Direzione e uffici C.I.B.

Direzione CIB:
Prof. Claudio Schneider
Email: claudio.schneider@Lncib.it

Segreteria CIB:
Prof. Roberto Gambari
Email: roberto.gambari@unife.it

SEGRETERIA ORGANIZZATIVA:
Elisabetta Lambertini
Tel: 0532/974451
Fax: 0532/974484
E-mail: lmblbt@unife.it

AMMINISTRAZIONE:
Vanessa Florit
Area di Ricerca
Padriciano, 99 - 34012 Trieste
Tel: 040/398979
Fax: 040/398990
E-mail: cib@lncib.it

Posta certificata C.I.B.:
cib@poste-certificate.it

Login



Colombi Marina Stampa
RESPONSABILE DELLA U. O.

Cognome e Nome Colombi Marina
Qualifica FULL PROFESSOR OF CELL BIOLOGY
Facoltà MEDICAL FACULTY, UNIVERSITY OF BRESCIA
Dipartimento BIOMEDICAL SCIENCES AND BIOTECHNOLOGY, DIVISION OF BIOLOGY AND GENETICS
Settore Scientifico Disciplinare BIO13 BIOLOGIA APPLICATA
E-mail Questo indirizzo e-mail è protetto dallo spam bot. Abilita Javascript per vederlo.

PERSONALE STRUTTURATO

Cognome e Nome Nicoletta Zoppi
Qualifica RESEARCHER
Dipartimento Biomedical Sciences and Biotechnology
Ente di appartenenza University of Brescia
Cognome e Nome
Rita Gardella
Qualifica RESEARCHER
Dipartimento Biomedical Sciences and Biotechnology
Ente di appartenenza University of Brescia
Cognome e Nome Sergio Ferraboli
Qualifica RESEARCHER
Dipartimento Biomedical Sciences and Biotechnology
Ente di appartenenza University of Brescia
Cognome e Nome
Qualifica
Dipartimento
Ente di appartenenza
Cognome e Nome
Qualifica
Dipartimento
Ente di appartenenza
Cognome e Nome
Qualifica
Dipartimento
Ente di appartenenza

PERSONALE NON STRUTTURATO

Cognome e Nome Drera Bruno
Qualifica Medical Dr. Medical Genetics Specialization student
Dipartimento Biomedical Sciences and Biotechnology
Ente di appartenenza University of Brescia
Cognome e Nome Ritelli Marco
Qualifica Dr. in Biology, Specialist in Medical Genetics. Fellowship
Dipartimento Biomedical Sciences and Biotechnology
Ente di appartenenza University of Brescia
Cognome e Nome
Qualifica
Dipartimento
Ente di appartenenza
Cognome e Nome
Qualifica
Dipartimento
Ente di appartenenza
Cognome e Nome
Qualifica
Dipartimento
Ente di appartenenza
Cognome e Nome
Qualifica
Dipartimento
Ente di appartenenza

LINEE DI RICERCA

1. Characterization of a 13 amino acid fibronectin (FN13) peptide with anti-tumorigenic properties to be used in preclinical studies. We identified a 13 amino acid human fibronectin (FN) peptide (FN13) which induces the formation of an extracellular matrix (ECM) of FN in several defective human tumor derived cell lines and in Rous sarcoma virus in vitro transformed avian fibroblasts. A minigene encoding FN13 was contructed and stably expressed in three human tumor cell lines. The trasfectants, as well as the untransfected cells treated with the purified synthetic peptide, organized the FN-ECM and significantly reduced their invasive potential in Matrigel matrix. This was associated with the induction of v3 FN integrin receptor organization, since cells not organizing this integrin did not reduce their invasive properties. The tumor cell lines stably expressing FN13 will be subcutaneously and intravenously injected in nude mice in order to study the effect of FN13 on tumor growth and metastasis in vivo. In case FN13 will show anti-invasive and- anti-metastatic potential, preclinical studies in mice bearing chemically-induced tumors will be performed, either by gene-delivered FN13 or by purified FN13 treatment.
2. Characterization of patients affected with dystrophic epidermolysis bullosa (DEB) and search of modulator genes. DEB is caused by dominant or recessive mutations in type VII collagen gene (COL7A1). Since several years we study COL7A1 genotype-phenotype correlation in DEB patients. We intend to investigate molecular determinants, additional to COL7A1, acting on phenotype variability in DEB patients. To this purpose we will take advantage from the large cohort of DEB affected individuals collected and characterized in past years. Among these patients, we have identified subgroups composed of at least two affected individuals carrying the same COL7A1 mutation(s), i.e. siblings or subjects from different kindred sharing same homozygous/heterozygous mutation(s). Some of the selected subgroups of patients show significant intra-familial or inter-familial phenotypic variability, while others display similar clinical features. An analysis of gene expression profile in keratinocytes and fibroblasts from couples of DEB siblings, showing significant phenotype variability, will be carried out. The expression levels of de-regulated genes with potential interest will be tested by real-time RT-PCR and immunodetection techniques. We will investigate in parallel the involvement of matrix metalloproteinases (MMPs) in DEB by functional polymorphisms analysis. The mRNA and protein expression levels and enzymatic activity of all relevant MMPs will be analysed in primary keratinocytes and fibroblasts cultures. Altogether, the proposed investigations are expected to lead to the identification of novel molecular determinants of DEB expressiveness and ascertain the role of MMPs proteolytic pathway in the modulation of DEB patients’ phenotypes. This study will be carried on in collaboration with Dr. Giovanna Zambruno research group at the Istituto Dermopatico dell’Immacolata, Rome.
3. Characterization of patients affected with Ehlers-Danlos syndromes. Ehlers-Danlos syndromes (EDSs) are hereditary connective tissue disorders with clinical, genetic and allelic heterogeneity. In the six EDS variants, mutations in genes encoding type I, III and V collagens, lysyl hydroxylase, ADAMTS-2 and tenascin X have been reported. EDS patients clinical dignosis, following the Villefranche Nosology criteria, must be confirmed at molecular level. Protein and mutation characterizations are performed starting from cultured patients skin fibroblasts. We defined a test for EDSs fibroblasts based on the immunofluorescence analysis of a pannel of proteins entering into the formation and organization of the extracellular matrix (ECM) of cultured cells. This approach allows to distinguish EDS fibroblasts from cells derived from patients affected with other connective tissue disorders for the lack of specific proteins in the extracellular matrix. Furthermore, the test allows the identification of the different EDS variants therefore addressing the molecular characterization. In EDS fibroblasts, restoring a control phenotype after treatment with the protein they miss as a consequence of specific genes mutations, we are performing gene expression profile studies by mean of cDNA array approach.
4. Characterization of the gene responsible of the arterial tortuosity syndrome. Arterial tortuosity syndrome (ATS) is a rare autosomal recessive disorder characterized by tortuosity, elongation and aneurysm formation of the major arteries and pulmonary artery stenosis due to disruption of elastic fibres of the media. Homozygosity mapping in two consanguineous families, from Morocco and Italy respectively, identified a critical region of 4.1 Mb on chromosome 20q13.1. Haplotype sharing in another family originating from the same Moroccan region reduced the candidate interval to 1.2 Mb containing 7 genes (SLC13A3, TP53RK, SLC2A10, EYA2, PRKCBP1, NCOA3, SULF2) and 1 pseudogene (RPL35AP). Mutations in GLUT10/SLC2A10, a member of the facilitative glucose transporters (GLUTs), were identified in 6 ATS families: homozygous nonsense mutations or base pair deletions leading to premature stopcodons in 4 families and one identical missense mutation in 2 other families. We are studying the effect of these mutations on GLUT10 function alteration and on the phenotypic defects in ATS patients.

TECNOLOGIE IN POSSESSO DELL'U. O.

  • Mutation detection analysis: from heteroduplex to DHPLC analysis
  • Gene profile expression analysis
  • RT-PCR and Quantitative Real-Time PCR
  • Immunofluorescence analysis on fixed cells and histological sections
  • Confocal and time-lapse microscopy
  • Western blot analysis
  • In situ hybridization
  • DNA cloning and expression in pro-eukaryotic cells
  • Nude mice human cells transfer
  • Fibroblasts and smooth muscle cells cultures establishment

STRUMENTAZIONE

Denominazione
Struttura ove la strumentazione è allocata
Responsabile della strumentazione
DNA sequencer Applied Biosystems 3100
Biomedical Sciences and Biotechnology, University of Brescia
Prof. Sergio Barlati, Direttore del Dipartimento
DHPLC Transgenomic
Biomedical Sciences and Biotechnology, University of Brescia
Prof. Sergio Barlati, Direttore del Dipartimento
Confocal Microscope Ziess
Biomedical Sciences and Biotechnology, University of Brescia
Prof. Sergio Barlati, Direttore del Dipartimento
Real-Time PCR BioRad
Biomedical Sciences and Biotechnology, University of Brescia
Prof. Sergio Barlati, Direttore del Dipartimento
Fluorescence Microscope and CCD camera Zeiss
Biomedical Sciences and Biotechnology, University of Brescia
Prof. Sergio Barlati, Direttore del Dipartimento
Gene Chip System Affymetyrix for expression analys
Department of Pediatrics University of Brescia
Prof. Luigi Notarangelo

PUBBLICAZIONI

1. De Panfilis G., Ghidini A., Graifemberghi S., Barlati S., Zoppi N., Colombi M. Dexamethasone-induced healing of chronic leg ulcers in a patient with defective organization of the extraxellular matrix of fibronectin. Br.J. Dermatol. 2005, 142: 166-170.
2. Gardella R., Barlati S., Zoppi N., Tadini G., Colombi M. A –96CT mutation in the promoter of collagen type VII gene (COL7A1) abolishing the transcription in a patient affected by recessive dystrophic epidermolysis bullosa. Hum. Mutat. 2000, 16:275 (Online Mutation in Brief#364, pag. 1-6)
3. Gardella R., Nuytinck L., Barlati S., Van Acker P., Tadini G., De Paepe A., Colombi M. Characterization of mutations leading to epidermolysis bullosa dystrophica and Marfan syndrome in a single patient. Exp. Dermatol. 2001, 26:710-713.
4. Gardella R., Zoppi N., Zambruno G., Barlati S., Colombi M. Different phenotypes in recessive dystrophic epidermolysis bullosa patients sharing the same mutation in compound heterozygosity with two novel mutations in COL7A1. Br. J. Dermatol. 2002,147:450-457.
5. Gardella R., Castiglia D., Posteraro P., Paradisi M., Bernardini S., Zoppi N., Tadini G., Barlati S., McGrath J.A., Zambruno G., Colombi M. Genotype-phenotype correlation in Italian patients affected with epidermolysis bullosa dystrophica. J. Invest. Dermatol. 2002, 119:1456-1462.
6. Colombi M., Zoppi N., De Petro G., Marchina E., Gardella R., Tavian D., Ferraboli S., Barlati S. Matrix assembly induction and cell migration and invasion inhibition by a 13-amino acid fibronectin peptide. J. Biol. Chem. 2003, 278:14346-14355.
7. Coucke P.J., Wessels M.W., Van Acker P., Gardella R., Barlati S., Willems P.J., Colombi M., De Paepe A. Homozygosity mapping of a gene for arterial tortuosity syndrome to chromosome 20q13. J. Med. Genet. 2003, 40:747-751.
8. Gardella R., Zoppi N., Assanelli D., Muiesan M. L., Barlati S., Colombi M. Exclusion of candidate genes in a family with arterial tortuosity syndrome. Am. J. Med. Genet. 2004, 126A:221-228.
9. Zoppi N., Gardella R., De Paepe A., Barlati S., Colombi M. Human fibroblasts carrying mutations in COL5A1 and COL3A1 genes do not organize the extracellular matrix, down-regulate 21 integrin and recruit v3 instead of 51 integrin. J. Biol. Chem. 2004, 279:18157-18168.
10. Posteraro P., Pascucci M. Colombi M., Barlati S., Giannetti A., Paradisi M., Mustonen A., Zambruno G., Castiglia D. Denaturing HPLC-based approach for detection of COL7A1 gene mutations causing dystrophic epidermolysis bullosa: identification of nine novel mutations. B.B.R.C. 2005, 338:1391-1401

DOTTORATI DI RICERCA

Componente U.O. Dottorato di Ricerca Coordinatore Sede
Colombi Marina
Genetica Molecolare Applicata alle Scienze Mediche
Prof. Sergio Barlati
University of Brescia
Gardella Rita
Genetica Molecolare Applicata alle Scienze Mediche
Prof. Sergio Barlati
University of Brescia

CONGRESSI C.I.B.

Congressi Partecipazione
CNB4

CNB5

CNB6

CNB7

CNB8

CNB9
CNB10