NON-COMMUNICABLE DISEASES / Cardiovascular Disorders
Cardiovascular disorders, cardiac regeneration, adeno-associated virus (AAV), gene therapy, angiogenesis, microRNAs. Molecular biology of HIV-1 infection
Description of Research
Projects aim to identify 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. Recent work from the laboratory has led to the identification of microRNAs promoting cardiac regeneration in vivo. 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 interest of the Group is in the field of AIDS research, where the focus lies in 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 transcriptional latency. Another interest is the viral protein Integrase, which is essential for the integration of the proviral DNA into the host cell genome. The laboratory has reported the post translational regulation of this enzyme by acetylation and phosphorylation and that the latter modification is essential for HIV-1 genome integration in resting T-lymphocytes.
Lesizza, P., Prosdocimo, G., Martinelli, V., Sinagra, G., Zacchigna, S., Giacca, M. 2017. Single-Dose Intracardiac Injection of Pro-Regenerative MicroRNAs Improves Cardiac Function After Myocardial Infarction. Circ Res 120, 1298-1304 PubMed link
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 6, 7388 PubMed link
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 PubMed link
Mano, M., Ippodrino, R., Zentilin, L., Zacchigna, S., Giacca, M. 2015. Genome-wide RNAi screening identifies host restriction factors critical for in vivo AAV transduction. Proc Natl Acad Sci USA 112, 11276-81121 PubMed link
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, 665-677 PubMed link
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 PubMed link