Fax :+39064457529
giulia.guarguaglini@uniroma1.it
Senior Researcher
Istitute of Molecular Biology and Pathology - National Research Council
Department of Biology and Biotecnology - Charles Darwin
Sapienza University of Rome - Via degli Apuli 4 00185 Roma
Mitotic kinases are key regulators of centrosome function and spindle assembly. Our research focuses on the mitotic centrosomal kinase Aurora-A and its major regulator TPX2, two key spindle regulators frequently overexpressed in cancer. We have found that the microtubule-binding protein TPX2 regulates- in addition to spindle localization and kinase activity- Aurora-A protein stability by protecting it fom proteasome degradation (Giubettini et al., 2011) suggesting that Aurora-A stabilization by TPX2 may represent a poorly explored route to increased levels of Aurora-A in cancer (Asteriti et al., 2010). We study the regulation and function of the Aurora-A/TPX2 complex in mammalian cells, the mechanisms through which it contributes to cell transformation when deregulated and its potential as target in anti-cancer therapies. In ongoing projects we investigate: (i) chromosomal instability in non-transformed cells overexpressing the Aurora-A/TPX2 complex (Naso et al., 2020); (ii) the link between spindle mis-orientation induced by Aurora-A deregulation and chromosomal instability (Gallini et al., 2016; Polverino et al., 2021); (iii) the development of protein-protein interaction inhibitors to disrupt the Aurora-A/TPX2 complex, as a selective and innovative approache to target Aurora-A in cancer (Asteriti et al., 2014 and 2017). The unit has recently focused interests on nuclear kinase-independent AURKA oncogenic roles (Naso et al., 2021).The unit also runs the microscopy imaging platform at the IBPM Nikon Reference Center for Central and Southern Italy and developes imaging protocols – also in an automated mode- for the investigation of dynamic cellular processes. |
1. Naso FD, Boi D, Ascanelli C, Pamfil G, Lindon C, Paiardini A, Guarguaglini G. Nuclear localisation of Aurora-A: its regulation and significance for Aurora-A functions in cancer. Oncogene. 2021 May 13. doi: 10.1038/s41388-021-01766-w. Online ahead of print. 7. Asteriti IA, Di Cesare E, De Mattia F, Hilsenstein V, Neumann B, Cundari E, Lavia P, Guarguaglini G. (2014) The Aurora-A inhibitor MLN8237 affects multiple mitotic processes and induces dose-dependent mitotic abnormalities and aneuploidy. Oncotarget.. 5:6229-42 8. Asteriti I.A., Giubettini M., Lavia P. and Guarguaglini G. (2011). Aurora-A inactivation causes mitotic spindle pole fragmentation by unbalancing microtubule-generated forces. Mol Cancer. 10:131. 9. Giubettini M., De Luca M., Asteriti I.A., Scrofani J., Lindon C., Lavia P. and Guarguaglini G. (2011). Control of Aurora-A stability through interaction with TPX2. J Cell Sci. 124:113-22. 10. Asteriti I.A., Rensen W. M., Lindon C., Lavia P. and Guarguaglini G. (2010). The Aurora-A/TPX2 complex: a novel oncogenic holoenzyme? Biochim Biophys Acta. Rev. Cancer 1806:230-9. |
| Lia Asteriti, CNR researcher Federica Polverino, post-doc Dalila Boi, PhD student Linda Latini, Master student |
Within IBPM: With other institutions: • Alessandro Paiardini, Department of Biochemical Science, Sapienza University of Rome, IT |
Education - 2000: PhD degree in Genetics and Molecular Biology, Sapienza University of Rome (Best PhD Thesis award from the Italian Association of Genetics in 2000) - 1995: Degree in Biological Sciences cum Laude, Sapienza University of Rome
Research positions and activity - 2019-today : CNR senior research scientist appointment at IBPM - 2003-2005: Italian Foundation for Cancer Research (FIRC) research fellow at IBPM - 2000-2003: Marie-Curie post-doctoral fellow at the Max-Planck Institute for Biochemistry, Munich, DE (lab head: Erich Nigg) - 1998-1999: EMBO short-term fellow at EMBL, Heidelberg, DE (Lab head: Iain Mattaj) - 1996-1999: PhD student, Center of Evolutionary Genetics, CNR, Doctorate School in Genetics and Molecular Biology, Sapienza University of Rome, IT (Lab head: Patrizia Lavia) - 1996: Post-graduate training at the Center of Evolutionary Genetics, CNR, Rome - 1993-1995: Thesis internship at Center of Evolutionary Genetics, CNR, Rome (Supervisor: Patrizia Lavia)
Funding awards: - 2018: Royal Society Exchange Grant (2 years funding; co-applicant) on the project “Optimizing allosteric inhibitors of the AURKA mitotic kinase to challenge its non-mitotic roles in oncogenesis” - 2013: grant from AIRC- Italian Association for Cancer Research (3 years funding) on the project “Investigation of the Aurora-A/TPX2 complex as an oncogenic "holoenzyme" and novel target in cancer therapy”. - 2011: grant from Fondazione Monte dei Paschi di Siena (2 years funding) on the project “Cellular imaging applied to the development of novel anti-cancer drugs” - 2009: grant from Assicurazioni Generali spa and Fondazione Roma-Terzo Settore to acquire state of the art microscopes to develop the project “Investigating regulators of cell division: roles in tumorigenesis and use as targets in anti-cancer therapies” - 2004: Marie Curie Reintegration grant (MERG-CT-2004-511059; one year) on the project “Study of centrosome maturation as a pivotal process between G2 checkpoints and mitotic entry in mammalian cells”
Membership in scientific societies: member of the Italian Society of Molecular Biology and Biophysics, Italian Association of Cell Biology and Differentiation, EMBL Alumni Association
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