Giuseppe
Mancuso
Email:
giuseppe.mancuso@unime.it
ALTRE INFORMAZIONI
SSD: MED/07
Profilo: Professori Associati
CURRICULUM
Curriculum
Titoli di studio-Laurea in Medicina e Chirurgia (110/110 e lode) presso l'Università degli studi di Messina nell'anno accademico 1984-1985.
-Abilitazione all'esercizio della professione di Medico-Chirurgo presso l'Università degli studi di Messina nella sessione estivo-autunnale dell'anno 1985.
-Specializzazione in Virologia (con lode) presso l'Università degli studi di Messina nell'anno 1988.
-Diploma di Dottore di Ricerca in Discipline Microbiologiche conseguito presso il Ministero dell'Università e della Ricerca Scientifica nell'anno 1994.
-Specializzazione in Microbiologia e Virologia (con lode) presso l'Università degli studi di Messina nell'anno 1997.
Percorso professionale
-Nominato ricercatore universitario per il raggruppamento scientifico-disciplinare MED/04 in data 08/03/1999 presso il Dipartimento di Patologia e Microbiologia Sperimentale della Facoltà di Medicina e Chirurgia dell’Università degli studi di Messina. Dal 01/10/2012 ha afferito al Dipartimento di Scienze Pediatriche, Ginecologiche, Microbiologiche e Biomediche dell’Università degli studi di Messina.
-Direttore dello Stabilimento Utilizzatore ed Allevatore del Dipartimento di Patologia e Microbiologia Sperimentale (2006-2010), del Dipartimento di Scienze Pediatriche, Ginecologiche, Microbiologiche e Biomediche (2010-2015) e del Dipartimento di Patologia Umana dell'adulto e dell'età evolutiva "G. Barresi) (2015 a tutt'oggi).
-Nel 2014 ha conseguito l'Abilitazione Scientifica Nazionale per Professore Associato di Microbiologia Generale e Microbiologia Clinica (SSD MED07) e di Patologia Generale (SSD MED04).
-Nominato professore associato per il raggruppamento scientifico-disciplinare MED/07 in data 01/11/2014 presso il Dipartimento di Scienze Pediatriche, Ginecologiche, Microbiologiche e Biomediche dell’Università degli studi di Messina.
-Vicepresidente dell'Organismo Preposto al Benessere Animale (OPBA) dell'Università degli studi di Messina (2014 a tutt'oggi).
-Dal 01/10/2015 afferisce in qualità di professore associato al Dipartimento di Patologia Umana dell'adulto e dell'età evolutiva "G. Barresi" dell'Università degli studi di Messina.
-Dirigente Medico di I° livello presso l’Unità Operativa Complessa di Micologia e Micobatteriologia dell’Azienda Ospedaliera Universitaria “G. Martino” di Messina dal 1999 al 2009.
-Dirigente Medico di I° livello presso la sezione di Micologia e Micobatteriologia ed il laboratorio centralizzato dell’Unità Operativa Complessa di Patologia Clinica dell’Azienda Ospedaliera Universitaria “G. Martino” di Messina dal 2010 al 31/03/2017.
-Dirigente Medico di I° livello presso la UOC di Microbiologia Clinica dell’Azienda Ospedaliera Universitaria “G. Martino” di Messina dal 01/04/2017 a tutt'oggi.
-Dal 14/04/2011 titolare di un incarico di Alta Professionalità conferitogli dal Direttore Generale dell’Azienda Ospedaliera Universitaria “G. Martino” di Messina.
-Dal 6 aprile 2020 Responsabile del Laboratorio Covid della AOU "G. Martino" di Messina, Centro di Riferimento Regionale per la Provincia di Messina.
-Dal 1 luglio 2021 Direttore della UOC di Microbiologia Clinica della AOU "G. Martino" di Messina.
Attività didattica
-Docente di Microbiologia nel Corso di Laurea di Fisioterapista della Facoltà di Medicina e Chirurgia dell’Università degli studi di Messina per gli aa 2000-2001 e 2001-2002.
-Docente di Virologia Clinica applicata alla Microbiologia nella scuola di Specializzazione di Microbiologia e Virologia della Facoltà di Medicina e Chirurgia dell’Università degli studi di Messina dall’anno accademico 1999-2000.
-Docente di Patologia Genetica nella scuola di Specializzazione di Patologia Clinica della Facoltà di Medicina e Chirurgia dell’Università degli studi di Messina per l’anno accademico 2002-2003.
-Docente di Microbiologia generale e Microbiologia clinica nel Corso di Laurea per Ortottisti assistenti di Oftalmologia della Facoltà di Medicina e Chirurgia dell’Università degli studi di Messina dall’aa 2002-2003.
-Coordinatore Corso Integrato di Scienze Biologiche I nel Corso di Laurea per Ortottisti assistenti di Oftalmologia della Facoltà di Medicina e Chirurgia dell’Università degli studi di Messina dall’aa 2011 a tutt'oggi.
-Docente di Microbiologia Clinica nel corso integrato di Medicina di Laboratorio nel CdL di Medicina e Chirurgia nell'aa 2014-2015 e 2015-2016.
-Docente di Microbiologia generale e Microbiologia clinica nel corso integrato di Basi Biologiche e Molecolari del CdL di Fisioterapia dall'aa 2015-2016 a tutt'oggi.
-Docente di Microbiologia generale e Microbiologia clinica nel corso integrato di Promozione della Salute e della Sicurezza del CdL di Infermieristica dall'aa 2015-2016 a tutt'oggi e Coordinatore dello stesso Corso Integrato dal 1 ottobre del 2018 a tutt'oggi.
-Docente di Microbiologia generale e Microbiologia clinica nel corso integrato di Scienze Biologiche del CdL di Tecniche della Prevenzione nell'ambiente e nei luoghi di lavoro dall'aa 2015-2016 a tutt'oggi.
-Docente di Microbiologia generale e Microbiologia clinica nel CdL di Medicina e Chirurgia dall'aa 2015-2020 a tutt'oggi.
-Docente di Statistica Medica nella scuola di Specializzazione di Microbiologia e Virologia della Facoltà di Medicina e Chirurgia dell’Università degli studi di Messina dall’anno accademico 2010-2011 all'aa 2014.
-Docente di Patologia Generale nella scuola di Specializzazione di Microbiologia e Virologia della Facoltà di Medicina e Chirurgia dell’Università degli studi di Messina dall’anno accademico 2010-2011 all'aa 2014.
-Docente di Microbiologia generale e Microbiologia Clinica nella scuola di Specializzazione di Microbiologia e Virologia dell’Università degli studi di Messina dall’anno accademico 2014 a tutt'oggi.
-Docente di Microbiologia generale e Microbiologia Clinica nelle Scuole di Specializzazione di Pneumologia, Malattie Infettive, Chirurgia Plastica, Chirurgia Maxillo-Facciale, Oculistica dell’Università degli studi di Messina.
-Coordinatore della Scuola di Specializzazione di Microbiologia e Virologia area medica non sanitaria dell’Università degli studi di Messina dall’anno accademico 2018-2019 e Direttore della stessa dal 1 aprile 2021.
-Docente della Scuola di Specializzazione di Microbiologia e Virologia area medica dell’Università degli studi di Catania e Coordinatore della sede di Messina dall’anno accademico 2019-2020.
-Docente di Virologia molecolare nel Dottorato di Ricerca in Biotecnologie Microbiche e della Proliferazione Cellulare dell’Università degli studi di Messina dall’anno accademico 2005-2006 all'aa 2011-2012. Nell’ambito dei vari cicli del suddetto dottorato ha fatto parte di diverse commissioni di ammissione e/o di diploma.
-Docente nel Dottorato di Ricerca in Biotecnologie Mediche e Chirurgiche dell'Università degli studi di Messina dall'aa 2013 a tutt'oggi.
-Membro del Collegio del Dottorato di Ricerca in "Translational molecular medicine and surgery" dell'Università degli studi di Messina
Partecipazione scientifica a progetti di ricerca
-Componente partecipante al progetto 01_00117 PON "Antigeni ed adiuvanti per vaccini ed immunoterapie" (Luglio 2011-Ottobre 2015).
-Responsabile Scientifico del suddetto PON dal maggio 2014.
-Responsabile Scientifico della Unità Partner del Progetto di ricerca "Biochemical and immunological analysis of surface/secreted proteins and their use as potential components of a multivavalent anti-Staphylococcus aureus vaccine" svolto dall'Università degli studi di Messina e finanziato dalla Fondazione Cariplo (n. di riferimento 2009-3546; 2011-2295; 2012-1881) (2013/2014).
-Componente partecipante al progetto 10911 PON "Vaccino innovativo contro il gruppo A dello streptococco" (2001-2006).
-Componente partecipante al PRIN "Vettori per la presentazione di vaccini anti-idiotipici" (dal 12/12/2001 al 23/01/2004).
-Responsabile Scientifico dei seguenti Progetti di Ricerca di Ateneo (PRA) dell'Università degli studi di Messina dall'anno accademico 1999-2000:
PRA 1999:Sviluppo di anticorpi ricombinanti ad uso vaccinale
PRA 2000:Ruolo delle tirosin-chinasi nell'attivazione cellulare indotta dallo streptococco di gruppo B
PRA 2001:Patogenesi dello shock settico da streptococco di gruppo B: ruolo del rilascio di prodotti batterici in seguito ad esposizione ad antibiotici
PRA 2002:Identificazione dei recettori Toll-simili coinvolti nell'attivazione di cellule fagocitarie da parte di lipopolisaccaride di Bacteroides fragilis
PRA 2003:Ruolo dei recettori Toll-simili e della molecola adattatrice MyD88 in modelli sperimentali di sepsi da streptococco di gruppo B
PRA 2004:Induzione di citochine da parte di proteine ricombinanti di streptococco di gruppo B
PRA 2005:Ruolo dei recettori Toll-simili nella patogenesi delle infezioni da Bartonella henselae
PRA 2006/2007:Identificazione di antigeni proteici pneumococcici capaci di indurre risposte protettive nel corso di infezioni causate da Streptococcus pneumoniae
PRA 2008/2009:Ruolo svolto da differenti componenti batterici nella patogenesi delle infezioni da streptococchi di gruppo A (GAS)
Partecipazione ad attività di ricerca svolta nell'ambito dei seguenti progetti di ricerca internazionali
-Progetto AIDS-finanziato dall'Istituto Superiore di Sanità (1996-2001)
-Progetto "PEPSAC-MIMIC" finanziato dalla Comunità Europea, contratto n. QLK2-CT-1999-00854 (durata 3 anni)
-Progetto "HOSPATH" finanziato dalla Comunità Europea, contratto n. QLK2-CT-2000-00336 (durata 3 anni)
-FP6-2003-LIFESCIHEALTH-I:European Virtual Institute for Functional Genomics of Bacterial Pathogens (durata 5 anni)
-Progetto "NoE Pathogenomics" finanziato dalla Comunità Europea, contratto n. 512061 (durata 3 anni)
Altri titoli
-Responsabile della sperimentazione animale per il progetto di ricerca “Sviluppo di nuovi vaccini ed anticorpi monoclonali per il controllo di infezioni causate da ceppi antibiotico-resistenti di Staphylococcus aureus” (2021-2024)
-Responsabile della sperimentazione animale per il progetto di ricerca "Ruolo dei recettori dell'immunita innata nella suscettibilità alle infezioni da pneumoccocco" (2019-2022)
-Responsabile della sperimentazione animale per il progetto di ricerca "Ruolo del regolatore trascrizionale CodY nella patogenesi della meningite neonatale e delle sepsi causate da Streptococco di gruppo B" (2019-2022).
-Responsabile della sperimentazione animale per il progetto di ricerca " Corso teorico/pratico in Scienza degli Animali da Laboratorio (LAS) per figure professionali A, B, C e D" (2018-2023).
-Responsabile della sperimentazione animale per il progetto di ricerca "Selezione di candidati vaccinali per il controllo delle infezioni invasive causate da Neisseria meningitidis", contratto finanziato dalla GSK (2017-2020).
-Responsabile della sperimentazione animale per il progetto di ricerca "Allestimento di un vaccino sperimentale nei confronti delle infezioni causate da Staphylococcus aureus", contratto finanziato dalla GSK (2016-2019).
-Responsabile della sperimentazione animale per il progetto di ricerca "Sviluppo di un vaccino contro ceppi patogeni intestinali ed extraintestinali di Escherichia coli", contratto finanziato dalla GSK (2015-2018).
-Responsabile della sperimentazione animale per il progetto di ricerca "Ruolo dell'immunità innata nelle infezioni da Streptococco di gruppo B", contratto finanziato dalla GSK (2015-2018).
-Responsabile della sperimentazione animale per il progetto di ricerca "Identificazione di molecole dell’immunità innata coinvolte nella patogenesi dell’infezione da Clostridium difficile", contratto finanziato dalla GSK (2015-2017).
-Responsabile della sperimentazione animale per il progetto di ricerca "Identificazione di candidati vaccinali per l'allestimento di un vaccino innovativo contro le infezioni causate da Staphylococcus aureus", contratto finanziato dalla Ditta Novartis Vaccines and Diagnostic S.r.l. (2011-2012).
-Responsabile della sperimentazione animale per il progetto di ricerca "Identificazione delle vie di trasduzione del segnale attivate dagli adiuvanti alum e MF59", contratto finanziato dalla Ditta Novartis Vaccines and Diagnostic S.r.l. (2011- 2012).
-Responsabile della sperimentazione animale per il progetto di ricerca "Candidati vaccinali per la prevenzione di infezioni da stafilococco aureo", contratto finanziato dalla Ditta Novartis Vaccines and Diagnostic S.r.l. (2008-2009).
-Responsabile della sperimentazione animale per il progetto di ricerca "Valutazione dell'attività protettiva da parte di proteine di pneumococco in modelli sperimentali murini", contratto finanziato dalla Ditta Novartis Vaccines and Diagnostic S.r.l. (2007-2009).
-Responsabile della sperimentazione animale per il progetto di ricerca "Identificazione di candidati vaccinali per la prevenzione di infezioni da streptococco di gruppo A (GAS)", contratto finanziato dalla Ditta Novartis Vaccines and Diagnostic S.r.l. (2007-2009).
Partecipazioni a corsi di formazione/meeting sulla sperimentazione animale
-Giornata di incontro con gli OPBA di Sicilia: "Attività del Comitato Nazionale per la Protezione degli Animali usati a fini scientifici (CNPA)", Accademia Peloritana dei Pericolanti, Università degli Studi di Messina, 28 febbraio 2018, Messina.
-"Benessere ed utilizzo scientifico degli animali:prospettive attuali della relazione uomo-animale", Aula Magna Unical, 4-5 dicembre 2017, Cosenza
-" Il principio delle 3R: applicazioni e innovazione”. Istituto Superiore di Sanità, 16-17 ottobre 2017, Roma.
-Corso di aggiornamento degli utilizzatori di animali a fini scientifici su nuove funzionalità della Banca Dati Sperimentazione Animale. Ministero della Salute, 12 luglio 2017, Roma.
-"Gli OPBA e la valutazione tecnico scientifica dei progetti sperimentali con animali: procedure, contenuti e professionalità. Indirizzo farmacologico". Istituto Superiore Sanità, 24-25 novembre 2015, Roma.
-L’utilizzo della “banca dati telematica sperimentazione animale” per la raccolta dei dati statistici annuali. Ministero della Salute, 6-7 ottobre 2014, Roma.
-Giornate di assistenza per la compilazione dei dati statistici 2014 (Rendicontazione Alures), Roma c/o Ministero della Salute, 22 ottobre 2015.
-Giornata di studio su "Aspetti legislativi ed etici nella sperimentazione animale: attualità e prospettive" Università di Messina, 27 gennaio 2016, Messina
-Corso di Base in LAS e 3Rs, Università degli Studi di Messina, 25-29 Gennaio 2016, Messina---"Tutela degli animali e qualità della scienza: analisi e considerazioni a due anni dal recepimento italiano della Direttiva Europea 63/2010", Istituto Superiore di Sanità, 3 Ottobre 2016, Roma
Partecipazioni a Congressi e Workshop
-Seminars on shock: septic shock caused by gram-positive bacteria 10-12 Ottobre 1998, Vibo Valentia, Italia
-Anti-idiotypes and mimotopes in vaccine development. Vibo Valentia Seminars. 17-19 Maggio 2000. Vibo Valentia, Italia
-30° Congresso Nazionale Società Italiana di Microbiologia, 6-9 Ottobre 2002, Catania, Italia
-3rd Cryptococcus neoformans Genomics Conference, 9-10 Agosto 2003, University of British Columbia, Canada
-International Cytokine Society Annual Meeting, Trinity College 20-24 Setembre 2003, Dublino, Irlanda
-Invited speaker al 32° Congresso Nazionale Società Italiana di Microbiologia, 26-29 Settembre 2004, Milano, Italia con la relazione dal titolo "Ruolo dei recettori Toll-simili nella fisiopatologia delle sepsi"
-Toll 2004 Meeting, 8-11 Maggio 2004, Taormina, Italia
-Invited speaker al 34° Congresso Nazionale Società Italiana di Microbiologia, 15-18 Ottobre 2006, Genova, Italia con la relazione dal titolo "Ruolo dell'interferon di tipo I nelle infezioni batteriche e fungine"
-35°Congresso Nazionale Società Italiana di Microbiologia, 30 Settembre-3 Ottobre 2007, Catania, Italia
-Invited speaker al 36° Congresso Nazionale Società Italiana di Microbiologia, 12-15 Ottobre 2008, Roma, Italia con la relazione dal titolo "Induzione di interferon alpha/beta da parte di batteri:ruolo nella patogenesi e vie di trasduzione del segnale"
-Nobel Symposium,June 11-13, 2009, Stokholm, Svezia
-Invited speaker al 37° Congresso Nazionale Società Italiana di Microbiologia, 11-14 Ottobre 2009, Torino, Italia con la relazione dal titolo "Ruolo della via di trasduzione del segnale TLR7/TLR9/MyD88/IRF1 nella difesa dell'ospite contro infezioni batteriche e fungine"
-Recent progresses in post-genomics. Dipartimento Patologia e Microbiologia Sperimentale, Università di Messina, 24-25 Febbraio 2010, Messina, Italia
-I vaccini nell'era globale. Dipartimento Patologia e Microbiologia Sperimentale, Università di Messina, 24-25 Marzo 2011, Messina, Italia
-SHOCK, 31 Agosto-2 Settembre 2011, Taormina, Italia
-XVIII Lancefield International Symposium, 4-8 Sttembre 2011, Palermo, Italia
-39° Congresso Nazionale Società Italiana di Microbiologia, 3-6 Ottobre 2011, Riccione, Italia
-41° Congresso Nazionale Società Italiana di Microbiologia, 13-16 Ottobre 2013, Riccione, Italia
-43° Congresso Nazionale Società Italiana di Microbiologia, 27-30 Settembre 2015, Napoli, Italia
-Intrinsic And innate immunity to pathogens, 23-25 June 2016, Novara, Italy
-100 Years of phagocytes, 19-22 September 2016, Giardini Naxos, Italy
-44° Congresso Nazionale Società Italiana di Microbiologia, 25-28 Settembre 2016, Pisa, Italia
-XLV Congresso Nazionale AMCLI, 6-9 novembre 2016 Rimini
-45° Congresso Nazionale Società Italiana di Microbiologia, 27-30 Ottobre 2017, Genova, Italia
-CEMIR Annual Meeting, 19 ottobre 2017, Taormina
-Nuove frontiere della diagnostica microbiologica, AOUP P. Giaccone, 29 gennaio 2018.
Attività di ricerca
Il percorso scientifico e di ricerca del Prof. Mancuso nel corso di questi anni ha riguardato diversi settori della microbiologia e dell'immunità innata in particolare ed ha dato luogo a rilevanti contributi scientifici testimoniati dalla loro collocazione editoriale in accreditate e qualificate riviste internazionali.
Le principali tematiche di ricerca che hanno caratterizzato il percorso scientifico del Prof. Mancuso hanno riguardato:
- Studio del ruolo svolto da differenti mediatori endogeni dell’ospite quali citochine pro-infiammatorie ed anti-infiammatorie nella patogenesi dello shock endotossico causato dai batteri gram-negativi e dello shock settico del neonato, con particolare riferimento alle infezioni causate dagli streptococchi di gruppo B (SGB), un gruppo di batteri gram-positivi che sono causa di gravi e, spesso fatali, casi di sepsi neonatali.
-Studio di vaccini a DNA, di mimiche molecolari e della risposta dell’ospite ad agenti infettivi e a vaccini, con particolare riguardo alla prevenzione delle infezioni da batteri capsulati. Per quel che riguarda la prevenzione, è stata presa in esame la messa a punto di vaccini sperimentali volti a stimolare una risposta immunitaria umorale nei confronti degli SGB e della Neisseria meningitidis di gruppo B (MenB), due importanti cause di mortalità e di deficit neurologici permanenti, mediante mimiche molecolari degli stessi carboidrati. Allo scopo di indurre una risposta anti-idiotipica sono stati dapprima prodotti e caratterizzati anticorpi monoclonali tipo-specifici dotati di elevata attività protettiva. Questi anticorpi erano diretti nei confronti di epitopi protettivi dei polisaccaridi capsulari e svolgevano attività terapeutica in modelli murini neonatali di infezione sperimentale. Le nostre ricerche hanno inoltre dimostrato che questi anticorpi erano in grado di evocare una risposta anti-idiotipica protettiva. In un’altra serie di ricerche, sono stati identificati dei dodecapeptidi in grado di mimare le caratteristiche antigeniche del polisaccaride capsulare di MenB. Questi peptidi erano particolarmente immunogenici quando somministrati sotto forma di minigeni inseriti in opportuni vettori plasmidici per la vaccinazione a DNA. In altri studi è stata analizzata l’immunogenicità e l’attività protettiva di vari antigeni di Cryptococcus neoformans.
-L’identificazione dei recettori, delle vie di trasduzione del segnale e delle citochine coinvolti nelle risposte dell’ospite nei confronti di microrganismi patogeni capsulati di origine batterica e fungina o di loro componenti. Questi studi hanno messo in evidenza l’importanza del recettore Toll-like 2, della proteina adattatrice MyD88 e delle “Mitogen-activated protein kinases” come fattori cruciali nelle risposte difensive nei confronti di specifici microrganismi quali gli streptococchi di gruppo B, Haemophilus influenzae e Cryptococcus neoformans. Al contrario, il recettore Toll-like 4 risultava fondamentale nel mediare le risposte dirette contro Bacteroides fragilis. Queste ricerche inoltre hanno dimostrato il duplice ruolo (da un lato come fattori di resistenza alle infezioni, dall’altro come fattori patogenetici) dei recettori Toll-simili e di alcune citochine pro-infiammatorie nel corso di queste infezioni.
-Lo studio dei meccanismi della risposta immune innata nella patogenesi delle infezioni invasive sperimentali causate da batteri capsulati e della criptococcosi, una patologia infettiva emergente sempre più frequente per la sua associazione con la malattia da HIV. I risultati ottenuti in questi progetti di ricerca hanno dimostrato che gli interferoni di tipo I, un’importante famiglia di citochine primarie, svolgono un ruolo fondamentale nella patogenesi di questo tipo di infezioni in quanto topi difettivi per il recettore degli IFN di tipo I o per l’IFN-beta sono incapaci a controllare la crescita in vivo di questi microrganismi; ciò era correlato alla capacità degli IFN di tipo I di modulare in maniera differente la produzione di diversi mediatori nel corso delle diverse infezioni batteriche e di regolare, nel caso dell’infezione criptococcica, la polarizzazione della risposta citochinica dell’ospite orientandola verso una risposta linfocitaria protettiva di tipo Th1.
-L’identificazione dei meccanismi di difesa antimicrobica messi in atto dall’ospite nei confronti delle infezioni causate da batteri extracellulari. La ricerca, pubblicata su Nature Immunology, ha permesso di identificare l’esistenza di un sistema di riconoscimento batterico a livello fagosomiale, biologicamente rilevante e non ridondante, capace di operare in alcune cellule dell’immunità innata quali le cellule dendritiche convenzionali ma non nei macrofagi o nelle cellule dendritiche plasmocitoidi, che presumibilmente viene “allertato” dalla presenza di RNA batterico; pertanto, alcune categorie di batteri, eludendo i processi di maturazione fagosomiale o alterando l’integrità del fagosoma stesso, sono in grado di evitare non soltanto il killing diretto, ma anche il riconoscimento immunitario che avviene all’interno del lisosoma. E’ stato dimostrato in questo studio che questo sistema di riconoscimento richiede la presenza del recettore endosomiale TLR7, della molecola adattatrice MyD88 e del fattore di trascrizione IRF1, il quale svolge un ruolo cruciale nelle risposte sia dell’immunità innata che di quella adattativa.
-L’analisi del ruolo svolto da alcune citochine primarie nel corso delle infezioni causate da Candida albicans, il più frequente agente patogeno fungino umano, che sebbene si comporti in condizioni normali come un abituale commensale delle mucose umane di alcuni distretti anatomici, è capace di causare severe infezioni in pazienti ospedalizzati o immunocompromessi. I risultati sperimentali ottenuti hanno permesso di identificare alcuni importanti componenti di C. albicans, quali RNA e DNA, capaci di svolgere un ruolo importante nella patogenesi delle infezioni sostenute da questo microrganismo grazie alla loro abilità a determinare la produzione di differenti citochine primarie, in particolare di interferon beta, servendosi di recettori presenti sulle cellule dell’immunità innata (rispettivamente TLR7 e TLR9) per l’attivazione di diverse vie di traduzione del segnale (MyD88/IRF1).
-Lo studio del ruolo svolto dagli inflammasomi, degli importanti complessi multiproteici intracellulari, localizzati a livello citosolico, la cui attivazione determina l’induzione della caspasi-1, un enzima capace di indurre la maturazione di molecole quali l’interleuchina-1 beta e l’interleuchina-18, due citochine coinvolte nei meccanismi di difesa dell’ospite nei confronti delle infezioni. I dati del nostro lavoro di ricerca hanno dimostrato che gli streptococchi di gruppo B erano in grado di indurre la secrezione di alti livelli di IL-1 beta e di IL-18 nelle cellule dendritiche convenzionali e che la produzione di queste due citochine dipendeva dall’induzione della caspasi-1 e dalla conseguente attivazione dell’inflammasoma NLRP3 e della sua molecola adattatrice ASC. I risultati ottenuti con gli esperimenti in vitro venivano confermati in vivo grazie all’utilizzo di un modello sperimentale murino d’infezione streptococcica ed all’impiego di topi geneticamente difettivi per la caspasi-1, NLRP3 ed ASC.
-In qualità di Responsabile scientifico della sperimentazione animale ha coordinato diversi progetti di ricerca, condotti in collaborazione con la Ditta Novartis & Vaccines Diagnostic di Siena, riguardanti l’identificazione di nuovi adiuvanti e di nuovi antigeni candidati per l’allestimento di vaccini innovativi nei confronti di differenti agenti patogeni di origine batterica. Grazie alla messa a punto di diversi modelli sperimentali in vivo di immunizzazione ed infezione murina e sfruttando l’approccio sperimentale della “reverse vaccinology” è stato possibile identificare alcuni antigeni di S. pneumoniae, streptococco di gruppo A e Staphylococcus aureus quali possibili candidati vaccinali.
Attività assistenziale
Nell'ambito clinico-assistenziale l'attività del Prof. Mancuso si esplica a tutt'oggi nel campo della microbiologia clinica con particolare attenzione alla diagnostica micobatteriologica e micologica. Nell'ambito della diagnostica microbiologica l'attività assistenziale è stata rivolta all'identificazione tramite tecniche automatizzate o di biologia molecolare di varie specie batteriche in campioni clinici di differente tipologia ottenuti da pazienti ricoverati nelle diverse UOC della struttura sanitaria o di provenienza esterna ed alla diagnosi sierologica indiretta della risposta anticorpale nei confronti di numerose malattie infettive. Nel settore della micobatteriologia il contributo assistenziale viene esplicitato nelle attività diagnostiche erogate dalla UOC quali la ricerca di micobatteri mediante esame microscopico e colturale con metodo tradizionale e fluorimetrico, identificazione ed antibiogramma di Mycobacterium tubercolosis da vari campioni biologici e la ricerca diretta su campione biologico di M. tubercolosis mediante amplificazione genica e Real-Time PCR; particolare attenzione è rivolta alla determinazione diagnostica della presenza di infezione tubercolare latente fra determinate categorie a rischio della popolazione ed all'isolamento ed identificazione mediante ibridazione di micobatteri atipici nei pazienti affetti da fibrosi cistica. Nell'ambito della micologia, il Prof. Mancuso si occupa, oltre delle attività diagnostiche micologiche di base, della sperimentazione e successiva applicazione di tecniche molecolari per il rilevamento di miceti da campioni di sangue. Questa intensa attività ha portato alla messa a punto di metodi alternativi (più economici e rapidi) per l'identificazione di miceti da colonia.
Iscrizione a società scientifiche ed attività di referaggio
Il Prof. Mancuso è iscritto alla Società Italiana di Microbiologia e svolge attività di referee per diverse riviste internazionali (J.Immunol., Journal of Drug Targeting, International Journal of molecular science, Eur. J. Immunology, Journal of Leukocyte Biology).
Curriculum
Qualifications
- Degree in Medicine and Surgery (110/110 cum laude) at the University of Messina in the academic year 1984-1985.
- Qualification to practice as a Doctor-Surgeon at the University of Messina in the summer-autumn session of the year 1985.
-Specialization in Virology (with honors) at the University of Messina in 1988.
-Diploma of PhD in Microbiological Disciplines obtained at the Ministry of University and Scientific Research in 1994.
-Specialization in Microbiology and Virology (with honors) at the University of Messina in 1997.
Professional path
- Appointed university researcher for the scientific-disciplinary group MED / 04 on 08/03/1999 at the Department of Experimental Pathology and Microbiology of the Faculty of Medicine and Surgery of the University of Messina. From 01/10/2012 he joined the Department of Pediatric, Gynecological, Microbiological and Biomedical Sciences of the University of Messina.
-Director of the User and Breeder Plant of the Department of Pathology and Experimental Microbiology (2006-2010), of the Department of Pediatric, Gynecological, Microbiological and Biomedical Sciences (2010-2015) and of the Department of Human Pathology of adults and developmental age "G. Barresi) (2015 to date).
-In 2014 he obtained the National Scientific Qualification for Associate Professor of General Microbiology and Clinical Microbiology (SSD MED07) and of General Pathology (SSD MED04).
- Appointed associate professor for the scientific-disciplinary group MED / 07 on 01/11/2014 at the Department of Pediatric, Gynecological, Microbiological and Biomedical Sciences of the University of Messina.
-Vice-President of the Body in charge of Animal Welfare (OPBA) of the University of Messina (2014 to date).
-From 01/10/2015 he has been an associate professor at the Department of Human Pathology of the adult and developmental age "G. Barresi" of the University of Messina.
- 1st level Medical Director at the Complex Operating Unit of Mycology and Mycobacteriology of the University Hospital "G. Martino "in Messina from 1999 to 2009.
- 1st level Medical Director at the Mycology and Mycobacteriology section and the centralized laboratory of the Complex Operational Unit of Clinical Pathology of the University Hospital "G. Martino "of Messina from 2010 to 31/03/2017.
- 1st level Medical Director at the UOC of Clinical Microbiology of the University Hospital "G. Martino "in Messina from 01/04/2017 to date.
- From 14/04/2011 holder of a High Professional position conferred on him by the General Manager of the University Hospital "G. Martino ”of Messina.
-From 6 April 2020 Head of the Covid Laboratory of the AOU "G. Martino" of Messina, Regional Reference Center for the Province of Messina.
-From 1 July 2021 Director of the UOC of Clinical Microbiology of the AOU "G. Martino" of Messina.
Teaching activity
- Professor of Microbiology in the Physiotherapist Degree Course of the Faculty of Medicine and Surgery of the University of Messina for the years 2000-2001 and 2001-2002.
- Professor of Clinical Virology applied to Microbiology in the Specialization School of Microbiology and Virology of the Faculty of Medicine and Surgery of the University of Messina from the academic year 1999-2000.
- Professor of Genetic Pathology in the Specialization School of Clinical Pathology of the Faculty of Medicine and Surgery of the University of Messina for the academic year 2002-2003.
- Professor of General Microbiology and Clinical Microbiology in the Degree Course for Orthoptists Assistant Ophthalmology of the Faculty of Medicine and Surgery of the University of Messina from the academic year 2002-2003.
-Coordinator of the Integrated Course of Biological Sciences I in the Degree Course for Orthoptists Assistant of Ophthalmology of the Faculty of Medicine and Surgery of the University of Messina from 2011 to present.
- Professor of Clinical Microbiology in the integrated course of Laboratory Medicine in the Degree Course of Medicine and Surgery in the academic year 2014-2015 and 2015-2016.
- Professor of General Microbiology and Clinical Microbiology in the integrated course of Biological and Molecular Bases of the Physiotherapy Degree Course from 2015-2016 to today.
- Professor of General Microbiology and Clinical Microbiology in the integrated course of Health and Safety Promotion of the Nursing Degree Course from the 2015-2016 academic year to date and Coordinator of the same Integrated Course from 1 October 2018 to date.
- Professor of General Microbiology and Clinical Microbiology in the integrated course of Biological Sciences of the Degree in Prevention Techniques in the environment and in the workplace from the academic year 2015-2016 to date.
- Professor of General Microbiology and Clinical Microbiology in the Degree in Medicine and Surgery from 2015-2020 to today.
- Professor of Medical Statistics in the Specialization School of Microbiology and Virology of the Faculty of Medicine and Surgery of the University of Messina from the academic year 2010-2011 to the academic year 2014.
- Professor of General Pathology in the Specialization School of Microbiology and Virology of the Faculty of Medicine and Surgery of the University of Messina from the academic year 2010-2011 to the academic year 2014.
- Professor of General Microbiology and Clinical Microbiology in the Postgraduate School of Microbiology and Virology of the University of Messina from the 2014 academic year to date.
- Professor of General Microbiology and Clinical Microbiology in the Specialization Schools of Pneumology, Infectious Diseases, Plastic Surgery, Maxillofacial Surgery, Ophthalmology at the University of Messina.
-Coordinator of the Postgraduate School of Microbiology and Virology in the non-health medical area of the University of Messina from the 2018-2019 academic year and Director of the same from 1 April 2021.
- Professor of the Postgraduate School of Microbiology and Virology in the medical area of the University of Catania and Coordinator of the Messina branch from the academic year 2019-2020.
- Professor of Molecular Virology in the PhD in Microbial Biotechnology and Cell Proliferation of the University of Messina from the 2005-2006 academic year to the 2011-2012 academic year. As part of the various cycles of the aforementioned doctorate, he has been part of various admission and / or diploma commissions.
-Professor in the PhD in Medical and Surgical Biotechnology of the University of Messina from 2013 to present.
-Member of the College of the Research Doctorate in "Translational molecular medicine and surgery" of the University of Messina
Scientific participation in research projects
-Component participating in the project 01_00117 PON "Antigens and adjuvants for vaccines and immunotherapies" (July 2011-October 2015).
-Scientific Manager of the aforementioned PON since May 2014.
-Scientific Director of the Partner Unit of the research project "Biochemical and immunological analysis of surface / secreted proteins and their use as potential components of a multivavalent anti-Staphylococcus aureus vaccine" carried out by the University of Messina and funded by the Cariplo Foundation (n . reference 2009-3546; 2011-2295; 2012-1881) (2013/2014).
-Component participating in the 10911 PON project "Innovative vaccine against streptococcal group A" (2001-2006).
-Component participating in the PRIN "Vectors for the presentation of anti-idiotypic vaccines" (from 12/12/2001 to 23/01/2004).
-Scientific Director of the following University Research Projects (PRA) of the University of Messina from the academic year 1999-2000:
PRA 1999: Development of recombinant antibodies for vaccine use
PRA 2000: Role of tyrosine kinases in cell activation induced by group B streptococcus
PRA 2001: Pathogenesis of group B streptococcal septic shock: role of release of bacterial products following exposure to antibiotics
PRA 2002: Identification of Toll-like receptors involved in the activation of phagocytic cells by the lipopolysaccharide of Bacteroides fragilis
PRA 2003: Role of Toll-like receptors and the adapter molecule MyD88 in experimental models of group B streptococcal sepsis
PRA 2004: Induction of cytokines by recombinant group B streptococcal proteins
PRA 2005: Role of Toll-like receptors in the pathogenesis of Bartonella henselae infections
PRA 2006/2007: Identification of pneumococcal protein antigens capable of inducing protective responses in infections caused by Streptococcus pneumoniae
PRA 2008/2009: Role played by different bacterial components in the pathogenesis of group A streptococcal infections (GAS)
Participation in research activities carried out within the following international research projects
-AIDS project-funded by the Higher Institute of Health (1996-2001)
- "PEPSAC-MIMIC" project financed by the European Community, contract no. QLK2-CT-1999-00854 (duration 3 years)
- "HOSPATH" project financed by the European Community, contract no. QLK2-CT-2000-00336 (duration 3 years)
-FP6-2003-LIFESCIHEALTH-I: European Virtual Institute for Functional Genomics of Bacterial Pathogens (duration 5 years)
- "NoE Pathogenomics" project funded by the European Community, contract no. 512061 (duration 3 years)
Other titles
- Head of animal testing for the research project "Development of new vaccines and monoclonal antibodies for the control of infections caused by antibiotic-resistant strains of Staphylococcus aureus" (2021-2024)
-Head of animal experimentation for the research project "Role of innate immune receptors in susceptibility to pneumoccoccal infections" (2019-2022)
-Head of animal experimentation for the research project "Role of the transcriptional regulator CodY in the pathogenesis of neonatal meningitis and sepsis caused by group B Streptococcus" (2019-2022).
-Responsible for animal experimentation for the research project "Theoretical / practical course in Laboratory Animal Science (LAS) for professionals A, B, C and D" (2018-2023).
-Responsible for animal testing for the research project "Selection of vaccine candidates for the control of invasive infections caused by Neisseria meningitidis", contract funded by GSK (2017-2020).
-Responsible for animal testing for the research project "Preparation of an experimental vaccine against infections caused by Staphylococcus aureus", contract funded by GSK (2016-2019).
-Responsible for animal testing for the research project "Development of a vaccine against intestinal and extra-intestinal pathogenic strains of Escherichia coli", contract funded by GSK (2015-2018).
-Responsible for animal experimentation for the research project "Role of innate immunity in group B Streptococcal infections", contract funded by GSK (2015-2018).
- Head of animal testing for the research project "Identification of innate immunity molecules involved in the pathogenesis of Clostridium difficile infection", contract funded by GSK (2015-2017).
- Responsible for animal testing for the research project "Identification of vaccine candidates for the preparation of an innovative vaccine against infections caused by Staphylococcus aureus", contract funded by the Novartis Vaccines and Diagnostic S.r.l. (2011-2012).
-Responsible for animal experimentation for the research project "Identification of signal transduction pathways activated by adjuvants alum and MF59", contract funded by Novartis Vaccines and Diagnostic S.r.l. (2011- 2012).
-Responsible for animal testing for the research project "Vaccine candidates for the prevention of staphylococcal aureus infections", contract funded by the Novartis Vaccines and Diagnostic S.r.l. (2008-2009).
-Responsible for animal experimentation for the research project "Evaluation of the protective activity of pneumococcal proteins in experimental mouse models", contract funded by the Novartis Vaccines and Diagnostic S.r.l. (2007-2009).
-Responsible for animal testing for the research project "Identification of vaccine candidates for the prevention of group A streptococcal infections (GAS)", contract funded by the Novartis Vaccines and Diagnostic S.r.l. (2007-2009).
Participation in training courses / meetings on animal experimentation
-Day of meeting with the OPBA of Sicily: "Activities of the National Committee for the Protection of Animals used for scientific purposes (CNPA)", Peloritana Academy of Dangers, University of Messina, 28 February 2018, Messina.
- "Welfare and scientific use of animals: current perspectives of the human-animal relationship", Aula Magna Unical, 4-5 December 2017, Cosenza
- "The 3R principle: applications and innovation." Istituto Superiore di Sanità, 16-17 October 2017, Rome.
- Updating course of animal users for scientific purposes on new functions of the Animal Experimentation Database. Ministry of Health, 12 July 2017, Rome.
- "The OPBAs and the technical-scientific evaluation of experimental projects with animals: procedures, contents and professionalism. Pharmacological orientation". Istituto Superiore Sanità, 24-25 November 2015, Rome.
- The use of the "telematic animal experimentation database" for the collection of annual statistical data. Ministry of Health, 6-7 October 2014, Rome.
-Days of assistance for the compilation of statistical data 2014 (Alures Reporting), Rome c / o Ministry of Health, 22 October 2015.
- Study day on "Legislative and ethical aspects in animal experimentation: current events and perspectives" University of Messina, 27 January 2016, Messina
- Basic Course in LAS and 3Rs, University of Messina, 25-29 January 2016, Messina --- "Animal protection and quality of science: analysis and considerations two years after the Italian implementation of the European Directive 63/2010" , Higher Institute of Health, 3 October 2016, Rome
Participation in Congresses and Workshops
-Seminars on shock: septic shock caused by gram-positive bacteria 10-12 October 1998, Vibo Valentia, Italy
-Anti-idiotypes and mimotopes in vaccine development. Vibo Valentia Seminars. May 17-19, 2000. Vibo Valentia, Italy
-30th National Congress of the Italian Society of Microbiology, 6-9 October 2002, Catania, Italy
-3rd Cryptococcus neoformans Genomics Conference, 9-10 August 2003, University of British Columbia, Canada
- International Cytokine Society Annual Meeting, Trinity College 20-24 September 2003, Dublin, Ireland
-Invited speaker at the 32nd National Congress of the Italian Society of Microbiology, 26-29 September 2004, Milan, Italy with the paper entitled "Role of Toll-like receptors in the pathophysiology of sepsis"
-Toll 2004 Meeting, 8-11 May 2004, Taormina, Italy
-Invited speaker at the 34th National Congress of the Italian Society of Microbiology, 15-18 October 2006, Genoa, Italy with the paper entitled "Role of type I interferon in bacterial and fungal infections"
-35th National Congress of the Italian Society of Microbiology, 30 September-3 October 2007, Catania, Italy
-Invited speaker at the 36th National Congress of the Italian Society of Microbiology, 12-15 October 2008, Rome, Italy with the paper "Induction of interferon alpha / beta by bacteria: role in pathogenesis and signal transduction pathways"
-Nobel Symposium, June 11-13, 2009, Stokholm, Sweden
-Invited speaker at the 37th National Congress of the Italian Society of Microbiology, 11-14 October 2009, Turin, Italy with the paper entitled "Role of the TLR7 / TLR9 / MyD88 / IRF1 signal transduction pathway in the defense of the host against bacterial infections and fungal "
-Recent progresses in post-genomics. Department of Pathology and Experimental Microbiology, University of Messina, 24-25 February 2010, Messina, Italy
-Vaccines in the global era. Department of Pathology and Experimental Microbiology, University of Messina, 24-25 March 2011, Messina, Italy
-SHOCK, August 31-September 2, 2011, Taormina, Italy
-XVIII Lancefield International Symposium, 4-8 September 2011, Palermo, Italy
-39th National Congress of the Italian Society of Microbiology, 3-6 October 2011, Riccione, Italy
-41 ° National Congress of the Italian Society of Microbiology, 13-16 October 2013, Riccione, Italy
-43 ° National Congress of the Italian Society of Microbiology, 27-30 September 2015, Naples, Italy
-Intrinsic And innate immunity to pathogens, 23-25 June 2016, Novara, Italy
-100 Years of phagocytes, 19-22 September 2016, Giardini Naxos, Italy
-44th National Congress of the Italian Society of Microbiology, 25-28 September 2016, Pisa, Italy
-XLV AMCLI National Congress, 6-9 November 2016 Rimini
-45 ° National Congress of the Italian Society of Microbiology, 27-30 October 2017, Genoa, Italy
-CEMIR Annual Meeting, 19 October 2017, Taormina
-New frontiers of microbiological diagnostics, AOUP P. Giaccone, 29 January 2018.
Research activity
The scientific and research path of Prof. Mancuso over the years has concerned various sectors of microbiology and innate immunity in particular and has given rise to relevant scientific contributions evidenced by their editorial position in accredited and qualified international journals.
The main research topics that characterized Prof. Mancuso's scientific path concerned:
- Study of the role played by different endogenous host mediators such as pro-inflammatory and anti-inflammatory cytokines in the pathogenesis of endotoxic shock caused by gram-negative bacteria and septic shock of the newborn, with particular reference to infections caused by group B streptococci (GBS), a group of gram-positive bacteria that cause severe and often fatal cases of neonatal sepsis.
-Study of DNA vaccines, molecular mimics and host response to infectious agents and vaccines, with particular regard to the prevention of infections by encapsulated bacteria. As regards prevention, the development of experimental vaccines aimed at stimulating a humoral immune response against GBS and group B Neisseria meningitidis (MenB), two important causes of mortality and neurological deficits, was examined. permanent, through molecular mimics of the same carbohydrates. In order to induce an anti-idiotypic response, type-specific monoclonal antibodies with high protective activity were first produced and characterized. These antibodies were directed against the protective epitopes of the capsular polysaccharides and performed therapeutic activity in neonatal mouse models of experimental infection. Our research also demonstrated that these antibodies were able to evoke a protective anti-idiotypic response. In another series of researches, dodecapeptides were identified capable of mimicking the antigenic characteristics of the MenB capsular polysaccharide. These peptides were particularly immunogenic when administered in the form of minigens inserted into suitable plasmid vectors for DNA vaccination. In other studies, the immunogenicity and protective activity of various Cryptococcus neoformans antigens were analyzed.
-Identification of receptors, signal transduction pathways and cytokines involved in host responses to encapsulated pathogenic microorganisms of bacterial and fungal origin or their components. These studies have highlighted the importance of the Toll-like 2 receptor, the adapter protein MyD88 and the "Mitogen-activated protein kinases" as crucial factors in the defensive responses against specific microorganisms such as group B streptococci, Haemophilus influenzae and Cryptococcus neoformans. Conversely, the Toll-like 4 receptor was found to be crucial in mediating responses directed against Bacteroides fragilis. These researches also demonstrated the dual role (on the one hand as resistance factors to infections, on the other as pathogenetic factors) of Toll-like receptors and some pro-inflammatory cytokines in the course of these infections.
-The study of the mechanisms of the innate immune response in the pathogenesis of experimental invasive infections caused by encapsulated bacteria and cryptococcosis, an increasingly frequent emerging infectious disease due to its association with HIV disease. The results obtained in these research projects have shown that type I interferons, an important family of primary cytokines, play a fundamental role in the pathogenesis of this type of infections as mice that are defective for the type I IFN receptor or for IFN-beta are unable to control the in vivo growth of these microorganisms; this was related to the ability of type I IFNs to modulate in different ways the production of different mediators during the different bacterial infections and to regulate, in the case of cryptococcal infection, the polarization of the host's cytokine response, orienting it towards a lymphocytic response protective type Th1.
- Identification of the antimicrobial defense mechanisms put in place by the host against infections caused by extracellular bacteria. The research, published in Nature Immunology, has made it possible to identify the existence of a bacterial recognition system at phagosomal level, biologically relevant and not redundant, capable of operating in some cells of innate immunity such as conventional dendritic cells but not in macrophages. or in plasmacytoid dendritic cells, which presumably is "alerted" by the presence of bacterial RNA; therefore, some categories of bacteria, evading phagosomal maturation processes or altering the integrity of the phagosome itself, are able to avoid not only direct killing, but also the immune recognition that occurs within the lysosome. It was shown in this study that this recognition system requires the presence of the endosomal receptor TLR7, the adapter molecule MyD88 and the transcription factor IRF1, which plays a crucial role in the responses of both innate and adaptive immunity.
-The analysis of the role played by some primary cytokines in the course of infections caused by Candida albicans, the most frequent human fungal pathogen, which, although it behaves in normal conditions as a habitual commensal of the human mucous membranes of some anatomical districts, is capable of cause severe infections in hospitalized or immunocompromised patients. The experimental results obtained made it possible to identify some important components of C. albicans, such as RNA and DNA, capable of playing an important role in the pathogenesis of infections caused by this microorganism thanks to their ability to determine the production of different primary cytokines, in particular of interferon beta, using receptors present on innate immunity cells (TLR7 and TLR9 respectively) for the activation of different signal translation pathways (MyD88 / IRF1).
-The study of the role played by inflammasomes, of the important intracellular multiprotein complexes, located at the cytosolic level, whose activation determines the induction of caspase-1, an enzyme capable of inducing the maturation of molecules such as interleukin-1 beta and l 'interleukin-18, two cytokines involved in the host's defense mechanisms against infections. The data from our research work showed that group B streptococci were able to induce the secretion of high levels of IL-1 beta and IL-18 in conventional dendritic cells and that the production of these two cytokines depended on the induction of caspase-1 and the consequent activation of the NLRP3 inflammasome and its adapter molecule ASC. The results obtained with in vitro experiments were confirmed in vivo thanks to the use of a mouse experimental model of streptococcal infection and the use of genetically defective mice for caspase-1, NLRP3 and ASC.
-As Scientific Head of Animal Experimentation, he coordinated several research projects, conducted in collaboration with the Novartis & Vaccines Diagnostic Company of Siena, concerning the identification of new adjuvants and new candidate antigens for the preparation of innovative vaccines against of different pathogens of bacterial origin. Thanks to the development of various in vivo experimental models of murine immunization and infection and exploiting the experimental approach of "reverse vaccinology" it was possible to identify some S. pneumoniae, group A streptococcus and Staphylococcus aureus antigens as possible vaccine candidates.
Assistance activity
In the clinical-assistance field, the activity of Prof. Mancuso is still carried out in the field of clinical microbiology with particular attention to mycobacteriological and mycological diagnostics. In the field of microbiological diagnostics, the assistance activity was aimed at the identification through automated techniques or molecular biology of various bacterial species in clinical samples of different types obtained from patients hospitalized in the different UOCs of the health facility or of external origin and the diagnosis indirect serological analysis of the antibody response to numerous infectious diseases. In the field of mycobacteriology, the assistance contribution is made explicit in the diagnostic activities provided by the UOC such as the research of mycobacteria by means of microscopic and cultural examination with traditional and fluorimetric method, identification and antibiogram of Mycobacterium tuberculosis from various biological samples and direct research on biological sample of M. tuberculosis by gene amplification and Real-Time PCR; particular attention is paid to the diagnostic determination of the presence of latent tuberculous infection among certain risk categories of the population and to the isolation and identification by hybridization of atypical mycobacteria in patients with cystic fibrosis. In the field of mycology, Prof. Mancuso deals, in addition to basic mycological diagnostic activities, with the experimentation and subsequent application of molecular techniques for the detection of fungi from blood samples. This intense activity has led to the development of alternative methods (cheaper and faster) for the identification of colony fungi.
Membership in scientific societies and refereeing activities
Prof. Mancuso is a member of the Italian Society of Microbiology and referees for several international journals (J.Immunol., Journal of Drug Targeting, International Journal of molecular science, Eur. J. Immunology, Journal of Leukocyte Biology).
- Degree in Medicine and Surgery (110/110 cum laude) at the University of Messina in the academic year 1984-1985.
- Qualification to practice as a Doctor-Surgeon at the University of Messina in the summer-autumn session of the year 1985.
-Specialization in Virology (with honors) at the University of Messina in 1988.
-Diploma of PhD in Microbiological Disciplines obtained at the Ministry of University and Scientific Research in 1994.
-Specialization in Microbiology and Virology (with honors) at the University of Messina in 1997.
Professional path
- Appointed university researcher for the scientific-disciplinary group MED / 04 on 08/03/1999 at the Department of Experimental Pathology and Microbiology of the Faculty of Medicine and Surgery of the University of Messina. From 01/10/2012 he joined the Department of Pediatric, Gynecological, Microbiological and Biomedical Sciences of the University of Messina.
-Director of the User and Breeder Plant of the Department of Pathology and Experimental Microbiology (2006-2010), of the Department of Pediatric, Gynecological, Microbiological and Biomedical Sciences (2010-2015) and of the Department of Human Pathology of adults and developmental age "G. Barresi) (2015 to date).
-In 2014 he obtained the National Scientific Qualification for Associate Professor of General Microbiology and Clinical Microbiology (SSD MED07) and of General Pathology (SSD MED04).
- Appointed associate professor for the scientific-disciplinary group MED / 07 on 01/11/2014 at the Department of Pediatric, Gynecological, Microbiological and Biomedical Sciences of the University of Messina.
-Vice-President of the Body in charge of Animal Welfare (OPBA) of the University of Messina (2014 to date).
-From 01/10/2015 he has been an associate professor at the Department of Human Pathology of the adult and developmental age "G. Barresi" of the University of Messina.
- 1st level Medical Director at the Complex Operating Unit of Mycology and Mycobacteriology of the University Hospital "G. Martino "in Messina from 1999 to 2009.
- 1st level Medical Director at the Mycology and Mycobacteriology section and the centralized laboratory of the Complex Operational Unit of Clinical Pathology of the University Hospital "G. Martino "of Messina from 2010 to 31/03/2017.
- 1st level Medical Director at the UOC of Clinical Microbiology of the University Hospital "G. Martino "in Messina from 01/04/2017 to date.
- From 14/04/2011 holder of a High Professional position conferred on him by the General Manager of the University Hospital "G. Martino ”of Messina.
-From 6 April 2020 Head of the Covid Laboratory of the AOU "G. Martino" of Messina, Regional Reference Center for the Province of Messina.
-From 1 July 2021 Director of the UOC of Clinical Microbiology of the AOU "G. Martino" of Messina.
Teaching activity
- Professor of Microbiology in the Physiotherapist Degree Course of the Faculty of Medicine and Surgery of the University of Messina for the years 2000-2001 and 2001-2002.
- Professor of Clinical Virology applied to Microbiology in the Specialization School of Microbiology and Virology of the Faculty of Medicine and Surgery of the University of Messina from the academic year 1999-2000.
- Professor of Genetic Pathology in the Specialization School of Clinical Pathology of the Faculty of Medicine and Surgery of the University of Messina for the academic year 2002-2003.
- Professor of General Microbiology and Clinical Microbiology in the Degree Course for Orthoptists Assistant Ophthalmology of the Faculty of Medicine and Surgery of the University of Messina from the academic year 2002-2003.
-Coordinator of the Integrated Course of Biological Sciences I in the Degree Course for Orthoptists Assistant of Ophthalmology of the Faculty of Medicine and Surgery of the University of Messina from 2011 to present.
- Professor of Clinical Microbiology in the integrated course of Laboratory Medicine in the Degree Course of Medicine and Surgery in the academic year 2014-2015 and 2015-2016.
- Professor of General Microbiology and Clinical Microbiology in the integrated course of Biological and Molecular Bases of the Physiotherapy Degree Course from 2015-2016 to today.
- Professor of General Microbiology and Clinical Microbiology in the integrated course of Health and Safety Promotion of the Nursing Degree Course from the 2015-2016 academic year to date and Coordinator of the same Integrated Course from 1 October 2018 to date.
- Professor of General Microbiology and Clinical Microbiology in the integrated course of Biological Sciences of the Degree in Prevention Techniques in the environment and in the workplace from the academic year 2015-2016 to date.
- Professor of General Microbiology and Clinical Microbiology in the Degree in Medicine and Surgery from 2015-2020 to today.
- Professor of Medical Statistics in the Specialization School of Microbiology and Virology of the Faculty of Medicine and Surgery of the University of Messina from the academic year 2010-2011 to the academic year 2014.
- Professor of General Pathology in the Specialization School of Microbiology and Virology of the Faculty of Medicine and Surgery of the University of Messina from the academic year 2010-2011 to the academic year 2014.
- Professor of General Microbiology and Clinical Microbiology in the Postgraduate School of Microbiology and Virology of the University of Messina from the 2014 academic year to date.
- Professor of General Microbiology and Clinical Microbiology in the Specialization Schools of Pneumology, Infectious Diseases, Plastic Surgery, Maxillofacial Surgery, Ophthalmology at the University of Messina.
-Coordinator of the Postgraduate School of Microbiology and Virology in the non-health medical area of the University of Messina from the 2018-2019 academic year and Director of the same from 1 April 2021.
- Professor of the Postgraduate School of Microbiology and Virology in the medical area of the University of Catania and Coordinator of the Messina branch from the academic year 2019-2020.
- Professor of Molecular Virology in the PhD in Microbial Biotechnology and Cell Proliferation of the University of Messina from the 2005-2006 academic year to the 2011-2012 academic year. As part of the various cycles of the aforementioned doctorate, he has been part of various admission and / or diploma commissions.
-Professor in the PhD in Medical and Surgical Biotechnology of the University of Messina from 2013 to present.
-Member of the College of the Research Doctorate in "Translational molecular medicine and surgery" of the University of Messina
Scientific participation in research projects
-Component participating in the project 01_00117 PON "Antigens and adjuvants for vaccines and immunotherapies" (July 2011-October 2015).
-Scientific Manager of the aforementioned PON since May 2014.
-Scientific Director of the Partner Unit of the research project "Biochemical and immunological analysis of surface / secreted proteins and their use as potential components of a multivavalent anti-Staphylococcus aureus vaccine" carried out by the University of Messina and funded by the Cariplo Foundation (n . reference 2009-3546; 2011-2295; 2012-1881) (2013/2014).
-Component participating in the 10911 PON project "Innovative vaccine against streptococcal group A" (2001-2006).
-Component participating in the PRIN "Vectors for the presentation of anti-idiotypic vaccines" (from 12/12/2001 to 23/01/2004).
-Scientific Director of the following University Research Projects (PRA) of the University of Messina from the academic year 1999-2000:
PRA 1999: Development of recombinant antibodies for vaccine use
PRA 2000: Role of tyrosine kinases in cell activation induced by group B streptococcus
PRA 2001: Pathogenesis of group B streptococcal septic shock: role of release of bacterial products following exposure to antibiotics
PRA 2002: Identification of Toll-like receptors involved in the activation of phagocytic cells by the lipopolysaccharide of Bacteroides fragilis
PRA 2003: Role of Toll-like receptors and the adapter molecule MyD88 in experimental models of group B streptococcal sepsis
PRA 2004: Induction of cytokines by recombinant group B streptococcal proteins
PRA 2005: Role of Toll-like receptors in the pathogenesis of Bartonella henselae infections
PRA 2006/2007: Identification of pneumococcal protein antigens capable of inducing protective responses in infections caused by Streptococcus pneumoniae
PRA 2008/2009: Role played by different bacterial components in the pathogenesis of group A streptococcal infections (GAS)
Participation in research activities carried out within the following international research projects
-AIDS project-funded by the Higher Institute of Health (1996-2001)
- "PEPSAC-MIMIC" project financed by the European Community, contract no. QLK2-CT-1999-00854 (duration 3 years)
- "HOSPATH" project financed by the European Community, contract no. QLK2-CT-2000-00336 (duration 3 years)
-FP6-2003-LIFESCIHEALTH-I: European Virtual Institute for Functional Genomics of Bacterial Pathogens (duration 5 years)
- "NoE Pathogenomics" project funded by the European Community, contract no. 512061 (duration 3 years)
Other titles
- Head of animal testing for the research project "Development of new vaccines and monoclonal antibodies for the control of infections caused by antibiotic-resistant strains of Staphylococcus aureus" (2021-2024)
-Head of animal experimentation for the research project "Role of innate immune receptors in susceptibility to pneumoccoccal infections" (2019-2022)
-Head of animal experimentation for the research project "Role of the transcriptional regulator CodY in the pathogenesis of neonatal meningitis and sepsis caused by group B Streptococcus" (2019-2022).
-Responsible for animal experimentation for the research project "Theoretical / practical course in Laboratory Animal Science (LAS) for professionals A, B, C and D" (2018-2023).
-Responsible for animal testing for the research project "Selection of vaccine candidates for the control of invasive infections caused by Neisseria meningitidis", contract funded by GSK (2017-2020).
-Responsible for animal testing for the research project "Preparation of an experimental vaccine against infections caused by Staphylococcus aureus", contract funded by GSK (2016-2019).
-Responsible for animal testing for the research project "Development of a vaccine against intestinal and extra-intestinal pathogenic strains of Escherichia coli", contract funded by GSK (2015-2018).
-Responsible for animal experimentation for the research project "Role of innate immunity in group B Streptococcal infections", contract funded by GSK (2015-2018).
- Head of animal testing for the research project "Identification of innate immunity molecules involved in the pathogenesis of Clostridium difficile infection", contract funded by GSK (2015-2017).
- Responsible for animal testing for the research project "Identification of vaccine candidates for the preparation of an innovative vaccine against infections caused by Staphylococcus aureus", contract funded by the Novartis Vaccines and Diagnostic S.r.l. (2011-2012).
-Responsible for animal experimentation for the research project "Identification of signal transduction pathways activated by adjuvants alum and MF59", contract funded by Novartis Vaccines and Diagnostic S.r.l. (2011- 2012).
-Responsible for animal testing for the research project "Vaccine candidates for the prevention of staphylococcal aureus infections", contract funded by the Novartis Vaccines and Diagnostic S.r.l. (2008-2009).
-Responsible for animal experimentation for the research project "Evaluation of the protective activity of pneumococcal proteins in experimental mouse models", contract funded by the Novartis Vaccines and Diagnostic S.r.l. (2007-2009).
-Responsible for animal testing for the research project "Identification of vaccine candidates for the prevention of group A streptococcal infections (GAS)", contract funded by the Novartis Vaccines and Diagnostic S.r.l. (2007-2009).
Participation in training courses / meetings on animal experimentation
-Day of meeting with the OPBA of Sicily: "Activities of the National Committee for the Protection of Animals used for scientific purposes (CNPA)", Peloritana Academy of Dangers, University of Messina, 28 February 2018, Messina.
- "Welfare and scientific use of animals: current perspectives of the human-animal relationship", Aula Magna Unical, 4-5 December 2017, Cosenza
- "The 3R principle: applications and innovation." Istituto Superiore di Sanità, 16-17 October 2017, Rome.
- Updating course of animal users for scientific purposes on new functions of the Animal Experimentation Database. Ministry of Health, 12 July 2017, Rome.
- "The OPBAs and the technical-scientific evaluation of experimental projects with animals: procedures, contents and professionalism. Pharmacological orientation". Istituto Superiore Sanità, 24-25 November 2015, Rome.
- The use of the "telematic animal experimentation database" for the collection of annual statistical data. Ministry of Health, 6-7 October 2014, Rome.
-Days of assistance for the compilation of statistical data 2014 (Alures Reporting), Rome c / o Ministry of Health, 22 October 2015.
- Study day on "Legislative and ethical aspects in animal experimentation: current events and perspectives" University of Messina, 27 January 2016, Messina
- Basic Course in LAS and 3Rs, University of Messina, 25-29 January 2016, Messina --- "Animal protection and quality of science: analysis and considerations two years after the Italian implementation of the European Directive 63/2010" , Higher Institute of Health, 3 October 2016, Rome
Participation in Congresses and Workshops
-Seminars on shock: septic shock caused by gram-positive bacteria 10-12 October 1998, Vibo Valentia, Italy
-Anti-idiotypes and mimotopes in vaccine development. Vibo Valentia Seminars. May 17-19, 2000. Vibo Valentia, Italy
-30th National Congress of the Italian Society of Microbiology, 6-9 October 2002, Catania, Italy
-3rd Cryptococcus neoformans Genomics Conference, 9-10 August 2003, University of British Columbia, Canada
- International Cytokine Society Annual Meeting, Trinity College 20-24 September 2003, Dublin, Ireland
-Invited speaker at the 32nd National Congress of the Italian Society of Microbiology, 26-29 September 2004, Milan, Italy with the paper entitled "Role of Toll-like receptors in the pathophysiology of sepsis"
-Toll 2004 Meeting, 8-11 May 2004, Taormina, Italy
-Invited speaker at the 34th National Congress of the Italian Society of Microbiology, 15-18 October 2006, Genoa, Italy with the paper entitled "Role of type I interferon in bacterial and fungal infections"
-35th National Congress of the Italian Society of Microbiology, 30 September-3 October 2007, Catania, Italy
-Invited speaker at the 36th National Congress of the Italian Society of Microbiology, 12-15 October 2008, Rome, Italy with the paper "Induction of interferon alpha / beta by bacteria: role in pathogenesis and signal transduction pathways"
-Nobel Symposium, June 11-13, 2009, Stokholm, Sweden
-Invited speaker at the 37th National Congress of the Italian Society of Microbiology, 11-14 October 2009, Turin, Italy with the paper entitled "Role of the TLR7 / TLR9 / MyD88 / IRF1 signal transduction pathway in the defense of the host against bacterial infections and fungal "
-Recent progresses in post-genomics. Department of Pathology and Experimental Microbiology, University of Messina, 24-25 February 2010, Messina, Italy
-Vaccines in the global era. Department of Pathology and Experimental Microbiology, University of Messina, 24-25 March 2011, Messina, Italy
-SHOCK, August 31-September 2, 2011, Taormina, Italy
-XVIII Lancefield International Symposium, 4-8 September 2011, Palermo, Italy
-39th National Congress of the Italian Society of Microbiology, 3-6 October 2011, Riccione, Italy
-41 ° National Congress of the Italian Society of Microbiology, 13-16 October 2013, Riccione, Italy
-43 ° National Congress of the Italian Society of Microbiology, 27-30 September 2015, Naples, Italy
-Intrinsic And innate immunity to pathogens, 23-25 June 2016, Novara, Italy
-100 Years of phagocytes, 19-22 September 2016, Giardini Naxos, Italy
-44th National Congress of the Italian Society of Microbiology, 25-28 September 2016, Pisa, Italy
-XLV AMCLI National Congress, 6-9 November 2016 Rimini
-45 ° National Congress of the Italian Society of Microbiology, 27-30 October 2017, Genoa, Italy
-CEMIR Annual Meeting, 19 October 2017, Taormina
-New frontiers of microbiological diagnostics, AOUP P. Giaccone, 29 January 2018.
Research activity
The scientific and research path of Prof. Mancuso over the years has concerned various sectors of microbiology and innate immunity in particular and has given rise to relevant scientific contributions evidenced by their editorial position in accredited and qualified international journals.
The main research topics that characterized Prof. Mancuso's scientific path concerned:
- Study of the role played by different endogenous host mediators such as pro-inflammatory and anti-inflammatory cytokines in the pathogenesis of endotoxic shock caused by gram-negative bacteria and septic shock of the newborn, with particular reference to infections caused by group B streptococci (GBS), a group of gram-positive bacteria that cause severe and often fatal cases of neonatal sepsis.
-Study of DNA vaccines, molecular mimics and host response to infectious agents and vaccines, with particular regard to the prevention of infections by encapsulated bacteria. As regards prevention, the development of experimental vaccines aimed at stimulating a humoral immune response against GBS and group B Neisseria meningitidis (MenB), two important causes of mortality and neurological deficits, was examined. permanent, through molecular mimics of the same carbohydrates. In order to induce an anti-idiotypic response, type-specific monoclonal antibodies with high protective activity were first produced and characterized. These antibodies were directed against the protective epitopes of the capsular polysaccharides and performed therapeutic activity in neonatal mouse models of experimental infection. Our research also demonstrated that these antibodies were able to evoke a protective anti-idiotypic response. In another series of researches, dodecapeptides were identified capable of mimicking the antigenic characteristics of the MenB capsular polysaccharide. These peptides were particularly immunogenic when administered in the form of minigens inserted into suitable plasmid vectors for DNA vaccination. In other studies, the immunogenicity and protective activity of various Cryptococcus neoformans antigens were analyzed.
-Identification of receptors, signal transduction pathways and cytokines involved in host responses to encapsulated pathogenic microorganisms of bacterial and fungal origin or their components. These studies have highlighted the importance of the Toll-like 2 receptor, the adapter protein MyD88 and the "Mitogen-activated protein kinases" as crucial factors in the defensive responses against specific microorganisms such as group B streptococci, Haemophilus influenzae and Cryptococcus neoformans. Conversely, the Toll-like 4 receptor was found to be crucial in mediating responses directed against Bacteroides fragilis. These researches also demonstrated the dual role (on the one hand as resistance factors to infections, on the other as pathogenetic factors) of Toll-like receptors and some pro-inflammatory cytokines in the course of these infections.
-The study of the mechanisms of the innate immune response in the pathogenesis of experimental invasive infections caused by encapsulated bacteria and cryptococcosis, an increasingly frequent emerging infectious disease due to its association with HIV disease. The results obtained in these research projects have shown that type I interferons, an important family of primary cytokines, play a fundamental role in the pathogenesis of this type of infections as mice that are defective for the type I IFN receptor or for IFN-beta are unable to control the in vivo growth of these microorganisms; this was related to the ability of type I IFNs to modulate in different ways the production of different mediators during the different bacterial infections and to regulate, in the case of cryptococcal infection, the polarization of the host's cytokine response, orienting it towards a lymphocytic response protective type Th1.
- Identification of the antimicrobial defense mechanisms put in place by the host against infections caused by extracellular bacteria. The research, published in Nature Immunology, has made it possible to identify the existence of a bacterial recognition system at phagosomal level, biologically relevant and not redundant, capable of operating in some cells of innate immunity such as conventional dendritic cells but not in macrophages. or in plasmacytoid dendritic cells, which presumably is "alerted" by the presence of bacterial RNA; therefore, some categories of bacteria, evading phagosomal maturation processes or altering the integrity of the phagosome itself, are able to avoid not only direct killing, but also the immune recognition that occurs within the lysosome. It was shown in this study that this recognition system requires the presence of the endosomal receptor TLR7, the adapter molecule MyD88 and the transcription factor IRF1, which plays a crucial role in the responses of both innate and adaptive immunity.
-The analysis of the role played by some primary cytokines in the course of infections caused by Candida albicans, the most frequent human fungal pathogen, which, although it behaves in normal conditions as a habitual commensal of the human mucous membranes of some anatomical districts, is capable of cause severe infections in hospitalized or immunocompromised patients. The experimental results obtained made it possible to identify some important components of C. albicans, such as RNA and DNA, capable of playing an important role in the pathogenesis of infections caused by this microorganism thanks to their ability to determine the production of different primary cytokines, in particular of interferon beta, using receptors present on innate immunity cells (TLR7 and TLR9 respectively) for the activation of different signal translation pathways (MyD88 / IRF1).
-The study of the role played by inflammasomes, of the important intracellular multiprotein complexes, located at the cytosolic level, whose activation determines the induction of caspase-1, an enzyme capable of inducing the maturation of molecules such as interleukin-1 beta and l 'interleukin-18, two cytokines involved in the host's defense mechanisms against infections. The data from our research work showed that group B streptococci were able to induce the secretion of high levels of IL-1 beta and IL-18 in conventional dendritic cells and that the production of these two cytokines depended on the induction of caspase-1 and the consequent activation of the NLRP3 inflammasome and its adapter molecule ASC. The results obtained with in vitro experiments were confirmed in vivo thanks to the use of a mouse experimental model of streptococcal infection and the use of genetically defective mice for caspase-1, NLRP3 and ASC.
-As Scientific Head of Animal Experimentation, he coordinated several research projects, conducted in collaboration with the Novartis & Vaccines Diagnostic Company of Siena, concerning the identification of new adjuvants and new candidate antigens for the preparation of innovative vaccines against of different pathogens of bacterial origin. Thanks to the development of various in vivo experimental models of murine immunization and infection and exploiting the experimental approach of "reverse vaccinology" it was possible to identify some S. pneumoniae, group A streptococcus and Staphylococcus aureus antigens as possible vaccine candidates.
Assistance activity
In the clinical-assistance field, the activity of Prof. Mancuso is still carried out in the field of clinical microbiology with particular attention to mycobacteriological and mycological diagnostics. In the field of microbiological diagnostics, the assistance activity was aimed at the identification through automated techniques or molecular biology of various bacterial species in clinical samples of different types obtained from patients hospitalized in the different UOCs of the health facility or of external origin and the diagnosis indirect serological analysis of the antibody response to numerous infectious diseases. In the field of mycobacteriology, the assistance contribution is made explicit in the diagnostic activities provided by the UOC such as the research of mycobacteria by means of microscopic and cultural examination with traditional and fluorimetric method, identification and antibiogram of Mycobacterium tuberculosis from various biological samples and direct research on biological sample of M. tuberculosis by gene amplification and Real-Time PCR; particular attention is paid to the diagnostic determination of the presence of latent tuberculous infection among certain risk categories of the population and to the isolation and identification by hybridization of atypical mycobacteria in patients with cystic fibrosis. In the field of mycology, Prof. Mancuso deals, in addition to basic mycological diagnostic activities, with the experimentation and subsequent application of molecular techniques for the detection of fungi from blood samples. This intense activity has led to the development of alternative methods (cheaper and faster) for the identification of colony fungi.
Membership in scientific societies and refereeing activities
Prof. Mancuso is a member of the Italian Society of Microbiology and referees for several international journals (J.Immunol., Journal of Drug Targeting, International Journal of molecular science, Eur. J. Immunology, Journal of Leukocyte Biology).
I dati visualizzati nella sezione sono recuperati dalla Procedura Gestione Carriere e Stipendi del Personale (CSA), dalla Procedura Gestione Studenti (ESSE3), da Iris e dal Sito Docenti MIUR.
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