Paolo Maria Vezzoni

@article{paulis_chromosome_2015,

title = {Chromosome transplantation as a novel approach for correcting complex genomic disorders},

author = {Marianna Paulis and Alessandra Castelli and Lucia Susani and Michela Lizier and Irina Lagutina and Maria Luisa Focarelli and Camilla Recordati and Paolo Uva and Francesca Faggioli and Tui Neri and Eugenio Scanziani and Cesare Galli and Franco Lucchini and Anna Villa and Paolo Vezzoni},

doi = {10.18632/oncotarget.6143},

issn = {1949-2553},

year  = {2015},

date = {2015-11-01},

journal = {Oncotarget},

volume = {6},

number = {34},

pages = {35218--35230},

abstract = {Genomic disorders resulting from large rearrangements of the genome remain an important unsolved issue in gene therapy. Chromosome transplantation, defined as the perfect replacement of an endogenous chromosome with a homologous one, has the potential of curing this kind of disorders. Here we report the first successful case of chromosome transplantation by replacement of an endogenous X chromosome carrying a mutation in the Hprt genewith a normal one in mouse embryonic stem cells (ESCs), correcting the genetic defect. The defect was also corrected by replacing the Y chromosome with an X chromosome. Chromosome transplanted clones maintained in vitro and in vivo features of stemness and contributed to chimera formation. Genome integrity was confirmed by cytogenetic and molecular genome analysis. The approach here proposed, with some modifications, might be used to cure various disorders due to other X chromosome aberrations in induced pluripotent stem (iPS) cells derived from affected patients.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{neri_targeted_2015,

title = {Targeted Gene Correction in Osteopetrotic-Induced Pluripotent Stem Cells for the Generation of Functional Osteoclasts},

author = {Tui Neri and Sharon Muggeo and Marianna Paulis and Maria Elena Caldana and Laura Crisafulli and Dario Strina and Maria Luisa Focarelli and Francesca Faggioli and Camilla Recordati and Samantha Scaramuzza and Eugenio Scanziani and Stefano Mantero and Chiara Buracchi and Cristina Sobacchi and Angelo Lombardo and Luigi Naldini and Paolo Vezzoni and Anna Villa and Francesca Ficara},

doi = {10.1016/j.stemcr.2015.08.005},

issn = {2213-6711},

year  = {2015},

date = {2015-10-01},

journal = {Stem Cell Reports},

volume = {5},

number = {4},

pages = {558--568},

abstract = {Autosomal recessive osteopetrosis is a human bone disease mainly caused by TCIRG1 gene mutations that prevent osteoclasts resorbing activity, recapitulated by the oc/oc mouse model. Bone marrow transplantation is the only available treatment, limited by the need for a matched donor. The use of induced pluripotent stem cells (iPSCs) as an unlimited source of autologous cells to generate gene corrected osteoclasts might represent a powerful alternative. We generated iPSCs from oc/oc mice, corrected the mutation using a BAC carrying the entire Tcirg1 gene locus as a template for homologous recombination, and induced hematopoietic differentiation. Similarly to physiologic fetal hematopoiesis, iPSC-derived CD41(+) cells gradually gave rise to CD45(+) cells, which comprised both mature myeloid cells and high proliferative potential colony-forming cells. Finally, we differentiated the gene corrected iPSC-derived myeloid cells into osteoclasts with rescued bone resorbing activity. These results are promising for a future translation into the human clinical setting.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{lo_iacono_osteopetrosis_2012,

title = {Osteopetrosis rescue upon RANKL administration to Rankl(-/-) mice: a new therapy for human RANKL-dependent ARO},

author = {Nadia {Lo Iacono} and Harry C Blair and Pietro L Poliani and Veronica Marrella and Francesca Ficara and Barbara Cassani and Fabio Facchetti and Elena Fontana and Matteo M Guerrini and Elisabetta Traggiai and Francesca Schena and Marianna Paulis and Stefano Mantero and Antonio Inforzato and Serenella Valaperta and Alessandra Pangrazio and Laura Crisafulli and Virginia Maina and Paul Kostenuik and Paolo Vezzoni and Anna Villa and Cristina Sobacchi},

doi = {10.1002/jbmr.1712},

issn = {1523-4681},

year  = {2012},

date = {2012-12-01},

journal = {Journal of Bone and Mineral Research: The Official Journal of the American Society for Bone and Mineral Research},

volume = {27},

number = {12},

pages = {2501--2510},

abstract = {In the last decades the molecular basis of monogenic diseases has been largely unraveled, although their treatment has often remained unsatisfactory. Autosomal recessive osteopetrosis (ARO) belongs to the small group of genetic diseases that are usually treated with hematopoietic stem cell transplantation (HSCT). However, this approach is not effective in the recently identified form carrying mutations in the receptor activator of NF-κB ligand (RANKL) gene. In this subset, therapy replacement approach based on RANKL delivery has a strong rationale. Here we demonstrate that the systematic administration of RANKL for 1 month to Rankl(-/-) mice, which closely resemble the human disease, significantly improves the bone phenotype and has beneficial effects on bone marrow, spleen and thymus; major adverse effects arise only when mice are clearly overtreated. Overall, we provide evidence that the pharmacological administration of RANKL represents the appropriate treatment option for RANKL-deficient ARO patients, to be validated in a pilot clinical trial.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{villa_partial_1998,

title = {Partial V(D)J recombination activity leads to Omenn syndrome.},

author = {A Villa and S Santagata and F Bozzi and S Giliani and A Frattini and L Imberti and L B Gatta and H D Ochs and K Schwarz and L D Notarangelo and P Vezzoni and E Spanopoulou},

url = {http://www.ncbi.nlm.nih.gov/pubmed/9630231},

issn = {0092-8674},

year  = {1998},

date = {1998-05-01},

journal = {Cell},

volume = {93},

number = {5},

pages = {885--96},

abstract = {Genomic rearrangement of the antigen receptor loci is initiated by the two lymphoid-specific proteins Rag-1 and Rag-2. Null mutations in either of the two proteins abrogate initiation of V(D)J recombination and cause severe combined immunodeficiency with complete absence of mature B and T lymphocytes. We report here that patients with Omenn syndrome, a severe immunodeficiency characterized by the presence of activated, anergic, oligoclonal T cells, hypereosinophilia, and high IgE levels, bear missense mutations in either the Rag-1 or Rag-2 genes that result in partial activity of the two proteins. Two of the amino acid substitutions map within the Rag-1 homeodomain and decrease DNA binding activity, while three others lower the efficiency of Rag-1/Rag-2 interaction. These findings provide evidence to indicate that the immunodeficiency manifested in patients with Omenn syndrome arises from mutations that decrease the efficiency of V(D)J recombination.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{macchi_mutations_1995,

title = {Mutations of Jak-3 gene in patients with autosomal severe combined immune deficiency (SCID)},

author = {P Macchi and A Villa and S Giliani and M G Sacco and A Frattini and F Porta and A G Ugazio and J A Johnston and F Candotti and J J O'Shea},

doi = {10.1038/377065a0},

issn = {0028-0836},

year  = {1995},

date = {1995-09-01},

journal = {Nature},

volume = {377},

number = {6544},

pages = {65--68},

abstract = {Severe combined immune deficiency (SCID) represents a heterogenous group of hereditary diseases. Mutations in the common gamma-chain (gamma c), which is part of several cytokine receptors including those for interleukin (IL)-2, IL-4, IL-7, IL-9 and IL-15, are responsible for X-linked SCID, which is usually associated with a lack of circulating T cells and the presence of B lymphocytes (T- B+ SCID). The gene(s) responsible for autosomal recessive T- B+ SCID is still unknown. The Jak-3 protein kinase has been found to associate with the gamma c-chain-containing cytokine receptors. Therefore Jak-3 or other STAT proteins with which it interacts are candidate genes for autosomal recessive T- B+ SCID. Here we investigate two unrelated T- B+ SCID patients (both from consanguineous parents) who have homozygous mutations in the gene for Jak-3. One patient carries a mutation (Tyr100-->Cys) in a conserved tyrosine residue in the JH7 domain of Jak-3 which is absent in more than 150 investigated chromosomes. The other patient carries a homozygous 151-base-pair deletion in the kinase-like domain, leading to a frameshift and premature termination. Both mutations resulted in markedly reduced levels of Jak-3. These findings show that abnormalities in the Jak/STAT signalling pathway can account for SCID in humans.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}