Commessa MagaSection Maga    
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Development and mechanism of action of nucleotide analogues and nucleoside compounds with antiproliferative and antiviral activities: new compounds and new targets for therapy



Head: Dott. Giovanni Maga


Staff: Federico Focher, Emmanuele Crespan, Anna Cleta Croce, Giuliano Mazzini


The line of research "Innovative approaches in molecular medicine: from drug discovery to diagnostics" qualifies as an integrated platform for the development and application of innovative approaches in the biomedical field. It embodies the spirit of translational research, in which basic research, aimed at acquiring new information on the biological processes of interest, merges with applied research, oriented to the translation of knowledge in the application field. A goal of this research unit is to establish synergies with the private sector (SMEs).

The activity focuses on two main lines of research.

1) Identification of new targets and development new molecules with antiviral, antiprotozoal, antibacterial and anti-tumor activities.

Development of pharmacological inhibitors of proteins with biomedical interest. For this activity proteins of interest are expressed in bacteria, yeast or insect cells and biochemically tested. The list of analyzed proteins includes i) the tyrosine kinase Hck, involved in leukemias and in the HIV-1 life cycle, ii) the endonuclease PA-X encoded by the human Influenza A virus iii) the Pim kinases with a role in the regulation of the cell cycle; iv) the thymidine kinase of herpes virus. Studies are underway to clarify the mechanisms of action of inhibitory compounds.

Part of this Unit investigates the effects of berberine derivatives on the metabolism of cancer cells. Moreover, in collaboration with the Department of Engineering, the unit is developing photonic devices to separate cells with different motility and elasticity. This device can be applied to study the impact of the microenvironment on tumor cells. Finally, this unit is involved in a project aimed at identifying biomarkers of cellular stress in subjects exposed to endogenous or environmental sources of stress (eg Arsenic).

Part of the activity focuses on the analysis basic research topics that promote new applicative studies. For example, 1) the analysis of the mechanism of action of specialized DNA polymerase lambda involved the non-homologous end joining (NHEJ) DNA repair pathways and 2) the characterization of the role of poly (ADP-ribosylation) in different types of cell death: apoptosis, autophagy, and parthanatos necroptosis.

2) The second line of research concerns the development of new instrumentations and optical methods for basic research and clinical applications. IGM scientists involved in this field set up methodologies and instruments to measure cellular auto-fluorescence and to monitor cancer cells and suffering tissues during surgical operations (optical biopsy). Protocols are being developed to study differentiation of stem cells. Recently, this activity gained the interest by several SMEs.

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