I obtained my first level degree in Biology (specializing in Biotechnology) in 2013 at the University of Barcelona. Then I obtained a Master degree in Neuroscience defending the thesis “Neuropsychiatric synthoms on dementias” at the European University Miguel de Cervantes, in Madrid. On 2015 I reached a Master degree in Genetics and Genomics at the University of Barcelona, defending the thesis “Identification of lncRNAs acting as competing endogenous RNAs (ceRNAs) in breast cancer cells”, an experimental work realized during a 6 month stage at the Bioindustry Park in Ivrea, Italy. In 2015 I joined the University of Torino, Dept. of Clinical and Biological Sciences in Orbassano, with a PhD fellowship (PhD School in Life and Health Sciences). I obtained my PhD on May 9 th 2019 defending the thesis “Luminal breast cancer circRNAs uncovered by a novel tool for data analysis”. The multidisciplinary background obtained from the PhD program in Complex Systems for life Sciences gave me the opportunity to study biological problems by using combined computational and experimental approaches. Currently, I have a Postdoc research fellowship in Milan, in Center for Genomic Science of IIT@SEMM, Istituto Italiano di Tecnologia.
EDUCATION
Oct 2015/May 2019: PhD - Complex System for Life Science at Università degli Studi di Torino (Torino, Italy)
Sep 2014/Sep 2015: Master in Genetics and Genomics at University of Barcelona (Barcelona, Spain)
Sep 2013/Sep 2014: Master in Neuroscience at European University Miguel de Cervantes (Madrid, Spain)
Jan 2008/Oct 2013: Degree in Biotechnology at University of Barcelona (Barcelona, Spain)
RESEARCH EXPERIENCE
Nov 2019/Present: Post-doctoral Fellowship at Center for Genomic Science of IIT@SEMM, Istituto Italiano di Tecnologia (Milano, Italy)
May2019/Oct2019: Post-doctoral Fellowship at Department of Clinical and Biological Sciences, Universitá degli studi di Torino (Torino, Italy)
Although dysregulation of m6A methylation has been reported in many human cancers, its role in cancer drug resistance is still unclear. Recent studies have enlightened the importance of the epitranscriptome on Hepatocellular carcinoma (HCC) and various m6A effectors seem to be involved in HCC progression development. Furthermore, in a recent study, some of these m6A effectors have been associated with drug resistance or sensitivity.
We hypnotize that we may revert cell resistance to the drugs by altering the fate of modified RNAs through perturbation of specific m6A effectors. We want to investigate whether m6A-dependent alterations of the RNA metabolism are central in the drug resistance. And, since some of these drugs interfere with the action of RNA Polymerase II (RNAPII) we want to unravel the role of the interplay between RNAPII and m6A epitranscriptome.
This research has the potential to reveal an unexpected role for the modifications of RNA in the context of HCC drug resistance. Moreover, the data generated by cutting edge genomics approaches will allow to closely test the involvement of specific molecular mechanisms, through which epitranscriptional alterations results in HCC aberrant transcriptional programs.
The epitranscriptome is emerging as a novel possible druggable target in cancer. However, we still have a limited knowledge on the functional role of this layer of regulation. Our results are expected to reveal previously unanticipated functional consequences of epitranscriptional alterations, which could disclose novel therapeutic targets and mechanisms for HCC diagnosis and treatment.
Characterization of the interplay between RNAPII and m6A
A few recent studies have suggested that the establishment of m6A patterns occurs in the early phases of transcription and could be coupled with the transcriptional machinery. RNAPII is a key factor in genes’ transcription and a complex regulatory hub that could profoundly affect and be affected by the m6A epitranscriptome. We have an in house tool able to de-convolute the different RNAPII life cycle steps by computational modelling. We will quantify epitranscriptional dynamics and profile the binding of the RNAPII complex by ChIP-seq using different drugs that cause an acute perturbation of the RNAPII life cycle. The analysis of the effects of these drugs over time in the context of mESCs with METTL3 KD will allow us interfering with crucial phases of the RNAPII life cycle, and will stress the system to reveal how the phases are effected by the lack of m6A.
1) Docker4Circ: A Framework for the Reproducible Characterization of circRNAs from RNA-Seq Data.
Ferrero G, Licheri N, Coscujuela Tarrero L, De Intinis C, Miano V, Calogero RA, Cordero F, De Bortoli M, Beccuti M
INT J MOL SCI 2019 Dec; 21: | PMID: 31906249
2) The expression of LINE1-MET chimeric transcript identifies a subgroup of aggressive breast cancers.
Miglio U, Berrino E, Panero M, Ferrero G, Coscujuela Tarrero L, Miano V, Dell'Aglio C, Sarotto I, Annaratone L, Marchiò C, Comoglio PM, De Bortoli M, Pasini B, Venesio T, Sapino A
INT J CANCER 2018 12; 143: 2838-2848 | PMID: 30144023
3) Luminal breast cancer-specific circular RNAs uncovered by a novel tool for data analysis.
Coscujuela Tarrero L, Ferrero G, Miano V, De Intinis C, Ricci L, Arigoni M, Riccardo F, Annaratone L, Castellano I, Calogero RA, Beccuti M, Cordero F, De Bortoli M
ONCOTARGET 2018 03; 9: 14580-14596 | PMID: 29581865
4) The new world of RNA biomarkers and explorers' prudence rules.
De Bortoli M, Miano V, Coscujuela Tarrero L
INT J BIOL MARKER 2018 08; 33: 239-243 | PMID: 29683070
5) A Novel Functional Domain of Tab2 Involved in the Interaction with Estrogen Receptor Alpha in Breast Cancer Cells.
Reineri S, Agati S, Miano V, Sani M, Berchialla P, Ricci L, Iannello A, Coscujuela Tarrero L, Cutrupi S, De Bortoli M
PLOS ONE 2016; 11: e0168639 | PMID: 27992601
L’Istituto Italiano di Tecnologia (IIT) è una fondazione di diritto privato - cfr. determinazione Corte dei Conti 23/2015 “IIT è una fondazione da inquadrare fra gli organismi di diritto pubblico con la scelta di un modello di organizzazione di diritto privato per rispondere all’esigenza di assicurare procedure più snelle nella selezione non solo nell’ambito nazionale dei collaboratori, scienziati e ricercatori ”.
IIT è sotto la vigilanza del Ministero dell'Istruzione, dell'Università e della Ricerca e del Ministero dell'Economia e delle Finanze ed è stato istituito con la Legge 326/2003. La Fondazione ha l'obiettivo di promuovere l'eccellenza nella ricerca di base e in quella applicata e di favorire lo sviluppo del sistema economico nazionale. La costruzione dei laboratori iniziata nel 2006 si è conclusa nel 2009.
Lo staff complessivo di IIT conta circa 1440 persone. L’area scientifica è rappresentata da circa l’85% del personale. Il 45% dei ricercatori proviene dall’estero: di questi, il 29% è costituito da stranieri provenienti da oltre 50 Paesi e il 16% da italiani rientrati. Oggi il personale scientifico è composto da circa 60 principal investigators, circa 110 ricercatori e tecnologi di staff, circa 350 post doc, circa 500 studenti di dottorato e borsisti, circa 130 tecnici. Oltre 330 posti su 1400 creati su fondi esterni. Età media 34 anni. 41% donne / 59 % uomini.
Nel 2015 IIT ha ricevuto finanziamenti pubblici per circa 96 milioni di euro (80% del budget), conseguendo fondi esterni per 22 milioni di euro (20% budget) provenienti da 18 progetti europei, 17 finanziamenti da istituzioni nazionali e internazionali, circa 60 progetti industriali
La produzione di IIT ad oggi vanta circa 6990 pubblicazioni, oltre 130 finanziamenti Europei e 11 ERC, più di 350 domande di brevetto attive, oltre 12 start up costituite e altrettante in fase di lancio. Dal 2009 l’attività scientifica è stata ulteriormente rafforzata con la creazione di dieci centri di ricerca nel territorio nazionale (a Torino, Milano, Trento, Parma, Roma, Pisa, Napoli, Lecce, Ferrara) e internazionale (MIT ed Harvard negli USA) che, unitamente al Laboratorio Centrale di Genova, sviluppano i programmi di ricerca del piano scientifico 2015-2017.
Istituto Italiano di Tecnologia (IIT) is a public research institute that adopts the organizational model of a private law foundation. IIT is overseen by Ministero dell'Istruzione, dell'Università e della Ricerca and Ministero dell'Economia e delle Finanze (the Italian Ministries of Education, Economy and Finance). The Institute was set up according to Italian law 326/2003 with the objective of promoting excellence in basic and applied research andfostering Italy’s economic development. Construction of the Laboratories started in 2006 and finished in 2009.
IIT has an overall staff of about 1,440 people. The scientific staff covers about 85% of the total. Out of 45% of researchers coming from abroad 29% are foreigners coming from more than 50 countries and 16% are returned Italians. The scientific staff currently consists of approximately 60 Principal Investigators, 110 researchers and technologists, 350 post-docs and 500 PhD students and grant holders and 130 technicians. External funding has allowed the creation of more than 330 positions . The average age is 34 and the gender balance proportion is 41% female against 59% male.
In 2015 IIT received 96 million euros in public funding (accounting for 80% of its budget) and obtained 22 million euros in external funding (accounting for 20% of its budget). External funding comes from 18 European Projects, other 17 national and international competitive projects and approximately 60 industrial projects.
So far IIT accounts for: about 6990 publications, more than 130 European grants and 11 ERC grants, more than 350 patents or patent applications, 12 up start-ups and as many which are about to be launched. The Institute’s scientific activity has been further strengthened since 2009 with the establishment of 11 research nodes throughout Italy (Torino, Milano, Trento, Parma, Roma, Pisa, Napoli, Lecce, Ferrara) and abroad (MIT and Harvard University, USA), which, along with the Genoa-based Central Lab, implement the research programs included in the 2015-2017 Strategic Plan.
