Our team aims to utilize cutting edge innovative technologies and to link high technology to clinical application by extensive validation of the new findings in patient samples from relevant clinical settings.
Our team success and its translational value will very much depend on the access to liver samples from well-defined categories of patients. This will be achieved through the collaboration with a vast net of leading clinical groups in HBV and HCC research in Italy and France.
Altogether, our research efforts will generate new knowledge and provide new insights on the molecular pathogenesis of virus-related HCCs but will also, hopefully, provide data for the rationale use of anti-Ezh2/PRC2 in HCC treatment and lead to the development of biomarkers for early diagnosis, prognostication and treatment allocation of liver cancer patients.
HCC is one of the most frequent tumors worldwide and due to its poor prognosis, is the 2nd cause of cancer death worldwide. In Europe, HCC incidence and mortality rates are of 65,000 and 60,240 cases in Europe, respectively.
HCC development is driven by multiple viruses (HBV, HCV) and chronic metabolic alterations leading to chronic inflammation, DNA damage, epigenetic and genetic changes that affect both “common” and “etiology specific” oncogenic pathways. Importantly, whereas mutations and chromosomal aberrations, with the only exception of TERT promoter mutation, have been consistently found in tumor tissues, deregulation of signaling pathways and epigenetic changes (DNA methylation, post-translational histone modifications and noncoding RNA-mediated silencing pathways) are also detected early in the natural history of HCC development, at the stage of chronic hepatitis, cirrhosis or dysplastic nodules. Epigenetic changes include, occur early in the development of HCC.
The EpiHep team investigates the epigenetic changes that precede and accompany HCC development and progression mainly, but not exclusively, in the setting of HBV chronic liver diseases.
Specific research projects aim to:
- Define the contribution of the viral protein HBx and HBc in HBV pathogenicity, liver tumors development and progression;
- Study the expression profiles of exhausted antigen specific CD8 lymphocytes in chronic HBV carriers and HBV-related HCCs and test new pharmacological correction strategies;
- Identify the gene network controlled by the PRC2/Ezh2 complex in normal and neoplastic liver cells and to investigate the functional consequences of Ezh2 genetic knockdown and pharmacological manipulation;
- Identify genes and ncRNAs co-regulated by IL6/STAT3 and the PRC2 complex in HBV, HCV and NASH-related cancers and investigate their modulation by AMPK and metformin.
Membres de l'équipe
Post-doctorante ANRS - Equipe Levrero
Professeur Universitaire - Praticien Hospitalier UCBL/HCL - Equipe Levrero
GNS561, a new autophagy inhibitor active against cancer stem cells in hepatocellular carcinoma and hepatic metastasis from colorectal cancer
Brun S, Pascussi JM, Gifu EP, Bestion E, Macek-Jilkova Z, Wang G, Bassissi F, Mezouar S, Courcambeck J, Merle P, Decaens T, Pannequin J, Halfon P, Caron de Fromentel C Journal of CancerImpact of 2016 Enhanced Recovery After Surgery (ERAS) Recommendations on Outcomes after Hepatectomy in Cirrhotic and Non-Cirrhotic Patients
Lunel T, Mohkam K, Merle P, Bonnet A, Gazon M, Dumont PN, Ducerf C, Mabrut JY, Lesurtel M World Journal of SurgeryThe lncRNAs in HBV-Related HCCs: Targeting Chromatin Dynamics and Beyond
Alfano V, Zeisel MB, Levrero M, Guerrieri F CancersPatient-reported outcomes with atezolizumab plus bevacizumab versus sorafenib in patients with unresectable hepatocellular carcinoma (IMbrave150): an open-label, randomised, phase 3 trial
Galle PR, Finn RS, Qin S, Ikeda M, Zhu AX, Kim TY, Kudo M, Breder V, Merle P, Kaseb A, Li D, Mulla S, Verret W, Xu DZ, Hernandez S, Ding B, Liu J, Huang C, Lim HY, Cheng AL, Ducreux M Lancet OncologyHost Epigenetic Alterations and Hepatitis B Virus-Associated Hepatocellular Carcinoma
Zeisel MB, Guerrieri F, Levrero M Journal of Clinical MedicineRNA helicase DDX5 enables STAT1 mRNA translation and interferon signalling in hepatitis B virus replicating hepatocytes
Sun J, Wu G, Pastor F, Rahman N, Wang WH, Zhang Z, Merle P, Hui L, Salvetti A, Durantel D, Yang D, Andrisani O GutCombination therapy for advanced hepatocellular carcinoma: do we see the light at the end of the tunnel
Zhang T, Merle P, Wang H, Zhao H, Kudo M HepatoBiliary Surgery and NutritionPhase 1b/2 trial of tepotinib in sorafenib pretreated advanced hepatocellular carcinoma with MET overexpression
Decaens T, Barone C, Assenat E, Wermke M, Fasolo A, Merle P, Blanc JF, Grando V, Iacobellis A, Villa E, Trojan J, Straub J, Bruns R, Berghoff K, Scheele J, Raymond E, Faivre S British Journal of CancerHealth-related quality-of-life impact of pembrolizumab versus best supportive care in previously systemically treated patients with advanced hepatocellular carcinoma: KEYNOTE-240
Ryoo BY, Merle P, Kulkarni AS, Cheng AL, Bouattour M, Lim HY, Breder V, Edeline J, Chao Y, Ogasawara S, Yau T, Garrido M, Chan SL, Daniele B, Norquist JM, Chen E, Siegel AB, Zhu AX, Finn RS, Kudo M CancerExternal validation of the French alpha-fetoprotein model for hepatocellular carcinoma liver transplantation in a recent unicentric cohort – a retrospective study
Mourad M, Lebossé F, Merle P, Levrero M, Antonini T, Lesurtel M, Ducerf C, Zoulim F, Mabrut JY, Mohkam K Transplant InternationalDissecting the Molecular Determinants of GABA A Receptors Current Rundown, a Hallmark of Refractory Human Epilepsy
Cifelli P, Di Angelantonio S, Alfano V, Morano A, De Felice E, Aronica E, Ruffolo G, Palma E Brain ScienceDownregulation of miR-326 and its host gene β-arrestin1 induces pro-survival activity of E2F1 and promotes medulloblastoma growth
Miele E, Po A, Mastronuzzi A, Carai A, Besharat ZM, Pediconi N, Abballe L, Catanzaro G, Sabato C, De Smaele E, Canettieri G, Di Marcotullio L, Vacca A, Mai A, Levrero M, Pfister SM, Kool M, Giangaspero F, Locatelli F, Ferretti E Molecular OncologyPreliminary Evidence for Hepatitis Delta Virus Exposure in Patients Who Are Apparently Not Infected With Hepatitis B Virus
Chemin I, Pujol FH, Scholtès C, Loureiro CL, Amirache F, Levrero M, Zoulim F, Pérez-Vargas J, Cosset FL HepatologyTargeting clinical epigenetic reprogramming for chemoprevention of metabolic and viral hepatocellular carcinoma
Jühling F, Hamdane N, Crouchet E, Li S, El Saghire H, Mukherji A, Fujiwara N, Oudot MA, Thumann C, Saviano A, Roca Suarez AA, Goto K, Masia R, Sojoodi M, Arora G, Aikata H, Ono A, Tabrizian P, Schwartz M, Polyak SJ, Davidson I, Schmidl C, Bock C, Schuster C, Chayama K, Pessaux P, Tanabe KK, Hoshida Y, Zeisel MB, Duong FH, Fuchs BC, Baumert TF GutThe New Immuno-Oncology-Based Therapies and Their Perspectives in Hepatocellular Carcinoma
Merle P CancersHepatitis B virus-associated hepatocellular carcinoma is still a matter of concern in the French Caribbean Island of Guadeloupe
Benard J, Lafrance MJ, Gordien E, Amaral L, Levrero M, Zoulim F, Saillard E, Gelu-Simeon M Clin Res Hepatol Gastroenterol
Essential Oils as Alternative Biocides for the Preservation of Waterlogged Archaeological Wood
Antonelli F, Bartolini M, Plissonnier ML, Esposito A, Galotta G, Ricci S, Davidde Petriaggi B, Pedone C, Di Giovanni A, Piazza S, Guerrieri F*, Romagnoli M* MicroorganismsUse of next-generation sequencing to evaluate the risk of biodegradation
Antonelli, F., Esposito, A., Galotta, G., ...Romagnoli, M., Guerrieri, F Applied Sciences (Switzerland)Blockade of EIF5A hypusination limits colorectal cancer growth by inhibiting MYC elongation
Coni S, Serrao SM, Yurtsever ZN, Di Magno L, Bordone R, Bertani C, Licursi V, Ianniello Z, Infante P, Moretti M, Petroni M, Guerrieri F, Fatica A, Macone A, De Smaele E, Di Marcotullio L, Giannini G, Maroder M, Agostinelli E, Canettieri G Cell Death & Diseasep53 functional loss, stemness and hepatocellular carcinoma
Caron de Fromentel C, Levrero M Hepatoma ResearchDLEU2 lncRNA and sustains viral and host transcription
Salerno D, Chiodo L, Cottone G, Pallocca M, Jeddari S, Levrero M, Guerrieri F Gut. Effect of ramucirumab on ALBI grade in patients with advanced HCC: Results from REACH and REACH-2
Kudo M, Galle PR, Brandi G, Kang YK, Yen CJ, Finn RS, Llovet JM, Assenat E, Merle P, ....., Widau RC, Zhu AX JHEP ReportsPARP inhibitors and radiation potentiate liver cell death in vitro. Do hepatocellular carcinomas have an achilles’ heel?
Gerossier L, Dubois A, Paturel A, Fares N, Cohen D, Merle P, …, Bieche I, Hernandez-Vargas H, Hall J, Chemin I Clin Res Hepatol GastroenterolManagement of immune checkpoint inhibitors-induced liver toxicity in cancer
Lebossé F, Bancel B, Levrero M, Merle P Bulletin du CancerSerum Alpha-fetoprotein Levels and Clinical Outcomes in the Phase III CELESTIAL Study of Cabozantinib versus Placebo in Patients with Advanced Hepatocellular Carcinoma
Kelley RK, Meyer T, Rimassa L, Merle P, Park JW, Yau T, Chan SL, Blanc JF, Tam VC, Tran A, Dadduzio V, Markby DW, Kaldate R, Cheng AL, El-Khoueiry AB, Abou-Alfa GK Clinical Cancer ResearchRestoration of RNA helicase DDX5 suppresses hepatitis B virus (HBV) biosynthesis and Wnt signaling in HBV-related hepatocellular carcinoma
Mani SKK, Yan B, Cui Z, Sun J, Utturkar S, Foca A, Fares N, Durantel D, Lanman N, Merle P, Kazemian M, Andrisani O TheranosticsRamucirumab in elderly patients with hepatocellular carcinoma and elevated alpha-fetoprotein after sorafenib in REACH and REACH-2
Kudo M, Galle PR, Llovet JM, Finn RS, Vogel A, Motomura K, Assenat E, Merle P, Brandi G, ...., Yoshikawa R, Zhu AX Liver InternationalStructural Variations of Vaginal and Endometrial Microbiota: Hints on Female Infertility
Riganelli L, Iebba V, Piccioni M, Illuminati I, ..., Levrero M, Merlino L, ..., Schippa S, Guerrieri F Front Cell Infect MicrobiolProteomics analysis of FUS mutant human motoneurons reveals altered regulation of cytoskeleton and other ALS-linked proteins via 3’UTR binding
Garone MG*, Alfano V*, Salvatori B, Braccia C, Peruzzi G, Colantoni A, Bozzoni I, Armirotti A, Rosa A Scientific ReportsChlamydia trachomatis elicits TLR3 expression but disrupts the inflammatory signaling down-modulating NFκB and IRF3 transcription factors in human Sertoli cells
Di Pietro M, Filardo S, Alfano V, Pelloni M, Splendiani E, Po A, Paoli D, Ferretti E, Sessa R J Biol Regul Homeost AgentsNasal Microbiota in RSV Bronchiolitis
Schippa S, Frassanito A, Marazzato M, Nenna R, Petrarca L, Neroni B, Bonfiglio G, Guerrieri F, Frasca F, Oliveto G, Pierangeli A, Midulla F MicroorganismsAtezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma
Finn RS, Qin S, Ikeda M, ..., Merle P, Kaseb AO, ..., Zhu AX, Cheng AL; IMbrave150 Investigators New Engl J MedElectrophysiological features of chronic inflammatory demyelinating polyradiculoneuropathy associated with IgG4 antibodies targeting neurofascin 155 or contactin 1 glycoproteins
Kouton L, Boucraut J, Devaux J, ...., Merle P, ...., Attarian S, Delmont E Clinical NeurophysiologyHepatitis C Virus Entry: An Intriguingly Complex and Highly Regulated Process
Colpitts CC, Tsai PL, Zeisel MB Int J Mol SciA Hyper-Glycosylation of HBV Surface Antigen Correlates with HBsAg-Negativity at Immunosuppression-Driven HBV Reactivation in Vivo and Hinders HBsAg Recognition in Vitro
Salpini R, Piermatteo L, Battisti A, ...., Levrero M, Perno CF, Belloni L, Svicher V VirusesA functional microRNA screen uncovers O-linked N-acetylglucosamine transferase as a host factor modulating hepatitis C virus morphogenesis and infectivity
Herzog K, Bandiera S,..., Zeisel MB. GUTA combined small molecule and loss-of-function screen uncovers estrogen 2 receptor alpha and CAD as host factors for HDV infection and antiviral targets
Verrier ER,…, Zeisel MB,…, Baumert GutTargeting p53 and histone methyltransferases restores exhausted CD8+ T cells in HCV infection
Barili V, Fisicaro P, Montanini B, ...., Guerrieri F, ...., Levrero M, Ottonello S, Ferrari C Nature CommunicationsCharacterization of black patina from the Tiber River embankments using Next-Generation Sequencing
Antonelli A, Esposito A, Calvo L, Licursi V, Tysseire P, Ricci S, Romagnoli M, Piazza S, Guerrieri F PLoS OneHepatitis Delta Virus histone mimicry drives the recruitment of chromatin remodelers for viral RNA replication
Abeywickrama-Samarakoon N, Cortay JC, Sureau C, Müller S, Alfaiate D, Guerrieri F, Chaikuad A, Schröder M, Merle P, Levrero M, Dény P Nature Communications
Inducing and Characterizing Vesicular Steatosis in Differentiated HepaRG Cells
Di Cocco S, Belloni L, Nunn ADG, Salerno D, Piconese S, Levrero M, Pediconi N. J Vis ExpEZH2, JMJD3, and UTX epigenetically regulate hepatic plasticity inducing retro-differentiation and proliferation of liver cells
Pediconi N, Salerno D, Lupacchini L, Angrisani A, Peruzzi G, De Smaele E, Levrero M, Belloni L Cell Death DisSerum hepatitis B core-related antigen (HBcrAg) correlates with covalently closed circular DNA transcriptional activity in chronic hepatitis B patients.
Testoni B, Lebossé F, Scholtes C, Berby F, Miaglia C, Subic M, Loglio A, Facchetti F, Lampertico P, Levrero M, Zoulim F J HepatolHCV-induced epigenetic changes associated with liver cancer risk persist after sustained virologic response
Hamdane N, Jühling F,…, Zeisel MB,…, Baumert TF Gastroenterology.Microglia-Derived Microvesicles Affect Microglia Phenotype in Glioma
Grimaldi A, Serpe C, Chece G, Nigro V, Sarra A, Ruzicka B, Relucenti M, Familiari G, Ruocco G, Pascucci GR, Guerrieri F, Limatola C, Catalano M. Front Cell NeurosciEffect of food preservatives and additives in promoting intestinal inflammation
Laudisi F, Di Fusco D, Dinallo V, Stolfi C, Di Grazia A, Marafini I, Colantoni A, Ortenzi A, Alteri C, Guerrieri F, Ceccherini-Silberstein F, Federici M, Monteleone I, and Monteleone G Cell Mol Gastroenterol Hepatol
The novel HBx mutation F30V correlates with hepatocellular carcinoma in vivo, reduces hepatitis B virus replicative efficiency and enhances anti-apoptotic activity of HBx N terminus in vitro
Salpini R,…, Levrero M,…, Svicher V Clin Microbiol Infect .Targeting a phospho-STAT3-miRNAs pathway improves vesicular hepatic steatosis in an in vitro and in vivo model
Belloni L,…, Guerrieri F,…, Levrero M, Pediconi N Sci RepCombining amplicon sequencing and metabolomics in cirrhotic patients highlights distinctive microbiota features involved in bacterial translocation, systemic inflammation and hepatic encephalopathy
Iebba V, Guerrieri F, Di Gregorio V, Levrero M, Gagliardi A, Santangelo F, Sobolev AP, Circi S, Giannelli V, Mannina L, Schippa S, Merli M Sci RepmiR-135a-5p-mediated downregulation of protein tyrosine phosphatase receptor delta is a candidate driver of HCV-associated hepatocarcinogenesis
Van Renne N,…, Zeisel MB,…, Lupberger J. GUT
Reciprocal antagonism between the netrin-1 receptor uncoordinated-phenotype-5A (UNC5A) and the hepatitis C virus
Plissonnier ML, Lahlali T, Raab M, Michelet M, Romero-López C, Rivoire M, Strebhardt K, Durantel D, Levrero M, Mehlen P, Zoulim F, Parent R OncogeneCell death and restoration of TRAIL-sensitivity by ciglitazone in resistant cervical cancer cells
Plissonnier ML, Fauconnet S, Bittard H, Mougin C, Rommelaere J, Lascombe I ONcotargetPRMT5 Restricts Hepatitis B Virus Replication via Epigenetic Repression of cccDNA Transcription and Interference with pgRNA Encapsidation
Zhang W, Chen J, Wu M, Zhang X, Zhang M, Yue L, Li Y, Liu J, Li B, Shen F, Wang Y, Bai L, Protzer U, Levrero M, Yuan Z HepatologyGenome-wide identification of direct HBx genomic targets
Guerrieri F, Belloni L, D'Andrea D, Pediconi N, Le Pera L, Testoni B, Scisciani C, Floriot O, Zoulim F, Tramontano A, Levrero M BMC GenomicsTargeting mitochondrial dysfunction can restore antiviral activity of exhausted HBV-specific CD8 T cells in chronic hepatitis B
Fisicaro P, Barili V, Montanini B, Acerbi G, Ferracin M, Guerrieri F, Salerno D, Boni C, Massari M, Cavallo MC, Grossi G, Giuberti T, Lampertico P, Missale G, Levrero M, Ottonello S, Ferrari C Nat Med