Research Groups

Molecular Medicine

Research Interests and Description
Group Members

Mauro Giacca

Director-General ICGEB
Group Leader

International Centre for Genetic Engineering and Biotechnology
Padriciano 99
34149 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 2014, Director-General of the International Centre for Genetic Engineering and Biotechnology, ICGEB
2004-2014, Director of the Trieste Component, 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

Current research interest focuses on the development of novel biotherapeutics for cardiovascular disorders, with special emphasis on the identification of growth factors and microRNAs able to induce new blood vessel formation and cardiac regeneration in patients with myocardial infarction or heart failure. He also maintains a strong interest in the molecular biology of HIV-1 infection.
Research activity is funded through grants from various public and private bodies, including the European Research Council (ERC Advanced Investigator Grants), the Italian Ministry for Education and Research, the World Antidoping Agency (WADA) Canada, the JDRF USA, the Telethon Foundation Italy, among others.
M. Giacca regularly reviews scientific manuscripts for international journals in the fields of gene therapy, cardiovascular disorders and HIV infection, and grant applications in the context of calls from the European Commission and various granting bodies throughout Europe and has published over 240 papers in peer-reviewed international journals and 20 reviews or chapters in published books and university text books. He is the author of the book "Gene Therapy", Springer ed., 2010. He regularly presents his research activity at meetings and seminars worldwide.

Selected publications

Giacca M on PubMed

Selected publications (out of a total of over 270):

Woitek, F., Zentilin, L., Hoffman, N.E., Powers, J., Ottiger, I., Parikh, S., Kulczycki, A.M., Hurst, M., Ring, N., Wang, T., Shaihk, F., Gross, P., Singh, H., Kolpakov, M.A., Linke, A., Houser, S.R., Rizzo, V., Sabri, A., Madesh, M., Giacca, M., Recchia, F.A. 2015. Therapeutic intracoronary gene delivery of VEGF-B167 in a pre-clinical animal model of dilated cardiomyopathy. J. Am. Coll. Cardiol., in press

Ruozi, G., Bortolotti, F., Falcione, A., Dal Ferro, M., Ukovich, L., Macedo, A., Zentilin, L., Filigheddu, N., Gortan Cappellari, G., Baldini, G., Zweyer, M., Brazzoni, R., Graziani, A., Zacchigna, S., Giacca, M. 2015. AAV-mediated in vivo functional selection of tissue-protective factors against ischaemia. Nature Commun, in press

Marini, B., Kertesz-Farkas, A., Ali, H., Lucic, B., Lisek, K., Manganaro, L., Pongor, S., Luzzati, R., Recchia, A., Mavilio, F., Giacca*, M., Lusic*, M. 2015. Nuclear architecture dictates HIV-1 integration site selection. Nature 521, 227-31; * last co-authorship

Zecchin, A., Pattarini, L., Gutierrez, M.I., Mano, M., Mai, A., Valente, S., Myers, M.P., Pantano, S., Giacca, M. 2014. Reversible acetylation regulates vascular endothelial growth factor receptor-2 activity. J Mol Cell Biol 6, 116-27.

Zacchigna, S., Zentilin, L., Giacca, M. 2014. Adeno-Associated Virus Vectors as Therapeutic and Investigational Tools in the Cardiovascular System. Circ Res 114, 1827-1846.

Zacchigna, S., Giacca, M. 2014. Extra- and intracellular factors regulating cardiomyocyte proliferation in postnatal life. Cardiovasc Res 102, 312-20.

Sadek, H.A., Martin, J.F., Takeuchi, J.K., Leor, J., Nei, Y., Giacca, M., Lee, R.T. 2014. Multi-Investigator Letter on Reproducibility of Neonatal Heart Regeneration following Apical Resection. Stem Cell Reports 3, 1

Puente, B.N., Kimura, W., Muralidhar, S.A., Moon, J., Amatruda, J.F., Phelps, K.L., Grinsfelder, D., Rothermel, B.A., Chen, R., Garcia, J.A., Santos, C.X., Thet, S., Mori, E., Kinter, M.T., Rindler, P.M., Zacchigna, S., Mukherjee, S., Chen, D.J., Mahmoud, A.I., Giacca, M., Rabinovitch, P.S., Aroumougame, A., Shah, A.M., Szweda, L.I., Sadek, H.A. 2014. The Oxygen-Rich Postnatal Environment Induces Cardiomyocyte Cell-Cycle Arrest through DNA Damage Response. Cell 157, 565-79

Maudet, C., Mano, M., Sunkavalli, U., Sharan, M., Giacca, M., Forstner, K.U., Eulalio, A. 2014. Functional high-throughput screening identifies the miR-15 microRNA family as cellular restriction factors for Salmonella infection. Nat Commun 5, 4718

Lusic, M., Giacca, M. 2014. Ground Control to Major Tom: "Prepare for HIV Landing". Cell Host Microbe 16, 557-559

Felician, G., Collesi, C., Lusic, M., Martinelli, V., Ferro, M.D., Zentilin, L., Zacchigna, S., Giacca, M. 2014. Epigenetic modification at notch responsive promoters blunts efficacy of inducing notch pathway reactivation after myocardial infarction. Circ Res 115, 636-49

Lusic, M., Marini, B., Ali, H., Lucic, B., Luzzati, R., Giacca, M. 2013. Proximity to PML Nuclear Bodies Regulates HIV-1 Latency in CD4+ T Cells. Cell Host Microbe 13, 665-77

Lovric, J., Mano, M., Zentilin, L., Eulalio, A., Zacchigna, S., Giacca, M. 2012. Terminal Differentiation of Cardiac and Skeletal Myocytes Induces Permissivity to AAV Transduction by Relieving Inhibition Imposed by DNA Damage Response Proteins. Mol Ther 20, 2087-97

Giacca, M., Zacchigna, S. 2012. VEGF gene therapy: therapeutic angiogenesis in the clinic and beyond. Gene Ther 19, 622-9

Giacca, M., Zacchigna, S. 2012. Virus-mediated gene delivery for human gene therapy. J Control Release 161, 377-88

Eulalio, A., Mano, M., Dal Ferro, M., Zentilin, L., Sinagra, G., Zacchigna, S., Giacca, M. 2012. Functional screening identifies miRNAs inducing cardiac regeneration. Nature 492, 376-81

Carrer, A., Moimas, S., Zacchigna, S., Pattarini, L., Zentilin, L., Ruozi, G., Mano, M., Sinigaglia, M., Maione, F., Serini, G., Giraudo, E., Bussolino, F., Giacca, M. 2012. Neuropilin-1 identifies a subset of bone marrow Gr1- monocytes that can induce tumor vessel normalization and inhibit tumor growth. Cancer Res 72, 6371-81

Giacca, M., Baker, A.H. 2011. Heartening results: the CUPID gene therapy trial for heart failure. Mol Ther 19, 1181-2

Allouch, A., Di Primio, C., Alpi, E., Lusic, M., Arosio, D., Giacca, M., Cereseto, A. 2011. The TRIM Family Protein KAP1 Inhibits HIV-1 Integration. Cell Host Microbe 9, 484-95

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, 1467-78

Van de Veire, S., Stalmans, I., Heindryckx, F., Oura, H., Tijeras-Raballand, A., Schmidt, T., Loges, S., Albrecht, I., Jonckx, B., Vinckier, S., Van Steenkiste, C., Tugues, S., Rolny, C., De Mol, M., Dettori, D., Hainaud, P., Coenegrachts, L., Contreres, J.O., Van Bergen, T., Cuervo, H., Xiao, W.H., Le Henaff, C., Buysschaert, I., Kharabi Masouleh, B., Geerts, A., Schomber, T., Bonnin, P., Lambert, V., Haustraete, J., Zacchigna, S., Rakic, J.M., Jimenez, W., Noel, A., Giacca, M., Colle, I., Foidart, J.M., Tobelem, G., Morales-Ruiz, M., Vilar, J., Maxwell, P., Vinores, S.A., Carmeliet, G., Dewerchin, M., Claesson-Welsh, L., Dupuy, E., Van Vlierberghe, H., Christofori, G., Mazzone, M., Detmar, M., Collen, D., Carmeliet, P. 2010. Further pharmacological and genetic evidence for the efficacy of PlGF inhibition in cancer and eye disease. Cell 141, 178-90

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, 1893-903

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. Nature Med 16, 329-33

Giacca, M. 2010. Non-redundant functions of the protein isoforms arising from alternative splicing of the VEGF-A pre-mRNA. Transcription 1, 149-153

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, 663-71

Paolinelli, R., Mendoza-Maldonado, R., Cereseto, A., Giacca, M. 2009. Acetylation by GCN5 regulates CDC6 phosphorylation in the S phase of the cell cycle. Nature Struct Mol Biol 16, 412-20

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, 3356-72

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, 2062-75

Sabo, A., Lusic, M., Cereseto, A., Giacca, M. 2008. Acetylation of conserved lysines in the catalytic core of cyclin-dependent kinase 9 inhibits kinase activity and regulates transcription. Mol Cell Biol 28, 2201-12

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

Giacca, M. 2008. Gene therapy to induce cellular resistance to HIV-1 infection: lessons from clinical trials. Adv Pharmacol 56, 297-325

Collesi, C., Zentilin, L., Sinagra, G., Giacca, M. 2008. Notch1 signaling stimulates proliferation of immature cardiomyocytes. J Cell Biol 183, 117-28

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, 349-57

Zentilin, L., Giacca, M. 2007. Competitive PCR for precise nucleic acid quantification. Nature Protoc 2, 2092-104

Fischer, C., Jonckx, B., Mazzone, M., Zacchigna, S., Loges, S., Pattarini, L., Chorianopoulos, E., Liesenborghs, L., Koch, M., De Mol, M., Autiero, M., Wyns, S., Plaisance, S., Moons, L., van Rooijen, N., Giacca, M., Stassen, J.M., Dewerchin, M., Collen, D., Carmeliet, P. 2007. Anti-PlGF Inhibits Growth of VEGF(R)-Inhibitor-Resistant Tumors without Affecting Healthy Vessels. Cell 131, 463-75

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, 3546-54

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, 6855-64

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, 954-61

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, 981-91

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, 567-75

Recchia, F.A., Giacca, M. 2005. Targeted uptake-1 carrier to rescue the failing heart. Circ Res 97, 847-9

Fittipaldi, A., Giacca, M. 2005. Transcellular protein transduction using the Tat protein of HIV-1. Adv Drug Deliv Rev 57, 597-608

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, 3070-81

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

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, 844-54

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

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

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

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

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

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

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

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

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

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

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

Demarchi, F., Gutierrez, M.I., Giacca, M. 1999. Human Immunodeficiency Virus type 1 Tat protein activates transcription factor NF-kappaB through the cellular interferon-inducible, double-stranded RNA-dependent protein kinase, PKR. J. Virol. 73, 7080-7086

Marzio, G., Tyagi, M., Gutierrez, M.I., Giacca, M. 1998. HIV-1 Tat transactivator recruits p300 and CBP histone acetyl transferases to the viral promoter. Proc. Natl. Acad. Sci. USA 95, 13519-13524

Giacca, M., Pelizon, C., Falaschi, A. 1997. Mapping replication origins by quantifying relative abundance of nascent DNA strands using competitive polymerase chain reaction. Methods 13, 301-312

Comar, M., Simonelli, C., Zanussi, S., De Paoli, P., Vaccher, E., Tirelli, U., Giacca, M. 1997. Dynamics of HIV-1 mRNA expression in patients with non-progressive HIV-1 infection. J Clin Invest 100, 893-903

Pelizon, C., Diviacco, S., Falaschi, A., Giacca, M. 1996. High resolution mapping of the origin of DNA replication in the hamster dihydrofolate reductase gene domain by competitive polymerase chain reaction. Mol. Cell. Biol. 16, 5358-5364

Kumar, S., Giacca, M., Norio, P., Biamonti, G., Riva, S., Falaschi, A. 1996. Utilization of the same DNA replication origin by human cells of different derivation. Nucleic Acids Res. 24, 3289-3294

Demarchi, F., d'Adda di Fagagna, F., Falaschi, A., Giacca, M. 1996. Activation of transcription factor NF-kB by the Tat protein of human immunodeficiency virus-1. J. Virol. 70, 4427-4437

d'Adda di Fagagna, F., Marzio, G., Gutierrez, M.I., Kang, L.Y., Falaschi, A., Giacca, M. 1995. Molecular and functional interactions of transcription factor USF with the long terminal repeat of human immunodeficiency virus type 1. J. Virol. 69, 2765-2775.

Giacca, M., Zentilin, L., Norio, P., Diviacco, S., Dimitrova, D., Contreas, G., Biamonti, G., Perini, G., Weighardt, F., Riva, S., Falaschi, A. 1994. Fine mapping of a replication origin of human DNA. Proc. Natl. Acad. Sci. USA 91, 7119-7123

Demarchi, F., D'Agaro, P., Falaschi, A., Giacca, M. 1993. In vivo footprinting analysis of constitutive and inducible protein-DNA interactions at the long terminal repeat of human immunodeficiency virus type 1. J. Virol. 67, 7450-7460

Demarchi, F., D'Agaro, P., Falaschi, A., Giacca, M. 1992. Probing protein-DNA interactions at the long terminal repeat of human immunodeficiency virus type 1 by in vivo footprinting. J. Virol. 66, 2514-2518

 

 

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