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. 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.
Since March 2020, he has redeployed part of the research of his group to elucidate the mechanisms that regulate SARS-CoV-2 infection. These studies have led to the discovery of a new mechanism that regulate the coronavirus Spike protein function and is involved in COVID-19 pathogenesis.
Braga L, Ali H, Secco I, Chiavacci E, Neves G, Goldhill D, Penn R, Jimenez-Guardeño JM, Ortega-Prieto AM, Bussani R, Cannatà A, Rizzari G, Collesi C, Schneider E, Arosio D, Shah AM, Barclay WS, Malim MH, Burrone J, Giacca M. 2021. Drugs that inhibit TMEM16 proteins block SARS-CoV-2 spike-induced syncytia. Nature 594, 88-93 PubMed link
Gladka MM, Kohela A, Molenaar B, Versteeg D, Kooijman L, Monshouwer-Kloots J, Kremer V, Vos HR, Huibers MMH, Haigh JJ, Huylebroeck D, Boon RA, Giacca M, van Rooij E. 2021. Cardiomyocytes stimulate angiogenesis after ischemic injury in a ZEB2-dependent manner. Nat Commun 12, 84 PubMed link
Gabisonia K, Prosdocimo G, Aquaro GD, Carlucci L, Zentilin L, Secco I, Ali H, Braga L, Gorgodze N, Bernini F, Burchielli S, Collesi C, Zandonà L, Sinagra G, Piacenti M, Zacchigna S, Bussani R, Recchia FA, Giacca M. 2019. MicroRNA therapy stimulates uncontrolled cardiac repair after myocardial infarction in pigs. Nature 569, 418-422 PubMed link
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
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