{"id":1188,"date":"2025-01-25T20:28:18","date_gmt":"2025-01-25T20:28:18","guid":{"rendered":"https:\/\/staging.irccs.com\/?post_type=laboratory&p=1188"},"modified":"2025-11-11T16:52:29","modified_gmt":"2025-11-11T16:52:29","slug":"translational-transcriptomics","status":"publish","type":"laboratory","link":"https:\/\/irccs.com\/it\/laboratori\/translational-transcriptomics\/","title":{"rendered":"RNA TRANSLATIONAL RESEARCH"},"content":{"rendered":"\n

<\/span>Research Topic<\/h2>\n\n\n\n

Our lab investigates how RNAs contribute to cancer and how they can be transformed into therapeutic targets. We study both coding RNAs, which produce proteins, and noncoding RNAs, which regulate essential cellular processes. By resolving RNA functions at the level of isoforms and internal domains, we uncover hidden vulnerabilities that sustain tumor growth. Building on these insights, we are developing next-generation RNA therapies, including antisense oligonucleotides and small molecules that target RNA, to deliver more precise treatments for patients.<\/p>\n\n\n\n

<\/span>Background<\/h2>\n\n\n\n

Cancer therapies have traditionally targeted DNA with chemotherapy and proteins with small molecules or antibodies. In contrast, RNA has remained an underexplored layer of biology and medicine. Yet RNAs, whether coding or noncoding, are not only intermediates between genes and proteins but also active regulators of cellular processes. They control gene expression, protein homeostasis, and stress responses, and many are directly implicated in cancer development and progression. Recognizing RNA as both a driver of disease and a therapeutic opportunity is reshaping our understanding of cancer biology and opening new paths for precision medicine.<\/p>\n\n\n\n

<\/span>Research achievements<\/h2>\n\n\n\n

We have contributed to defining the roles of RNA in cancer and advancing RNA-based therapeutic strategies. In multiple myeloma, an aggressive blood cancer, we showed that microRNAs can function as either tumor promoters or suppressors. Building on these insights, we pioneered pri-miRNA therapeutics, culminating in the first-in-primate study of a multi-miRNA inhibitor. We then extended our work to long noncoding RNAs (lncRNAs), identifying hundreds that are essential for tumor growth and showing that different versions of the same RNA (isoforms) can have distinct roles in cancer. Using the IsoScan platform, we mapped these dependencies at isoform resolution, providing a framework to pinpoint the RNA variants that truly sustain cancer. These discoveries are now guiding the development of therapeutic inhibitors of oncogenic lncRNAs, including antisense oligonucleotides that block disease-driving domains and first-generation small molecules designed to target RNA.<\/p>\n\n\n\n

<\/span>Conclusions and Perspectives<\/h2>\n\n\n\n

Our research has established RNA as a central player in cancer biology and has identified it as a promising therapeutic class. By advancing technologies such as IsoScan and pioneering inhibitors of oncogenic lncRNAs, we have laid the groundwork for next-generation RNA therapies. Moving forward, we aim to expand these efforts to broader classes of coding and noncoding RNAs, decode their structural and functional logic, and translate this knowledge into precision interventions. In parallel, we remain committed to training the next generation of cancer researchers and fostering collaborations across disciplines to accelerate the path from discovery to patient benefit.<\/p>\n\n\n\n

<\/span>Publications<\/h2>\n\n\n\n

At this link<\/a><\/strong>, you can find all the scientific publications of the Principal Investigator.<\/p>\n\n\n\t

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Selected publications<\/h2>\n\t\t\t\t
\n\t\t\t\t\t\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t\t\t\t\t\t\tCRISPR-Cas13d functional transcriptomics reveals widespread isoform-selective cancer dependencies on lncRNAs. <\/a>\n\t\t\t\t\t\t\t\t\t\t\t\t

1.\tMorelli E*, Aktas-Samur A*, Maisano D*, Gao C, Favasuli V, Papaioannou D, De Nola G, Henninger JE, Liu N, Turi M, Folino P, Vreux L, Cumerlato M, Chen L, Aifantis I, Fulciniti M, Anderson KC, Lytton-Jean AKR, Gull\u00e0 A, Young RA, Samur MK, Munshi NC. <\/p>\n\t\t\t\t\t<\/div>\n\t\t\t\t\t\t\t\t\t

\n\t\t\t\t\t\t\t\t\t\t\t\t\tTargeting Acetyl-CoA Carboxylase Suppresses De Novo Lipogenesis and Tumor Cell Growth in Multiple Myeloma. <\/a>\n\t\t\t\t\t\t\t\t\t\t\t\t

2.\tMorelli E*, Ribeiro CF*, Rodrigues SD*, Gao C, Socciarelli F, Maisano D, Favasuli V, Liu N, Todoerti K, Chakraborty C, Yao Y, Fulciniti M, Samur M, Aktas-Samur A, Amodio N, Turi M, Barello F, Penailillo J, Giallongo C, Romano A, Gulla A, Anderson KC, Inghirami G, Munshi NC, Loda M. <\/p>\n\t\t\t\t\t<\/div>\n\t\t\t\t\t\t\t\t\t

\n\t\t\t\t\t\t\t\t\t\t\t\t\tA MIR17HG-derived long noncoding RNA provides an essential chromatin scaffold for protein interaction and myeloma growth. <\/a>\n\t\t\t\t\t\t\t\t\t\t\t\t

Morelli E, Fulciniti M, Samur MK, Ribeiro CF, Wert-Lamas L, Henninger JE, et al. Blood. 2023 Jan 26;141(4):391-405. doi: 10.1182\/blood.2022016892. PMID: 36126301.\r\n<\/p>\n\t\t\t\t\t<\/div>\n\t\t\t\t\t\t\t\t\t

\n\t\t\t\t\t\t\t\t\t\t\t\t\tTherapeutic vulnerability of multiple myeloma to MIR17PTi, a first-in-class inhibitor of pri-miR-17-92. <\/a>\n\t\t\t\t\t\t\t\t\t\t\t\t

Morelli E, Biamonte L, Federico C, Amodio N, Di Martino MT, Gallo Cantafio ME, et al. Blood. 2018 Sep 6;132(10):1050-1063. doi: 10.1182\/blood-2018-03-836601. PMID: 29997223. \r\n<\/p>\n\t\t\t\t\t<\/div>\n\t\t\t\t\t\t\t\t\t

\n\t\t\t\t\t\t\t\t\t\t\t\t\tSelective targeting of IRF4 by synthetic microRNA-125b-5p mimics induces anti-multiple myeloma activity in vitro and in vivo. <\/a>\n\t\t\t\t\t\t\t\t\t\t\t\t

Morelli E, Leone E, Cantafio ME, Di Martino MT, Amodio N, Biamonte L, et al. Leukemia. 2015 Nov;29(11):2173-83. doi: 10.1038\/leu.2015.124. PMID: 25987254. 21.\t\r\n<\/p>\n\t\t\t\t\t<\/div>\n\t\t\t\t\t\t\t\t\t<\/div>\n\t<\/div>\n<\/div>\n\n\t<\/div>\n","protected":false},"featured_media":0,"template":"","meta":{"_acf_changed":true,"footnotes":""},"class_list":["post-1188","laboratory","type-laboratory","status-publish","hentry"],"acf":[],"yoast_head":"\nRNA TRANSLATIONAL RESEARCH - Istituto di Candiolo<\/title>\n<meta name=\"description\" content=\"Research Topic Our lab investigates how RNAs contribute to cancer and how they can be transformed into therapeutic targets. 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