• Istituto di Biologia e Patologia Molecolari


Tel :+390649912555
Fax :+39064456866
mariagrazia.giansanti@uniroma1.it
MARIAGRAZIA GIANSANTI
Senior Researcher

Istitute of Molecular Biology and Pathology - National Research Council
Department of Biology and Biotecnology - Charles Darwin
Sapienza University of Rome - Istituto di Genetica Piazzale A. Moro 5, 00185 Roma
A major focus of our research studies concerns the mechanisms underlying cytokinesis. Cytokinesis partitions the cytoplasmic organelles and the duplicated genome from one mother cell into two daughter cells at the end of cell division. In animal cell cytokinesis, assembly and constriction of the contractile apparatus must be finely coordinated with plasma membrane remodeling at the cleavage furrow. Accurate control of cytokinesis represents a fundamental task in normal development and is also essential for maintaining ploidy and preventing neoplastic transformation. Cytokinesis errors have been associated with several human diseases including blood disorders, Lowe syndrome, female infertility and cancer. In the context of cancer disease, cytokinesis failures promote tumorigenesis by generating tetraploid cells, whose mitotic division causes chromosomal instability. Thus, analysis of the molecular pathways involved in cytokinesis, might contribute to develop new therapeutic strategies against cancer and other diseases. Most of our studies are carried out in Drosophila melanogaster, which offer numerous advantages for combined genetic and cytological studies of the structural and morphological events that characterize cytokinesis. We use Drosophila male meiotic cells and larval neuroblasts, as a model system to dissect the molecular pathways involved in contractile ring dynamics and membrane trafficking during cytokinesis.
Our research studies are currently focusing on the following projects:
1) The oncoprotein GOLPH3 and membrane trafficking in Drosophila cytokinesis. Project funded by Associazione Italiana per la Ricerca sul Cancro (AIRC). The highly conserved Golgi phosphoprotein 3 (GOLPH3) protein, characterized as a Phosphatidylinositol 4-phosphate [PI(4)P] effector at the Golgi, is commonly amplified in several solid tumors and associated with more aggressive tumors. We have demonstrated that GOLPH3 accumulates at the cleavage furrow and is essential for cytokinesis in Drosophila melanogaster. The purpose of this research project is to elucidate the molecular mechanisms underlying the role of GOLPH3 in vesicle trafficking and cytoskeletal dynamics.
2) A Drosophila model for COG7-associated disease and other COG-related genetic disorders. Project funded by Fondazione Telethon. Mutations in human COG7 and other COG genes cause distinct forms of inherited, autosomal recessive, congenital disorders of glycosylation (CDG) associated with multisystemic deficiencies. Drosophila Cog7 localizes to Golgi stacks and is required for normal cytokinesis in both spermatocytes and larval neuroblasts. Cytokinesis failures have been proposed to affect neurogenesis thus contributing to microcephaly, one of the neurological traits of COG7-CDG patients. We are dissecting the molecular interactions involving Cog7, GOLPH3 and other vesicle trafficking proteins involved in brain cytokinesis.

1.                   1)    Giansanti MG, Bonaccorsi S, Williams BC, Williams EV, Santolamazza C, Goldberg ML and Gatti M. 1998. Cooperative interactions between the central spindle and the contractile ring during Drosophila cytokinesis. Genes and Dev. 12: 396-410.

2) Bonaccorsi S, Giansanti MG, Gatti M. 1998. Spindle self-organization and cytokinesis during male meiosis in asterless mutants of Drosophila melanogaster. J Cell Biol. 1998 142(3):751-61.

3)   Giansanti MG, Bonaccorsi S and Gatti M. 1999. The role of anillin during meiotic cytokinesis of Drosophila males. J. Cell Sci. 112: 2323-2334.

4)   Bonaccorsi S, Giansanti MG and Gatti M 2000. Spindle assembly in Drosophila neuroblasts and ganglion mother cells. Nature Cell Biol., 2: 54-56.

5)   Giansanti MG, Bonaccorsi S, Gatti M. 2001. The role of centrosomes and astral microtubules during asymmetric division of Drosophila neuroblasts. Development 128:1137-1145.

6)   Giansanti# MG, Bonaccorsi S, Bucciarelli E, Gatti M. 2001. Drosophila male meiosis as a model system for the study of cytokinesis in animal cells. Cell Structure and Function  26:609-617

7)  Farkas RM, Giansanti MG, Gatti M, Fuller MT. 2003. The Drosophila Cog5 homologue is required for cytokinesis, cell elongation, and assembly of specialized Golgi architecture during spermatogenesis. Mol. Biol. Cell 14:190-200.

8)   Bucciarelli E, Giansanti* MG, Bonaccorsi S., Gatti M. 2003. Spindle assembly and cytokinesis in the absence of chromosomes. J. Cell Biol. 160:993-999. Comment in J. Cell Biol. 160:989-990.

9)   Giansanti MG, Farkas RM, Bonaccorsi S, Lindsley DL, Wakimoto BT, Fuller MT, Gatti M. 2004. Genetic dissection of meiotic cytokinesis in Drosophila males. Mol Biol Cell. 15:2509-2522.

10) Giansanti MG, Bonaccorsi S, Kurek R, Farkas RM, Dimitri P, Fuller MT, Gatti M. 2006. The class I PITP Giotto is required for Drosophila cytokinesis. Curr. Biol. 16: 195-201.

11) Giansanti# MG, Belloni G, Gatti M. 2007. Rab11 is required for membrane trafficking and actomyosin ring constriction in meiotic cytokinesis of Drosophila males. Mol. Biol. Cell. 18:5034-5047.

12) Bonaccorsi S, Mottier V, Giansanti MG, Bolkan BJ, Williams B, Goldberg ML,   Gatti M. 2007. The Drosophila Lkb1 kinase is required for spindle formation and asymmetric neuroblast division. Development. 134:2183-2193.

13)  Somma MP, Ceprani F, Bucciarelli E, Naim V, De Arcangelis V, Piergentili R, Palena A, Ciapponi L, Giansanti MG, Pellacani C, Petrucci R, Cenci G, Vernì F, Fasulo B, Goldberg ML, Di Cunto F, Gatti M. 2008. Identification of Drosophila mitotic genes by combining co-expression analysis and RNA interference. PLoS Genet. 18:4(7):e1000126.

14)  Giansanti MG, Bucciarelli E, Bonaccorsi S, Gatti M. 2008. Drosophila SPD-2 is an essential centriole component required for PCM recruitment and astral-microtubule nucleation. Curr. Biol. 18:303-309.

15) Gao S, Giansanti MG, Buttrick GJ, Ramasubramanyan S, Auton A, Gatti M, Wakefield JG. 2008. Australin: a chromosomal passenger protein required specifically for Drosophila melanogaster male meiosis. J. Cell Biol. 180:521-535.

16) Szafer-Glusman E, Giansanti MG, Nishihama R, Bolival B, Pringle J, Gatti M, Fuller MT. 2008. A role for very-long-chain fatty acids in furrow ingression during cytokinesis in Drosophila spermatocytes. Curr. Biol. 18:1426-1431. IF (2008) 10,777. Comment in Curr Biol, 18:R921-R923

17)  Robinett CC, Giansanti* MG, Gatti M, Fuller MT. 2009. TRAPPII is required for cleavage furrow ingression and localization of Rab11 in dividing male meiotic cells of Drosophila. J. Cell Sci. 122:4526-4534

18)  Szafer-Glusman E, Fuller MT, Giansanti MG. 2011. Role of Survivin in cytokinesis revealed by a separation-of-function allele. Mol. Biol. Cell. 22:3779-3390.

19)  Wainman A., Giansanti MG., Goldberg M.L. and Gatti M. 2012. The Drosophila RZZ complex: roles in membrane traffic and cytokinesis. J. Cell Sci. 125:4014-4025.

20)  Giansanti MG#, Sechi S, Frappaolo A, Belloni G, Piergentili R. 2012. Cytokinesis in Drosophila male meiosis. Spermatogenesis 2:185-196.

21) Giansanti MG# , Fuller MT. 2012. What Drosophila spermatocytes tell us about the mechanisms underlying cytokinesis. Cytoskeleton 69:869-891.

22)  Belloni G, Sechi S, Riparbelli MG, Fuller MT, Callaini G, Giansanti MG# 2012. Mutations in Cog7 affect Golgi structure, meiotic cytokinesis and sperm development during Drosophila spermatogenesis. J. Cell Sci. 125:185-196.

23) Sechi S, Colotti G, Belloni G, Mattei V, Frappaolo A, Raffa GD, Fuller MT, Giansanti MG#. 2014. GOLPH3 is essential for contractile ring formation and Rab11 localization to the cleavage site during cytokinesis in Drosophila melanogaster. PLoS Genet. 10(5):e1004305. doi: 10.1371/journal.pgen.1004305.

24)  D’Avino PP, Giansanti MG, Petronczki M. 2015. Cytokinesis in Animal Cells. Cold Spring Harb Perspect Biol. 7(4):a015834. doi: 10.1101/cshperspect.a015834.

25) Sechi S, Frappaolo A, Belloni G, Giansanti MG#. 2015. The roles of the oncoprotein GOLPH3 in contractile ring formation and membrane trafficking during cytokinesis. Biochem Soc Trans. 43:117-121

26) Sechi S, Frappaolo A, Belloni G, Colotti G, Giansanti MG#. 2015. The mutiple cellular functions of the oncoprotein Golgi phosphoprotein 3. Oncotarget 6: 3493-3506.

27) Giansanti MG#, Vandelìrleest TE, Jewett CE, Sechi S, Frappaolo A, Fabian L, Robinett CC, Brill JA, Loerke D, Fuller MT, Blankenship JT. 2015. Exocyst-dependent membrane addition is required for anaphase cell elongation and cytokinesis in Drosophila. PLoS Genet. 11(11):e1005632. doi:10.1371/journal.pgen.1005632

28) Frappaolo A, Sechi S, Belloni G., Piergentili R. and Giansanti MG#. 2016 Visualization of cleavage furrow proteins in fixed dividing spermatocytes. Methods Cell Biology. doi.org/10.1016/bs.mcb.2016.03.035

29) Sechi S, Frappaolo A, Fraschin R, Capalbo L, Gottardo M, Belloni G, Glover D, Wainman A, and Giansanti MG# 2017. Rab1 interacts with GOLPH3 and controls Golgi structure and contractile ring constriction during cytokinesis in Drosophila melanogaster. Open Biol. 2017. 7(1). pii: 160257

30) Frappaolo A., Sechi S., Kumagai T., Robinson S., Fraschini R., Karimpour Ghahnavieh A., Belloni G., Piergentili R. Tiemeyer KH., Tiemeyer M., Giansanti MG#. 2017 COG7 deficiency in Drosophila generates multifaceted developmental, behavioral, and protein glycosylation phenotypes. J. Cell Sci. pii: jcs.209049. doi: 10.1242/jcs.209049.

       (*) Joint first author; (#) Corresponding author

Maria Grazia Giansanti Group Leader

Stefano Sechi, IBPM Researcher

Anna Frappaolo, IBPM Researcher

Roberto Piergentili, IBPM researcher

Angela Karimpour, Graduate Fellow (Assegnista di Ricerca)

Within IBPM

 

•Dr. Gianni Colotti (www)

•Dr. Roberto Piergentili

 

With Other Istitutions

 

  • Prof. Margaret Fuller Departments of Developmental Biology and Genetics, Stanford University School of Medicine, California, USA
  • Prof. James Wakefield, University of Exeter, UK
  • Prof. Pier Paolo D'Avino, Department of Pathology, University of Cambridge, UK
  • Prof. Michael Tiemeyer, Complex Carbohydrate Research Center, University of Georgia USA
  • Prof. Giuliano Callaini Dipartimento di Scienze della Vita, Università di Siena
  • Dr. Vincenzo Mattei Dipartimento di Medicina Sperimentale Polo Didattico di Rieti
EDUCATION 
1997 Residency in Applied Genetics University of Rome “La Sapienza”
1996 PhD in Genetics and Molecular Biology University of Rome “La Sapienza” (PhD thesis Cenci Bolognetti award) 
1991 Degree (Laurea) cum Laude in Biology University of Rome “La Sapienza”, 
 
RESEARCH POSITIONS
2001-to date: CNR Researcher, Istituto di Biologia e Patologia Molecolari, Rome
2000-01: Postdoctoral Fellow, Dipartimento di Genetica e Biologia Molecolare,  University of Rome “La Sapienza”, M. Gatti Lab
1998-99: Postdoctoral Fellow, Department of Genetics and Developmental Biology,  Stanford University (USA), Margaret Fuller  Lab
 
GRANTS AND PROJECTS
2018-ongoing AIRC Grant IG 2017-Id.20779
2013-2017 AIRC Grant IG 2013-Id.14671  
2015-2016  Telethon-Italy GEP 14076  
2010-2013: AIRC Grant IG 2010- Id.10775
2009-10: PRIN 2008 Grant  2008ZCP2ZB 
 
INVITED LECTURES 

2015 Biozentrum, University of Basel, Switzerland, Invited Seminar: “Drosophila melanogaster as a model system to study cytokinesis"

2014 Joint Conference of the British Society for Cell Biology and the Biochemical Society “The Dynamic Cell” Cambridge, UK:  “The roles of the oncoprotein GOLPH3 in contractile ring assembly and membrane trafficking during cytokinesis”

2014 55th Annual Drosophila Research Conference; San Diego California: “The Drosophila orthologue of human GOLPH3 is required for contractile ring formations and membrane trafficking during cytokinesis”    

2013
EMBO Workshop “Drosophila cell division cycle” Totness (Exeter), UK: “The Drosophila orthologue of the oncoprotein GOLPH3 is required for contractile ring assembly during cytokinesis”

2011  Dipartimento di Biologia Evolutiva, Università di Siena, Invited Seminar “Genetic Dissection of cytokinesis in Drosophila”    

2001
Research conference on cytokinesis “A New century of cytokinesis”; Tokyo Japan. “Genetic 2006-2012 dissection of cytokinesis in Drosophila males”.

2001 Minisymposium “Mitosis and Meiosis” ASCB Annual meeting, Washington: “Spindle assembly and cytokinesis in the absence of chromosomes during Drosophila male meiosis”. 

2000 EMBO Workshop Regulation of cell division in Drosophila; Cortona Italy:" Relationship between the central spindle and the contractile ring during meiotic cytokinesis of Drosophila males."

1999 40th Annual Drosophila Research conference; Bellevue Washington: "Mutations affecting cytokinesis during Drosophila male meiosis"

 
ACADEMIC APPOINTMENTS

2006-2013 Adjunct Professor, Fundamental Genetics; Università Sapienza of Rome, Polo Didattico di Rieti

 2007-2008 Adjunct Professor, Medical Genetics; Università Sapienza of Rome, Polo Didattico di Rieti