CURRICULUM VITAE, MAURIZIO BRIGOTTI
Born in 1962
Place of birth: Bologna (Italy)
EDUCATION
1987, Degree in Biological Sciences cum laude (University of Bologna, Italy)
1993, PhD in Experimental Pathology (University of Bologna, Italy)
1993-1996, Postdoctoral fellow, Department of Experimental Pathology (University of Bologna, Italy), Fellowships from National Research Council (CNR), and from Regione Emilia-Romagna, Italy
CAREER:
1996, Professor of General Pathology on annual contract (School of Medicine, University of Parma, Italy)
1997 to 2020, Assistant Professor, Department of Experimental Pathology, (since 2012, Department of Experimental, Diagnostic and Specialty Medicine, School of Medicine, University of Bologna, Italy)
2006 to 2020, Aggregate Professor, Department of Experimental Pathology (since 2012, Department of Experimental, Diagnostic and Specialty Medicine, School of Medicine, University of Bologna, Italy)
2017, Italian national licence for Associate Professor of General Pathology
2017, Italian national licence for Full Professor of General Pathology
2018, Member of the PhD program in Oncology, Hematology and Pathology (School of Medicine, University of Bologna)
2020 to present, Associate Professor of General Pathology, Department of Experimental, Diagnostic and Specialty Medicine, School of Medicine, University of Bologna, Italy
2023, Research and teaching activities are carried out in the Department of Medical and Surgical Sciences (DIMEC) after the joining of DIMES to the latter Department
TEACHING
1999 to present, General Pathology, General Physiopathology (in English), Immunology, Molecular Pathology, and Cellular Pathology, School of Medicine, University of Bologna (mean of students’ evaluation 8.8/10, positive evaluations 95%).
SCIENTIFIC ACTIVITY: Author of more than 80 scientific publications on international journals ((Nature Protocols, Nucleic Acids Research, Journal of Pathology, Emerging Infectious Diseases, ACS Applied Materials & Interfaces, American Journal of Pathology, Journal of Immunology, FASEB Journal, Cancer Research, Pediatrics, Thrombosis & Haemostasis, Journal of Biological Chemistry, Toxins, Journal of Clinical Microbiology, Journal of Pediatrics, Scientific Reports, RNA, Molecular Microbiology, Cellular Microbiology, Journal of Leukocyte Biology, Infection and Immunity, Experimental Cell Research, Journal of Physiology, DNA repair, Biochemical Journal, FEBS Letters, Pediatric Infectious Disease Journal).
1987-2001: Research team member, Principal investigators: Prof. Lucio Montanaro and Prof. Simonetta Sperti, (Department of Experimental Pathology, University of Bologna, Italy)
2001 to present: Principal investigator, Department of Experimental Pathology (since 2012, Department of Experimental, Diagnostic and Specialty Medicine, School of Medicine, University of Bologna, Italy)
2001 to present: Collaboration with the National Reference Laboratory for Escherichia coli infections, Istituto Superiore di Sanità, Rome (since 2006, European Reference Laboratory).
2001 to present: Research activity in the framework of the National Registry of hemolytic uremic syndrome
2010 to present: Setup of a regional network (Lombardia, Italy) aimed at early diagnosis of Shiga toxin-producing E. coli infections in children (53 pediatric units, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico di Milano, Centro per la Cura e lo Studio della Sindrome Emolitico Uremica di Milano, Istituto Superiore di Sanità di Roma, Progetto ALICE ONLUS Associazione per la lotta alla SEU, Department of Experimental Pathology (since 2012, Department of Experimental, Diagnostic and Specialty Medicine, School of Medicine, University of Bologna, Italy)
2019 to present: Formal collaboration (Membership) with CNR (National Research Council), Institute of Applied Sciences & Intelligent Systems-ISASI, Pozzuoli (Naples)
Main results obtained:
(i) Studies on the molecular mechanism of action of plant ribosome-inactivating proteins (RIPs): identification of the cellular tRNAs involved in the stimulation of RIPs, identification of the tRNA identity elements required (1989-2001);
(ii) Studies on the molecular mechanism of action of specific bacterial toxins namely Shiga toxins: demonstration of the damaging effect of these toxins on nuclear DNA in human endothelial cells, discovery of small ring compounds inhibiting the enzymatic activity of these toxins, demonstration of the inhibitory effect of the toxins on DNA repair (1997-2007).
(iii) Studies on the pathogenesis of hemolytic uremic syndrome (HUS) caused by Shiga toxin-producing E. coli strains (VTEC/STEC): set up of rapid methods for the detection of Shiga toxins bound to neutrophils (indirect flow cytometric analysis) or free in sera (inhibition of translation in Raji cells) of patients. We have recently identified the Toll-like receptor 4 as the membrane molecule of human neutrophils that recognizes Shiga toxins. Moreover, the antibiotic polymyxin b, as well as the non-toxic derivative NAB815, were found to inhibit the interactions of Shiga toxins with TLR4 on neutrophils and the related functional consequences. Finally, the structure of Shiga toxins (holotoxin or nicked toxin) dictates the interactions of the toxins with blood components; i.e. binding to neutrophils (only holotoxin), activation of the complement system (nicked toxin). Recent findings have provided additional elements to foster the understanding of the pathophysiology of HUS. By comparing patients developing HUS and patients who recovered, we have found Shiga toxin 2 bound to circulating cells and then appearing in blood in particulate form, as in the case of extracellular vesicles, allowing the triggering of HUS. Finally, we have developed and patented the drug NAB815 which is capable of impairing the release of pathogenic microvesicles in human blood treated with Shiga toxin 2, thus blocking their toxic effects in cellular and animal models (2004-2023).
iv) Studies on the molecular pathology of ribosomes and protein synthesis. The methods employed in the studies on the effect of bacterial toxins on nucleic acids and ribosomes (see above) have been used to pursue other topics in collaboration with different research teams: effect of hyperosmolar stress on protein synthesis in vitro, protective effect of deuterated amino acids against oxidative damage in proteins, structural and functional alterations of ribosomes in cancer. A new protocol describing the isolation of stringently purified ribosomes from human cells for evaluating efficiency and fidelity of cis-acting elements mediated-translation in vitro has been developed and published on Nature Protocols (2003-2023).
PATENTS:
2019, nr 102019000025414 “Compound for the treatment of hemolytic-uremic syndrome” Alma Mater Studiorum – University of Bologna; Inventors: Maurizio Brigotti, Domenica Carnicelli, Elisa Porcellini, Elisabetta Galassi; 2021, WO2021130700 (A1) EU, USA, Canada, Japan e Brazil.
POSITION
Head of the Laboratory of Molecular Pathology of Bacterial Toxins, (Department of Experimental, Diagnostic and Specialty Medicine, School of Medicine, University of Bologna, Italy)
INVITED LECTURES
1997, May 29: Accademia delle Scienze, Istituto di Bologna
1999, June 15: Istituto di Patologia generale, Università di Parma
2004, June 22: Dipartimento di Medicina sperimentale, Università di Parma
2005, December 1-2: V National Workshop Enternet, Sorveglianza e Prevenzione delle infezioni gastroenteriche; Istituto Superiore di Sanità, Rome
2005, December 5-7: Speaker and chairman, VT/Shiga toxin and HUS patho-physiology Session, Consenus meeting: Pathogenesis of verocytotoxin (VT)-producing Escherichia coli (VTEC) infection: defining a new paradigm for pathogenic VTEC organized in the framework of the European network of excellence MED-VET-NET (VI program of EU research), Istituto Superiore di Sanità, Rome
2008, March 6-7: International Conference on E. coli: Pathogenicity, Virulence and Emerging Pathogenic Strains; Pathogenic Escherichia coli Network (PEN) (VI program of EU research), Istituto Superiore di Sanità, Rome
2010, October 8: 5th Annual workshop of the National Reference Laboratories for E. coli in the EU, Istituto Superiore di Sanità, Rome
2011, June 8-10: II Summer School Pathogen-Host interactions, International Graduate School Molecular Interactions of Pathogens with Biotic and Abiotic Surfaces, University of Münster, Germany
2012, May 6-9: Chairman, Pathogenesis, host response and animal models Session, 8thInternational Symposium on Shiga Toxin (Verocytotoxin) Producing Escherichia coliinfections, Amsterdam, The Netherlands
2012, September 26, II Summer School Pathogen-Host interactions, International Graduate School Molecular Interactions of Pathogens with Biotic and Abiotic Surfaces, University of Münster, Germany
2014, June 4-6: III Summer School Pathogen-Host interactions at cellular barrier, International Graduate School Molecular Interactions of Pathogens with Biotic and Abiotic Surfaces, University of Münster, Germany
2015, July 12-14: 5th International conference: HUS and related disorders, Innsbruck, Austria
2015, December 2: Division of Hygiene & Medical Microbiology Department of Hygiene, Microbiology and Social Medicine, Innsbruck Medical University, Innsbruck, Austria
2017, June 11-13: 6th International conference: HUS and related disorders, Innsbruck, Austria
2023, May 7-10, 11th International Symposium on Shiga Toxin (Verocytotoxin) Producing Escherichia coli Infections (VTEC 2021), Banff, Alberta (Canada)
2023, July 25: Division of Hygiene & Medical Microbiology Department of Hygiene, Microbiology and Social Medicine, Innsbruck Medical University, Innsbruck, Austria
INTERNATIONAL CONGRESS AND MEETING ORGANIZATION
2005, December 5-7: Organization of the VT/Shiga toxin and HUS patho-physiology Session, Consenus meeting: Pathogenesis of verocytotoxin (VT)-producing Escherichia coli (VTEC) infection: defining a new paradigm for pathogenic VTEC organized in the framework of the European network of excellence MED-VET-NET (VI program of EU research), Istituto Superiore di Sanità, Rome
2016, January, Member of the Local Organizing Committee for The 10th International Symposium on Shiga Toxin (Verocytotoxin) Producing Escherichia coli Infections (VTEC 2018), Florence, Italy, from 6 to 9 May, 2018
2016, December, Member of the International Scientific Committee for The 10th International Symposium on Shiga Toxin (Verocytotoxin) Producing Escherichia coli Infections (VTEC 2018), Florence, Italy, from 6 to 9 May, 2018
2019, December, Member of the International Scientific Committee for The 11th International Symposium on Shiga Toxin (Verocytotoxin) Producing Escherichia coli Infections (VTEC 2021), Banff Alberta (Canada) May 9-12, 2021
FUNDING
• University of Bologna, funds for basic research (2001-2022) 94,000 Euro
• University of Bologna funds for selected research topics (2000) 13,000 Euro
• Italian Ministry of University and Scientific and Technological Research (2004) 40,000 Euro (as participant of research unit)
• Italian Ministry of University and Scientific and Technological Research (2009) 56,000 Euro
• Italian Ministry of University and Scientific and Technological Research (2022) 61,000 Euro
• Roberto and Cornelia Pallotti's legacy (2004-2021) 182,000 Euro
• Regione Lombardia (2010) 12,500 Euro
• Progetto ALICE ONLUS Associazione per la lotta alla SEU (2011-2023) 84,000 Euro
• School of Medicine of the University of Bologna, fellowship (2008) 12,000 Euro
• Private funds, fellowships (2005-2009) 69,000 Euro
• Vodafone (2011) 15,000 Euro
• FFARB (2017) 3,000 Euro
• Proof of concept (UNIBO) 20,000 Euro
EDITORIAL ACTIVITY: translation of two texts of General Pathology
1994 "Oxford textbook of Pathology. Vol. 1 Principles of Pathology" edited by Zanichelli: “Patologia 1. I Principi” Chapters 5, 6, 10, 11.
2000 "Robbins. Pathologic basis of disease" edited by Piccin: “Robbins. Le basi patologiche delle malattie” Vol. I, Chapters 3, 10.
2016 to present: Review Editor, Frontiers in Cellular and Infection Microbiology
2018 to present: Guest Editor, Toxins (MDPI), special issue “Pathogenesis of Hemolytic Uremic Syndrome Caused by Shiga Toxin-Producing Escherichia coli Infections”
SCIENTIFIC ASSOCIATIONS
2016 to present: Regular Member, American Association of Immunologists (AAI)
