Research Groups
Molecular Medicine
Research Interests and Description
Research Interests
Gene therapy of cardiovascular disorders, adeno-associated virus (AAV), angiogenesis, Molecular biology of HIV-1 infection.Description of Research
The Group has two main interests in the field of Molecular Medicine. One project is aimed at identifying proteins or microRNAs controlling vascular and cardiac function that might also be exploited for the therapy of cardiovascular disorders. A large part of the activity exploits viral vectors based on the adeno-associated virus (AAV) to deliver to genes in the heart that induce therapeutic angiogenesis or promote tissue regeneration. In this area, the laboratory has developed procedures for the direct, in vivo selection of therapeutically useful genes upon transduction of cDNA and microRNA libraries cloned into AAV. The laboratory also hosts a high throughput screening facility exploiting whole genome, mouse and human synthetic siRNA and microRNA libraries, and is actively screening these libraries for genes involved in cardiac proliferation and differentiation. Finally, the laboratory is also interested in some basic aspects of the molecular biology of AAV, with particular reference to the identification of the cellular proteins that regulate AAV infection.
A second major interest of the Group is in the field of AIDS research. This project focuses on unraveling the molecular properties of different HIV-1 proteins, with particular reference to the processes of viral integration and transcription. The laboratory has contributed to the understanding of the role that chromatin exerts on viral gene expression and to its regulation by the viral Tat transactivator. Another interest of the laboratory is the viral protein Integrase, which is essential for the integration of the proviral DNA into the host cell genome. The laboratory has recently reported that this enzyme is post-translationally regulated by acetylation and phosphorylation and that, in particular, the latter modification is essential for HIV-1 genome integration in resting T-lymphocytes.
Recent Publications
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, 484-495 PubMed link
Giacca, M. 2010. Gene Therapy. Springer-Verlag. pp. 1-309
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
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
Zentilin, L., Puligadda, U., Lionetti, V., Zacchigna, S., Collesi, C., Pattarini, L., Ruozi, G., Camporesi, S., Sinagra, G., Pepe, M., et al. 2010. Cardiomyocyte VEGFR-1 activation by VEGF-B induces compensatory hypertrophy and preserves cardiac function after myocardial infarction. FASEB J 24, 1467-1478
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
