Grazia Raffaella Tundo

Grazia Raffaella Tundo

Via Montpellier, 1, 00100, Università di Roma Tor Vergata

Telefono +390677208722; +393209736540

E-mail: grazia.raffaella.tundo@uniroma2.it

Formazione

• Laurea Magistrale in Biotecnologie Mediche (2006);
• Dottorato di Ricerca in Biochimica e Biologia Molecolare (2011);
• Laurea Magistrale in Medicina e Chirurgia (2018);

Ruoli

• Assegnista di ricerca 2011-2018 (Università di Roma Tor Vergata ed altri enti di ricerca);
• Docente di Chimica Medica e Propedeutica Biochimica, Università “Madre Teresa del Buon Consiglio”, Tirana, Albania (2013-2014);
• Ricercatrice presso Università di Catania (2015);
• Professore di Chimica Medica e Propedeutica Biochimica, Università Unicamillus, Roma (2018-2020)
• Ricercatore presso Fondazione IRCCS-Fondazione G.B. Bietti. (2018-2022);
• Attuale: RTD-B presso l'Università di Roma Tor Vergata

Membro delle Società Scientifiche

• Membro della Società di Chimica Italiana – Divisione di Chimica dei Sistemi Biologici

Attività Editoriale come Reviewer

• Editor della rivista Biomolecules;
• Attività di reviewer per le principali riviste di biochimica internazionali

Riconoscimenti

• Premio “Raeli” come miglior laureato in Biotecnologie Mediche (2007)

Attività di ricerca

Characterization of dy-regulation of UPS in glaucoma and ocular diseases, in collaboration with Doctor Francesco Oddone, IRCSS Fondazione Bietti, Rome, Italy, Prof. Assfalg, University of Verona.

Characterization of Insulin-degrading-enzyme-proteasome interaction, in collaboration with Prof. Purrello, University of Catania, Prof. Bolognesi, Università di Milano, Van Endert, Institut Necker Des Malades, Paris, France and prof. Deprez-Poulain, University of Lille, France, Prof

Characterization of IDE role in the Heat-shock –response, in collaboration with Prof.Orlandi, University of Rome Tor Vergata and prof. Van Endert, Institut Necker Des Malades.

Characterization of autophagy and UPS dys-regulation in Rett Syndrome, in collaboration with Prof. Curatolo, University of Rome Tor Vergata, Prof. Defelice, University of Siena, Italy and Prof. Valacchi, University of Ferrara, Italy.

Characterization of dys-regulation of proteasome activity in Huntigton Disease in collaboration with prof. Reits,  Institut fu¨r Biochemie/CCM, Charite´-Universita¨tsmedizin Berlin, Germany

Characterization of dy-regulation of UPS in Multiple Sclerosis in collaboration with prof. Ale,Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russian Federation.

Lista completa delle pubblicazioni

H-Index:  19 (Scopus, 05-06-2024)

Ciaccio C*, TundoGR*, Grasso G, Spoto G, Marasco D, Ruvo M, Gioia M, Rizzarelli E, Coletta M. Somatostatin: a novel substrate and a modulator of insulin-degrading enzyme activity.J Mol Biol. 2009385:1556-67. *These authors have equally contributed to the study.

Ascenzi P, Bolli A, di Masi A, TundoGR, Fanali G, Coletta M, Fasano M. Isoniazid and rifampicin inhibit allosterically heme binding to albumin and peroxynitrite isomerization by heme-albumin.J Biol Inorg Chem.2011 16:97-108. 2016.

Grasso G, Pietropaolo A, Spoto G, Pappalardo G, TundoGR, Ciaccio C, Coletta M, Rizzarelli E. Copper(I) and copper(II) inhibit Aβpeptides proteolysis by insulin-degrading enzyme differently: implications for metallostasis alteration in Alzheimer's disease.Chemistry. 201117:2752-62.

Ascenzi P, Cao Y, TundoGR, Coletta M, Fanali G, Fasano M. Ibuprofen and warfarin modulate allosterically ferrous human serum heme-albumin nitrosylation.Biochem Biophys Res Commun. 2011411: 185-9.

Cao Y, Nicoletti FP, De Sanctis G, Bocedi A, Ciaccio C, Gullotta F, Fanali G,Tundo GR, di Masi A, Fasano M, Smulevich G, Ascenzi P, Coletta M.Evidence for pH-dependent multiple conformers in iron(II) heme-human serum albumin: spectroscopic and kinetic investigation of carbon monoxide binding.J Biol Inorg Chem. 2012 (1):133-47.

Sbardella D., Fasciglione GF, Gioia M, Ciaccio C,Tundo, GR, Marini S, Coletta M. Human matrix metalloproteinases: An ubiquitarian class of enzymes involved in several pathological processes. Molecular Aspects of Medicine. 2012,33 119-208.

TundoGR, Ciaccio C, Sbardella D, Boraso M, Viviani B, Coletta M, Marini S. Somatostatin modulates insulin-degrading-enzyme metabolism: implications for the regulation of microglia activity in AD.PLoS One. 2012 7.

Grasso G, Salomone F,Tundo GR, Pappalardo G, Ciaccio C, Spoto G, Pietropaolo A, Coletta M, Rizzarelli E. Metal ions affect insulin-degrading enzyme activity. J Inorg Biochem. 2012 117:351-8.

TundoGR, Sbardella D, Ciaccio C, Bianculli A, Orlandi A, Desimio MG, Arcuri G, Coletta M, Marini S. Insulin-degrading enzyme (IDE): a novel heat shock-like protein.J Biol Chem. 2013 26:1821-31.

Ciaccio C, Pesce A, TundoGR, Tilleman L, Bertolacci L, Dewilde S, Moens L, Ascenzi P, Bolognesi M, Nardini M, Coletta M. Functional and structural roles of the N-terminal extension in Methanosarcina acetivorans protoglobin.Biochim Biophys Acta. 2013 1834:1813-23.

Bocedi A, De Sanctis G, Ciaccio C, Tundo GR, Di Masi A, Fanali G, Nicoletti FP, Fasano M, Smulevich G, Ascenzi P, Coletta M. Reciprocal allosteric modulation of carbon monoxide and warfarin binding to ferrous human serum heme-albumin.PLoS One. 2013 8-31.

Ascenzi P,TundoGR, Fanali G,Coletta M, Fasano M. Warfarin modulates the nitrite reductase activity of ferrous human serum heme-albumin.J Biol Inorg Chem. 2013 18:939-46.

Ascenzi P, di Masi A,TundoGR, Pesce A, Visca P,Coletta M. Nitrosylation mechanisms of Mycobacterium tuberculosis and Campylobacter jejuni truncated hemoglobins N, O, and P.PLoS One. 2014 9:e102811.

Sbardella D,TundoGR, Fasciglione GF, Gioia M, Bisicchia S, Gasbarra E, Ippolito E. Tarantino U,Coletta M, Marini S. Role of metalloproteinases in tendon pathophysiology.Mini Rev Med Chem. 2014 14:978-87.

Ciaccio C, Ocaña-Calahorro F, Droghetti E,Tundo GR, Sanz-Luque E, Polticelli F, Visca P, Smulevich G, Ascenzi P, Coletta M. Functional and Spectroscopic Characterization of Chlamydomonas reinhardtii Truncated Hemoglobins.PLoS One. 2015, 10(5).

TundoGR, Sbardella D, De Pascali SA, Ciaccio C, Coletta M, Fanizzi FP, Marini S. Novel Platinum(II) compounds modulate insulin-degrading enzyme activity and induce cell death in neuroblastoma cells.J Biol Inorg Chem. 2015 20:101-8.

Sbardella D, TundoGR, SciandraF,BozziM,Gioia M, Ciaccio C, Tarantino U, Brancaccio A, Coletta M, Marini S. Proteasome Activity Is Affected by Fluctuations in Insulin-Degrading Enzyme Distribution.. PLoS One. 2015, 10(7).

TundoGR, SbardellaD, CiaccioC, De pascaliS, CampanellaV, CozzaP, TarantinoU, ColettaM, FanizziFP, MariniS. Effect of cisplatin on proteasome activity. J Inorg Biochem. 2015, 153:253-8.

2016

Donatucci B., Sbardella D.,Tundo GR, Casasco M., Di Daniele N., Rogliani P., Marini S. Antioxidant supplement and sportsMedicina dello Sport 2015, 68, 359-366.

Santoro AM, Cunsolo A, D'Urso A, Sbardella D,Tundo GR, Ciaccio C, Coletta M, Diana D, Fattorusso, R, Persico M, Di Dato A, Fattorusso C, Milardi D, Purrello R. Cationic porphyrins are tunable gatekeepers of the 20S proteasomeChemical Science2016, 7, 1286-1297.

Tundo GR, Di Muzio E, Ciaccio C, Sbardella D, Di Pierro D, Polticelli F, Coletta M, Marini S. Multiple allosteric sites are involved in the modulation of insulin-degrading-enzyme activity by somatostatin.FEBS J. 2016, 283, 3755-3770.

Ciaccio C, Di Pierro D, Sbardella D, Tundo GR, Curatolo P, Galasso C, Santarone ME, Casasco M, Cozza P, Cortelazzo A, Rossi M, De Felice C, Hayek J, Coletta M, Marini S. Oxygen exchange and energy metabolism in erythrocytes of Rett syndrome and their relationships with respiratory alterations.Mol Cell Biochem. 2017, 426, 205-213.

Grasso G; Santoro AM, Lanza V , Sbardella D, Tundo GR, Ciaccio C, Marini S, Coletta M, Milardi D. The double faced role of copper in A beta homeostasis: A survey on the interrelationship between metal dyshomeostasis, UPS functioning and autophagy in neurodegeneration. Coordination chemistry reviews. 2017, 347: 1-22.

Gioia M, Tomao L, Sbardella D, Ciaccio C, Tundo GR, Di Masi A, Fasciglione GF, Marini S, Cozza P, Ascenzi P, Coletta M. Enzyme catalysis: the case of the prostate-specific antigenHide ResearcherID and ORCID. Rendiconti Lincei-scienze fisiche e naturali. 2017, 28: 229-237.

Tundo GR, Sbardella D, Ciaccio C, Grasso G, Gioia M, Coletta A., Polticelli F, Di Pierro D. Milardi D, Van Endert P, Marini S, Coletta M.Multiple functions of insulin-degrading enzyme: a metabolic crosslight? Crit Rev Biochem Mol Biol. 2017, 52:554-582. 2016.

Sbardella D*, TundoGR*, Campagnolo L,Valacchi G, Orlandi A, Curatolo P, Borsellino G, D’Esposito M, Ciaccio C, Di Cesare S, Di Pierro D, Galasso C, Santarone ME, Hayek J, Coletta M, Marini S. Retention of Mitochondria in Mature Human Red Blood Cells as the Result of Autophagy Impairment in Rett Syndrome. Sci Rep. 2017. 26:12297. *These authors have equally contributed to the study.

Dato AD, Cunsolo A, Persico M, Santoro AM, D'Urso A, Milardi D, Purrello R, Stefanelli M, Paolesse R, Tundo GR, Sbardella D, Fattorusso C, Coletta M. Electrostatic Map Of Proteasome α-Rings Encodes The Design of Allosteric Porphyrin-Based Inhibitors Able To Affect 20S Conformation By Cooperative Binding.Sci Rep.2017. 7: 17098.

Sbardella D*, Tundo GR,* Coletta A, Marcoux J, Koufogeorgou EI, Ciaccio C, Santoro AM, Milardi D, Grasso G, Cozza P, Bousquet-Dubouch MP, Marini S, Coletta M. The Insulin Degrading Enzyme is an Allosteric Modulator of the 20S Proteasome and a Potential Competitor of the 19S. Cell Molecular Life Sciences 2018. 18:3441-3456.*These authors have equally contributed to the study.

Ascenzi P, TundoGR, Coletta M. The nitrite reductase activity of ferrous human hemoglobin:haptoglobin 1-1 and 2-2 complexes.J. Inorg. Biochem. 2018. 187:116-122.

TundoGR, Sbardella D, Coletta M. Insights into Proteasome Conformation Dynamics and Intersubunit Communication.Trends Biochem Sci.2018. 43:852-853.

Tundo GR, Sbardella D, Lacal PM, Graziani G, Marini S. On the Horizon: Targeting Next-Generation Immune Checkpoints for Cancer Treatment.Chemotherapy. 2019;64(2):62-80.

Milardi D, Santoro AM, Lanza V, Bellia F, Sbardella D, Tundo GR, Cannizzo A, Grasso G, Arizzi M, Nicoletti VG, Alcaro S, Costa G, Pietropaolo A, Malgieri G, D'Abrosca G, Fattorusso R, García-Viñuales S, Ahmed IMM, Coletta M. Pyrazolones activate proteasome by gating mechanisms and protect neuronal cells from Aβamyloid toxicity.ChemMedChem. 2019 15(3):302-316.

Bellia F, Lanza V, García-Viñuales S, Ahmed IMM, Pietropaolo A, Iacobucci C, Malgieri G, D'Abrosca G, Fattorusso R, Nicoletti VG, Sbardella D, Tundo GR, Coletta M, Pirone L, Pedone E, Calcagno D, Grasso G, Milardi D. Ubiquitin binds the amyloid β peptide and interferes with its clearance pathways. Chem Sci. 2019 Jan 10;10(9):2732-2742.

Santoro AM, Lanza V, Bellia F, Sbardella D, Tundo GR, Cannizzo A, Grasso G, Arizzi M, Nicoletti VG, Alcaro S, Costa G, Pietropaolo A, Malgieri G, D'Abrosca G, Fattorusso R, García-Viñuales S, Ahmed IMM, Coletta M, Milardi D. Pyrazolones Activate the Proteasome by Gating Mechanisms and Protect Neuronal Cells from β-Amyloid Toxicity. ChemMedChem. 2020 Feb 5;15(3):302-316.

Di Pierro D, Ciaccio C, Sbardella D, Tundo GR, Bernardini R, Curatolo P, Galasso C, Pironi V, Coletta M, Marini S. Effects of oral administration of common antioxidant supplements on the energy metabolism of red blood cells. Attenuation of oxidative stress-induced changes in Rett syndrome erythrocytes by CoQ10. Mol Cell Biochem. 2020 Jan;463(1-2):101-113.

Tundo GR, Sbardella D, Santoro AM, Coletta A, Oddone F, Grasso G, Milardi D, Lacal PM, Marini S, Purrello R, Graziani G, Coletta M. The proteasome as a druggable target with multiple therapeutic potentialities: Cutting and non-cutting edges. Pharmacol Ther. 2020.

Ascenzi P, De Simone G, Tundo GR, Platas-Iglesias C, Coletta M. Ferric nitrosylated myoglobin catalyzes peroxynitrite scavenging. J Biol Inorg Chem. 2020 May;25(3):361-370.

Ascenzi P, De Simone G, Tundo GR, Coletta M. Kinetics of cyanide and carbon monoxide dissociation from ferrous human haptoglobin:hemoglobin(II) complexes. J Biol Inorg Chem. 2020 May;25(3):351-360.

Sbardella D, Coletta A, Tundo GR, Ahmed IMM, Bellia F, Oddone F, Manni G, Coletta M.

Structural and functional evidence for citicoline binding and modulation of 20S proteasome activity: Novel insights into its pro-proteostatic effect. Biochem Pharmacol. 2020.

Sbardella D, Tundo GR, Cunsolo V, Grasso G, Cascella R, Caputo V, Santoro AM, Milardi D, Pecorelli A, Ciaccio C, Di Pierro D, Leoncini S, Campagnolo L, Pironi V, Oddone F, Manni P, Foti S, Giardina E, De Felice C, Hayek J, Curatolo P, Galasso C, Valacchi G, Coletta M, Graziani G, Marini S. Defective proteasome biogenesis into skin fibroblasts isolated from Rett syndrome subjects with MeCP2 non-sense mutations. Biochim Biophys Acta Mol Basis Dis. 2020.

Gioia G,  Ciaccio C,Calligari P,  De Simone G, Sbardella D,  Tundo GR,  Fasciglione GF, Di Masi A, Di Pierro D, Bocedi A, Ascenzi P , Coletta M.Role of proteolytic enzymes in the COVID-19 infection and promising therapeutic approaches. Biochem Pharmacol. 2020. 182:114225.

Santoro AM, D'Urso A,  Cunsolo A,  Milardi D,  Purrello R, Sbardella D,  Tundo GR, Donatella D,  Fattorusso R,  Di Dato A ,  Paladino A, Persico M,  ColettaM, Fattorusso C. Cooperative Binding of the Cationic Porphyrin Tris-T4 Enhances Catalytic Activity of 20S Proteasome Unveiling a Complex Distribution of Functional States Int J Mol Sci. 2020. 21(19):7190.

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G.R. Tundo, D. Sbardella, A.M. Santoro, A. Coletta, F. Oddone, G. Grasso, D. Milardi, P.M. Lacal, S. Marini, R. Purrello, G. Graziani, M. Coletta. The proteasome as a druggable target with multiple therapeutic potentialities: Cutting and non-cutting edgesPharmacol Ther. 2020 Sep; 213: 107579. 

Diego Sbardella, Grazia Raffaella Tundo, Massimo Coletta, Gianluca Manni, Francesco Oddone. Dexamethasone Downregulates Autophagy through Accelerated Turn-Over of the Ulk-1 Complex in a Trabecular Meshwork Cells Strain: Insights on Steroid-Induced Glaucoma Pathogenesis. Int J Mol Sci. 2021 Jun; 22(11): 5891.

García-Viñuales, Sara, Sciacca, Michele F.M, Lanza, Valeria; Santoro, Anna Mariaa; Grasso, Giulia; Tundo, Grazia R.; Sbardella, Diego; Coletta, Massimiliano; Grasso, Giuseppe; La Rosa, Carmelo; Milardi, DaniloThe interplay between lipid and Aβamyloid homeostasis in Alzheimer's Disease: risk factors and therapeutic opportunities Chemistry and Physics of Lipids2021. 23: 105072.

Benvenuto, M., Ciuffa, S., Focaccetti, C., Tundo, G.R.,  ...Coletta, M., Bei, R.Proteasome inhibition by bortezomib parallels a reduction in head and neck cancer cells growth, and an increase in tumor-infiltrating immune cellsScientific Reports, 2021, 11(1), 19051.

Tundo, Grazia R; Sbardella, Diego; Oddone, Francesco; Kudriaeva, Anna A.Lacal, Pedro M; Belogurov, Alexey A; Graziani, Grazia; Marini, Stefano At the cutting edge against cancer: A perspective on immunoproteasome and immune checkpoints modulation as a potential therapeutic intervention. Cancers202113:4852.

Tundo, G.R., Sbardella, D., Oddone, F., ...Parravano, M., Coletta, M.Insulin-Degrading Enzyme Is a Non Proteasomal Target of Carfilzomib and Affects the 20S Proteasome Inhibition by the Drug. Biomolecules, 2022, 12(2), 315.

Tundo GR, Cascio P, Milardi D, Santoro AM, Graziani G, Lacal PM, Bocedi A, Oddone F, Parravano M, Coletta A, Coletta M, Sbardella D Targeting immunoproteasome in neurodegeneration: A glance to the future. Pharmacol Ther. 2023 Jan;241:108329. doi: 10.1016/j.pharmthera.2022.108329. 

Sbardella D, Tundo GR, Mecchia A, Palumbo C, Atzori MG, Levati L, Boccaccini A, Caccuri AM, Cascio P, Lacal PM, Graziani G, Varano M, Coletta M, Parravano M. A novel and atypical NF-KB pro-inflammatory program regulated by a CamKII-proteasome axis is involved in the early activation of Muller glia by high glucose. Cell Biosci. 2022 Jul 16;12(1):108. doi: 10.1186/s13578-022-00839-x.

Persico M, Santoro AM, D'Urso A, Milardi D, Purrello R, Cunsolo A, Gobbo M, Fattorusso R, Diana D, Stefanelli M, Tundo GR, Sbardella D, Coletta M, Fattorusso C. Modulation of the 20S Proteasome Activity by Porphyrin Derivatives Is Steered through Their Charge Distribution.Biomolecules. 2022 May 24;12(6):741. doi: 10.3390/biom12060741

Persico M, García-Viñuales S, Santoro AM, Lanza V, Tundo GR, Sbardella D, Coletta M, Romanucci V, Zarrelli A, Di Fabio G, Fattorusso C, Milardi D. Silybins are stereospecific regulators of the 20S proteasome.Bioorg Med Chem. 2022 Jul 15;66:116813. doi: 10.1016/j.bmc.2022.116813.

De Simone G, Tundo GR, Coletta A, Coletta M, Ascenzi P. Hydroxylamine-induced oxidation of ferrous nitrobindins.J Biol Inorg Chem. 2022 Aug;27(4-5):443-453. doi: 10.1007/s00775-022-01940-9. 

Boccaccini A, Cavaterra D, Carnevale C, Tanga L, Marini S, Bocedi A, Lacal PM, Manni G, Graziani G, Sbardella D, Tundo GR.Novel frontiers in neuroprotective therapies in glaucoma: Molecular and clinical aspects.Mol Aspects Med. 2023 Dec; 94:101225. doi: 10.1016/j.mam.2023.101225. Epub 2023 Nov 24.

Tundo GR, Grasso G, Persico M, Tkachuk O, Bellia F, Bocedi A, Marini S, Parravano M, Graziani G, Fattorusso C, Sbardella D. The Insulin-Degrading Enzyme from Structure to Allosteric Modulation: New Perspectives for Drug Design.Biomolecules. 2023 Oct 7;13(10):1492. doi: 10.3390/biom13101492.

Benvenuto M, Angiolini V, Focaccetti C, Nardozi D, Palumbo C, Carrano R, Rufini A, Bei R, Miele MT, Mancini P, Barillari G, Cirone M, Ferretti E, Tundo GR, Mutti L, Masuelli L, Bei R.Antitumoral effects of Bortezomib in malignant mesothelioma: evidence of mild endoplasmic reticulum stress in vitro and activation of T cell response in vivo.Biol Direct. 2023 Apr 17;18(1):17. doi: 10.1186/s13062-023-00374-w.

Riccardo Lorrai, Dario Cavaterra, Sara Gianmaria , Diego Sbardella , Grazia Raffaella Tundo, Alessandra Boccaccini  Eye diseases: when the solution comes from plant alkaloids. Planta Med 2024 Mar 7. doi: 10.1055/a-2283-2350. 

Vesci L*, Tundo Grazia Raffaella*, Soldi S, Galletti S, Stoppoloni D, Bernardini R, Modolea AB, Luberto L, Marra E, Giorgi F, Marini S. A Novel Lactobacillus brevis Fermented with a Vegetable Substrate (AL0035) Counteracts TNBS-Induced Colitis by Modulating the Gut Microbiota Composition and Intestinal Barrier.Nutrients. 2024 Mar 24;16(7):937. doi: 10.3390/nu16070937.mmhjj. *These authors have equally contributed to this work

Finanziamenti

Principal Investigator categoria under 40 per il progetto “Analysis of functional and structural properties of different proteasome populations: implication in neurodegeneration”, “Prin 2022 - Decreto Direttoriale n. 104 del 02-02-2022 “ (ricerca PRIN2022R9WCZS_001).

Brevetti

2017: Methods for the Quick Diagnosis of Rett Syndrome. Patent number: 102016000117469