Research Groups

Molecular Medicine

Group Leader

Research Interests and Description
Group Members

Mauro Giacca

Director, ICGEB Trieste Component

International Centre for Genetic Engineering and Biotechnology
Padriciano 99
34012 Trieste, Italy

E-mail: giacca@icgeb.org
Office tel: +39-040-3757324
Lab tel: +39-040-3757325
Office fax: +39-040-3757380

Education

Faculty of Medicine, University of Trieste, Italy, MD, 1984
Admitted to the Medical Doctors and Surgeons Register, 1985
University of Genova, Italy, PhD, 1989

Career History

Since July 2004, Director of the Trieste Component of the International Centre for Genetic Engineering and Biotechnology (ICGEB), Trieste, Italy.
2000-2004, Director of the Molecular Biology Laboratory of the Scuola Normale Superiore in Pisa, Italy.
Since 1995, Senior Scientist and Group Leader of the Molecular Medicine Laboratory of the ICGEB in Trieste.
1988-1994, Assistant Research Scientist at ICGEB, Trieste.
1986-1987, PhD student at the IGBE, CNR, Pavia.
1980-1985, Pre-doctoral student and fellow at the Institute of Microbiology of the University of Trieste.

Teaching Activity

Since 2005, Full Professor, University of Trieste.
2000-2005, Associate Professor of Molecular Biology at the Scuola Normale Superiore in Pisa.
Since 2001, external Professor in the course Gene Therapy at the Medical School at the University of Trieste.
1989-1999, external Professor in different courses of Microbiology and Medical Genetics at the Faculty of Medicine of the University of Trieste.
1991-1996, Lecturer in the PhD Course of Molecular Genetics of the International School for Advanced Studies (ISAS) of Trieste, Italy.

Scientific Activity

Research interests focus on two major topics in the field of Molecular Medicine. The first project concerns the development of viral vectors for human gene therapy, with special emphasis on vectors based on the adeno-associated virus (AAV) and their application for gene therapy of cardiovascular disorders. The second project concerns several aspects of the molecular biology of HIV-1 infection with particular reference to the study of the interactions of some viral proteins (Tat, integrase) with cellular factors.

In the last 5 years, more than 50 seminars presented on own research activity in Europe, USA and Japan. Over 190 full papers published, of which more than 160 in peer-reviewed international journals, in addition to several articles on newspapers or popular science magazines.

Selected publications

Cervelli, T., Palacios, J.A., Zentilin, L., Mano, M., Schwartz, R.A., Weitzman, M.D., Giacca, M. 2008. Processing of recombinant AAV genomes occurs in specific nuclear structures that overlap with foci of DNA-damage-response proteins. J Cell Sci 121, 349-357

Collesi C, Zentilin L, Sinagra G, Giacca M. 2008. Notch1 signaling stimulates proliferation of immature cardiomyocytes. J. Cell Biol. 183, 117-128

Giacca, M. 2008. Gene Therapy to Induce Cellular Resistance to HIV-1 Infection: Lessons from Clinical Trials. Adv Pharmacol 56, 297-325

Perkins, K.J., Lusic, M., Mitar, I., Giacca, M., Proudfoot, N.J. 2008. Transcription-Dependent Gene Looping of the HIV-1 Provirus Is Dictated by Recognition of Pre-mRNA Processing Signals. Mol Cell 29, 56-68

Sabo, A., Lusic, M., Cereseto, A., Giacca, M. 2008. Acetylation of conserved lysines in the catalytic core of CDK9 inhibits kinase activity and regulates transcription. Mol Cell Biol 7, 2201-2012 Vardabasso, C., Manganaro, L., Lusic, M., Marcello, A., Giacca, M. 2008. The histone chaperone protein Nucleosome Assembly Protein-1 (hNAP-1) binds HIV-1 Tat and promotes viral transcription. Retrovirology 28, 5-8

Zacchigna, S., Ostli, E.K., Arsic, N., Pattarini, L., Giacca, M., Djurovic, S. 2008. A novel myogenic cell line with phenotypic properties of muscle progenitors. J. Mol. Med. 86, 105-115

Zacchigna, S., Pattarini, L., Zentilin, L., Moimas, S., Carrer, A., Sinigaglia, M., Arsic, N., Tafuro, S., Sinagra, G., Giacca, M. 2008. Bone marrow cells recruited through the neuropilin-1 receptor promote arterial formation at the sites of adult neoangiogenesis in mice. J. Clin. Invest. 118, 2062-2075

Cardarelli, F., Serresi, M., Bizzarri, R., Giacca, M., Beltram, F. 2007. In vivo study of HIV-1 Tat arginine-rich motif unveils Its transport properties. Mol. Ther. 15, 1313-1322

Crotti, A., Lusic, M., Lupo, R., Lievens, P.M., Liboi, E., Chiara, G.D., Tinelli, M., Lazzarin, A., Patterson, B.K., Giacca, M., Bovolenta, C., Poli, G. 2007. Naturally occurring C-terminally truncated STAT5 is a negative regulator of HIV-1 expression. Blood 109, 5380-5389

Fisher, C., Jonckx, B., Mazzone, M., Zacchigna, S., Autiero, M., Chorianopoulos, E., Demol, M., Deparaetere, H., Wyns, S., Ngo, H., Pattarini, L., Plaisance, S., Dewerchin., M., Giacca, M., Moons, L., Stassen, J.-M., Collen, D., Carmeliet, P. 2007. A monoclonal anti-PlGF antibody inhibits tumor growth and lymphatic metastasis without affecting healthy vessels. Cell 131, 463-475

Giacca, M. 2007. Gene therapy to induce cellular resistance to HIV-1 infection: lessons from clinical trials. In: Advances in Pharmacology. HIV-1: Molecular Biology and Pathogenesis: Clinical Applications (K. Teh-Jeang, Ed.), Vol. 56, pp. Elsevier

Giacca, M. 2007. Virus-mediated gene transfer to induce therapeutic angiogenesis: where do we stand? Int. J. Nanomedicine 2, 527-540

Manasseri, B., Cuccia, G., Moimas, S., D'Alcontres, F.S., Polito, F., Bitto, A., Altavilla, D., Squadrito, F., Geuna, S., Pattarini, L., Zentilin, L., Collesi, C., Puligadda, U., Giacca, M., Colonna, M.R. 2007. Microsurgical arterovenous loops and biological templates: a novel in vivo chamber for tissue engineering. Microsurgery 27, 623-629

Messina, S., Mazzeo, A., Bitto, A., Aguennouz, M., Migliorato, A., De Pasquale, M.G., Minutoli, L., Altavilla, D., Zentilin, L., Giacca, M., Squadrito, F., Vita, G. 2007. VEGF overexpression via adeno-associated virus gene transfer promotes skeletal muscle regeneration and enhances muscle function in mdx mice. Faseb J 21, 3737-3746

Ramirez, Y.J., Tasciotti, E., Gutierrez-Ortega, A., Torres, A.J., Flores, M.T., Giacca, M., Lim, M.A. 2007. Fruit-specific expression of the human immunodeficiency virus type 1 tat gene in tomato plants and its immunogenic potential in mice. Clin Vaccine Immunol 14, 685-692

Schwartz, R.A., Palacios, J.A., Cassell, G.D., Adam, S., Giacca, M., Weitzman, M.D. 2007. The Mre11/Rad50/Nbs1 complex limits adeno-associated virus transduction and replication. J. Virol. 81, 12936-12945

Zacchigna, S., Tasciotti, E., Kusmic, C., Arsic, N., Sorace, O., Marini, C., Marzullo, P., Pardini, S., Petroni, D., Pattarini, L., Moimas, S., Giacca, M., Sambuceti, G. 2007. In vivo imaging shows abnormal function of vascular endothelial growth factor-induced vasculature. Hum. Gene Ther. 18, 515-524

Zentilin, L., Giacca, M. 2007. Competitive PCR for precise nucleic acid quantification. Nat. Protoc. 2, 2092-2104

Benigni, A., Tomasoni, S., Turka, L.A., Longaretti, L., Zentilin, L., Mister, M., Pezzotta, A., Azzollini, N., Noris, M., Conti, S., Abbate, M., Giacca, M., Remuzzi, G. 2006. Adeno-Associated Virus-Mediated CTLA4Ig Gene Transfer Protects MHC-Mismatched Renal Allografts from Chronic Rejection. J. Am. Soc. Nephrol. 17, 1665-1672

Ferrarini, M., Arsic, N., Recchia, F.A., Zentilin, L., Zacchigna, S., Xu, X., Linke, A., Giacca, M., Hintze, T.H. 2006. Adeno-associated virus-mediated transduction of VEGF165 improves cardiac tissue viability and functional recovery after permanent coronary occlusion in conscious dogs. Circ. Res. 98, 954-961

Pegoraro, G., Marcello, A., Myers, M.P., Giacca, M. 2006. Regulation of Adeno-Associated Virus DNA Replication by the Cellular TAF-I/Set Complex. J Virol 80, 6855-6864

Secchiero, P., Candido, R., Corallini, F., Zacchigna, S., Toffoli, B., Rimondi, E., Fabris, B., Giacca, M., Zauli, G. 2006. Systemic tumor necrosis factor-related apoptosis-inducing ligand delivery shows antiatherosclerotic activity in apolipoprotein E-null diabetic mice. Circulation 114, 1522-1530

Zentilin, L., Tafuro, S., Zacchigna, S., Arsic, N., Pattarini, L., Sinigaglia, M., Giacca, M. 2006. Bone marrow mononuclear cells are recruited to the sites of VEGF-induced neovascularization but are not incorporated into the newly formed vessels. Blood 107, 3546-3554

Zacchigna, S., Papa, G., Antonini, A., Novati, F., Moimas, S., Carrer, A., Arsic, N., Zentilin, L., Visintini, V., Pascone, M., Giacca, M. 2005. Improved survival of ischemic cutaneous and musculocutaneous flaps after vascular endothelial growth factor gene transfer using adeno-associated virus vectors. Am. J. Pathol. 167, 981-991

Cereseto, A., Manganaro, L., Gutierrez, M.I., Terreni, M., Fittipaldi, A., Lusic, M., Marcello, A., Giacca, M. 2005. Acetylation of HIV-1 integrase by p300 regulates viral integration. EMBO J. 24, 3070-3081

Galbiati, L., Mendoza-Maldonado, R., Gutierrez, M.I., Giacca, M. 2005. Regulation of E2F-1 after DNA damage by p300-mediated acetylation and ubiquitination. Cell Cycle 4, 930-939

Giacca, M. 2005. HIV-1 Tat, apoptosis and the mitochondria: a tubulin link? Retrovirology 2, 7.

Marchio, S., Alfano, M., Primo, L., Gramaglia, D., Butini, L., Gennero, L., De Vivo, E., Arap, W., Giacca, M., Pasqualini, R., Bussolino, F. 2005. Cell surface-associated Tat modulates HIV-1 infection and spreading through a specific interaction with gp120 viral envelope protein. Blood 105, 2802-2811

Recchia, F.A., Giacca, M. 2005. Targeted uptake-1 carrier to rescue the failing heart. Circ. Res. 97, 847-849

Tasciotti, E., Giacca, M. 2005. Fusion of the human immunodeficiency virus type 1 tat protein transduction domain to thymidine kinase increases bystander effect and induces enhanced tumor killing in vivo. Hum. Gene Ther. 16, 1389-1403

Todorovic, V., Giadrossi, S., Pelizon, C., Mendoza-Maldonado, R., Masai, H., Giacca, M. 2005. Human origins of DNA replication selected from a library of nascent DNA. Mol. Cell. 19, 567-575

Arsic, N., Zacchigna, S., Zentilin, L., Ramirez-Correa, G., Pattarini, L., Salvi, A., Sinagra, G., Giacca, M. 2004. Vascular endothelial growth factor stimulates skeletal muscle regeneration in vivo. Mol Ther 10, 844-854

Di Leva, F., Ferrante, M.I., Demarchi, F., Caravelli, A., Matarazzo, M.R., Giacca, M., D'Urso, M., D'Esposito, M., Franze, A. 2004. Human synaptobrevin-like 1 gene basal transcription is regulated through the interaction of selenocysteine tRNA gene transcription activating factor-zinc finger 143 factors with evolutionary conserved cis-elements. J. Biol. Chem. 279, 7734-7739

Lidonnici, M.R., Rossi, R., Paixao, S., Mendoza-Maldonado, R., Paolinelli, R., Arcangeli, C., Giacca, M., Biamonti, G., Montecucco, A. 2004. Subnuclear distribution of the largest subunit of the human origin recognition complex during the cell cycle. J. Cell Sci. 117, 5221-5231

Marcello, A., Lusic, M., Pegoraro, G., Pellegrini, V., Beltram, F., Giacca, M. 2004. Nuclear organization and the control of HIV-1 transcription. Gene 326, 1-11

Ramirez Correa, G.A., Zacchigna, S., Arsic, N., Zentilin, L., Salvi, A., Sinagra, G., Giacca, M. 2004. Potent inhibition of arterial intimal hyperplasia by TIMP1 gene transfer using AAV vectors. Mol. Ther. 9, 876-884

Zacchigna, S., Zentilin, L., Morini, M., Dell'Eva, R., Noonan, D.M., Albini, A., Giacca, M. 2004. AAV-mediated gene transfer of tissue inhibitor of metalloproteinases-1 inhibits vascular tumor growth and angiogenesis in vivo. Cancer Gene Ther. 11, 73-80

Arsic, N., Zentilin, L., Zacchigna, S., Santoro, D., Stanta, G., Salvi, S., Sinagra, G., Giacca, M. 2003. Induction of functional neovascularization by combined VEGF and angiopoietin-1 gene transfer using AAV vectors. Mol. Ther. 7, 450-459

Ferrari, A., Pellegrini, V., Arcangeli, C., Fittipaldi, A., Giacca, M., Beltram, F. 2003. Caveolae-mediated internalization of extracellular HIV-1 Tat fusion proteins visualized in real time. Mol. Ther. 8, 284-294

Fittipaldi, A., Ferrari, A., Zoppe, M., Arcangeli, C., Pellegrini, V., Beltram, F., Giacca, M. 2003. Cell membrane lipid rafts mediate caveolar endocytosis of HIV-1 Tat fusion proteins. J. Biol. Chem. 278, 34141-34149

Gabellini, D., Colaluca, I.N., Vodermaier, H.C., Biamonti, G., Giacca, M., Falaschi, A., Riva, S., Peverali, F.A. 2003. Early mitotic degradation of the homeoprotein HOXC10 is potentially linked to cell cycle progression. EMBO J. 22, 3715-3724

Galeano, M., Deodato, B., Altavilla, D., Cucinotta, D., Arsic, N., Marini, H., Torre, V., Giacca, M., Squadrito, F. 2003. Adeno-associated viral vector-mediated human vascular endothelial growth factor gene transfer stimulates angiogenesis and wound healing in the genetically diabetic mouse. Diabetologia 46, 546-555

Lusic, M., Marcello, A., Cereseto, A., Giacca, M. 2003. Regulation of HIV-1 gene expression by histone acetylation and factor recruitment at the LTR promoter. EMBO J. 22, 6550-6561

Marcello, A., Ferrari, A., Pellegrini, V., Pegoraro, G., Lusic, M., Beltram, F., Giacca, M. 2003. Recruitment of human cyclin T1 to nuclear bodies through direct interaction with the PML protein. EMBO J. 22, 2156-2166

Tasciotti, E., Zoppe, M., Giacca, M. 2003. Transcellular transfer of active HSV-1 thymidine kinase mediated by an 11-amino-acid peptide from HIV-1 Tat. Cancer Gene Ther. 10, 64-74

Deodato, B., Arsic, N., Zentilin, L., Galeano, M., Santoro, D., Torre, V., Altavilla, D., Valdembri, D., Bussolino, F., Squadrito, F., Giacca, M. 2002. Recombinant AAV vector encoding human VEGF165 enhances wound healing. Gene Ther. 9, 777-785

Mendoza-Maldonado, R., Zentilin, L., Fanin, R., Giacca, M. 2002. Purging of chronic myelogenous leukemia cells by retrovirally-expressed anti-bcr/abl ribozymes with specific cellular compartmentalization. Cancer Gene Ther. 9, 71-86

Marcello, A., Cinelli, R.A., Ferrari, A., Signorelli, A., Tyagi, M., Pellegrini, V., Beltram, F., Giacca, M. 2001. Visualization of in vivo direct interaction between HIV-1 Tat and human cyclin T1 in specific subcellular compartments by fluorescence resonance energy transfer. J. Biol. Chem. 276, 39220-39225

Tyagi, M., Rusnati, M., Presta, M., Giacca, M. 2001. Internalization of HIV-1 Tat requires cell surface heparan sulfate proteoglycans. J. Biol. Chem. 276, 3254-3261

Zentilin, L., Marcello, A., Giacca, M. 2001. Involvement of cellular double-strand DNA break-binding proteins in processing of recombinant adeno-associated virus (AAV) genome. J. Virol. 75, 12279-12287

Abdurashidova, G., Deganuto, M., Klima, R., Riva, S., Biamonti, G., Giacca, M., Falaschi, A. 2000. Start sites of bidirectional DNA synthesis at the human lamin B2 origin. Science 287, 2023-2026.

Marcello, A., Massimi, P., Banks, L., Giacca, M. 2000. Adeno-associated virus type 2 Rep protein inhibits human papillomavirus type 16 E2 recruitment of the transcriptional coactivator p300. J. Virol. 74, 9090-9098

Marzio, G., Wagener, C., Gutierrez, M.I., Cartwright, P., Helin, K., Giacca, M. 2000. E2F family members are differentially regulated by reversible acetylation. J. Biol. Chem. 275, 10887-10892