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

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
https://www.frontiersin.org/articles/10.3389/fcell.2022.1041938/abstract

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; 82:75-89.e9. doi: 10.1016/j.molcel.2021.11.032

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; 478:133-145. 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;9:49. doi: 10.3390/cells9010049.

Importin-beta/karyopherin-beta1 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;39:454-68. doi: 10.1038/s41388-019-0989-x.  

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. (2018) Sci Rep. 8:1850.  

The small molecule SI113 synergizes with mitotic spindle poisons in arresting the growth of

human glioblastoma multiforme.

Abbruzzese C, Catalogna G, Gallo E, di Martino S, Mileo AM, Carosi M, Dattilo  V, Schenone S, Musumeci F, Lavia P, Perrotti N, Amato R, Paggi MG.  (2017) Oncotarget 8:110743-55.  

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. (2017) J Cell Sci. 130:2564-2578

Mitotic cell death induction by targeting the mitotic spindle with tubulin-inhibitory indole

derivative molecules.

Di Cesare E, Verrico A, Miele A, Giubettini M, Rovella P, Coluccia A, Famiglini V, La Regina G, Cundari E, Silvestri R, Lavia P. (2017) Oncotarget  8:19738-59.

Targeting nuclear transporters in cancer: Diagnostic, prognostic and therapeutic potential

Stelma T, Chi A, van der Watt PJ, Verrico A, Lavia P, Leaner VD  (2016). IUBMB Life.68:268-80. 

The GTPase RAN regulates multiple steps of the centrosome life cycle.

Lavia P. (2016) Chromosome Res. 24:53-65.

New indole tubulin assembly inhibitors cause stable arrest of mitotic progression, enhanced

stimulation of natural killer cell cytotoxic activity, and repression of Hedgehog-dependent cancer.

La Regina G, Bai R, Coluccia A, Famiglini V, Pelliccia S, Passacantilli S, Mazzoccoli C, Ruggieri V, Verrico A, Miele A, Monti L, Nalli M, Alfonsi R, Di Marcotullio L, Gulino A, Ricci B, Soriani A, Santoni A, Caraglia M, Porto S, Da Pozzo E, Martini C, Brancale A, Marinelli L, Novellino E, Vultaggio S, Varasi M,  Mercurio C, Bigogno C, Dondio G, Hamel E, Lavia P, Silvestri R. (2015)

 J Med Chem. 58:5789-807.

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. (2013)  Oncogene 32:4572-8.  

Importin-ß 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. (2012) J Cell Biol 196:435-50.

FULL PUBLICATION LIST

https://www.ncbi.nlm.nih.gov/pubmed/?term=LAVIA+P

orcid.org/0000-0003-3310-6701

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)