Graziella Cappelletti
e-mail: graziella.cappelletti AT unimi.it
affiliation: Università di Milano
research area(s): Cell Biology, Neuroscience
Course:
Biomolecular Sciences
University/Istitution: Università di Milano
University/Istitution: Università di Milano
Education:
1986 Degree in Biological Sciences (110/110 cum laude), University of Milan. Title of thesis: "Isolamento di una banda fosforilata 65 kD e sua possibile identificazione come prodotto di fosforilazione dell'enzima fosfoenolpiruvato carbossichinasi in Saccharomyces cerevisiae".
1988 Qualification as biologist (University of Milan).
1991 Specialisation in Experimental Endocrinology (70/70 cum laude), University of Milan. Title of the thesis: "Valutazione del pH intracrosomiale in spermatozoi di coniglio".
Employment and Research experience
September 2005 " now: Lecturer of Comparative Anatomy and Cytology Assistant professor), tenured position, and Research group leader, University of Milan, Italy.
2001 " 2005: Research Associate (Comparative Anatomy and Cytology), tenured position, University of Milan, Italy.
June 2000 and February-March 2001: Visiting scientist at the Department of Cell Biology, EMBL, Heidelberg, Germany. (Director: Dr. E. Karsenti)
1990 " 2001: High scientific officer, tenured position, at the Department of Biology, University of Milan, Italy.
1990 - 1993: Maternity leave.
1989 " 1990: Postgraduate fellow, at the department of Biology, University of Milan, (Mentor: Prof. M. Camatini).
1987-89 Fellowship at Neurological Institute "C.Besta" of Milan. Title of research project: A study of the intracellular antioxidant systems as possible etiopathogenetic cause of Parkinson Disease".
1986 Post-graduation training at Neurological Institute "C.Besta" of Milan (Laboratory of Neuropharmacology).
1986 Degree in Biological Sciences (110/110 cum laude), University of Milan. Title of thesis: "Isolamento di una banda fosforilata 65 kD e sua possibile identificazione come prodotto di fosforilazione dell'enzima fosfoenolpiruvato carbossichinasi in Saccharomyces cerevisiae".
1988 Qualification as biologist (University of Milan).
1991 Specialisation in Experimental Endocrinology (70/70 cum laude), University of Milan. Title of the thesis: "Valutazione del pH intracrosomiale in spermatozoi di coniglio".
Employment and Research experience
September 2005 " now: Lecturer of Comparative Anatomy and Cytology Assistant professor), tenured position, and Research group leader, University of Milan, Italy.
2001 " 2005: Research Associate (Comparative Anatomy and Cytology), tenured position, University of Milan, Italy.
June 2000 and February-March 2001: Visiting scientist at the Department of Cell Biology, EMBL, Heidelberg, Germany. (Director: Dr. E. Karsenti)
1990 " 2001: High scientific officer, tenured position, at the Department of Biology, University of Milan, Italy.
1990 - 1993: Maternity leave.
1989 " 1990: Postgraduate fellow, at the department of Biology, University of Milan, (Mentor: Prof. M. Camatini).
1987-89 Fellowship at Neurological Institute "C.Besta" of Milan. Title of research project: A study of the intracellular antioxidant systems as possible etiopathogenetic cause of Parkinson Disease".
1986 Post-graduation training at Neurological Institute "C.Besta" of Milan (Laboratory of Neuropharmacology).
The scientific interest of Graziella Cappelletti has been focused on cell biology of the cytoskeleton and its pivotal role in health and disease. Moving from purified proteins to cell cultures and mice models, she is currently studying the microtubule system, its organization and dynamics, in gene- and toxin-based models of Parkinson’s disease. The molecular mechanisms underlying neurodegeneration are investigated through multiple approaches ranging from in vitro assays to biochemistry and microscopy analyses in cultured neurons and brain sections by means of over-expression, silencing or incubation with recombinant proteins. In addition, live cell imaging and video-microscopy are used to look at microtubule dynamics and microtubule-dependant processes crucial to maintain neuronal functions, including vesicles recycling and axonal transport.
Graziella Cappelletti is engaged in several national and international collaborations allowing her to address research projects through a multidisciplinary approach.
Graziella Cappelletti is engaged in several national and international collaborations allowing her to address research projects through a multidisciplinary approach.
D. Cartelli, C. Ronchi, M.G. Maggioni, S. Rodighiero, E. Giavini, G. Cappelletti 2010. Microtubule dysfunction precedes transport impairment and mitochondria damage in MPP+-induced neurodegeneration. J. Neurochem. 115 (1) 247-258
D. Passarella, B. Peretto, R. Blasco y Yepes, G. Cappelletti, D. Cartelli, C. Ronchi, J. Snaith, G. Fontana, B. Danieli, J. Borlak. 2010. Synthesis and biological evaluation of novel thiocolchicine-podophyllotoxin conjugates. Eur J Med Chem. 45 (1) 219-26.
V. Appierto, P. Tiberio, E. Cavadini, P. Casalini, G. Cappelletti, F. Formelli. 2009. Antimitotic effect of the retinoid 4-oxo-fenretinide through inhibition of tubulin polymerization: a novel mechanism of retinoid growth-inhibitory activity. Mol. Cancer Ther. 8(12) 3360-3368.
S. Pieraccini, G. Saladino, G. Cappelletti, D. Cartelli, P. Francescato, G. Speranza, P. Manitto, M-M. Sironi. 2009. In silico design of tubulin-targeted antimitotic peptides. Nature Chemistry 1(8), 642-648.
E. Riano, M. Martignoni, G. Mancuso, D. Cartelli, F. Crippa, I. Toldo, G. Siciliano, D. Di Bella, F. Taroni, M.T. Bassi, G. Cappelletti, E.I. Rugarli. 2009. Pleiotropic effects of spastin on neurite growth depending on expression levels. J. Neurochem. 108 (5) 1277-1288.
G. Cappelletti, M. Galbiati, C. Ronchi, M.G. Maggioni, E. Onesto and A. Poletti. 2007. Neuritin (cpg15) enhances the differentiating effect of NGF on neuronal PC12 cells. J. Neurosci. Res., 85: 2702-13.
G. Tedeschi, G. Cappelletti, S. Nonnis, F. Taverna, A. Negri, C. Ronchi and S. Ronchi. 2007. Tyrosine nitration is a novel post-translational modification occurring on the neural intermediate filament protein peripherin. Neurochem. Res., 32: 433-41.
G. Cappelletti, M.G. Maggioni, C. Ronchi, R. Maci and G. Tedeschi. 2006. Protein tyrosine nitration is associated with cold- and drug-resistant microtubules in neuronal-like PC12 cells. Neurosci. Lett., 401: 159-164.
G. Cappelletti, T. Surrey and R. Maci. 2005. The parkinsonism producing neurotoxin MPP+ affects microtubule dynamics acting as a destabilising factor⮠FEBS Lett., 579: 4781-6.
D. Passarella, B. Peretto, R. Blasco y Yepes, G. Cappelletti, D. Cartelli, C. Ronchi, J. Snaith, G. Fontana, B. Danieli, J. Borlak. 2010. Synthesis and biological evaluation of novel thiocolchicine-podophyllotoxin conjugates. Eur J Med Chem. 45 (1) 219-26.
V. Appierto, P. Tiberio, E. Cavadini, P. Casalini, G. Cappelletti, F. Formelli. 2009. Antimitotic effect of the retinoid 4-oxo-fenretinide through inhibition of tubulin polymerization: a novel mechanism of retinoid growth-inhibitory activity. Mol. Cancer Ther. 8(12) 3360-3368.
S. Pieraccini, G. Saladino, G. Cappelletti, D. Cartelli, P. Francescato, G. Speranza, P. Manitto, M-M. Sironi. 2009. In silico design of tubulin-targeted antimitotic peptides. Nature Chemistry 1(8), 642-648.
E. Riano, M. Martignoni, G. Mancuso, D. Cartelli, F. Crippa, I. Toldo, G. Siciliano, D. Di Bella, F. Taroni, M.T. Bassi, G. Cappelletti, E.I. Rugarli. 2009. Pleiotropic effects of spastin on neurite growth depending on expression levels. J. Neurochem. 108 (5) 1277-1288.
G. Cappelletti, M. Galbiati, C. Ronchi, M.G. Maggioni, E. Onesto and A. Poletti. 2007. Neuritin (cpg15) enhances the differentiating effect of NGF on neuronal PC12 cells. J. Neurosci. Res., 85: 2702-13.
G. Tedeschi, G. Cappelletti, S. Nonnis, F. Taverna, A. Negri, C. Ronchi and S. Ronchi. 2007. Tyrosine nitration is a novel post-translational modification occurring on the neural intermediate filament protein peripherin. Neurochem. Res., 32: 433-41.
G. Cappelletti, M.G. Maggioni, C. Ronchi, R. Maci and G. Tedeschi. 2006. Protein tyrosine nitration is associated with cold- and drug-resistant microtubules in neuronal-like PC12 cells. Neurosci. Lett., 401: 159-164.
G. Cappelletti, T. Surrey and R. Maci. 2005. The parkinsonism producing neurotoxin MPP+ affects microtubule dynamics acting as a destabilising factor⮠FEBS Lett., 579: 4781-6.
Project Title:
Microtubule dysfunction and neurodegeneration.
Microtubules (MTs) are highly dynamic polymers that control many aspects of neuronal function: they provide a scaffold to sustain axonal and dendritic architecture and supply the railway for axonal transport. Proper regulation of the MT system is fundamental for the survival of neurons since there is only a limited range of acceptable MT dynamic behaviours in neurons, outside of which MTs cannot function normally and the cells cannot survive. Dysfunction of microtubule system is emerging as a novel contributing factor in several neurodegenerative processes including Parkinson�s disease (PD). Very recent data indicate that microtubules interact with some of the proteins mutated in PD, alpha synuclein and parkin, and that microtubules are involved in the mechanism of action of model drugs in PD, MPP+ and rotenone. The goal of the present project is to investigate in detail MT organization and dynamics and MT-dependent functions (i.e. axonal transport and synaptic trafficking) in triggering neuronal cell death in experimental models of PD. The two major tasks we want to pursue are: a) the study of MT dynamics and MT-related functions in primary mesencephalic cell cultures and mice exposed to the parkinsonism-inducing neurotoxin MPP+; b) the analyses of MT dynamics and MT-related functions in genetic models including Parkin knockout mice (Goldberg et al., 2003) and Parkin-silenced neuronal cells. Improved understanding of the role played by MT cytoskeleton dysfunction in PD pathogenesis and novel insights into crucial target for therapy is the expected outcome.