Tutti i giorni per appuntamento: Tel. 055 4574261; fragai@cerm.unifi.it
marco.fragai@unifi.it
Centro di Risonanze Magnetiche, via Sacconi 6, Sesto Fiorentino
Every day by appointment: Tel. 055 4574261; fragai@cerm.unifi.it
Magnetic Resonance Center, via Sacconi 6, Sesto Fiorentino
Posizione attuale 2015-oggi – Professore Associato di Chimica (CHIM03/B1), Università degli studi di Firenze Carriera universitaria 2005-2015 – Ricercatore di Chimica (CHIM03/B1), Università degli studi di Firenze 2002-2004 – Assegnista di ricerca presso il Centro di Risonanze Magnetiche (CERM), Università degli studi di Firenze Istruzione e formazione 2001 – Dottorato di ricerca in Scienze Chimiche, Università degli studi di Firenze Titolo della tesi: Nuclear Spin Relaxation and Electron-Nucleus Interactions in Paramagnetic Complexes and Biological Macromolecules 1996 – Laurea in Chimica e Tecnologia Farmaceutiche (110/110 cum laude), Università degli studi di Firenze Insegnamenti 2005-2008 – Esercitazioni di Chimica 2008-oggi – Chimica Generale e Inorganica Incarichi – Membro del consiglio scientifico del Centro di Risonanze Magnetiche (CERM), Università degli studi di Firenze – Responsabile scientifico del laboratorio pubblico-privato “Recombinat protein JOYNLAB”, Dipartimento di Chimica & Centro di Risonanze Magnetiche (CERM) – Membro del comitato scientifico dello spin-off univeristario Giotto Biotech s.r.l. – Membro del consiglio dei docenti del Dottorato Internazionale in Biologia Strutturale, Università degli studi di Firenze (2009-2012) – Membro del consiglio dei docenti del Dottorato in Scienze Chimiche, Università degli studi di Firenze (2013-oggi) – Tutore negli anni di 12 studenti del Dottorato Internazionale in Biologia Strutturale (3 dei quali nell’ambito delle “Marie Skłodowska-Curie actions”, Horizon2020 contratti n°. 813239 e n° 956758) e di 1 studente del Dottorato in Scienze Chimiche. Ricerca La sua attività di ricerca è focalizzata sullo studio delle interazioni fra proteine sia a livello intracellulare che extracellulare. Attraverso l’utilizzo delle tecniche di risonanza magnetica nucleare si è dedicato alla caratterizzazione della struttura e delle proprietà dinamiche di proteine e di acidi nucleici, con particolare attenzione a quelle biomolecole che costituiscono potenziali bersagli farmacologici. I suoi studi hanno contribuito a chiarire diversi passaggi del meccanismo catalitico delle metalloproteinase di matrice e a dimostrare la presenza di mobilità interdominio e l’eterogeneità conformazionale che caratterizza questa famiglia di enzimi. In particolare la sua attività di ricerca ha contribuito a fornire un dettagliato un meccanismo (favorito dal punto di vista energetico) per la collagenolisi dove il dominio emopexinico svolge un ruolo fondamentale nel riconoscimento del substrato. Le sue competenze scientifiche spaziano dagli agenti di contrasto per MRI, all’utilizzo delle tecniche NMR e computazionali per il drug discovery e lo “structure-based drug design”. Ha inoltre sfruttato i metalli paramagnetici per aumentare la sensibilità delle metodologie di screening via NMR e ha sviluppato nuovi inibitori delle metalloproteinasi di matrice. Pìù recentemente si è dedicato allo sviluppo di metodologie per la caratterizzazione dei farmaci biologici anche attraverso l’utilizzo delle tecniche di risonanza magnetica allo stato solido e allo studio delle proteine amiloidogeniche. E’ coautore di 146 articoli su riviste internazionali, di 5 capitoli di libro e di 4 brevetti nell’ambito del drug design. Il suo h-index è 33 e le sue citazioni 3495 (scopus). Esperienze in laboratori esteri 2008 - Laboratory of Dr. Ramos Andres - National Institute for Medical Research (MRC), London (UK) 2006 - Laboratory of Biomolecular Mass spectrometry and Proteomics - University of Utrecht (NL) 2003 - Laboratory of Prof. Maurizio Pellecchia - Sanford Burnham Prebys Medical Discovery Institute (SBP), San Diego (USA) Brevetti - Functionalized hyaluronic acid - WO2018029588 (Al)-15-02-2018 - AZA-Tanshinone derivatives, process for their preparation and their use in therapy - WO2017216732 (A1)-2017-12-21 - Use of matrix metalloproteinases, mutated and not mutated, for the preparation of pharmaceutical compositions, and mutated metalloproteinases with increased stability - US2010047894 (A1)-2010-02-25 - Derivatives of arylsulfonamido-substituted hydroxamic acid as matrix metalloproteinases inhibitors - WO2006013193 (A2)-2006-02-09 Finanziamenti - Pathway-27 "Pivotal assessment of the effects of bioactives on health and wellbeing. - From human genoma to food industry" http://pathway27.eu/ FP7-KBBE-THEME 2 2007-2013- Third party-clausola 10 - Financed by the European Commission, Contract number 311876 - Finanziamento annuale individuale delle attività base di ricerca (2017) - "Development of Innovative Strategies to Characterize Therapeutic Protein-Polymer Conjugates at Atomic Detail" - Ente Cassa di Risparmio di Firenze (2017) - Caratterizzazione di biomolecole di interesse farmaceutico mediante tecniche di risonanza magnetica - Ricerca conto terzi - Dompè Farmaceutici S.p.a. (2019) - Application of 2D NMR to HOS characterization studies: making NMR a routine approach - Ricerca conto terzi - Merck-Serono S.p.a. (2019) - iNEXT-Discovery "Infrastructure for transnational access and discovery in structural biology" -Third party- Financed by the European Commission HORIZON2020, Contract number 871037 - Glytunes "a multidisciplinary training network for the bioinspired development of glycomimetics tuning the Siglec-Sialoglycan axis" - Horizon 2020 - Excelllence Science - MSCA-ITN-2020, Project Number 956758. - GlycoNoVi "Understanding the Role of Glycans in Human Norovirus Infection: a Key to Unlock New Therapies" European Union’s Horizon Research and Innovation programme under the Marie Skłodowska-Curie (HORIZON-MSCA-2021-DN-01) Grant agreement No. 101072717 - GLYDOME "Molecular recognition of Fusobacterium envelope glycans by Siglecs" PRIN 2022 Project Number 2022ZEZS45 Highlights - Fields G.: F1000Prime Recommendation of [Bertini I. et al., Proc.Natl.Acad.Sci. U S A 2005, 102(15):5334-9]. In F1000Prime, 21 Oct 2005; DOI: 10.3410/f.1028538.342177. F1000Prime.com/1028538#eval342177 - Silverman S: F1000Prime Recommendation of [Limongelli V. et al., Angew.Chem.Int.Ed.Engl. 2013, 52(8):2269-73]. In F1000Prime, 09 Apr 2013; DOI: 10.3410/f.717972271.793473734. F1000Prime.com/717972271#eval793473734 Attività come revisore Chemistry, Structure, Journal of Biological Inorganic Chemistry, Pharmaceuticals, ChemMedChem, Molecules
Legenda
Present appointments 2015-present - Associate Professor of Chemistry at the University of Florence Career 2005-2015 - Tenured Researcher of Chemistry at the University of Florence 2002-2004 - Postdoctoral fellow at the Magnetic Resonance Center, University of Florence Education 2001 - PhD in Chemistry, University of Florence. Dissertation: Nuclear Spin Relaxation and Electron-Nucleus Interactions in Paramagnetic Complexes and Biological Macromolecules 1996 - Degree in Chemistry and Pharmaceutical Technologies (110/110 cum laude) Teaching 2005- present - General and Inorganic Chemistry, University of Florence Offices - Member of the scientific committee of the Magnetic Resonance Center (CERM), University of Florence - Member of the academic board of the International Doctorate in Structural Biology (2009-2012), and of the Doctorate in Chemical Sciences (2013-present) at the University of Florence - Tutor of 12 PhD students of the International Doctorate in Structural Biology (3 PhD in the frame of Marie Skłodowska-Curie grant agreements No. 813239 and 956758), and 1 PhD student of the Doctorate in Chemical Sciences, University of Florence. - Scientific director of the joint research laboratory “Recombinat protein JOYNLAB”, Department of Chemistry, University of Florence - Member of the scientific committee of Giotto Biotech s.r.l. Research His research focus on understanding protein interactions inside cells and in the extracellular environment. He uses nuclear magnetic resonance (NMR) methodologies to determine the structure and dynamics of proteins and nucleic acids, particularly drug targets, and to probe protein–protein and protein–ligand interactions. His studies have contributed to reveal a large part of the catalytic steps of matrix metalloproteinases by using substrate models, and to demonstrate the interdomain mobility and conformational heterogeneity that characterize these proteolytic enzymes. Recently his research activity has contributed to provide a detailed, experimentally-derived, and energetically favorable collagenolytic mechanism, and a significant insight into the role of catalytic and hemopexin-like domains in substrate recognition and proteolysis. His scientific experience includes the development of contrast agents for MRI and the use of NMR in biological applications such as structure-based drug discovery, including computational and screening methodologies. In particular, he has used paramagnetic metal ions to improve the sensitivity of NMR-based ligand screening strategies and he has contributed to develop new highly soluble matrix metalloproteinases inhibitors. He has also focused on the development of solid-state NMR for the characterization of immobilized enzymes, conjugated biologics and vaccines. Currently, his research focused on the structural basis of α-synuclein aggregation, on small molecules as modulators of α-synuclein assembly. He is co-author of 146 research articles in international peer-reviewed journals with 3495 citations (scopus), and of 5 book chapters (h-index=33, Scopus). He holds 4 patents on drug design. Visiting research fellow 2008 - Laboratory of Dr. Ramos Andres - National Institute for Medical Research (MRC), London (UK) 2006 - Laboratory of Biomolecular Mass spectrometry and Proteomics - University of Utrecht (NL) 2003 - Laboratory of Prof. Maurizio Pellecchia - Sanford Burnham Prebys Medical Discovery Institute (SBP), San Diego (USA) Patents - Functionalized hyaluronic acid - WO2018029588 (Al)-15-02-2018 - AZA-Tanshinone derivatives, process for their preparation and their use in therapy - WO2017216732 (A1)-2017-12-21 - Use of matrix metalloproteinases, mutated and not mutated, for the preparation of pharmaceutical compositions, and mutated metalloproteinases with increased stability - US2010047894 (A1)-2010-02-25 - Derivatives of arylsulfonamido-substituted hydroxamic acid as matrix metalloproteinases inhibitors - WO2006013193 (A2)-2006-02-09 Funding - Pathway-27 "Pivotal assessment of the effects of bioactives on health and wellbeing. - From human genoma to food industry" http://pathway27.eu/ FP7-KBBE-THEME 2 2007-2013- Third party-clausola 10 - Financed by the European Commission, Contract number 311876 - Finanziamento annuale individuale delle attività base di ricerca (2017) - "Development of Innovative Strategies to Characterize Therapeutic Protein-Polymer Conjugates at Atomic Detail" - Ente Cassa di Risparmio di Firenze (2017) - Caratterizzazione di biomolecole di interesse farmaceutico mediante tecniche di risonanza magnetica - Ricerca conto terzi - Dompè Farmaceutici S.p.a. (2019-2020) - Application of 2D NMR to HOS characterization studies: making NMR a routine approach - Ricerca conto terzi - Merck-Serono S.p.a. (2019-2020) - iNEXT-Discovery "Infrastructure for transnational access and discovery in structural biology" -Third party- Financed by the European Commission HORIZON2020, Contract number 871037 (2020) - H2020-MSCA-ITN-2020 "Glytunes" EU project 956758 - To create a multidisciplinary training network for the bioinspired development of glycomimetics tuning the Siglec-Sialoglycan axis (2020-2023) - GlycoNoVi "Understanding the Role of Glycans in Human Norovirus Infection: a Key to Unlock New Therapies" European Union’s Horizon Research and Innovation programme under the Marie Skłodowska-Curie (HORIZON-MSCA-2021-DN-01) Grant agreement No. 101072717 - GLYDOME "Molecular recognition of Fusobacterium envelope glycans by Siglecs" PRIN 2022 Project Number 2022ZEZS45 Highlights - Fields G.: F1000Prime Recommendation of [Bertini I. et al., Proc.Natl.Acad.Sci. U S A 2005, 102(15):5334-9]. In F1000Prime, 21 Oct 2005; DOI: 10.3410/f.1028538.342177. F1000Prime.com/1028538#eval342177 - Silverman S: F1000Prime Recommendation of [Limongelli V. et al., Angew.Chem.Int.Ed.Engl. 2013, 52(8):2269-73]. In F1000Prime, 09 Apr 2013; DOI: 10.3410/f.717972271.793473734. F1000Prime.com/717972271#eval793473734 Service Journal peer reviewer (Chemistry, Structure, Journal of Biological Inorganic Chemistry, Pharmaceuticals, ChemMedChem, Molecules)