Focus. The research focus in our lab is on the mechanisms of mitosis and how regulatory networks control its programme in human cells. The loss of regulatory mechanisms can favour the onset of genomic instability in daughter cells, an established cancer hallmark.  

Research. Our laboratory has contributed to show that mitotic progression requires the concerted activity of molecules that regulate nucleo-cytoplasmic transport in interphase (including the GTPase RAN and nuclear transport receptors, e.g. importin and exportin vectors). At mitosis these factors take on regulatory roles in ensuring the spatial distribution, and the local activity, of key regulators of mitosis. Our overall goal is to understand how their dysfunction, or deregulated expression, which is typically found in many cancer types, affect the mitotic apparatus and hence the fidelity of chromosome segregation to daughter cells.

Research projects include:

• Investigating the role of protein SUMOylation, a post-translational modification of growing importance during mitosis.   
• Understanding how the loss of regulation of mitotic functions affects proliferation and organization of cells of the central nervous system.
• Developing live cell imaging methods to gain dynamic information on cellular responses to genetically engineered or drug-induced conditions that interfere with mitosis. 

To approach these questions we employ a variety of molecular and cellular methods.

• Our lab has been a team member of the recently concluded CNR National Flagship Project “InterOmics”, which gathered over 20 research groups to develop an integrated platform of advanced "omics" methods for applications in precision medicine.
• The lab is currently a partner of the MIUR-PRIN project “Microtubule and centrosome dynamics, from Omics to neurodevelopmental disorders of Central Nervous System”.

Imaging. The lab also hosts an advanced microscopy platform for high-resolution live cell imaging  http://bbcd.bio.uniroma1.it/bbcd/cnr-microscopy-platform-nikon-reference-center-ibpm

Distinct Mitotic Functions of Nucleolar and Spindle-Associated Protein 1 (NuSAP1) Are Controlled by Two Consensus SUMOylation Sites.
Damizia M, Altieri L, Costanzo V, Lavia P.
Cells (2023) doi:10.3390/cells12212545.

Aurora B SUMOylation Is Restricted to Centromeres in Early Mitosis and Requires RANBP2.
Di Cesare E, Moroni S, Bartoli J, Damizia M, Giubettini M, Koerner C, Krenn V, Musacchio A, Lavia P.
Cells (2023) doi:10.3390/cells12030372.

An Epigenetic LINE-1-Based Mechanism in Cancer.
Lavia P, Sciamanna I, Spadafora C.
Int J Mol Sci. (2022) doi:10.3390/ijms232314610.

Circular RNA ZNF609/CKAP5 mRNA interaction regulates microtubule dynamics and tumorigenicity.
Rossi F, Beltran M, Damizia M, Grelloni C, Colantoni A, Setti A, Di Timoteo G, Dattilo D, Centrón-Broco A, Nicoletti C, Fanciulli M, Lavia P, Bozzoni I.
Mol Cell (2022) doi: 10.1016/j.molcel.2021.11.032

Non-transport roles of nuclear import receptors: In need of the right balance.
Damizia M., Altieri L and Lavia P.
Front Cell Dev Biol.  (2022). doi: 10.3389/fcell.2022.1041938

Importin-β/karyopherin-β1 modulates mitotic microtubule function and taxane sensitivity in cancer cells via its nucleoporin-binding region.
Verrico A, Rovella P, Di Francesco L, Damizia M, Staid DS, Le Pera L, Schininà ME, Lavia P. Oncogene (2020) doi: 10.1038/s41388-019-0989-x. 

Reverse transcriptase inhibitors promote the remodelling of nuclear architecture and induce autophagy in prostate cancer cells.
Bellisai C, Sciamanna I, Rovella P, Giovannini D, Baranzini M, Pugliese GM, Zeya Ansari MS, Milite C, Sinibaldi-Vallebona P, Cirilli R, Sbardella G, Pichierri P, Trisciuoglio D, Lavia P, Serafino A, Spadafora C. 
Cancer Lett (2020) doi: 10.1016/j.canlet.2020.02.029. 

The Mitotic Apparatus and Kinetochores in Microcephaly and Neurodevelopmental Diseases.
Degrassi F, Damizia M, Lavia P. 
Cells (2019) doi: 10.3390/cells9010049.

Visualization of human karyopherin beta-1/importin beta-1 interactions with protein partners in mitotic cells by co-immunoprecipitation and proximity ligation assays.
Di Francesco L, Verrico A, Asteriti IA, Rovella P, Cirigliano P, Guarguaglini G, Schininà ME, and Lavia P.
Sci Rep. (2018) doi: 10.1038/s41598-018-19351-9.

Importin-β and CRM1 control a RANBP2 spatiotemporal switch essential for mitotic kinetochore function.
Gilistro E, de Turris V, Damizia M, Verrico A, Moroni S, De Santis R, Rosa A, and Lavia P.
J Cell Sci. (2017) doi: 10.1242/jcs.197905.

PARP inhibitors enhance replication stress and cause mitotic catastrophe in MYCN-dependent neuroblastoma.
Colicchia V, Petroni M, Guarguaglini G, Sardina F, Sahún-Roncero M, Carbonari M, Ricci B, Heil C, Capalbo C, Belardinilli F, Coppa A, Peruzzi G, Screpanti I, Lavia P, Gulino A, Giannini G. Oncogene (2017) doi: 10.1038/onc.2017.40

Targeting nuclear transporters in cancer: Diagnostic, prognostic and therapeutic potential
Stelma T, Chi A, van der Watt PJ, Verrico A, Lavia P, Leaner VD
IUBMB Life (2016) doi: 10.1002/iub.1484

The GTPase RAN regulates multiple steps of the centrosome life cycle.
Lavia P.
Chromosome Res. (2016) doi: 10.1007/s10577-015-9514-4.

Sgk1 enhances RANBP1 transcript levels and decreases taxol sensitivity in RKO colon carcinoma cells.
Amato R, Scumaci D, D'Antona L, Iuliano R, Menniti M, Di Sanzo M, Faniello MC, Colao E, Malatesta P, Zingone A, Agosti V, Costanzo FS, Mileo AM, Paggi MG, Lang F, Cuda G, Lavia P, Perrotti N.
Oncogene (2013) doi: 10.1038/onc.2012.470.

Importin-β negatively regulates multiple aspects of mitosis including RANGAP1 recruitment to kinetochores.
Roscioli E, Di Francesco L, Bolognesi A, Giubettini M, Orlando S, Harel A, Schininà ME and Lavia P.
J Cell Biol (2012) 196:435-50.

External collaborations 

• Maria Eugenia Schininà, Laboratory of Functional Proteomics, Dept. of Biochemical Sciences, Sapienza University, Rome 
• Patrizio Dimitri, Dept. of Biology and Biotechnology, Sapienza University, Rome
• Giuseppe Giannini, Dept. of Molecular Medicine, Sapienza University, Rome
• Romano Silvestri, Center  of Drug Synthesis and Design, Sapienza University, Rome
• Marco Paggi, Regina Elena N tional Cancer Institute, IRCCS, Roma
• Nicola Perotti, Magna Grecia University, Catanzaro
• Valeria de Turris, Istituto Italiano di Tecnologie @Sapienza, Roma 
• Pietro Cirigliano, Nikon Instruments S.p.A
• Virna Leaner, Transcriptional regulation and cancer biology group,  IDM, University of Cape Town (South Africa)