Functional Genomics and RNA-Based Therapeutics

Miguel Mano

PhD, Group Leader

The recently created ‘Functional Genomics and RNA-based Therapeutics’ laboratory is focused on applying large-scale functional genomics approaches, in particular image-based high-throughput screening and deep-sequencing technologies, to the identification and molecular characterization of novel cellular factors relevant to cardiovascular diseases, particularly relevant in the ageing population, with the ultimate goal of translating this knowledge into effective RNA-based therapeutic strategies.

The systematic nature of the experimental approaches applied rely on functional readouts and are completely unbiased and therefore are likely to lead to the identification of previously unknown or unexpected molecular players and pathways. The knowledge that results from these approaches constitutes a significant advancement of the state-of-the-art and has the potential to reveal novel opportunities for therapeutic intervention against different forms of diseases, based on the modulation of miRNAs and/or of their targets.

The ‘Functional Genomics and RNA-based Therapeutics’ laboratory, hosts a high-end, fully automated high-throughput screening platform. This platform is the only in Portugal equipped with the state-of-the-art instrumentation, and genome-wide siRNA/miRNA libraries required to perform this type of screenings. The screening platform can accommodate screenings focused on different biological questions and constitutes a unique and valuable resource, which is rendered available to researchers within the CIBB ecosystem as well as to extra-mural investigators, fostering scientific collaborations.

Group Members

Group Members

Group members are: Miguel Mano (PhD, Group Leader), Ana Sofia Varanda (PhD), Mariana Bexiga (PhD), Ricardo Silva, Flávia Rodrigues.

Selected Publications

Aguilar, C., Cruz, A. R., Rodrigues Lopes, I., Maudet, C., Sunkavalli, U., Silva, R. J., ... Eulalio, A. (2020). Functional screenings reveal different requirements for host microRNAs in Salmonella and Shigella infection. Nat Microbiol, 5(1), 192-205. doi:10.1038/s41564-019-0614-3.

Torrini, C., Cubero, R. J., Dirkx, E., Braga, L., Ali, H., Prosdocimo, G., ... Giacca, M. (2019). Common Regulatory Pathways Mediate Activity of MicroRNAs Inducing Cardiomyocyte Proliferation. Cell Rep, 27(9), 2759-2771 e2755. doi:10.1016/j.celrep.2019.05.005.

Ali, H., Mano, M., Braga, L., Naseem, A., Marini, B., Vu, D. M., ... Giacca, M. (2019). Cellular TRIM33 restrains HIV-1 infection by targeting viral integrase for proteasomal degradation. Nat Commun, 10(1), 926. doi:10.1038/s41467-019-08810-0.

Bertolio, R., Napoletano, F., Mano, M., Maurer-Stroh, S., Fantuz, M., Zannini, A., ... Del Sal, G. (2019). Sterol regulatory element binding protein 1 couples mechanical cues and lipid metabolism. Nat Commun, 10(1), 1326. doi:10.1038/s41467-019-09152-7.

Tawk, C., Nigro, G., Rodrigues Lopes, I., Aguilar, C., Lisowski, C., Mano, M., ... Eulalio, A. (2018). Stress-induced host membrane remodeling protects from infection by non-motile bacterial pathogens. EMBO J, 37(23). doi:10.15252/embj.201798529.

Ingallina, E., Sorrentino, G., Bertolio, R., Lisek, K., Zannini, A., Azzolin, L., ... Del Sal, G. (2018). Mechanical cues control mutant p53 stability through a mevalonate-RhoA axis. Nat Cell Biol, 20(1), 28-35. doi:10.1038/s41556-017-0009-8.

Sorrentino, G., Ruggeri, N., Zannini, A., Ingallina, E., Bertolio, R., Marotta, C., ... Del Sal, G. (2017). Glucocorticoid receptor signalling activates YAP in breast cancer. Nat Commun, 8, 14073. doi:10.1038/ncomms14073.

Cunningham, T. J., Yu, M. S., McKeithan, W. L., Spiering, S., Carrette, F., Huang, C. T., ... Colas, A. R. (2017). Id genes are essential for early heart formation. Genes Dev, 31(13), 1325-1338. doi:10.1101/gad.300400.117.

Eulalio, A., & Mano, M. (2015). MicroRNA Screening and the Quest for Biologically Relevant Targets. J Biomol Screen, 20(8), 1003-1017. doi:10.1177/1087057115578837.

Mano, M., Ippodrino, R., Zentilin, L., Zacchigna, S., & Giacca, M. (2015). Genome-wide RNAi screening identifies host restriction factors critical for in vivo AAV transduction. Proc Natl Acad Sci U S A, 112(36), 11276-11281. doi:10.1073/pnas.1503607112.

Selected Projects

Dissection of the role of microRNAs in cardiac fibrosis through functional genomics. FCT - Fundação para a Ciência e Tecnologia (2018-2021). PI: Miguel Mano.

Functional high-throughput analysis of the role of microRNAs in cardiac ischemia-reperfusion injury. European Commission (2016-2020). PI: Miguel Mano.

StaphIN, Intracellular Staphylococcus aureus: deciphering bacterial and cellular factors involved in host cell invasion by clinically relevant strains to define new therapeutic approaches’, ERA-NET Infect-ERA Consortium. PI: Miguel Mano.

CampyRNA, Combining high-throughput and single-cell analyses to study RNA regulators important for the early steps of Campylobacter infection’, ERA-NET Infect-ERA Consortium. PI: Miguel Mano.

Identification and functional characterization of microRNAs controlling cardiac ischemia-reperfusion injury. PTDC/BIM-MEC/2968/2014, FCT, Portugal. PI: Miguel Mano.

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