Marina Mapelli
Marina Mapelli
affiliation: IEO - Istituto Europeo di Oncologia
research area(s): Cell Biology, Molecular Biology
Course: Molecular Medicine: Molecular Oncology and Computational Biology
University/Istitution: Università di Milano, UNIMI-SEMM
1990–1995 Degree in Physics: University of Milan (summa cum laude) Milan (It)
Advisor: Prof. Giancarlo Baldini
1996–2000 PhD in Crystallography: Birkbeck College, University of London (Uk).
Advisor: Dr. Paul A. Tucker
Training at the EMBL, Heidelberg and Hamburg (De)
2000–2004 Post-doctoral fellow at the European Institute of Oncology, Milan (It).
Advisor: Dr. Andrea Mustacchio

2005–2008 Staff Scientist. Department of Experimental Oncology, European Institute of Oncology,
Milan (It)
2007-2011 Scientific supervisor of the Crystallization Facility, Cogentech, Milan (It)
2008–pres Group Leader, Department of Experimental Oncology, European Institute of Oncology,
Milan (It)

Short Term EMBO fellow (2003)
Post-doctoral fellow of FIRC (2002-2004)
EMBL doctoral fellow (1996-2000)

Faculty Activities
Graduate courses in Structural Biology at the SEMM School, Milan (It), 2006-pres
We are interested in the molecular pathways governing asymmetric cell divisions, with emphasis on the role of the mitotic spindle orientation in determining the daughter cells' fate.
The proper execution of asymmetric divisions is crucial in generating tissue diversity during development, as well as for tissue homeostasis and regeneration in adult organisms. An increasing body of literature supports the notion that certain human cancers arise from abnormalities in adult stem cells asymmetric divisions able to alter the daughter cells' fate and lead to over-proliferation (the so called cancer stem cell hypothesis). Indeed such failures in asymmetric divisions occur if the pathways coupling the cytokinesis plane with the cellular polarity are compromised.
To gain insight into the structural and functional organization of the molecular machines responsible for spindle coupling to polarity cues during stem cells asymmetric divisions we use a combination of high-resolution X-ray crystallography studies, biochemical analyses on reconstituted protein complexes and cell biology.
Our activity is organized in two main research lines. The first one deals with the structural and functional characterization of cortical force generators, the molecular motors pulling on astral microtubules to orchestrate the correct placement of the mitotic spindle. Our second research line addresses the issue of how force generators are specifically recruited at sites of polarization.
1. Mapelli§ M., Massimiliano L., Santaguida S. and Musacchio A. (2007) The Mad2 Conformational Dimer: Structure and Implications for the Spindle Assembly Checkpoint. Cell 131, 730-743.

2. Mapelli M. and Musacchio A. (2007) MAD contorsions: conformational dimerization boosts spindle checkpoint signaling. Curr. Opin. Struct. Biol. 17, 716-725.

3. Mapelli M., Filipp F.V., Rancati G., Massimiliano L., Nezi L., Stier G., Hagan R.S., Confalonieri S., Piatti S., Sattler M., Musacchio A. (2006) Determinants of conformational dimerization of Mad2 and its inhibition by p31comet. EMBO J. 25, 1273-84.

4. Penengo* L., Mapelli* M., Murachelli* A.G., Confalonieri S., Magri L., Musacchio A., Di Fiore P.P., Polo S., Schneider T.R. (2006) Crystal structure of the ubiquitin binding domains of rabex-5 reveals two modes of interaction with ubiquitin. Cell 124, 1183-95.

5. Sessa* F., Mapelli* M., Ciferri C., Tarricone C., Areces L.B., Schneider T.R., Stukenberg T.P. and Musacchio A. (2005) Mechanism of Aurora-B activation by INCENP and inhibition by Hesperadin. Mol. Cell 18, 379-91.

6. Mapelli M., Massimiliano L., Crovace C., Seeliger M.A., Tsai L.H., Meijer L. and Musacchio A. (2005) Mechanism of CDK5/p25 binding by CDK inhibitors. J. Med. Chem. 48, 671-679.

7. Mapelli* M., Panjikar* S. and Tucker P. (2005) The crystal structure of the HSV-1 ssDNA binding protein suggests the structural basis for flexible, cooperative single-stranded DNA. J. Biol. Chem. 280, 2990-97.
Project Title:
Molecular pathways underlying asymmetric stem cell divisions
The details of the available projects will be discussed with the interested students.