Giovanni Maga
Giovanni Maga
affiliation: Istituto di Genetica Molecolare-CNR, Pavia
research area(s): Molecular Biology, Chemical Biology
Course: Genetics, Molecular and Cellular Biology
University/Istitution: Università di Pavia
Degree in Biological Sciences at the University of Pavia 1989
Master in Genetics at the University of Pavia 1990
PhD degree in Applied Genetics at the University of Pavia 1993
Postdoctoral fellow at the Institute of Veterinary Biochemistry,
University of Zürich 1993-1996
Postdoctoral Fellow at the Institute of
Molecular Genetics-CNR, Pavia
(ICGEB Fellowship, ISS-AIDS Fellowship) 1997-1999
Contract Researcher at the Institute of
Molecular Genetics-CNR, Pavia 2000-2001
Researcher at the Institute of
Molecular Genetics-CNR, Pavia since Dec. 2001
First Researcher at the Institute of
Molecular Genetics-CNR, Pavia since Dec. 2005
Head of the DNA Enzymology
&Molecular Virology Section since June 2006

Guest Editor of Current Drug Metabolism (ISSN 1389-2002)
Guest Editor of Current Pharmaceutical Biotechnology (ISSN: 1389-2010)
Associate Editor of the American Journal of Biochemistry and Biotechnology (ISSN 1553-3468)
Associate Editor of the American Journal of Infectious Deseases (ISSN 1553-6203)
Editorial Advisor of The Biochemical Journal (ISSN 0264-6021)
Editorial Board Member of The Open Biology Journal (ISSN 1874-1967)
Editorial Board Member of the Journal of Biological Chemistry (ISSN 0021-9258)
Member of The Biochemical Society (London)
Member of the American Society for Biochemistry and Molecular Biology
Principal Investigator in the following European Projects:
- 5FP-Quality of life: "Flavitherapeutics"
-5FP-Quality of life:"DNA replication and Biotechnology-REPBIOTECH"
-6FP- Genomics and Biotechnology for Health: "Targeting Replication and Integration of HIV-TRIoH"
-6FP- Genomics and Biotechnology for Health: "Exploiting Cellular Export of Nuclear Tanscripts as HIV Innovative Therapy- ExCellENT-HIT"

Dr. Maga is author/co-author of 169 publications in international peer-reviewed journals (ISI WOS), his h-index is 32 (Google Scholar)

Scientific Interests:
Dr. G. Maga has been working since his graduation on the enzymology of DNA replication. His research has focused on the characterization of different enzymatic systems responsible for nucleotide metabolism and the duplication of the genetic information in human cells and viruses as well as in protozoal parasites. In recent years, he has also started to dissect the biochemical pathways involved in coupling the DNA replication and repair machinery to cell cycle regulation in human cells. His interest has been devoted both towards the elucidation of basic molecular processes and to the exploitation of novel enzymatic targets for antiviral and anticancer chemotherapy.
Presently his main lines of research are:
Enzymology of DNA replication in eukaryotic cells
Novel antiviral strategies against human hepatitis C virus
Development of novel anti-HIV compounds
Molecular basis for HIV drug-resistance
Novel targets and drugs for anticancer chemotherapy
1. Enzymology of DNA replication in eukaryotic cells
2. Novel antiviral strategies against human hepatitis C virus
3. Development of novel anti-HIV compounds
4. Molecular basis for HIV drug-resistance
5. Novel targets and drugs for anticancer chemotherapy

Enzymology of DNA replication
We are interested in understanding the complex relationships between the DNA synthetic machinery (replisome) and other aspects of cell metabolism such as DNA repair, DNA damage tolerance and cell cycle regulation. We have set up a protocol for the isolation of multiprotein complexes from the nuclei of HeLa cells which turned out to be DNA replication/repair proficient and to contain cell cycle regulatory proteins.
We are also studying the roles of the auxiliary proteins RP-A and PCNA on the mechanisms of DNA damage tolerance. We have shown that PCNA and RP-A largely determine the ability of various cellular DNA polymerases to cope with DNA lesions such as abasic sites and 8-oxo-dG.

Novel antiviral strategies against HCV/HIV/Influenza infections. We are studying the replication machinery of the HCV virus with the aim of finding novel valuable targets for chemotherapy. We have already identified a potent non-nucleosidic inhibitor of the helicase activity of the viral protein NS3. We are also interested in exploiting the host-virus relationships in the case of HIV infection, in order to find alternative strategies for antiviral treatment. We are currently focusing on two targets: the viral protein Vif and its cellular partners APOBEC3F/G; and the cellular protein DDX3, an RNA helicase, and its viral partner Rev. We are also characterizing the cellular interactors of the protein NS1 of the avian and human influenza A virus.

HIV drug resistance. Current anti-HIV drugs targeted to the reverse transcriptase are severly limited by the development of drug resistance. We are currently undertaking a sytematic evaluation of the impact of drug resistance mutations in the viral RT on the viral fitness and drug sensitivity. We clone multi-resistant HIV-1 RTs from clinical isolates coming from AIDS patients failing therapy, express and purify the recombinant enzymes and evaluate their enzymological parameters. With this approach we already identified uncommon inter-class drug resistance patterns for mutations such as Y181I/C, Q145M, G190S, T215Y.

Novel targets for anticancer chemotherapy. We are exploiting a number of enzymes as targets for cancer therapy. We are currently focusing on the human terminal transferases TDT and DNA polymerase λ as poential targets for treating leukemias and on tyrosine kinases such as FAK, Src-family and Abl, as targets for treatment of different type of tumors. We have already identified a number of active compounds targeting each of these enzymes.

1. La Regina G, et al., Novellino E, Silvestri R. New Nitrogen Containing Substituents at the Indole-2-carboxamide Yield High Potent and Broad Spectrum Indolylarylsulfone HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors. J Med Chem. 2012 Jul 26;55(14):6634-8.
2. Samuele A, et al. The power of enzyme kinetics in the drug development process. Curr Pharm Biotechnol. 2012 Mar 20. [Epub ahead of print]
3. Maga G. New targets and new drugs: from in silico planning to in vivo testing. Curr Pharm Biotechnol. 2012 Mar 20. [Epub ahead of print]
4. Rotili D, et al. 2-(Alkyl/aryl)amino-6-benzylpyrimidin-4(3H)-ones as inhibitors of wild-type and mutant HIV-1: enantioselectivity studies. J Med Chem. 2012 Apr 12;55(7):3558-62.
5. Radi M, et al. Synthesis, biological activity, and ADME properties of novel S-DABOs/N-DABOs as HIV reverse transcriptase inhibitors. ChemMedChem. 2012 May;7(5):883-96.
6. Crespan E, et al. Microhomology-mediated DNA strand annealing and elongation by human DNA polymerases λ and β on normal and repetitive DNA sequences. Nucleic Acids Res. 2012 Jul;40(12):5577-90
7. Radi M, et al. Discovery of the first small molecule inhibitor of human DDX3 specifically designed to target the RNA binding site: mtowards the next generation HIV-1 inhibitors. Bioorg Med Chem Lett. 2012 Mar 1;22(5):2094-8.
8. Manfroni G, et al. Pyridobenzothiazole derivatives as new chemotype targeting the HCV NS5B polymerase. Bioorg Med Chem. 2012 Jan 15;20(2):866-76.
9. Crespan E, Maga G, Hübscher U. A new proofreading mechanism for lesion bypass by DNA polymerase-λ. EMBO Rep. 2011 Dec 23;13(1):68-74.
10. Bavagnoli L, et al. The PDZ-Ligand and Src-Homology Type 3 Domains of Epidemic Avian Influenza Virus NS1 Protein Modulate Human Src Kinase Activity during Viral Infection. PLoS One. 2011;6(11):e27789.
11. Samuele A, et al. Mechanism of interaction of novel indolylarylsulfone derivatives with K103N and Y181I mutant HIV-1 reverse transcriptase in complex with its substrates. Antivir Chem Chemother. 2011 Nov 17;22(3):107-18.
12. Bavagnoli L, Maga G. The 2009 influenza pandemic: promising lessons for antiviral therapy for future outbreaks. Curr Med Chem. 2011 Dec 1;18(35):5466-75.
13. Arioli F, et al. N-[2-Methyl-5-(triazol-1-yl)phenyl]pyrimidin-2-amine as a scaffold for thesynthesis of inhibitors of Bcr-Abl. ChemMedChem. 2011 Nov 4;6(11):2009-18.
14. Crespan E, et al. Exploiting the nucleotide substrate specificity of repair DNA polymerases to develop novel anticancer agents. Molecules. 2011 Sep 16;16(9):7994-8019.
15. Hübscher U, Maga G. DNA replication and repair bypass machines. Curr Opin Chem Biol. 2011 Oct;15(5):627-35.
16. Radi M, et al. Identification of potent c-Src inhibitors strongly affecting the proliferation of human neuroblastoma cells. Bioorg Med Chem Lett. 2011 Oct 1;21(19):
17. Maga G, et al. Toward the discovery of novel anti-HIV drugs. Second-generation inhibitors of the cellular ATPase DDX3 with improved anti-HIV activity: synthesis, structure-activity relationship analysis, cytotoxicity studies, and target validation. ChemMedChem. 2011 Aug 1;6(8):1371-89. 21698775.
18. Crespan E, Zucca E, Maga G. Overcoming the drug resistance problem with second-generation tyrosine kinase inhibitors: from enzymology to structural models. Curr Med Chem. 2011;18(19):2836-47.
19. Garbelli A, et al. Targeting the human DEAD-box polypeptide 3 (DDX3) RNA helicase as a novel strategy to inhibit viral replication. Curr Med Chem. 2011;18(20):3015-27.
20. Butini S, et al. Enantioselective binding of second generation pyrrolobenzoxazepinones to the catalytic ternary complex of HIV-1 RT wild-type and L100I and K103N drug resistant mutants. Bioorg Med Chem Lett. 2011 Jul 1;21(13):3935-8.
21. Garbelli A, et al. A motif unique to the human DEAD-box protein DDX3 is important for nucleic acid binding, ATP hydrolysis, RNA/DNA unwinding and HIV-1 replication. PLoS One. 2011 May 12;6(5):e19810.
22. Radi M, et al. Design, synthesis, biological activity, and ADME properties of pyrazolo[3,4-d]pyrimidines active in hypoxic human leukemia cells: a lead optimization study. J Med Chem. 2011 Apr 28;54(8):2610-26.
23. Rotili, D., et al. (2011) Diarylpyrimidine-Dihydrobenzyloxopyrimidine Hybrids: New, Wide-Spectrum Anti-HIV-1 Agents Active at (Sub)-Nanomolar Level. J Med Chem 54(8), 3091-3096.
24. Radi, M., et al. (2011) Design, Synthesis, Biological Activity, and ADME Properties of Pyrazolo[3,4-d]pyrimidines Active in Hypoxic Human Leukemia Cells: A Lead Optimization Study. J Med Chem 54(8), 2610-26.
25. La Regina, G., et al. (2011) Indolylarylsulfones as HIV-1 non-nucleoside reverse transcriptase inhibitors: new cyclic substituents at indole-2-carboxamide. J Med Chem 54(6), 1587-98.
26. Amoroso, A., et al. (2011) Oxidative DNA Damage Bypass in Arabidopsis thaliana Requires DNA Polymerase {lambda} and Proliferating Cell Nuclear Antigen 2. Plant Cell 23(2), 806-22.
No projects are available to students for the current accademic year.