Antonio Rossi
e-mail: antrossi AT unipv.it
affiliation: Università di Pavia
research area(s): Chemical Biology, Molecular Biology
Course:
Biomolecular Sciences and Biotechnology
University/Istitution: Istituto Universitario di Studi Superiori, Pavia
University/Istitution: Istituto Universitario di Studi Superiori, Pavia
ACADEMIC POSITION:
Associate Professor of Biochemistry, University of Pavia
EDUCATION:
1985 University of Pavia (Italy), Biology Degree
1988-1992 University of Pavia (Italy), PhD in Biochemistry
1996-1997 Research Fellow at the Division of Metabolic and Molecular Diseases, Department of Paediatrics, University of Zurich, Zurich, Switzerland.
Associate Professor of Biochemistry, University of Pavia
EDUCATION:
1985 University of Pavia (Italy), Biology Degree
1988-1992 University of Pavia (Italy), PhD in Biochemistry
1996-1997 Research Fellow at the Division of Metabolic and Molecular Diseases, Department of Paediatrics, University of Zurich, Zurich, Switzerland.
Our research focus on the molecular, cellular and extracellular matrix aspects of specific heritable connective tissue disorders affecting bone, cartilage and skin. The specific aims are:
- the understanding of the molecular basis of heritable connective tissue diseases to gain a deep knowledge of the structure-function relationships of extracellular matrix components and of the contribution of cellular, molecular and genetic factors to the initiation and progression of the disorders;
- the development of effective approaches for the diagnosis, prevention and/or correction of the disorder course through new molecular, cellular and/or pharmacological trials.
Our studies are based on the generation and characterization of murine models (transgenic mice) of human diseases and on culture of control and patients cells.
- the understanding of the molecular basis of heritable connective tissue diseases to gain a deep knowledge of the structure-function relationships of extracellular matrix components and of the contribution of cellular, molecular and genetic factors to the initiation and progression of the disorders;
- the development of effective approaches for the diagnosis, prevention and/or correction of the disorder course through new molecular, cellular and/or pharmacological trials.
Our studies are based on the generation and characterization of murine models (transgenic mice) of human diseases and on culture of control and patients cells.
Bonafé L, Hastbacka J, de la Chapelle A, Campos-Xavier AB, Chiesa C, Forlino A, Superti-Furga A, Rossi A. (2008) A novel mutation in the sulphate transporter gene SLC26A2 (DTDST) specific to the Finnish population causes de la Chapelle dysplasia. J Med Genet. 45, 827-831.
Panaroni C, Gioia R, Lupi A, Besio R, Goldstein SA, Kreider J, Leikin S, Vera JC, Mertz EL, Perilli E, Baruffaldi F, Villa I, Farina A, Casasco M, Cetta G, Rossi A, Frattini A, Marini JC, Vezzoni P, Forlino A (2009) In utero transplantation of adult bone marrow decreases perinatal lethality and rescues the bone phenotype in the knockin murine model for classical, dominant osteogenesis imperfecta. Blood. 114, 459-68.
Gualeni B, Facchini M, De Leonardis F, Tenni R, Cetta G, Viola M, Passi A, Superti-Furga A, Forlino A, Rossi A. (2010) Defective proteoglycan sulfation of the growth plate zones causes reduced chondrocyte proliferation via an altered Indian hedgehog signalling. Matrix Biol. 29, 453-460.
Vissers LE, Lausch E, Unger S, Campos-Xavier AB, Gilissen C, Rossi A, Del Rosario M, Venselaar H, Knoll U, Nampoothiri S, Nair M, Spranger J, Brunner HG, Bonafé L, Veltman JA, Zabel B, Superti-Furga A. (2011) Chondrodysplasia and Abnormal Joint Development Associated with Mutations in IMPAD1, Encoding the Golgi-Resident Nucleotide Phosphatase, gPAPP.
Am J Hum Genet. 88, 608-615.
Panaroni C, Gioia R, Lupi A, Besio R, Goldstein SA, Kreider J, Leikin S, Vera JC, Mertz EL, Perilli E, Baruffaldi F, Villa I, Farina A, Casasco M, Cetta G, Rossi A, Frattini A, Marini JC, Vezzoni P, Forlino A (2009) In utero transplantation of adult bone marrow decreases perinatal lethality and rescues the bone phenotype in the knockin murine model for classical, dominant osteogenesis imperfecta. Blood. 114, 459-68.
Gualeni B, Facchini M, De Leonardis F, Tenni R, Cetta G, Viola M, Passi A, Superti-Furga A, Forlino A, Rossi A. (2010) Defective proteoglycan sulfation of the growth plate zones causes reduced chondrocyte proliferation via an altered Indian hedgehog signalling. Matrix Biol. 29, 453-460.
Vissers LE, Lausch E, Unger S, Campos-Xavier AB, Gilissen C, Rossi A, Del Rosario M, Venselaar H, Knoll U, Nampoothiri S, Nair M, Spranger J, Brunner HG, Bonafé L, Veltman JA, Zabel B, Superti-Furga A. (2011) Chondrodysplasia and Abnormal Joint Development Associated with Mutations in IMPAD1, Encoding the Golgi-Resident Nucleotide Phosphatase, gPAPP.
Am J Hum Genet. 88, 608-615.
Project Title:
Project Title:
The functional role of the Calcium Activated Nucleotidase 1 in the skeleton: an in vivo study with a mouse model of Desbuquois dysplasia
The objectives of the project are to define the physiological function of the Calcium Activated Nucleotidase 1 (CANT1) and its role in the etiology of Desbuquois dysplasia (DBQD), a recessive chondrodysplasia. Preliminary results suggest CANT1 involvement in protein glycosylation, namely in proteoglycan synthesis the main cartilage glycoprotein. The specific aims are:
a) to generate and characterize at the biochemical, molecular and morphological level a mouse model of DBQD;
b) to define the physiological function of the membrane bound and soluble form of CANT1.
These studies are designed to yield a deeper understanding of the function of CANT1 and of the pathogenesis of osteoarthropathies, so that effective therapies can be developed.
a) to generate and characterize at the biochemical, molecular and morphological level a mouse model of DBQD;
b) to define the physiological function of the membrane bound and soluble form of CANT1.
These studies are designed to yield a deeper understanding of the function of CANT1 and of the pathogenesis of osteoarthropathies, so that effective therapies can be developed.
Project Title:
Generation of Zebrafish models to understand human skeletal diseases and to develop novel therapeutic strategy
Among the genetic diseases Osteogenesis Imperfecta (OI) had long been considered a paradigmatic disorder to investigate bone physiology and new therapy for skeletal dysplasias. OI patients are characterized by an osteoporotic-like phenotype, with low bone mineral density and frequent bone fractures. OI is a disease affecting type I collagen biosynthesis and causing a broad range of clinical outcomes, ranging from very mild to lethal. Recently this disease has become the better example of connective tissue disorder caused not only by defect in structural genes, but also mutations in intracellular proteins involved in collagen synthesis. In fact the majority of OI cases with dominant transmission are caused by mutations in the genes coding for the alpha1 and alpha2 type I collagen chains (COL1A1 and COL1A2) the more abundant structural protein in bone, but very recently new recessive forms of OI had been discovered, caused by genes involved in collagen type I post translational modification (CRTAP, LEPRE 1, PPIB) and folding (FKBP10 and SERPINH1). These new findings have discovered a completely new etiologic and pathogenetic mechanisms that need to be further elucidated and taken into account in the analysis of genotype- phenotype correlation studies.
The specific aims of our project will be:
1. The generation of Zebrafish (Danio Rerio) models for the new identified recessive OI forms. Knock down or knock out technologies will be utilized. The molecular, biochemical and morphological characterization of the models, with specific attention to bone development, will be performed. The use of Zebrafish models will guarantee us the unique possibility to investigate the effect of the mutation at early developmental stages, analysis that will be very hard using the classical murine models.
2. The use of the Zebrafish models to develop novel therapeutic approaches, such us development of novel drug or cellular therapy based on transplantation of mesenchymal stem cells.
The specific aims of our project will be:
1. The generation of Zebrafish (Danio Rerio) models for the new identified recessive OI forms. Knock down or knock out technologies will be utilized. The molecular, biochemical and morphological characterization of the models, with specific attention to bone development, will be performed. The use of Zebrafish models will guarantee us the unique possibility to investigate the effect of the mutation at early developmental stages, analysis that will be very hard using the classical murine models.
2. The use of the Zebrafish models to develop novel therapeutic approaches, such us development of novel drug or cellular therapy based on transplantation of mesenchymal stem cells.