• Istituto di Biologia e Patologia Molecolari


Tel :+390649917537
Fax :+39064457529
giulia.guarguaglini@uniroma1.it
GIULIA GUARGUAGLINI
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; (ii) the link between spindle mis-orientation induced by Aurora-A deregulation and chromosomal instability (Gallini et al., 2016); (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 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. I.A. Asteriti, F. Daidone, G. Colotti, S. Rinaldo, P. Lavia, G. Guarguaglini *and A. Paiardini 2017. Identification of small molecule inhibitors of the Aurora-A/TPX2 complex. Oncotarget, 8:32117-32133. * co-last author
2. Asteriti IA, De Mattia F, Guarguaglini G. Cross-Talk between AURKA and Plk1 in Mitotic Entry and Spindle Assembly. Front Oncol. 2015; 5:283.
3. Gallini S, Carminati M, De Mattia F, Pirovano L, Martini E, Oldani A, Asteriti IA, Guarguaglini G*, Mapelli M. NuMA Phosphorylation by Aurora-A Orchestrates Spindle Orientation. Curr Biol. 2016;26:458-69. doi:10.1016/j.cub.2015.12.051. * co-corresponding author.

4. 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

5. Ooi W.F., Re A. , Sidarovich V., Canella V., Arseni N., Adami V., Guarguaglini G., Giubettini M., Scaruffi P., Stigliani S., Lavia P., Tonini G.P. and Quattrone A. (2012). Segmental chromosome aberrations converge on overexpression of mitotic spindle regulatory genes in high risk neuroblastoma. Gene Chromosome Canc.,  51:545-56.

6. 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.               

7. 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.        

8. 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. 

9. De Luca M., Brunetto L., Asteriti I.A., Giubettini M., Lavia P. and Guarguaglini G. (2008).  Aurora-A and ch-TOG act in a common pathway in control of spindle pole integrity. Oncogene. 27:6539-49.                 

10. De Luca M., Lavia P. and Guarguaglini G. (2006). A functional interplay between Aurora-A, Plk1 and TPX2 at spindle poles: Plk1 controls centrosomal localization of Aurora-A and TPX2 spindle association. Cell Cycle 5:296-303.                                                                         

 

Lia Asteriti, CNR researcher (T.I.) 
Federica Polverino, PhD student
Francesco Davide Naso, PhD student

Within IBPM:

• Dr Patrizia Lavia
• Dr Gianni Colotti

With other institutions:

• Alessandro Paiardini, Department of Biochemical Science, Sapienza University of Rome, IT
• Marina Mapelli, European Institute of Oncology, Milan, IT
• Sabrina Di Bartolomeo, University of Tor Vergata, Rome, IT
• Beate Neumann and Rainer Pepperkok, Advanced Light Microscopy Facility, EMBL, Heidelberg, DE
• Pietro Cirigliano, Nikon Instruments S.p.A, Campi Bisenzio, IT
• Catherine Lindon, 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

- 2006-present : 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:

- 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