Epigenetics, microenvironment and liver cancer

Objectifs

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.

Projets

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.
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Publications