{"id":10701,"date":"2023-02-23T18:16:27","date_gmt":"2023-02-23T17:16:27","guid":{"rendered":"https:\/\/www.istitutopasteuritalia.it\/2023\/18\/canettieri-gianluca\/"},"modified":"2026-07-16T14:31:43","modified_gmt":"2026-07-16T12:31:43","slug":"canettieri-gianluca","status":"publish","type":"post","link":"https:\/\/www.istitutopasteuritalia.it\/en\/2023\/18\/canettieri-gianluca\/","title":{"rendered":"Canettieri Gianluca"},"content":{"rendered":"\t\t
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Gianluca Canettieri<\/h2>\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t
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Laureato in Medicina e Chirurgia nel 1995 presso l\u2019Universit\u00e0 La Sapienza di Roma, dove ha poi svolto il dottorato di ricerca in Endocrinologia e Malattie Metaboliche.<\/p>

\u00c8 stato Visiting Fellow presso la Johns Hopkins University di Baltimora (1996) e, successivamente, post doctoral fellow presso il Salk Institute for Biological Studies di San Diego (2000-2005).<\/p>

\u00c8 tornato in Italia nel 2005 grazie al programma ministeriale \u201cRientro dei Cervelli\u201d, entrando nel 2008 nel ruolo universitario di Professore Associato. Dal 2019 \u00e8 professore Ordinario di Patologia Generale presso l\u2019Universit\u00e0 La Sapienza di Roma, dove dirige l\u2019Unit\u00e0 di Epigenetica, Metabolismo e Cancro del Dipartimento di Medicina Molecolare <\/p>\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t

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Lo stato ossidoriduttivo cellulare come bersaglio terapeutico nel cancro del Colon-retto<\/h4>\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t
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La metformina e la fenformina sono farmaci ampiamente usati nella cura del diabete di tipo 2, dotati di una significativa efficacia terapeutica verso alcuni tipi di tumore, tra cui quello del colon-retto. Il meccanismo mediante cui tali farmaci esercitano questa presunta azione terapeutica \u00e8 tuttavia ancora oscuro. Studi recenti condotti nei nostri laboratori suggeriscono che alla base del meccanismo d\u2019azione antitumorale possa esserci uno sbilanciamento dello stato ossidoriduttivo intracellulare, con aumento del NADH citoplasmatico e attivazione di specifici \u201csensori redox\u201d, responsabili dell\u2019azione antitumorale. <\/em><\/p>

Il presente progetto mira a caratterizzare in dettaglio la natura di tali alterazioni, definendo i recettori dei farmaci, i sensori e i target coinvolti e cercando di potenziare l\u2019effetto di questi meccanismi molecolari mediante specifici approcci farmacologici e regimi dietetici.<\/em><\/p>

Lo studio fornir\u00e0 informazioni rilevanti sul meccanismo d\u2019azione di una classe di farmaci ampiamente usata nella patologia umana, e contribuir\u00e0 a capire se tale effetto possa essere utilizzato e ottimizzato nella pratica clinica, per la prevenzione ed il trattamento dei tumori del colon-retto.<\/em><\/p>\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t

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Targeting Redox State in Colorectal Cancer<\/h4>\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t
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The biguanides metformin and phenformin are antidiabetic drugs associated to well-established antitumor properties in preclinical and clinical settings. Despite intensive efforts and studies, the mechanism of action of biguanides in cancer is still unclear. <\/p>

The most accepted model links the effect of these drugs to their ability to inhibit complex I of the mitochondrial electron transport chain, thereby decreasing respiration and causing energy stress and elevation of the redox state. However, this model has been questioned since inhibition of complex I requires millimolar concentrations of biguanides and these values cannot be reached in patients and animal models, where the maximum tolerated doses are within the low micromolar range. <\/p>

The present project aims at elucidating these critical issues using as a model colorectal cancer (CRC), a leading cause of cancer-related deaths worldwide, whose incidence is increased in type 2 diabetes, but reduced in patients treated with metformin.<\/p>

Our working model, based on previous work and preliminary findings, is that therapeutic doses of biguanides do not inhibit complex I but rather mitochondrial mGPD enzyme, which catalyzes the oxidation of Glycerol 3-Phosphate (G3P) to Dihydroxyacetone Phosphate (DHAP), causing an increase of cytoplasmic redox state and NADH. We hypothesize that the co-repressors C-terminal Binding Proteins (CtBPs) act as the key mediators of biguanide-dependent tumor inhibition, thanks to their ability to sense NADH elevations and respond through the binding of distinct partners involved in tumorigenesis. We propose that specific combinations of drugs, nutrients or metabolites that elevate NADH content can enhance this mechanism and be exploited for therapeutic purposes in CRC. To address these issues, we propose to 1) study the vulnerability of CRC cells to therapeutic concentrations of biguanides and analyze alterations of redox state and its role in the antitumor response. 2) characterize the biguanides receptor and test the effect of increased redox state on CRC growth using combinations of drugs and nutrients, 3) investigate the role and mechanism of action of the redox sensors CtBPs in response to biguanides and altered redox state. <\/p>\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t<\/div>\n\t\t","protected":false},"excerpt":{"rendered":"

Gianluca Canettieri Laureato in Medicina e Chirurgia nel 1995 presso l\u2019Universit\u00e0 La Sapienza di Roma, dove ha poi svolto il dottorato di ricerca in Endocrinologia e Malattie Metaboliche. \u00c8 stato Visiting Fellow presso la Johns Hopkins University di Baltimora (1996) e, successivamente, post doctoral fellow presso il Salk Institute for Biological Studies di San Diego …<\/p>\n","protected":false},"author":2,"featured_media":10700,"comment_status":"open","ping_status":"open","sticky":false,"template":"elementor_header_footer","format":"standard","meta":{"give_campaign_id":0,"footnotes":""},"categories":[193,192],"tags":[],"class_list":["post-10701","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-nuovi-finanziati","category-sapienza-researchers-funded-by-istituto-pasteur"],"_links":{"self":[{"href":"https:\/\/www.istitutopasteuritalia.it\/en\/wp-json\/wp\/v2\/posts\/10701","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.istitutopasteuritalia.it\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.istitutopasteuritalia.it\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.istitutopasteuritalia.it\/en\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.istitutopasteuritalia.it\/en\/wp-json\/wp\/v2\/comments?post=10701"}],"version-history":[{"count":1,"href":"https:\/\/www.istitutopasteuritalia.it\/en\/wp-json\/wp\/v2\/posts\/10701\/revisions"}],"predecessor-version":[{"id":10702,"href":"https:\/\/www.istitutopasteuritalia.it\/en\/wp-json\/wp\/v2\/posts\/10701\/revisions\/10702"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.istitutopasteuritalia.it\/en\/wp-json\/wp\/v2\/media\/10700"}],"wp:attachment":[{"href":"https:\/\/www.istitutopasteuritalia.it\/en\/wp-json\/wp\/v2\/media?parent=10701"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.istitutopasteuritalia.it\/en\/wp-json\/wp\/v2\/categories?post=10701"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.istitutopasteuritalia.it\/en\/wp-json\/wp\/v2\/tags?post=10701"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}