Lucia Anna Stivala, PhD, PI
Phone: (+39) 038298337
Lucia Anna Stivala, PI, Full Professor
Ornella Cazzalini, Associate Professor
Monica Savio, Associate Professor
Paola Perucca, Researcher
Martina Vetro, Specializzanda in Clinical Pathology and Biochemistry
Anna Tricarico, PhD student
Vittoria Livraghi, PhD student
Since many years one of the research of laboratory has been focused on the biological activity of natural or synthetic derived compounds with a potential role in the prevention of human pathological processes, such as cancer. We are currently evaluating new analogues of resveratrol, and in particular 4,4′-dihydroxy-stilbene (DHS), which is more effective in inhibiting tumour proliferation and metastasis formation, in part through its antiangiogenic activity. Other mechanisms appear to be triggered by this compound that appear to contribute significantly to its anticancer effect. Among these, we are studying the role of autophagy and apoptosis in contrasting tumour growth, of stromal and immune cells in modulating cancer microenvironment, as well as the impact of this compound on subpopulation of cancer stem cells. We are also focusing, in collaboration with other research groups, on combined therapeutic approaches with the most bioactive derivatives and traditional chemotherapeutic agents as a new study perspective aimed at synergize the anti-cancer activity of the drugs but reducing their toxic effects.
Our group has also been studying for years proteins involved in both cell cycle regulation and DNA replication and repair. Among these, the kinase inhibitor p21CDKN1A (p21), that plays an important role both in the checkpoints of G1 and G2 phases and in the direct inhibition of DNA synthesis by associating with PCNA. We have demonstrated that p21 is also involved in cell quiescence and in promoting the efficiency of Nucleotide Excision Repair (NER), in which the protein seems to be required to regulate epigenetic modification of some NER factors. In recent years, our attention has been focused on the protein DDB2 that exerts a key role in the recognition of DNA damage induced by UV radiation. Modifying a conserved region of DDB2, we have found an interaction site for PCNA, whose function is being studied since it seems to be necessary both for the correct NER process execution and cell cycle. At the moment, we are investigating the role of this interaction in i) the epithelial-mesenchymal transition (EMT), ii) the processes of invasion and metastasis and iii) the inflammatory/immune response cancer-associated and iv) the expression of stem cell markers in transformed cells
G. TICLI, O. CAZZALINI, L.A. STIVALA, E. PROSPERI. Revisiting the function of p21CDKN1A in DNA repair: the influence of protein interactions and stability. International Journal of Molecular Sciences, 2022. 23, 7058, doi:10.3390/ijms23137058.
I. GUARDAMAGNA, L. LONATI, M. SAVIO, L.A. STIVALA, A. OTTOLOENGHI, G. BAIOCCO. An Integrated Analysis of the Response of Colorectal Adenocarcinoma Caco-2 Cells to X-Ray Exposure. Frontiers in Oncology, 2021, 11:688919, doi: 10.3389/fonc.2021.688919.
I. GUARDAMAGNA, E. BASSI, M. SAVIO, P. PERUCCA, O. CAZZALINI, E. PROSPERI, L.A. STIVALA. A functional in vitro cell-free system for studying DNA repair in isolated nuclei. Journal of Cell Science, 2020, 8;133(11), doi: 10.1242/jcs.240010.
P. PERUCCA, R. MOCCHI, I. GUARDAMAGNA, E. BASSI, S. SOMMATIS, T. NARDO, E. PROSPERI, L.A. STIVALA, O. CAZZALINI. A damaged DNA binding protein 2 mutation disrupting interaction with proliferating-cell nuclear antigen affects DNA repair and confers proliferation advantage. Biochim Biophys Acta. 2018, 1865(6):898-907, doi: 10.1016/j.bbamcr.2018.03.012.
M. SAVIO, D. FERRARO, C. MACCARIO, R. VACCARONE, L.D. JENSEN, F. CORANA, B. MANNUCCI, L. BIANCHI, Y. CAO, L.A. STIVALA. Resveratrol-analogue 4, 4’-dihydroxy-trans-stilbene potently inhibits cancer invasion and metastasis. Sci. Rep, 2016, 6: 19973,. doi: 10.1038/srep19973.