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.

Keywords

Functional genomics

Cardiovascular diseases

High-throughput/high-content screening

microRNAs

Research Lines 

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

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

Miguel Mano PhD, Group Leader

Mariana Bexiga PhD, Assist. Researcher

Ana Sofia Varanda PhD, Junior Research

Ricardo Silva PhD Student

Flávia Rodrigues Assoc. Research

Highly motivated candidates (undergraduates, prospective PhD students and Postdocs) interested in joining the Functional Genomics and RNA-based Therapeutics laboratory are encouraged to contact the PI directly.

Ongoing Research Projects 

Dissection of the role of microRNAs in cardiac fibrosis through functional genomics

Stimulating CRISPR-mediated homology-directed DNA repair for precise genome editing in cardiovascular diseases

Publicitação
 

External Collaborations 

Mauro Giacca, King’s College London (London, United Kingdom)
Edécio Cunha Neto, Heart Institute, University of São Paulo (São Paulo, Brazil)
Giannino Del Sal, National Laboratory CIB (Trieste, Italy)

Funding Agencies 

• FCT 
• ERA-NET Infect-ERA Consortium

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