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).

1. Antonelli L, Polverino F, Albu A, Hada A, Asteriti IA, Degrassi F, Guarguaglini G*, Maddalena L, Guarracino MR.(2023). ALFI: Cell cycle phenotype annotations of label-free time-lapse imaging data from cultured human cells. Sci Data. 10(1):677. * co-last and co-corresponding author

2. Asteriti IA, Polverino F, Stagni V, Sterbini V, Ascanelli C, Naso FD, Mastrangelo A, Rosa A, Paiardini A, Lindon C, Guarguaglini G. (2023) AurkA nuclear localization is promoted by TPX2 and counteracted by protein degradation. Life Sci Alliance.; 6(5):e202201726.

3. Naso FD, Boi D, Ascanelli C, Pamfil G, Lindon C, Paiardini A, Guarguaglini G. (2021). Nuclear localisation of Aurora-A: its regulation and significance for Aurora-A functions in cancer. Oncogene. 40(23):3917-3928. 

4. Polverino F, Naso FD, Asteriti IA, Palmerini V, Singh D, Valente D, Bird AW, Rosa A, Mapelli M, Guarguaglini G. (2021). The Aurora-A/TPX2 Axis Directs Spindle Orientation in Adherent Human Cells by Regulating NuMA and Microtubule Stability. Curr Biol. 31:658-667.e5. 

5. Naso F.D., Sterbini V., Crecca E., Asteriti I. A., Russo A. D., Giubettini M., Cundari E., Lindon C., Rosa A., Guarguaglini G. (2020). Excess TPX2 interferes with microtubule disassembly and nuclei reformation at mitotic exit. Cells. 9(2). pii: E374. doi: 10.3390/cells9020374.

6. Asteriti IA, Daidone F, Colotti C, Rinaldo S, Lavia P, Guarguaglini G ^*and Paiardini A. (2017). Identification of small molecule inhibitors of the Aurora-A/TPX2 complex. Oncotarget, 8:32117-32133. * co-last author

7. Gallini S, Carminati M, De Mattia F, Pirovano L, Martini E, Oldani A, Asteriti IA, Guarguaglini G*, Mapelli M. (2016). NuMA Phosphorylation by Aurora-A Orchestrates Spindle Orientation. Curr Biol.; 26:458-69. * co-corresponding author.

8. 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

9. 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.
          
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.

Within IBPM:

• Dr Patrizia Lavia
• Dr Gianni Colotti
• Dr Venturina Stagni
• Dr Chiara Mozzetta

With other institutions:

• Alessandro Paiardini, Department of Biochemical Science, Sapienza University of Rome, IT
• Marina Mapelli, European Institute of Oncology, Milan, IT
• Pietro Cirigliano, Nikon Instruments S.p.A, Campi Bisenzio, IT
• Catherine Lindon, Laura Itzhaki, Department of Pharmacology, University of Cambridge, UK

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
- 2006-2019 : CNR research scientist appointment at IBPM
- 2004: Marie Curie Reintegration Grant and new unit start-up at IBPM-CNR

- 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:

- 2023: PRIN grant (2 years) on the project “A two-pronged approach to target the Aurora-A/N-Myc complex in MYCN- amplified Neuroblastoma” 

- 2022: IG-2021 AIRC grant (Associazione Italiana per la Ricerca sul Cancro; 5 years) on the project “The Aurora-A/TPX2 complex from mitosis to interphasic roles: novel therapeutic opportunities”

- 2022: Royal Society Exchange Grant (2 years) on the project “Designing New Tools To Disrupt AurkA-Dependent Oncogenic Functions Of Myc” (UK applicant: Prof. Laura Itzhaki)

- 2021: Regione Lazio – Progetto Gruppi di Ricerca 2020 (2 years) grant on the project “INNOVA3DIMAGING”

- 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”
- 2016: grant from AIRC- Italian Association for Cancer Research (3 years funding) on the project “The multifaceted Aurora-A/TPX2 complex in chromosome stability, tumorigenesis and anti-cancer therapy”.

- 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