For most of my research activity I have been interested in genome stability, a fundamental field of biology with implications in genome evolution, fertility and tumorigenesis. In my PhD research project I have identified and characterized the roles of the recombinase RAD-51 in the model organism Caenorhabditis elegans. I then moved to the field of cancer biology at the Regina Elena Cancer Institute (Rome) where I contributed to characterize a new pro-apoptotic regulator of the p53 oncosuppressor gene, the HIPK2 kinase.

I have started my own research group at IBPM, focusing on the role of HIPK2 in cytokinesis and in prevention of tetraploidization. Cytokinesis is a complex process that requires the interplay of many structural and regulatory factors. Its failure may lead to genetically unstable states (i.e. tetraploidization and multinucleation). These events can contribute to chromosomal instability, a hallmark of cancer, and are considered  early steps in tumorigenesis. The roles in cancer played by pathways impairing cytokinesis and inducing tolerance to the tetraploid state, however, remain poorly understood. 

My group is currently involved  mainly  in two research projects, one supported by the Italian Association for Cancer Research (AIRC) focusing on the role of HIPK2 in cytokinesis and its impact on pancreatic cancer and one supported by Fondazione Telethon and AFM Telethon on the role of HIPK2/spastin axis in hereditary spastic paraplegia.

 Sardina F, Monteonofrio L, Ferrara M, Magi F, Soddu S, Rinaldo C. HIPK2 Is Required for Midbody Remnant Removal Through Autophagy-Mediated Degradation. Front Cell Dev Biol. 2020 Sep 15;8:572094.

Gatti V, Ferrara M, Virdia I, Matteoni S, Monteonofrio L, di Martino S, Diodoro MG, Di Rocco G, Rinaldo C*, Soddu S. An Alternative Splice Variant of HIPK2 with Intron Retention Contributes to Cytokinesis. Cells. 2020 Feb 20;9(2):484. *co- last author.

Monteonofrio L, Valente D, Rinaldo C, Soddu S. Extrachromosomal Histone H2B Contributes to the Formation of the Abscission Site for Cell Division. Cells. 2019 Nov 5;8(11). pii: E1391.

Contadini C, Monteonofrio L, Virdia I, Prodosmo A, Valente D, Chessa L, Musio A, Fava LL, Rinaldo C, Di Rocco G, Soddu S. p53 mitotic centrosome localization preserves centrosome integrity and works as sensor for the mitotic surveillance pathway. Cell Death Dis. 2019 Nov 7;10(11):850.

Willan J, Cleasby AJ, Flores-Rodriguez N, Stefani F, Rinaldo C, Pisciottani A, Grant E, Woodman P, Bryant HE, Ciani B ESCRT-III is necessary for the integrity of the nuclear envelope in micronuclei but is aberrant at ruptured micronuclear envelopes generating damage. Oncogenesis. 2019 Apr 15;8(5):29.

A Pisciottani, L Biancolillo, M Ferrara, D Valente, F Sardina, L Monteonofrio, S Camerini, M Crescenzi, S Soddu, C Rinaldo. HIPK2 phosphorylates the microtubule-severing enzyme spastin at S268 for abscission. Cells, 2019 8(7), 684.

Scaglione A, Monteonofrio L, Parisi G, Cecchetti C, Siepi F, Rinaldo C, Giorgi A, Verzili D, Zamparelli C, Savino C, Soddu S, Vallone B, Montemiglio LC. Effects of Y361-auto-phosphorylation on structural plasticity of the HIPK2 kinase domain. Protein Sci. 2018 Mar;27(3):725-737

Monteonofrio L, Valente D, Ferrara M, Camerini S, Miscione R, Crescenzi M, Rinaldo C, Soddu S.
HIPK2 and extrachromosomal histone H2B are separately recruited by Aurora-B for cytokinesis. Oncogene. 2018 Jun;37(26):3562-3574. 

Barbiero I, Valente D, Chandola C, Magi F, Bergo A, Monteonofrio L, Tramarin M, Fazzari M, Soddu S, Landsberger N, Rinaldo C, Kilstrup-Nielsen C. CDKL5 localizes at the centrosome and midbody and is required for faithful cell division. Sci Rep. 2017 Jul 24;7(1):6228. doi: 10.1038/s41598-017-05875-

Pierantoni GM, Conte A, Rinaldo C, Tornincasa M, Gerlini R, Valente D, Izzo A, Fusco A. Hmga1 null mouse embryonic fibroblasts display downregulation of spindle assembly checkpoint gene expression associated to nuclear and karyotypic abnormalities. Cell Cycle. 2016;15(6):812-8.  

Pierantoni GM, Conte A, Rinaldo C, Tornincasa M, Gerlini R, Federico A, Valente D, Medico E, Fusco A. Deregulation of HMGA1 expression induces chromosome instability through regulation of spindle assembly checkpoint genes. Oncotarget. 2015 Jul 10;6(19):17342-53

Valente D, Bossi G, Moncada A, Tornincasa M, Indelicato S, Piscuoglio S, Karamitopoulou ED, Bartolazzi A, Pierantoni GM, Fusco A, Soddu S, Rinaldo C HIPK2 deficiency causes chromosomal instability by cytokinesis failure and increases tumorigenicity. Oncotarget. 2015 6:10320-34

C. Rinaldo, A. Moncada, A. Gradi, L. Ciuffini, D. D’Eliseo, F. Siepi, A. Prodosmo, A. Giorgi, G. M. Pierantoni, F. Trapasso, G. Guarguaglini, A. Bartolazzi, E. Cundari, M. E. Schinina`, A. Fusco, and S. Soddu. HIPK2 controls cytokinesis and prevents tetraploidization by phosphorylating histone H2B at the midbody. Molecular Cell 2012 47:87-98.

Rinaldo C, Prodosmo A, Siepi F, Moncada A, Sacchi A, Selivanova G, Soddu S. HIPK2 regulation by MDM2 determines tumor cell response to the p53-reactivating drugs Nutlin-3 and RITA. Cancer Res. 2009 69:6241-8

Rinaldo C, Siepi F. Prodosmo A, Soddu S. HIPKs: Jack of all trades in basic nuclear activities Biochim Biophys Acta. 2008 1783:2124-9

Rinaldo C, Prodosmo A, Siepi F, Soddu S. HIPK2: a multi-talented partner for transcription factors in DNA damage response and development. Biochem Cell Biol 2007 85:411-8

Rinaldo C, Prodosmo A, Mancini F, Iacovelli S, Sacchi A, Moretti F, Soddu S. p53 suppresses its own apoptotic activity by promoting the MDM2-mediated degradation of HIPK2. Mol Cell 2007 25:739-50

Rinaldo C, Bazzicalupo P, Ederle S, Hilliard M, La Volpe A. Roles for Caenorhabditis elegans rad-51 in meiosis and in resistance to ionizing radiation during development. Genetics 2002 160:471-479  

•Manuela Ferrara, pHD student
•Clara Dezi, student
•Davide Valente, post-Doc
•Francesca Sardina, post-Doc

within IBPM

•Enrico Cundari
•Gianluca Cestra 
•Giulia Guarguaglini
•Linda Montemiglio 
•Linda Savino

with other Institutions

•Carlo Casali (Sapienza, Rome) 
• Barbara Ciani (University of Sheffield, UK)

•Gianluca Grazi (Regina Elena Cancer Institute, Rome)

•Andrew Grierson (University of Sheffield, UK)

•Giovanna Maria Pierantoni (Università Federico II, Naples)

•Angelo Peschiaroli (IFT-CNR, Rome)

•Silvia Soddu (Regina Elena Cancer Institute, Rome)

•Beatrice Vallone (Sapienza, Rome)

•Beate Winner (Erlangen University, Germany) 

Education:

2002: PhD in Genetics, Univ. of Naples “Federico II”  (Best PhD Thesis award from  the Italian Association of Genetics in 2002)
1997: Degree in Biology cum Laude, Univ. of Naples "Federico II"

Research positions and activity:

2012-present: research scientist appointment at IBPM, CNR, Rome, Italy
2008-2011: research scientist at Regina Elena Cancer Institute (IRE), Rome, Italy
2004-2007: Italian Foundation for Cancer Research (FIRC) post-doctoral research fellow at IRE
2002-2003: post-doc at IRE, Rome, Italy
1999-2001: PhD at IGB-CNR, Naples-Italy
1998: post-graduate training at IGB- CNR, Naples, Italy
1995-1997: graduate student at IGB- CNR, Naples, Italy

Prizes and awards:
2009: “Guido Berlucchi Award” for young research scientists 
2007: “Caputo Award” for best young researcher in the field of oncology