CV
Titolo di studio Diploma di laurea (Facoltà): Laurea in Science Biologiche (110/110)
anno 1985 Università: Università di Roma "La Sapienza” Città: Roma
Dottore di Ricerca, titolo conseguito presso l’Università La Sapienza Roma. Settembre 1991
ATTUALE OCCUPAZ.NE
Ente: Università di Roma “Tor Vergata”,
Qualifica: Ricercatore confermato Bio10/ Professore Aggregato a seguito della legge ex art.1 comma 11 legge n.230/2005
Data ass.ne: 11/2000
ESPERIENZA PROF.LE:
Periodo: 1996-2000: Qualifica: Assistente Universitario a tempo determinato; Istituto di Genetica e Microbiologia, Facoltà di Scienze, Università di Vienna, Austria
Periodo: 1992-1996: Qualifica: Post-doc/Group Leader Istituto di Genetica e Microbiologia, Facoltà di Scienze, Università di Vienna, Austria
Periodo: 1990-1991 : Borsista Fondazione Pasteur-Cenci Bolognetti (Borsa di studio per l’Italia; Università di Roma La Sapienza, Dipartimento di Biologia Cellulare e dello Sviluppo, Laboratorio di Chimica delle Fermentazioni
Periodo: 1986-1988:Borsista Fondazione Pasteur- Cenci Bolognetti (borsa di studio per l’estero) Dipartimento di Biologie, Laboratorio Prof. Hiroshi Fukuhara, Institute Curie Universitè Paris Sud PARIS France
Corsi tenuti presso l' Universita di Roma Tor Vergata
2004-2010: Metodologie Biochimiche Corso di laurea Magistrale in Biologia Umana e in Biologia cellulare e molecolare
2010-presente: Corso di traffico intracellulare. AAS scielta Laurea Specialistica in Biologia Umana e Biologia Cellulare e Molecolare
Corsi tenuti precedentemente in Università estere
1994-2000 University of Vienna, at Max Perutz laboratories Dr.Bohrgasse 9 Vienna (Austria )
Wintersemester 1999/00 809141 UEExperimentelle Genetik III (Molekularbiologie)
Sommersemester 1999 809093 UEExperimentelle Genetik III (Molekulargenetik)
Wintersemester 1998/99 809141 UEExperimentelle Genetik III (Molekularbiologie)
Sommersemester 1998 809093 UEExperimentielle Genetik III (Molekulargenetik)
Wintersemester 1997/98 809141 UEExperimentelle Genetik III (Molekularbiologie)
Sommersemester 1997 809093 UEExperimentielle Genetik III (Molekulargenetik)
Wintersemester 1996/97 809141 UEExperimentelle Genetik III (Molekularbiologie)
Sommersemester 1996 809093 UEExperimentielle Genetik III (Molekulargenetik)
Wintersemester 1995/96 809141 UEExperimentelle Genetik III (Molekularbiologie) 809416 UEExperimentelle Genetik/Mikrobiologie III (Molekulargenetik)
Sommersemester 1995-809802 UEExp. Genetik/Mikrobiologie III (DNA/RNA Technol. u. Klonierg.)
Wintersemester 1994/95-809135 UEExperimentelle Genetik/Mikrobiologie III (DNA/RNA Technol. u. Klonierung)
CV of the Principal Investigator.
Dr. Antonella Ragnini
(Ragnini A; alias Ragnini-Wilson A.,)
Current position
2000-present: Agg Professor/Researcher E05; Bio10 , Department of Biology University of Rome Tor Vergata .
ORCID site : https://orcid.org/0000-0001-7963-7554;
SCOPUS: https://www.scopus.com/authid/detail.uri?authorId=6602198426
Web site:https://www.researchgate.net/profile/Antonella-Ragnini-Wilson/research
Previous positions in other research or academic institutiions :
1996-2000 Assistant position Department of Genetics University of Vienna , Dr. Bohrgasse 3, Vienna,Austria
2001-2002Guest Scientist at Department of Genetics, University of Vienna, Dr Bohrgasse 3, Vienna Austria,
2005-2015Guest Scientist, Head of Unit of Intracellular traffic; Head of the HCS microscopy Facility, at Consorzio Mario Negri SUD, S.M. Imbaro Chieti; Italy
Academic degree - Year and Institution
1985 Laurea in Biological Science ; University of Rome La Sapienza , Italy
1991: PhD 1991; University of Rome La Sapienza. One half of the PhD was developed at Department of Cellular and Developmental biology at University of Rome “La Sapienza” directed by Prof. Laura Frontali and one half at Laboratory of Molecular biology Directed by Prof. Hiroshi Fukuhara at University Paris-Sud, Orsay-FRANCE
Awards and Fellowships
1986-1988: Fellowship awarded by Institute Pasteur-Fondazione Cenci Bolognetti- to work at Laboratory of Molecular biology University Paris-Sud, Orsay-FRANCE
1990-1991 Fellowship awarded by Fondazione Cenci Bolognetti to work at Department of Developmental Biology- Laboratory Fermentation chemistry University of Rome “La Sapienza” (Italy)
Actual research
Since 2015 my laboratory has focused the activity on the identification and characterization of novel compounds acting in Central Nervous System (CNS) remyelination with the final goal to bring promyelinating compounds in clinic as co-therapy for Multiple Sclerosis disease. . Set up the High Content Screening Facility at Consorzio Mario Negri Sud equipped with ScanR microscopy acquisition and analysis. We mainly used this facility for DRUG and siRNA library screen. Main effort was done to identify drugs and reveal gene network involved in rare diseases, CNS and cell cycle-related pathologies (Sacco et al., 2012; Porcu et al., 2010; 2013, 2015, Alfieri et al., 2020; Palermo et al., 2021).- This HCS microscopy facility passed the requirement to become a EU NODE according to the 2012 Eurobioimage program for Advanced Microscopy HCS facilities. This facility acted as support of several screens and image-based validation analyses
Construction of cellular models for Phenotypical screens. We developed the Oli-neuM oligodendroglia mouse cell line to be used to study oligodendrocyte precursor cell differentiation (https://web.expasy.org/cellosaurus/CVCL_VL76), and for HTS phenotypical screens of promyelinating drugs and for their validation (Nocita et al., 2019; Del Giovane et al., 2022). Using This cell line we identified novel promyelinating drugs (Porcu et al., 2015). Among them the GSA-10 has strong promyelinating activity in vitro and in vivo (Del Giovane et al., 2022). Our main effort is currently devoted to elucidate promyelinating drugs mechanism of action in vitro and in vivo. Moreover we aim to create novel disease-relevant cellular models using direct reprogramming of fibroblast cells and iPSC technologies to be used to clarify how these compounds affects cellular activity in presence of patient's background. Clobetasol and GSA-10 are now on our focus as both targets directly or indirectly Smoothened receptor activity and our work has shown that the non-canonical activation of SMO by GSA-10 promotes Gli1 downregulation, Gli1 upregulation and MBP expression in vitro and OL recruitment at demyelinated area in vivo (Del Giovane et al., 2022). Our final goal will be to identify based on GSA-10 structure and/or activity novel compounds more bioactive that act in CNS remyelination at clinical level.
Previous research activity :
1991-2008. Identification and characterization of Rab protein regulators and interactors in the exocytic pathway. Main achievement: identification of the yeast Rab escort protein (REP) Mrs6 (Waldherr et al., 1993; Ragnini et al., 1994; Benito-Moreno et al., 1994). Identification of the main domain required for REP function (Bauer et al., 1996; Miaczynska M1997 and 2001) and demonstration that Mrs6 defects leads to vesicle trafficking defects due to the inability of Sec4/Rab proteins to bind the yeast myosin V motor Myo2. Identification of the MyosinV/Rab motor complex in yeast (Bialek-Wyrzykowska et al., 2000, Wagner et al., 2002). Characterization of the Myosin light chain 1 function in controlling yeast Saccharomyces cerevisiae cytokinesis and cargo interaction (Bielli et al., 2006; Pennestri et al., 2007; Casavola et al., 2008)
1985-1991Mitochondria biogenesis and evolution. My work focused on the identification of main promoters and transcription units of yeast mitochondria with the aim to identify how transcriptional units evolved during yeast speciation (see Ragnini A publications).
Foreign languages known
English (B2), French (A1), German elementary
D. Additional Information: Main Grants obtained: FISM 2023 (from 2024-03 to 2027-03) Title : Targeting Smoothened/AMPK pathway to boost central nervous system remyelination "
| Grant Associazione Italiana Sclerosi Multipla (Genoa, Italy, IT) GRANT_NUMBER:2023/R-Multi/001 PI and coordinator Antonella Ragnini (UniTV,ROme); collaborator PIs: Luciana Marinelli (UniFederico sceondo Naples); Daniela Arosio (SCITEC Mi, CNR) .Beyond the borders 2019 N-acetylaspartate in the spotlight: breaking new ground in ALS-associated dysmetabolism 12m PI MCiriolo, A Ragnini-Wilson, S. Iacovelli .; ARSEP foundation 2018 (France), M. Ruat, L. Tirou, A. Ragnini-Wilson Title: Development of novel genetic, pharmacological and 3D imaging tools for studying remyelination.1yMission sustainability (2017) 18 months (PI Traversa E.) title: NewMyelin: Tissue engineering to study myelination processes; Carichieti Foundation 2010-2015 grant: Identification of novel compounds acting in promoting regenerative process in the autoimmune demyelinating disease multiple sclerosis (MS); Principal investigator (5 years);Telethon GGP008143: Myosin V-based human inherited diseases: Molecular basis of myosin V recognition of intracellular cargo; (PI 3y); EUCilia :Pathophysiology of Rare Diseases due to Ciliary Dysfunction FP7-HEALTH-2007-A: Collaborator Partner 4 CMNS (1y); AIRC 2007 IG 1624: Identification of FTI targets using budding yeast cells as a model system; Principal investigator (3 years); Telethon GGP030341-Characterization of the organelle-anchoring machinery acting in human genetic disorders based on defects in organelle motility using an yeast model system;Principal investigator (PI 3y); CNR/MIUR- Genomica Funzionale Prog. CU04.00093, PI; FWF Standing-alone project 14272-MOBFWF (Austria) Control of vesicle polarisation during bud growth in Saccharomyces cerevisiae: Principal investigator (3 years)
Teaching experience: 2020-present AAS Regenerative medicine (EG) 2019-present AAS English for biologist (EG) 2015-2020: AAS High throughput technologies in drug discovery (EG). 2010-present AAS Intracellular traffic and related diseases LT in Biological Science, LM e LS in Cellular and Molecular Biology (IT); 2009; Invited Lecturer : Advanced Biochemistry University of Vienna (EG); 2004-2010: Methodologies in Biochemistry (IT); 1992-2000: Experimental Genetics III. University of Vienna, Austria (EG)• Supervisor of diploma and Ph.D. theses: 2002-present University of Tor Vergata 2008-2015: Life science of Open University UK; 1991-2002 University of Vienna; (EG= English courses; IT=Italian courses).
Ragnini’s Laboratory well established technologies:
Oligodendrocyte cells culture (Oli-neu, Oli-neuM, HOG), Neuronal cell culture (SH-SY5Y); primary NCS and OPC, cancer cell lines, HeLA. HTS microscopy technologies and image analyses based on ScanR (Olympus softwares) for drug screening, drug treatment and validation, in vitro assay for study intracellular signaling in mammalian and yeast cells. In addition the following techniques are used routinely
List of main publications of the applicant relevant to this application
Del Giovane, A; Russo, M; Tirou, L; Faure, H; Ruat, M; Balestri, S; Sposato, C; Basoli, F; Rainer, A; Kassoussi, A; Traiffort, E; Ragnini-Wilson, A. Smoothened/AMP-Activated Protein Kinase Signaling in Oligodendroglial Cell Maturation. FRONTIERS IN CELLULAR NEUROSCIENCE, 2022; 15 [10.3389/fncel.2021.801704].
Balestri S, Del Giovane A, Sposato C, Ferrarelli M, Ragnini-Wilson A. The Current Challenges for Drug Discovery in CNS Remyelination. Int J Mol Sci. Mar 12;22(6):2891. doi: 10.3390/ijms22062891
Palermo V, Stirpe M, Bianchi MM, Rinaldi T, Cirigliano A, Ragnini-Wilson A, Falcone C, Mazzoni C. The C-terminal region of yeast ubiquitin-proteinligase Not4 mediates its cellular localization and stress response. FEMS Microbiol Lett. 2021 Aug 17;368(15):fnab097. doi:10.1093/femsle/fnab097.
Alfieri M, Iaconis D, Tammaro R, Perone L, Calì G, Nitsch L, Dougherty GW, Ragnini-Wilson A, Franco B . The centrosomal/basal body protein OFD1 is required for microtubule organization and cell cycle progression. Tissue Cell. 2020 Jun;64:101369. doi: 10.1016/j.tice.2020.101369.
Nocita E, Del Giovane A, Tiberi M, Boccuni L, Fiorelli D, Sposato C, Romano E, Basoli F, Trombetta M, Rainer A, Traversa E, Ragnini-Wilson A . EGFR/ErbB Inhibition Promotes OPC Maturation up to Axon Engagement by Co-Regulating PIP2 and MBP. Cells. 2019 Aug 6;8(8):844. doi: 10.3390/cells8080844.
Del Giovane A, Ragnini-Wilson A Targeting Smoothened as a New Frontier in the Functional Recovery of Central Nervous System Demyelinating Pathologies. Int J Mol Sci. 2018 Nov 20;19(11):3677. doi: 10.3390/ijms19113677.
Beznoussenko GV, Ragnini-Wilson A, Wilson C, Mironov AA. Three-dimensional and immune electron microscopic analysis of the secretory pathway in Saccharomyces cerevisiae. Histochem Cell Biol. 2016 Nov;146(5):515-527. doi: 10.1007/s00418-016-1483-y.
Porcu G, Serone E, De Nardis V, Di Giandomenico D, Lucisano G, Scardapane M, Poma A, Ragnini-Wilson A. Clobetasol and Halcinonide Act as Smoothened Agonists to Promote Myelin Gene Expression and RxRγ Receptor Activation. PLoS One. 2015 Dec 10;10(12):e0144550. doi: 10.1371/journal.pone.0144550.
Porcu G, Parsons AB, Di Giandomenico D, Lucisano G, Mosca MG, Boone C, Ragnini-Wilson A. Combined p21-activated kinase and farnesyltransferase inhibitor treatment exhibits enhanced anti-proliferative activity on melanoma, colon and lung cancer cell lines. Mol Cancer. 2013 Aug 6;12(1):88. doi: 10.1186/1476-4598-12-88..
Mahfouz H, Ragnini-Wilson A, Venditti R, De Matteis MA, Wilson C. Mutational analysis of the yeast TRAPP subunit Trs20p identifies roles in endocytic recycling and sporulation. PLoS One. 2012;7(9):e41408. doi: 10.1371/journal.pone.0041408.
Sacco F, Gherardini PF, Paoluzi S, Saez-Rodriguez J, Helmer-Citterich M, Ragnini-Wilson A, Castagnoli L, Cesareni G. Mapping the human phosphatome on growth pathways. Mol Syst Biol. 2012;8:603. doi: 10.1038/msb.2012.36
Wilson C, Ragnini-Wilson A. Conserved molecular mechanisms underlying homeostasis of the Golgi complex. Int J Cell Biol. 2010;2010:758230. doi: 10.1155/2010/758230.
Porcu G, Wilson C, Di Giandomenico D, Ragnini-Wilson A. A yeast-based genomic strategy highlights the cell protein networks altered by FTase inhibitor peptidomimetics. Mol Cancer. 2010 Jul 23;9:197. doi: 10.1186/1476-4598-9-197.
Amata I, Gallo M, Pennestri M, Paci M, Ragnini-Wilson A, Cicero DO. N-lobe dynamics of myosin light chain dictates its mode of interaction with myosin V IQ1. Biochemistry. 2008 Nov 25;47(47):12332-45. doi: 10.1021/bi801178t
Casavola EC, Catucci A, Bielli P, Di Pentima A, Porcu G, Pennestri M, Cicero DO, Ragnini-Wilson A. Ypt32p and Mlc1p bind within the vesicle binding region of the class V myosin Myo2p globular tail domain. Mol Microbiol. 2008 Mar;67(5):1051-66. doi: 10.1111/j.1365-2958.2008.06106.x.
Pennestri M, Melino S, Contessa GM, Casavola EC, Paci M, Ragnini-Wilson A, Cicero DO. Structural basis for the interaction of the myosin light chain Mlc1p with the myosin V Myo2p IQ motifs. J Biol Chem. 2007 Jan 5;282(1):667-79. doi: 10.1074/jbc.M607016200.
Bielli P, Casavola EC, Biroccio A, Urbani A, Ragnini-Wilson A. GTP drives myosin light chain 1 interaction with the class V myosin Myo2 IQ motifs via a Sec2 RabGEF-mediated pathway. Mol Microbiol. 2006 Mar;59(5):1576-90. doi: 10.1111/j.1365-2958.2006.05041.x.
Luini A, Ragnini-Wilson A, Polishchuck RS, De Matteis MA. Large pleiomorphic traffic intermediates in the secretory pathway. Curr Opin Cell Biol. 2005 Aug;17(4):353-61. doi: 10.1016/j.ceb.2005.06.012.
Melino S, Pennestri M, Santoprete A, Bielli P, Paci M, Ragnini-Wilson A, Cicero DO. Assignment of the 1H, 13C and 15N resonances of Mlc1p from Saccharomices cerevisiae. J Biomol NMR. 2005 Apr;31(4):367-8. doi: 10.1007/s10858-005-0947
Wagner W, Bielli P, Wacha S, Ragnini-Wilson A. Mlc1p promotes septum closure during cytokinesis via the IQ motifs of the vesicle motor Myo2p. EMBO J. 2002 Dec 2;21(23):6397-408. doi: 10.1093/emboj/cdf650.
Miaczynska M, Wagner W, Bauer BE, Schweyen RJ, Ragnini A. Ypt protein prenylation depends on the interplay among levels of Rab escort protein and geranylgeranyl diphosphate in yeast cells. Yeast. 2001 Jun;18(8):697-709. doi: 10.1002/yea.719.
Bialek-Wyrzykowska U, Bauer BE, Wagner W, Kohlwein SD, Schweyen RJ, Ragnini A. Low levels of Ypt protein prenylation cause vesicle polarization defects and thermosensitive growth that can be suppressed by genes involved in cell wall maintenance. Mol Microbiol. 2000 Mar;35(6):1295-311. doi: 10.1046/j.1365-2958.2000.01782.x.
Ragnini-Wilson A. How to get to the right place at the right time: Rab/Ypt small GTPases and vesicle transport. Protoplasma. 1999;209(1-2):19-27. doi: 10.1007/BF01415697.
Bui DM, Gregan J, Jarosch E, Ragnini A, Schweyen RJ. The bacterial magnesium transporter CorA can functionally substitute for its putative homologue Mrs2p in the yeast inner mitochondrial membrane. J Biol Chem. 1999 Jul 16;274(29):20438-43. doi: 10.1074/jbc.274.29.20438
Miaczynska M, Lorenzetti S, Bialek U, Benito-Moreno RM, Schweyen RJ, Ragnini A. The yeast Rab escort protein binds intracellular membranes in vivo and in vitro. J Biol Chem. 1997 Jul 4;272(27):16972-7. doi: 10.1074/jbc.272.27.16972.
Bauer BE, Lorenzetti S, Miaczynska M, Bui DM, Schweyen RJ, Ragnini A. Amino- and carboxy-terminal domains of the yeast Rab escort protein are both required for binding of Ypt small G proteins. Mol Biol Cell. 1996 Oct;7(10):1521-33. doi: 10.1091/mbc.7.10.1521.
Van Dyck E, Jank B, Ragnini A, Schweyen RJ, Duyckaerts C, Sluse F, Foury F. Overexpression of a novel member of the mitochondrial carrier family rescues defects in both DNA and RNA metabolism in yeast mitochondria. Mol Gen Genet. 1995 Feb 20;246(4):426-36. doi: 10.1007/BF00290446.
Benito-Moreno RM, Miaczynska M, Bauer BE, Schweyen RJ, Ragnini A. Mrs6p, the yeast homologue of the mammalian choroideraemia protein: immunological evidence for its function as the Ypt1p Rab escort protein. Curr Genet. 1994 Dec;27(1):23-5. doi: 10.1007/BF00326574.
Ragnini A, Teply R, Waldherr M, Voskova A, Schweyen RJ. The yeast protein Mrs6p, a homologue of the rabGDI and human choroideraemia proteins, affects cytoplasmic and mitochondrial functions. Curr Genet. 1994 Oct;26(4):308-14. doi: 10.1007/BF00310494.
Ragnini A, Frontali L. Ordered processing of the polygenic transcripts from a mitochondrial tRNA gene cluster in K. lactis. Curr Genet. 1994 Apr;25(4):342-9. doi: 10.1007/BF00351488.
Waldherr M, Ragnini A, Schweyer RJ, Boguski MS. MRS6--yeast homologue of the choroideraemia gene. Nat Genet. 1993 Mar;3(3):193-4. doi: 10.1038/ng0393-193.