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

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Tripodi Marco Stampa
RESPONSABILE DELLA U. O.

Cognome e Nome
Tripodi Marco
Qualifica
P.O.
Facoltà
Medicina e Chirurgia
Dipartimento Biotecnologie Cellulari ed Ematologia
Settore Scientifico Disciplinare Bio13
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PERSONALE STRUTTURATO

Cognome e Nome Amicone Laura
Qualifica
RU
Dipartimento Biotecnologie Cellulari ed Ematologia
Ente di appartenenza
Univ. La Sapienza Roma
Cognome e Nome
Cicchini Carla
Qualifica
RU
Dipartimento Biotecnologie Cellulari ed Ematologia
Ente di appartenenza
Univ. La Sapienza Roma
Cognome e Nome Marchetti Alessandra
Qualifica
RU
Dipartimento Biotecnologie Cellulari ed Ematologia
Ente di appartenenza
Univ. La Sapienza Roma
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 Conigliaro Alice
Qualifica
Assegnista di ricerca
Dipartimento Biotecnologie Cellulari ed Ematologia
Ente di appartenenza Università La Sapienza Roma
Cognome e Nome
Mancone Carmine
Qualifica Contrattista
Dipartimento Biotecnologie Cellulari ed Ematologia
Ente di appartenenza INMI Lazzaro Spallanzani Roma
Cognome e Nome
Qualifica
Dipartimento
Ente di appartenenza
Cognome e Nome
Qualifica
Dipartimento
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Cognome e Nome
Qualifica
Dipartimento
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Cognome e Nome
Qualifica
Dipartimento
Ente di appartenenza

LINEE DI RICERCA

MECHANISMS CONTROLLING LIVER STEM CELL FATE

A- We recently isolated and established in lines, from embryonal and newborn mouse livers, resident liver stem cells (RLSCs) with immunophenotype and differentiative potentiality distinct from other previously described liver precursor/stem cells. RLSCs showed i) a metastable phenotype typical of the stem cells, with a coexpression of  epithelial and mesenchymal markers; ii) a multidifferentiative potentiality (hepatocytes/cholangiocytes and, if properly instructed, osteoblasts, condrocytes, glia and neurons) (Conigliaro A. et  al. Cell Death And Diff. 2008).

Taking advantage of our peculiar liver stem cell model, we investigated on  molecular mechanisms controlling the RLSC phenotype during self-renewal and differentiation. We clarified as Wnt/beta-catenin signalling integrates cellular program influencing both stemness maintenance and hepatocyte specific differentiation. In particular, RLSCs were proven to spontaneous differentiate into periportal hepatocytes that, following Wnt pathway activation, switch into perivenular hepatocytes highliting a direct convergence of the canonical Wnt signaling on the HNF4a-driven transcription in the hepatocyte post-differentiative metabolic “zonation” (Colletti et al., Gastroenterology 2009).

B-The concept that terminal differentiation allowing cellular tissue-specific functions is stably maintained once development is complete is questioned by numerous observations showing that differentiated epithelium may undergoes an Epithelial-to-Mesenchymal Transition (EMT). Both the EMT and the reverse process Mesenchymal-to-Epithelial Transition (MET) are typical events of development, tissue repair and tumor progression.

Our current efforts aim to the comprehension of the microenvironmental factors and the molecular mechanisms controlling the EMT/MET oscillations and hepatocyte differentiation.

In particular, we unveiled a delicate direct reciprocal regulation between the EMT master gene Snail and the hepatocyte differentiation master gene HNF4α, that is required during liver stem/precursors cell maintenance, hepatocyte differentiation and HCC progression. Moreover, we showed that  in the context of the whole liver HNF4α maintain  of the epithelial phenotype also  through the active repression of mesenchymal gene expression.

In conclusion, both HNF4α activator and repressor functions are necessary for the identity of hepatocytes.

 

C- We are currently investigating the contribution of liver stem cells to the onset and progression of hepatic fibrosis. Our unpublished evidences suggest the capability of RLSCs to differentiate into mesenchymal cells reminiscent of activated Hepatic Stellate Cells, the major fibrogenetic cells in cirrhotic liver thus suggesting a yet uncharacterised pathogenetic mechanism of hepatic fibro-cirrhosis.


TECNOLOGIE IN POSSESSO DELL'U. O.

Colture di cellule animali

DNA ricombinante

Elettroforesi Bidimensionale

Spettrometria di Massa (Maldi. Tof-Tof)

Analisi Computerizzata di Profili Elettroforetici

STRUMENTAZIONE

Denominazione
Struttura ove la strumentazione è allocata
Responsabile della strumentazione
Maldi –Tof-Tof
INMI L.Spallanzani
M. Tripodi
HPLC
FACS

PUBBLICAZIONI

1.    2006-  C. Agrati , T. Alonzi , R. De Santis , C. Castilletti , I. Abbate , M.R. Capobianchi , G. D’Offizi , F. Siepi, G.M. Fimia , M. Tripodi, and F. Poccia. “Activation of Vg9Vd2 T cells by non-peptidic antigens induces the inhibition of subgenomic HCV replication”. Int Immunol. 2006 Jan;18:11-8. Epub 2005 Dec. 16.  I.F. 07 3.29

2.    2006- S. Notari, C. Mancone, P. Narciso, M. Tripodi, Paolo Ascenzi. “Determination of anti-HIV drugs in human plasma by MALDI-TOF/TOF”. J Chromatogr B Analyt Technol Biomed Life Sci. 20;833:109-116. Epub 2006 Feb 28.                         I.F. 07 2.93

3.    2006- Cicchini C., D. Filippini, S. Coen, A. Marchetti, C. Cavallari, I. Laudadio, F.M. Spagnoli, T. Alonzi and M. Tripodi. “Snail controls both epithelial polarity and differentiation in hepatocytes”. (2006) J Cell Physiol. Oct; 209(1):230-8.                             I.F. 07 3.64

4.    2007- Mancone C., Amicone L., Fimia GM. Bravo E., Piacentini M., Tripodi M. and Alonzi T.: “Proteomic analysis of human very low-density lipoprotein by two-dimensional gel electrophoresis and MALDI-TOF/TOF. Proteomics.  Jan;7(1):143-54.                      I.F. 07   5.47

5.    2007- Napolitano M., A. Giuliani, T. Alonzi, C. Mancone, G. D’offizi, M. Tripodi and E. Bravo. “Very Low Density Lipoprotein and Low Density Lipoprotein isolated from HCV patients induce altered cellular lipid metabolism”. J Med Virol. 2007 Mar;79(3):254-8.                 I.F. 07  2.83

6.    2007- V. Bordoni, T. Alonzi, L. Zanetta, D. Khouri, A. Conti, M. Corazzari, F. Bertolini, P.Antoniotti, G. Pisani, F. Tognoli, E. Dejana and Marco Tripodi. “Hepatocyte conditioned medium sustains long term culture of CD34+ derived adult human hemangioblasts and induces their differentiation to endothelial cells”. Hepatology 2007 May; 45(5):1218-1228.                  I.F. 07  10.73

7.    2007- Papoutsi M., Dudas J.,  Becker J., Tripodi M., Opitz L., Ramadori G., Wilting  J. “Gene Regulation by the Homeobox Transcription Factor Prox1 in Murine Hepatoblasts”. Cell And Tissue Research. 2007 Nov; Vol.330(2); pp.209- 220.                         I.F. 07 2.61

8.    2008- Cicchini C., Laudadio I., Citarella F., Corazzari M., Steindler C., Conigliaro A., Fantoni A., Amicone L., M. Tripodi. “TGF-induced EMT requires Focal Adhesion Kinase (FAK) signalling”. Experimental  Cell Research. 2008 Jan 1;314(1):143-52. Epub 2007 Sep 18.            I.F. 07 3.69

9.    2008- Conigliaro A., Colletti M., Cicchini C., Guerra M.T.,  Manfredini R., Zini R., Bordoni V., Siepi F., Leopizzi M., Tripodi M., L. Amicone. “Isolation and characterization of murine liver resident stem cell”. Cell Death And Differentiation. 2008 Jan;15(1):123-33. Epub 2007 Oct 12.        I.F. 07 8.25

10.    2008- Zimmermann M., Flechsig C., La Monica N., Tripodi M., Adler G., And N. Dikopoulos. „Hepatitis C virus core protein impairs in vitro priming of specific T cell responses by dendritic cells and hepatocytes”.  Journal of Hepatology. 2008 Jan; 48(1):51-60. Epub 2007 Oct 15        I.F. 07 6.64

11.    2008- Nolan T., Cecere G., Chiofalo G., Mancone C., Alonzi T., Tripodi M., Catalanotto C., Cogoni C. “The RNA-dependent RNA polymerase essential for post-transcriptional gene silencing in Neurospora crassa interacts with replication protein A”. Nucleic acid research. 2008 Feb; 36(2): 532-8.    I.F. 07 6.95

12.    2008- Notari S., C. Mancone, T. Alonzi, M. Tripodi, P. Narciso, and P. Ascenzi. J Chromatography B. Submitted. “Determination of abacavir, amprenavir, didanosine, efavirenz, nevirapine, and stavudine concentration in human plasma by MALDI-TOF/TOF”. J Chromatogr B Analyt Technol Biomed Life Sci. 2008 Mar 1;863(2):249-57.                          I.F. 07 2.93

13.    2008- Alonzi T., Mancone C., Amicone L., Tripodi M. “Elucidation of lipoprotein particles structure by proteomic analysis”. Expert Rev Proteomics. 2008 Feb; 5(1):91-104.                I.F. 07 3.6

14.    2008- Marchetti A., Colletti M., Cozzolino A.M., Steindler C, Lunadei M., Mancone C., Tripodi M.: “ERK5/MAPK is activated by TGFbeta in hepatocytes and required for the GSK3beta-mediated Snail protein stabilization”. Cell Signal. 2008 Nov;20(11):2113-8. PMID: 18760348 [PubMed - in process]                                          I.F. 07 4.14

15.    2009- Agrati C., Cimini E., Sacchi A.,Bordoni V., Gioia C., Casetti R. , Turchi F. , Tripodi M. and Martini F. “Activated Vg9Vd2 T cells trigger granulocytes functions via MCP-2 release" Jan 1;182(1):522-9.The Journal of Immunology.    I.F. 07  6.06

16.    .2009- Wegert M,  La Monica N., Tripodi M. , Adler G.,  Dikopoulos N..” Impaired Interferon Type I Signalling in the Liver Modulates the Hepatic Acute Phase Response in Hepatitis C Virus Transgenic Mice” Journal of Hepatology. 2009 Aug;51(2):271-8. Epub 2009 Apr 23. I.F. 07 6.64

17.    Colletti M, Cicchini C., Conigliaro A., Santangelo  L.,  Alonzi  T. , Pasquini  E., Tripodi M, Amicone L. “Convergence of Wnt signaling on the HNF4a-driven transcription in controlling liver zonation” Gastroenterology. 2009 Aug;137(2):660-72. I.F. 08 12.6

18.    2009-Rossi M.N., Carbone M., Mostocotto C., Mancone C., Tripodi M., Maione R. and Amati P.: “Mitochondrial localization of PARP-1 requires interaction with mitofilin and is involved in the maintenance of mitochondrial dna integrity”. J Biol Chem Nov 13;284(46):31616-24.. [Epub ahead of print]. I.F. 08  5,52

19.    2010- Mancone C., Conti B., Amicone L., Bordoni V., Cicchini C., Calvo L., Basulto Perdomo A., Fimia G.M., Tripodi M. and Alonzi T.: “Proteomic analysis reveals a major role of contact inhibition in the execution of hepatocyte terminal differentiation”. J of Hepatology, 2010 Feb;52(2):234-43I   . I.F. 08    7,05

20.    2010- Notari S, Mancone C, Sergi M, Gullotta F, Bevilacqua N, Tempestilli M, Urso R, Lauria FN, Pucillo LP, Tripodi M, Ascenzi Determination of antituberculosis drug concentration in human plasma by MALDI-TOF/TOF. IUBMB Life. 2010 2010 May;62(5):387-93 I.F. 08   2.34

21. 2010- Mancone C, Steindler C, Santangelo L, Simonte G, Vlassi C, Longo MA, D'Offizi G, Di Giacomo C, Pucillo LP, Amicone L, Tripodi M, Alonzi T. Hepatitis C virus production requires apolipoprotein A-1 and affects its association with nascent low-density lipoproteins. Gut. 2010 Oct 12. [Epub ahead of print] I.F. 9.357


BREVETTI
National Patents: “Culture for maintenance, proliferation and differentiation of mammiferus     cells”. Application number RM2003A000395  12/08/2003. Inventors: V. Bordoni, T. Alonzi, MTripodi.
Property of IMNI, “L. Spallanzani” IRCCS: International extension in progress.

DOTTORATI DI RICERCA

Componente U.O. Dottorato di Ricerca Coordinatore Sede
Tripodi Marco
Scienze pasteuriane
Di Mauro Ernesto
Roma
Amicone Laura
Biologia Umana e Genetica
Paola Londei
Roma
Cicchini Carla
Biologia Umana e Genetica
Paola Londei
Roma
Marchetti Alessandra Biologia Umana e Genetica Paola Londei Roma

CONGRESSI C.I.B.

Congressi Partecipazione
CNB4

CNB5

CNB6

CNB7

CNB8

CNB9
CNB10