Current main project:
New therapeutic strategies based on the identification of novel effective anti-viral compounds
The primary objective of this project is to identify altered regulatory pathways involved in T cell exhaustion in chronic hepatitis C virus (HCV) and hepatitis C virus (HBV) infections and to set up targeted molecular strategies to correct their dysregulation, as a novel therapeutic approach toward the restoration of an efficient antiviral T cell functionality. This primary objective will be achieved through interconnected tasks:
- mRNA transcriptome analysis in virus-specific CD8+ T cells: i) to confirm the pathogenetic relevance of exhaustion-related genes previously described in murine and human models of chronic infection; ii) to identify new dysregulated genes and pathways related to T cell functional impairment.
- Identification of drugs able to disrupt the inhibitory receptor-ligand interactions, responsible of T cell exhaustion, through the screening of small molecules using BRET (Bioluminescence Resonance Energy Transfer) technology in yeast.
- Functional validation of newly identified, dysregulated protein coding genes and/or small molecules by restoration of virus-specific CD8+ T cell functions in vitro
Development of tools for protein-protein interaction analyses in yeast: screening of inhibitors of protein-protein interaction using yeast BRET (Biolumenescence Resonance Energy Transfer); screening for protein partners using yeast two hybrid.
Post-genomic functional characterization in yeast of transcription factors (transcriptional activator trap), nuclear proteins (nuclear transport trap), DNA methyltransferases, secreted protein, and functional complementation analysis of specific yeast mutants.
Transcriptomic and genome-wide DNA methylation data analyses. Genome annotation, with particular attention on transcription factors and transporters.