.; Bortul, R.; Mano, M.; Burrone, O.R.; Arnoldi, F., 2012. Journal of General Virology. 1474 - 1482. PART 7. 93. 2012. 10.1099/vir.0.040089-0 . Journal of General Virology

A Pin1/Mutant p53 Axis Promotes Aggressiveness in Breast Cancer

Girardini, J.; Napoli, M.; Piazza, S.; Rustighi, A.; Marotta, C.; Radaelli, E.; Capaci, V.; et al, 2011. Cancer Cell. 79 - 91. 1. 20. 2011. 10.1016/j.ccr.2011.06.004 . Cancer Cell

A candidate approach implicates the secreted Salmonella effector protein SpvB in P-body disassembly

Eulalio, A.; Fröhlich, K.S.; Mano, M.; Giacca, M.; Vogel, J., 2011. PLoS ONE. 3. 6. 2011. 10.1371/journal.pone.0017296 . PLoS ONE

Rotavirus replication requires a functional proteasome for effective assembly of viroplasms

Contin, R.; Arnoldi, F.; Mano, M.; Burrone, O.R., 2011. Journal of Virology. 2781 - 2792. 6. 85. 2011. 10.1128/JVI.01631-10 . Journal of Virology

Nanoparticles from lipid-based liquid crystals: Emulsifier influence on morphology and cytotoxicity

Murgia, S.; Falchi, A.M.; Mano, M.; Lampis, S.; Angius, R.; Carnerup, A.M.; Schmidt, J.; et al, 2010. Journal of Physical Chemistry B. 3518 - 3525. 10. 114. 2010. 10.1021/jp9098655 . Journal of Physical Chemistry B

Cell-penetrating peptides-mechanisms of cellular uptake and generation of delivery systems

Trabulo, S.; Cardoso, A.L.; Mano, M.; de Lima, M.C.P., 2010. Pharmaceuticals. 961 - 993. 4. 3. 2010. 10.3390/ph3040961 . Pharmaceuticals

S4<inf>13</inf>-PV cell-penetrating peptide forms nanoparticle-like structures to gain entry into cells

Padari, K.; Koppel, K.; Lorents, A.; Hällbrink, M.; Mano, M.; Pedroso De Lima, M.C.; Pooga, M., 2010. Bioconjugate Chemistry. 774 - 783. 4. 21. 2010. 10.1021/bc900577e . Bioconjugate Chemistry

Processing of recombinant AAV genomes occurs in specific nuclear structures that overlap with foci of DNA-damage-response proteins

Cervelli, T.; Palacios, J.A.; Zentilin, L.; Mano, M.; Schwartz, R.A.; Weitzman, M.D.; Giacca, M., 2008. Journal of Cell Science. 349 - 357. 3. 121. 2008. 10.1242/jcs.003632 . Journal of Cell Science

S4<inf>13</inf>-PV cell penetrating peptide and cationic liposomes act synergistically to mediate intracellular delivery of plasmid DNA

Trabulo, S.; Mano, M.; Faneca, H.; Cardoso, A.L.; Duarte, S.; Henriques, A.; Paiva, A.; et al, 2008. Journal of Gene Medicine. 1210 - 1222. 11. 10. 2008. 10.1002/jgm.1247 . Journal of Gene Medicine

Interaction of S4<inf>13</inf>-PV cell penetrating peptide with model membranes: Relevance to peptide translocation across biological membranes

Mano, M.; Henriques, A.; Paiva, A.; Prieto, M.; Gavilanes, F.; Simões, S.; Pedroso de Lima, M.C., 2007. Journal of Peptide Science. 301 - 313. 5. 13. 2007. 10.1002/psc.842 . Journal of Peptide Science

Cellular uptake of S4<inf>13</inf>-PV peptide occurs upon conformational changes induced by peptide-membrane interactions

Mano, M.; Henriques, A.; Paiva, A.; Prieto, M.; Gavilanes, F.; Simões, S.; Pedroso de Lima, M.C., 2006. Biochimica et Biophysica Acta - Biomembranes. 336 - 346. 3. 1758. 2006. 10.1016/j.bbamem.2006.01.014 . Biochimica et Biophysica Acta - Biomembranes

On the mechanisms of the internalization of S4<inf>13</inf>-PV cell-penetrating peptide

Mano, M.; Teodósio, C.; Paiva, A.; Simões, S.; Pedroso De Lima, M.C., 2005. Biochemical Journal. 603 - 612. 2. 390. 2005. 10.1042/BJ20050577 . Biochemical Journal

Cationic liposomes for gene delivery

Simões, S.; Filipe, A.; Faneca, H.; Mano, M.; Penacho, N.; Düzgünes, N.; de Lima, M.P., 2005. Expert Opinion on Drug Delivery. 237 - 254. 2. 2. 2005. 10.1517/17425247.2.2.237 . Expert Opinion on Drug Delivery

Voltammetric behaviour of oligonucleotide lipoplexes adsorbed onto glassy carbon electrodes

Piedade, J.A.P.; Mano, M.; Pedroso de Lima, M.C.; Oretskaya, T.S.; Oliveira-Brett, A.M., 2004. Journal of Electroanalytical Chemistry. 25 - 34. 1-2. 564. 2004. 10.1016/j.jelechem.2003.10.008 . Journal of Electroanalytical Chemistry

Electrochemical sensing of the behaviour of oligonucleotide lipoplexes at charged interfaces

Piedade, J.A.P.; Mano, M.; Pedroso De Lima, M.C.; Oretskaya, T.S.; Oliveira-Brett, A.M., 2004. Biosensors and Bioelectronics. 975 - 984. 5. 20. 2004. 10.1016/j.bios.2004.06.014 . Biosensors and Bioelectronics

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