Chromosome segregation errors produce aneuploidy and chromosome instability which have been found to have crucial roles in cancer. Our research goal is to understand the molecular mechanisms regulating chromosome segregation at mitosis and their role in cancer. This goal is achieved by using a combination of molecular cytogenetic approaches, quantitative light microscopy, live-cell imaging and protein inhibition in mammalian cells. 

The group is interested in investigating the role of alterations in the centromere/kinetochore structure in generating aneuploid karyotypes in normal and tumor cells, with specific emphasis on the formation and correction of abnormal kinetochore-microtubule interactions. In this field, we demonstrated that a major source of aneuploidy in mammalian cells is the connection of a single kinetochore to both spindle poles, named merotelic kinetochore orientation (Cimini et al., 2001,2005; Cimini and Degrassi, 2005)

Current research projects are devoted at investigating the cancer-promoting activity of the deregulated expression of Hec1, a component of the Hec1/Ndc80 multi-protein kinetochore complex that mediates kinetochore-microtubule interactions (Ferretti et al. 2010; Mattiuzzo et al. 2011). Special efforts are devoted to identify genetic strategies to modulate Hec1 function in tumour cells and develop chemical inhibitors of the Hec1/Ndc80 complex activity (Orticello et al. 2015; Ferrara et al. 2018). This will help to establish innovative anti-cancer therapies targeted to the mitotic process. 

1. Ferrara M, Sessa G, Fiore M, Bernard F, Asteriti I. A, Cundari E, Colotti G, Ferla S, Desideri M, Buglioni S, Trisciuoglio D, Del Bufalo D, Brancale A, Degrassi F. (2018) Small molecules targeted to the microtubule-Hec1 interaction inhibit cancer cell growth through microtubule stabilization Oncogene 37:231-240.

2. Traversi G, Fiore M, Percario Z, Degrassi F*, Cozzi R. (2017) The resveratrol analogue trimethoxystilbene inhibits cancer cell growth by inducing multipolar cell mitosis. Mol Carcinog. 56:1117-1126 * co-corresponding

3. Xanthium strumarium extract inhibits mammalian cell proliferation through mitotic spindle disruption mediated by xanthatin. Sánchez-Lamar A, Piloto-Ferrer J, Fiore M, Stano P, Cozzi R, Tofani D, Cundari E, Francisco M, Romero A, González ML, Degrassi F. (2016) J Ethnopharmacol.  194: 781-788.

4. De Santis Puzzonia M, Gonzalez L, Ascenzi S, Cundari E, Degrassi F. (2016) Tetraploid cells produced by absence of substrate adhesion during cytokinesis are limited in their proliferation and enter senescence after DNA replication. Cell Cycle.;15: 274-282.

5. Orticello M, Fiore M, Totta P, Desideri M, Barisic M, Passeri D, Lenzi J, Rosa A, Orlandi A, Maiato H, Del Bufalo D, Degrassi F (2015). N-Terminus modified Hec1 suppresses tumor growth by interfering with kinetochore-microtubule dynamics. Oncogene, 34: 3325-3335 7.519

6. M. Mattiuzzo, G. Vargiu, P. Totta, M. Fiore1, C. Ciferri, A. Musacchio and F. Degrassi. Abnormal Kinetochore-Generated Pulling Forces from Expressing a N-Terminally Modified Hec1 (2011) PlosOne, Jan 28;6(1): e16307.

7. Ferretti C, Totta P, Fiore M, Mattiuzzo M, Schillaci T, Ricordy R, Di Leonardo A, Degrassi F. (2010) Expression of the kinetochore protein Hec1 during the cell cycle in normal and cancer cells and its regulation by the pRb pathway. Cell Cycle. 9: 4174 - 4182

8. Torosantucci L, Puzzonia de Sanctis M, Cenciarelli C, Rens W, Degrassi F. (2009) Aneuploidy in mitosis of PtK1 cells is generated by random loss and nondisjunction of individual chromosomes. J Cell Science 122:3455-3461.

9. Torosantucci L, De Luca M, Guarguaglini G, Lavia P, Degrassi F. (2008) Localized RanGTP accumulation promotes microtubule nucleation at kinetochores in somatic mammalian cells. Mol Biol Cell. 19:1873-1882. 

10. Mattiuzzo M, Fiore M, Ricordy R, Degrassi F (2006) Aneuploidy-inducing capacity of two widely used pesticides. Carcinogenesis, 27: 2511-2518.

11. Rens W, Torosantucci L, Degrassi F, Ferguson-Smith MA (2006) Incomplete sister chromatid separation of long chromosome arms. Chromosoma, 115: 481-90.

12. Cimini D Degrassi F (2005) Aneuploidy: a matter of bad connection. Trends in Cell Biology 15:442-51.

13. Cimini D, Mattiuzzo M, Torosantucci L, Degrassi F (2003) Histone hyperacetylation in mitosis prevents sister chromatid separation and produces chromosome segregation defects. Molecular Biology of the Cell 14: 3821-3833.

14. Cimini D, Fioravanti D, Salmon ED, Degrassi F (2002) Merotelic kinetochore orientation versus chromosome mono-orientation in the origin of lagging chromosomes in human primary cells. J Cell Science 115: 507-515.

15. Cimini D, Howell B, Maddox P, Khodjakov A, Degrassi F, Salmon ED (2001) Merotelic kinetochore orientation is a major mechanism of aneuploidy in mitotic mammalian tissue cells. J. Cell Biology 153:517-527.       

• Mario Fiore, CTER  

• Irene Ventura, post-lauream trainee 

Positions and education

• 2002: Visiting investigator, University of North Carolina, Chapel Hill.
• 2001- : First researcher, Institute of Molecular Biology and Pathology, CNR
• 1985: Visiting investigator, Memorial Sloan Kettering Cancer Centre, New York N.Y 
• 1984-2001: Research scientist, Centre for Evolutionary Genetics, CNR
• 1981-82: Post-doc, Dept of Radiation Genetics and Chemical Mutagenesis, Leiden University (NL)
• 1979: Degree in Biology at Rome University.

Memberships and other notable achievements

• 2015: member of the Evaluation committee for the XXVI PhD in Biology, “Roma Tre” University
• 2014- : evaluator of Research Projects for the Italian Ministry of Economic Development
• 2013: panel chair in the evaluation of Research Projects founded by the Science and Technology Foundation of Portugal (FCT).
• 2009: Member of the scientific committee, 39^th International Conference on Environmental Mutagens
• 2006- : Reviewer for research grants from Padua University  
• 2005: Member of the organizing committee of the AGI/SIMA workshop “Cancer as a disease of genome instability”
• 1996: Member of the Scientific Committee of the 26^th European Environmental Mutagen Society
• Reviewer for the Journals Mutagenesis, Mutation Research, European Journal of Cell Biology, Cellular and Molecular Life Sciences, Cancer Research, Experimental Cell Research, Journal of Cell Science.
• Member of the Italian Genetics Association (AGI), Member of the Italian (SIMA) and European (EEMS) Mutagen Societies

Research grant responsibility:

• 2007-2009: Italian Association for Cancer Research: “Hec1, a mediator of microtubule-kinetochore interactions: role in promoting chromosome instability and cancer” .
• 2007 CNR grant: ”Role of centrosomes in the assembly of a bipolar spindle in mammalian cells.
• 2004–2005: Italian Health Ministry project: “Characterization of Aurora A and Hec1 mitotic proteins as molecular targets for anti-tumour therapy.
• 2002-2004: Italian Health Ministry project: “Strategies to control risk from occupational carcinogens”.
• 1997-1998: CNR bilateral programme Center for Evolutionary Genetics- ICRF, University of Oxford “Role of topoisomerase II in chromosome segregation at mitosis" .
• 1992-1994: European Community STEP programme "The detection and evaluation of aneugenic chemicals".
• 1988-1990: CNR bilateral programme Centre for Evolutionary Genetics -Department of Radiation Biology, Leiden "DNA damage from antitumour drugs: role of topoisomerase II inhibition in mammalian cells" ()
• 1987: CNR research programme "Mutagenesis": "Predictivity of cytogenetic test to cancer risk".

Teaching and mentoring activities

• Teaching contract for the course “Cytogenetics” at the “Roma Tre” University (2001-2006)
• Scientific supervisor in numerous master degree and PhD thesis and in several post-doctoral positions 

Dr. Degrassi’s research activity is reported in 66 papers and 7 review papers published in International peer-reviewed journals and in 5 book chapters.