Research Groups
Molecular Medicine
Group Leader
Research Interests and DescriptionGroup Members
Mauro Giacca
Director, ICGEB Trieste ComponentInternational 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, 1984Admitted 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 210 full papers in peer-reviewed international journals, in addition to several articles on newspapers or popular science magazines. Since 2010, recipient of an advanced grant from the European Research Council.
Selected publications
Giacca, M. 2010. Gene Therapy. Springer-Verlag
Mendoza-Maldonado, R., Paolinelli, R., Galbiati, L., Giadrossi, S., Giacca, M. 2010. Interaction of the retinoblastoma protein with Orc1 and its recruitment to human origins of DNA replication. PLoS One 5, e13720 PubMed link
Jablonski, J.A., Amelio, A.L., Giacca, M., Caputi, M. 2010. The transcriptional transactivator Tat selectively regulates viral splicing. Nucleic Acids Res. 38, 1249-1260 PubMed link
Lock, M., McGorray, S., Auricchio, A., et al. 2010. Characterization of a Recombinant Adeno-Associated Virus Type 2 Reference Standard Material. Hum Gene Ther. [Epub ahead of print] PubMed link
Manganaro, L., Lusic, M., Gutierrez, M.I., Cereseto, A., Del Sal, G., Giacca, M. 2010. Concerted action of cellular JNK and Pin1 restricts HIV-1 genome integration to activated CD4(+) T lymphocytes. Nat. Med. 16, 329-333 PubMed link
Pepe, M., Mamdani, M., Zentilin, L., Csiszar, A., Qanud, K., Zacchigna, S., Ungvari, Z., Puligadda, U., Moimas, S., Xu, X., Edwards, J.G., Hintze, T.H., Giacca, M., Recchia, F.A. 2010. Intramyocardial VEGF-B167 gene delivery delays the progression towards congestive failure in dogs with pacing-induced dilated cardiomyopathy. Circ Res. 106, 1893-1903 PubMed link
Terreni, M., Valentini, P., Liverani, V., Gutierrez, M.I., Di Primio, C., Di Fenza, A., Tozzini, V., Allouch, A., Albanese, A., Giacca, M., Cereseto, A. 2010. GCN5-dependent acetylation of HIV-1 integrase enhances viral integration. Retrovirology 7, 18 PubMed link
Van de Veire, S., Stalmans, I., Heindryckx, F., et al. 2010. Further pharmacological and genetic evidence for the efficacy of PlGF inhibition in cancer and eye disease. Cell. 141, 178-190 PubMed link
Zentilin, L., Giacca, M. 2010. The renaissance of competitive PCR as an accurate tool for precise nucleic acid quantification. Methods Mol Biol. 630, 233-248 PubMed link
Zentilin, L., Puligadda, U., Lionetti, V., Zacchigna, S., Collesi, C., Pattarini, L., Ruozi, G., Camporesi, S., Sinagra, G., Pepe, M., Recchia, F.A., Giacca, M. 2010. Cardiomyocyte VEGFR-1 activation by VEGF-B induces compensatory hypertrophy and preserves cardiac function after myocardial infarction. FASEB J. 24, 1467-1478 PubMed link
Maione, F., Molla, F., Meda, C., Latini, R., Zentilin, L., Giacca, M., Seano, G., Serini, G., Bussolino, F., Giraudo, E. 2009. Semaphorin 3A is an endogenous angiogenesis inhibitor that blocks tumor growth and normalizes tumor vasculature in transgenic mouse models. J Clin Invest. 119, 3356-3372 PubMed link
Paolinelli, R., Mendoza-Maldonado, R., Cereseto, A., Giacca, M. 2009. Acetylation by GCN5 regulates CDC6 phosphorylation in the S phase of the cell cycle. Nat Struct Mol Biol. 16, 412-420 PubMed link
Tafuro, S., Ayuso, E., Zacchigna, S., Zentilin, L., Moimas, S., Dore, F., Giacca, M. 2009. Inducible adeno-associated virus vectors promote functional angiogenesis in adult organisms via regulated vascular endothelial growth factor expression. Cardiovasc Res. 83, 663-671 PubMed link
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 PubMed link
Collesi C, Zentilin L, Sinagra G, Giacca M. 2008. Notch1 signaling stimulates proliferation of immature cardiomyocytes. J. Cell Biol. 183, 117-128 PubMed link
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 PubMed link
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 PubMed link
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, 2062-207 PubMed link
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
