MARIANGELA MORLANDO

Mariangela Morlando CV

Address:
Department of Biology and Biotechnologies, Sapienza University of Rome
P.le Aldo Moro 5
00185 Rome
Phone: +39 0649912341
e-mail: mariangela.morlando@uniroma.it

Education:
2004: PhD in Biology, Roma Tre University of Rome
2000: Degree (MD) with honors in Biology, Sapienza University of Rome

Academic career and research experience
March 2024 to date: Associate Professor of Molecular Biology, Department of Biology and Biotechnologies, Sapienza University of Rome
2018 to February 2024: Associate Professor of Molecular Biology, Department of Pharmaceutical Sciences, Perugia University, Italy
2008-2018 Research fellow as EP3, Department of Biology and Biotechnologies Sapienza University of Rome
2006-2008 Post-doctoral fellow, EMBO long-term, Sir Wiliam Dunn School of Pathology, Oxford University
2004-2006 Post-doctoral fellow, Department of Gentics and Molecular Biology , Sapienza University of Rome

Academic appointments:
2020 to date Member of PhD Committee in Pharmaceutical Sciences, Perugia University
2019-2024 date Member of the Committee of Scuola di Specializzazione in Farmacia Ospedaliera, Perugia University
2018 to 2024 Member of the Commitee of Scuola di Specializzazione in Malattie Infettive e Tropicali, Perugia University
2018-2019 External member of PhD Committee in Genetica e Biologia Molecolare, Sapienza University of Rome
2013-2019 Junior Research Fellow for the Scuola Superiore di Studi Avanzati Sapienza (SSAS), Sapienza University of Rome

Appointments external to the University
2020-2023 Annual Appointments as external collaborator of Istituto Italiano di Tecnologie, Genova, Italy.
2015 Appointment as external collaborator of Fondazione Telethon, Rome, Italy.

Fellowships, honours and awards
2010 - Selected as Young Italian Talent by the “Agenzia Nazionale per i Giovani”
2009 - “SIROCCO 2009 Annual Meeting” award for the Best Poster.
2007 - Medal from the Italian President Giorgio Napolitano, for the research activity carried out at the Oxford University (UK)
2006 - “EMBO Long Term” fellowship
2005 - “SIBBM” (Italian Society of Biophysic and Molecular Biology) award for best 2004 publication in the Biophysic or Molecular Biology fields.
2004 - “Giorgio Battistuzzi” Molecular Biology Award for MS degree, “Federico II” University of Naples.

National and international grants:
2025 – Partecipant: Fondo Ricerca Ateneo 2024, Sapienza University of Rome, grant n. RG12419107CD28D5, Role of the mechanotransduction network in the crosstalk between BMSCs and AML cells, 1 year.
2022 - Partecipant: Fondo Ricerca Ateneo 2022 Perugia University, Development of a nose-to-brain delivery system to target nuclear receptor-mediated mechanisms of neuroprotection in non-communicable and rare brain diseases (IN2-Brain), 1 year.
2021 - Partecipant: Fondo Ricerca Ateneo 2021 Perugia University, REGolazionE dell’Inflamm-Aging: costruzione di una piattaforma multidisciplinare per la decodifica della rete di interazione delle vescicole extracellulari – REGENIA, 1 year.
2019 - External collaborator of AIRC grant call 2019: grant number: 23053 “Circular RNAs: novel players and biomarkers in tumorigenesis”, 5 years.
2019 - External collaborator of ERC Synergy GRANT 2019: Assembly and phase transitions of ribonucleoprotein aggregates in neurons: from physiology to pathology, 6 years.
2017 - PI of pilot grant ARISLA 2017 “circRNALS, Circular RNAs characterization in human motor neurons carrying ALS -linked FUS mutations”, 1 year.
2016 - External collaborator Marie Sklodowska-Curie Inovative Training Networks 2016 (Horizon 2020), cicRtrain Circular RNA Bology Training Network: from biogenesis to biomarkers, 3 years.

Seminars and Lectures as Invited Speaker
2025 - “Non-Coding RNA Biology: New Roles and Diversity” Keystone Symposia, Keystone-Colorado (USA) January 27-30, “Functional Insights into circDlc1(2): A Key Regulator of microRNA Localization and Synaptic Translation in Neurons”.
2024 - “Il metabolismo dell’RNA nelle malattie neurologiche - IV edizione”14 June 2024, Fondazione Mondino, Pavia. “Funzioni fisiologiche e patologiche degli RNA circolari nel sistema Nervoso".
- “RNA Collaborative - RNA initiative at the Italian Institute of Technology” 19 June 2024, Web seminar, “A Novel Role of Non-Coding RNAs as Crucial Tethering Molecules in Regulating Gene Expression”
2023 - “EMBL in Italy 2023: Chance and necessity-the indispensable role of curiosity-driven life sciences” May 18-19 Turin, Italy. “Unveling the puzzling function of CircRNAs in ALS”.
2022 - “Amyotrophic lateral sclerosis – from mechanisms to novel therapeutics” October 27-28, Florence, Italy. “FUS mutant motor neurons display defects in CircRNA biogenesis and function”
- “Sistemi Modello Come Strumento Di Analisi Genetica” meeting organised by AGI (Italian Organization of Genetics), May 30-31, 2022 Cortona, Italy. “Cellular and animal models for fucntional studies of non coding RNAs”
2019 - Meeting AriSLA 2019, Milan, November 22-23. “Circular RNAs characterization in human motor neurons carrying ALS- linked FUS mutations”,
-“Small RNA players in Amyotrophic lateral sclerosis”, IRCCS Fondazione Mondino (Pavia), June 27-28. “Interplay between RNA binding proteins and non-coding RNAs"
2018 -Lecture for PhD school in Biology, “Federico II” University of Naples, November27. "Developing cellular model systems for the study of neurodegenerative disorders"
-"Il metabolismo dell’RNA nelle malattie neurologiche" IRCCS Fondazione Mondino (Pavia), July 6. " Gli RNA circolari: nuovi attori nello sviluppo neuronale e nelle patologie",
-Lecture for PhD school "Sistemi Complessi per le Scienze della Vita", Turin March 2. “Role of lncRNA and circRNA in muscle cell differentiation”.
2017 -VII meeting Stem Cell Research Italy, Chieti, May 25-27. “Non-coding DNA and cell differentiation”.
2013 - RNA DAY congress, Rome, September 11-13. “Biogenesis and function of long non coding RNA in muscle differentiation”,
-Symposium of training@VIB, Leuven, Belgium, April 29. “New roles for the non-coding transcriptome during muscle differentiation”
2012 -“Non-coding RNAs” Workshop, Centre Löwenberg, Muntelier, Switzerland, December 3-5. “Role of non-coding RNA in muscle differentiation and disease”
2008 - Lecture for the School of Genetics, AGI (Italian Organization of Genetics) Cortona (AR), October 30-3. “microRNA biogenesis and genomic organization”

She attended more than 30 national and international meetings and courses and in 13 of them she has been selected for oral presentation.

Publications and Patents
1. Felicetti T., Di Iacovo N., Della Fazia M.A., Piobbico D., Pieroni S., Pacetti M., Yu J., Sun Y., Massari S., Barreca M.L., Sabatini S.,Tabarrini O., Cecchetti V, Wang F, Pommier Y., Morlando M.,* Servillo G.,* Manfroni G.,* (2024) New anti-ovarian cancer quinolone derivatives acting by modulating microRNA processing machinery. (*corresponding authors) RSC Medicinal Chemistry in press
2. Silenzi V., D'Ambra E., Santini T., D'Uva S., Setti A., Salvi N., Nicoletti C., Scarfò R., Cordella F., Mongiardi B., Cavezza D., Liessi N., Ferrucci L., Ragozzino D., Armirotti A., Di Angelantonio S., De Leonibus E., Bozzoni I., Morlando M. (2024) A tripartite circRNA/mRNA/miRNA interaction regulates glutamatergic signaling in the mouse brain. Cell Rep. 43:114766.
3. Colantoni A., Capauto D., Alfano V., D’Ambra E., D’Uva S., Tartaglia G.G., Morlando M. (2023) FUS Alters circRNA Metabolism in Human Motor Neurons Carrying the ALS-Linked P525L Mutation. Int. J. Mol. Sci. 24:3181
4. Astolfi A., Milano F., Palazzotti D., Brea J., Pismataro M.C., Morlando M., Tabarrini O., Loza M.I., Massari S., Martelli M.P., Barreca M.L. (2022) From Serendipity to Rational Identification of the 5,6,7,8-Tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4(3H)-one Core as a New Chemotype of AKT1 Inhibitors for Acute Myeloid Leukemia. Pharmaceutics. 14:2295.
5. Nielsen A.F., Bindereif A., Bozzoni I., Hanan M., Hansen T.B., Irimia M., Kadener S., Kristensen L.S., Legnini I., Morlando M., Jarlstad Olesen M.T., Pasterkamp R.J., Preibisch S., Rajewsky N., Suenkel C., Kjems J. (2022) Best practice standards for circRNA research. Nature Methods 19:1208-1220
6. D'Ambra E., Santini T., Vitiello E., D'Uva S., Silenzi V., Morlando M.*, Bozzoni, I.* (2021) Circ-Hdgfrp3 shuttles along neurites and is trapped in aggregates formed by ALS-associated mutant FUS. (*corresponding authors). iScience, 24:103504
7. Garone M.G., Birsa N., Rosito M., Salaris F., Mochi M., de Turris V., Nair R.R., Cunningham T.J., Fisher E.M.C., Morlando M., Fratta P., Rosa A. (2021) ALS-related FUS mutations alter axon growth in motoneurons and affect HuD/ELAVL4 and FMRP activity. Commun Biol. 4:1025.
8. D'Ambra E. and Morlando M. (2021) Study of Circular RNA Expression by Nonradioactive Northern Blot Procedure. Methods Mol Biol. 2348:371-383.
9. Dobrowolny G., Martone J., Lepore E., Casola I., Petrucci A., Inghilleri M., Morlando M., Colantoni A., Scicchitano B.M., Calvo A., Bisogni G., Chiò A., Sabatelli M., Bozzoni I., Musarò A. (2021) A longitudinal study defined circulating microRNAs as reliable biomarkers for disease prognosis and progression in ALS human patients. Cell Death Discov. 7:4.
10. Reinoso-Sánchez J.F., Baroli G., Duranti G., Scaricamazza S., Sabatini S., Valle S., Morlando M., Casero R.A. Jr., Bozzoni I., Mariottini P., Ceci R., Cervelli M. (2020) Emerging Role for Linear and Circular Spermine Oxidase RNAs in Skeletal Muscle Physiopathology. Int. J. Mol. Sci. 21:8227.
11. Martone J., Mariani D., Santini T., Setti A., Shamloo S., Colantoni A., Capparelli F., Paiardini A., Dimartino D., Morlando M., Bozzoni I. (2020) SMaRT lncRNA controls translation of a G-quadruplex-containing mRNA antagonizing the DHX36 helicase. EMBO Rep. 21:e49942.
12. Di Timoteo G., Dattilo D., Centrón-Broco A., Colantoni A., Guarnacci M., Rossi F., Incarnato D., Oliviero S., Fatica A., Morlando M., Bozzoni I. (2020) Modulation of circRNA Metabolism by m6A Modification. Cell Rep. 31:107641.
13. Salvatori B., Biscarini S., Morlando M. (2020) Non-coding RNAs in Nervous System Development and Disease. Front Cell Dev Biol. 8:273.
14. D'Ambra E., Capauto D., Morlando M. (2019) Exploring the Regulatory Role of Circular RNAs in Neurodegenerative Disorders. Int J Mol Sci. 20:E5477.
15. Ajmone-Cat M.A., Onori A., Toselli C., Stronati E., Morlando M., Bozzoni I., Monni E., Kokaia Z., Lupo G., Minghetti L., Biagioni S., Cacci E. (2019) Increased FUS levels in astrocytes leads to astrocyte and microglia activation and neuronal death. Sci Rep. 9:4572.
16. Rossi F., Legnini I., Megiorni F., Colantoni A., Santini T., Morlando M., Di Timoteo G., Dattilo D., Dominici C., Bozzoni I. (2019) Circ-ZNF609 regulates G1-S progression in rhabdomyosarcoma. Oncogene 38:3843–3854.
17. Ballarino M., Cipriano A., Tita R., Santini T., Desideri F., Morlando M., Colantoni A., Carrieri C., Nicoletti C., Musarò A., Carroll DO. Bozzoni I. (2018) Deficiency in the nuclear long noncoding RNA Charme causes myogenic defects and heart remodeling in mice. EMBO J. 37:e99697.
18. Dimartino D., Colantoni A., Ballarino M., Martone J., Mariani D, Danner J., Bruckmann A., Meister G., Morlando M.* and Bozzoni I.* (2018) The long non coding RNA lnc-31 interacts with Rock1 mRNA and mediates its YB-1-dependent translation. (*corresponding authors) Cell Reports 23: 733-740.
19. Morlando M. and Fatica A. (2018) Alteration of Epigenetic Regulation by Long Noncoding RNAs in Cancer. Int J Mol Sci. 19: E570
20. Capauto D., Colantoni A., Lu L, Santini T, Peruzzi G, Biscarini S, Morlando M, Shneider NA, Caffarelli E, Laneve P, Bozzoni I. (2018) A Regulatory Circuitry Between Gria2, miR-409, and miR-495 Is Affected by ALS FUS Mutation in ESC-Derived Motor Neurons. Mol Neurobiol. 55: 7635-765.
21. Legnini I., Di Timoteo G., Rossi F., Morlando M., Briganti F., Sthandier O., Fatica A., Santini T., Andronache A., Wade M., Laneve P., Rajewsky N., Bozzoni I. (2017) Circ-ZNF609 Is a Circular RNA that Can Be Translated and Functions in Myogenesis. Mol Cell. 66: 22-37.
22. Errichelli L., Dini Modigliani S., Laneve P., Colantoni A., Legnini I., Capauto D., Rosa A., De Santis R., Scarfò R., Peruzzi G., Lei L., Caffarelli E., Shneider N.A., Morlando M.*, Bozzoni I.* (2017) FUS affects circular RNA expression in murine embryonic stem cell-derived motor neurons (*corresponding authors) Nature Communications 8:14741.
23. Ballarino M., Morlando M., Fatica A., Bozzoni I. (2016) Non-coding RNAs in muscle differentiation and musculoskeletal disease J Clin Invest. 126: 2021-2030.
24. Martone J., Briganti F., Legnini I., Morlando M., Picillo E., Sthandier O., Politano L. and Bozzoni I. (2016) The lack of the Celf2a splicing factor converts a Duchenne genotype into a Becker phenotype Nature Communications 7:10488.
25. Hughes J.M., Legnini I., Salvatori B., Masciarelli S., Marchioni M., Fazi F., Morlando M., Bozzoni I. and Fatica A. (2015) C/EBPα-p30 protein induces expression of the oncogenic long non-coding RNA UCA1 in acute myeloid leukemia Oncotarget 6:18534-18544.
26. Lenzi J., De Santis R., de Turris V., Morlando M., Laneve P., Calvo A., Caliendo V., Chio A., Rosa A. and Bozzoni I. (2015) ALS mutant FUS proteins are recruited into stress granules in induced pluripotent stem cell-derived motoneurons. Disease Models & Mechanisms 8:755-766.
27. Morlando M., Ballarino M and Fatica A. (2015) Long Non-Coding RNAs: New Players in Hematopoiesis and Leukemia. Front Med 2: 23
28. Ballarino M., Cazzella V. , D'Andrea D., Grassi L., Bisceglie L., Cipriano A., Santini T., Pinnarò C., Morlando M., Tramontano A and Bozzoni I. (2015) Novel long noncoding RNAs (lncRNAs) in myogenesis: a miR-31 overlapping lncRNA transcript controls myoblast differentiation. Mol Cell Biol. 35: 728-736.
29. Dini Modgliani S.*, Morlando M. *+, Errichelli L., Sabatelli M. and Bozzoni I. + (2014) An ALS-associated mutation in the FUS 3’-UTR disrupts a microRNA–FUS regulatory circuitry. Nature Communications 5:4335 (* this authors contributed equally; + corresponding authors). IF 11.470
30. Morlando M., Ballarino M., Fatica A. and Bozzoni I. (2014) The Role of Long Noncoding RNAs in the Epigenetic Control of Gene Expression. ChemMedChem. 9: 505-510.
31. Legnini I.*, Morlando M.*, Mangiavacchi A., Fatica A. and Bozzoni I. (2014) A Feedforward Regulatory Loop between HuR and the Long Noncoding RNA linc-MD1 Controls Early Phases of Myogenesis. (* this authors contributed equally) Mol Cell. 53: 506-514.
32. Di Carlo V., Grossi E., Laneve P., Morlando M., Dini Modigliani S., Ballarino M., Bozzoni I. and Caffarelli E. (2013) TDP-43 regulates the microprocessor complex activity during in vitro neuronal differentiation. Mol Neurobiol 48: 952-963.
33. Morlando M., Rosa, A., Caffarelli, E., Fatica, A. and Bozzoni, I. (2013) ”Non coding RNA in muscle differentiation ans disease” MicroRNA Journal, 2: 91-101
34. Twayana S., Legnini I., Cesana M., Cacchiarelli D., Morlando M., and Bozzoni, I (2013). Biogenesis and function of non coding RNAs in muscle differentiation and in Duchenne Muscular Dystrophy. Bioch. Soc. Trans. 41: 844-849.
35. Morlando M., Dini Modigliani S., Torrelli G., Rosa A., Di Carlo V., Caffarelli E., Bozzoni I. (2012) FUS stimulates microRNA biogenesis by facilitating co-transcriptional Drosha recruitment. EMBO J. 31: 4502-4510.
36. Cacchiarelli D., Martone J., Girardi E., Cesana M., Incitti T., Morlando M., Nicoletti C., Santini T., Sthandier O., Barberi L., Auricchio A., Musarò A. and Bozzoni I. (2010) “microRNAs involved in molecular circuitries relevant for the Duchenne Muscular Dystrophy pathogenesis are controlled by the dystrophin/nNOS pathway” Cell Metabolism. 12:341-351.
37. Ballarino M., Pagano F., Girardi E. Morlando M., Cacchiarelli D., Marchioni M., Proudfoot N., Bozzoni I., 2009. “Coupled RNA processing and transcription of intergenic primary microRNAs” Mol Cell Biol. 29: 5632-5638.
38. Morlando M., Ballarino M., Gromak N., Pagano F., Bozzoni I., Proudfoot N. 2008. “Primary micro-RNA transcripts are processed co-transcriptionally” Nature Structural & Molecular Biology, 15: 902-909.
39. Fatica. A., Rosa A., Ballarino M., Morlando M., De Angelis F., Caffarelli E., Nervi C. Bozzoni I. 2006. “miRNAs and hematopoietic differentiation” Cold Spring Arbor Symposiosum on Quantitative Biology “Regulatory RNA” vol. 71: 205-210.
40. Ballarino M., Morlando M., Pagano F., Fatica A., Bozzoni I. 2005. The cotranscriptional assembly of snoRNPs controls the biosynthesis of H/ACA snoRNAs in Saccharomyces cerevisiae. Mol Cell Biol. 25: 5396-5403.
41. Morlando M., Ballarino M., Greco P. Caffarelli E, Dichtl B, Bozzoni I. 2004. Coupling between snoRNP assembly and 3’ processing controls box C/D snoRNA biosynthesis in yeast. EMBO J. 23: 2392-2401
42. Morlando M., Greco P., Dichtl B., Fatica A., Keller W., Bozzoni I. 2002. Functional analysis of yeast snoRNA and snRNA 3'-end formation mediated by uncoupling of cleavage and polyadenylation. Mol Cell Biol. 22: 1379-1389
43. Fatica A., Morlando M., Bozzoni I. 2000. Yeast snoRNA accumulation relies on a cleavage-dependent/polyadenylation-independent 3'-processing apparatus. EMBO J. 19: 6218-6229.

Patent n. RM2014A000322: "miRNA modificati nella sequenza seed per il ripristino dei livelli cellulari di FUS/TLS"; University of Rome “LA SAPIENZA”. Inventors: Irene Bozzoni, Mariangela Morlando, Stefano Dini Modigliani

Patent n. RM2014A000322: "miRNA modificati nella sequenza seed per il ripristino dei livelli cellulari di FUS/TLS"; University of Rome “LA SAPIENZA”. Inventors: Irene Bozzoni, Mariangela Morlando, Stefano Dini Modigliani

Additional information

Mother toungue: Italian
Other languages: English

Organisational/managerial skills: currently coordinating the research work of a team of 2 post-doc, 1 PhD student, 2 master students. The coordinated research focuses on the study of non-coding RNAs expressed during neuronal and skeletal muscle differentiation in normal and in pathological conditions (Duchenne muscular Dystrophy and Amyotrophic lateral sclerosis). The aim of this work is the identification of novel molecular targets for the development of therapeutic strategies.

Job related skills: particularly skilled in cell handling and transfection, in cloning, RNA and protein extraction, purification and analysis. Also skilled in innovative techniques such as Next Generation sequencing, cell reprogramming and genome editing (CRIPSR-CAS9 and Talen) and Chromatin IP mediated by RNA (ChIRP, RAP, CHART).

She serves as referee of several international scientific journals (e-Life, EMBO Journal, EMBO Reports, EMBO Molecular Medicine, CNS & Neurological disorders-drug targets, Science Advances, Cell Death and Disease) and she is part of the editorial board of International Journal of Molecular Sciences.

Description of the main research results:
The research activity of Morlando's lab investigates the RNA metabolism in physiological and pathological conditions, focusing on Amyotrophic Lateral Sclerosis (ALS) linked to FUS mutations and Duchenne Muscular Dystrophy. The primary focus is on structural and functional characterizing non-coding RNAs, including short (microRNAs) and long non-coding RNAs (lncRNA and circRNA). Combining high-throughput approaches, bioinformatics, and biochemical/molecular techniques, the research of Morland's lab has identified deregulation of the non-coding transcriptome in cellular models of ALS and DMD. These models are used to study specific deregulated RNA transcripts, aiming to understand their function and contribution to disease pathogenesis. This involves: 1) pull-down experiments combined with transcriptomic and proteomic analyses to identify protein and RNA interactors; 2) advanced single-molecule imaging to detect these molecules in cells and tissues; and 3) in vivo and in vitro knockout/knockdown strategies using CRISPR/Cas9 system and RNA interference. Due to the low abundance and unique structure of lncRNAs and circRNAs, their study has required optimization of several procedures such as the application of ad hoc Sequencing procedures and Bioinformatic tools and the use of dedicated imaging approaches. The lab has established cellular models and differentiation protocols using cell lines and patient-derived induced pluripotent stem cells (iPSCs) for neuromuscular disease research.
All these approaches along with established collaborations with national and international laboratories have allowed to define the function of many non-coding RNAs such as Charme, lnc-31, lnc-SMaRT, and circ-Znf609 during physiological and pathological myogenesis. The function of two circRNAs, circ-Hdgfrp3 and circ-Dlc1(2), deregulated in FUS mutant conditions has been also unveiled using both in vitro and in vivo model systems. In particular, the MM team has recently investigated the function of the circ-Dlc1(2), a circRNA highly expressed in the murine cortex and striatum. The use of in vitro derived cortical neurons and the generation of a knockout mouse model allowed to determine that circ-Dlc1(2) plays a role in controlling the proper balance of the glutamatergic receptor subunits at the neuronal periphery.