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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Bussolino Federico Stampa
RESPONSABILE DELLA U. O.

Cognome e Nome
Bussolino Federico
Qualifica
P.O.
Facoltà
Medicina e Chirurgia. Università di Torino
Dipartimento Oncologia
Settore Scientifico Disciplinare BIO-10
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PERSONALE STRUTTURATO

Cognome e Nome
Arese Marco
Qualifica PA
Dipartimento
Oncologia
Ente di appartenenza
UNITO
Cognome e Nome
Primo Luca
Qualifica
PA
Dipartimento
Oncologia
Ente di appartenenza
UNITO
Cognome e Nome
Gualandris Anna
Qualifica
Tecnico
Dipartimento
Oncologia
Ente di appartenenza
UNITO
Cognome e Nome Serini Guido
Qualifica RU
Dipartimento
Scienze Oncologiche
Ente di appartenenza
UNITO
Cognome e Nome
VAldembri Donatella
Qualifica
Tecnico
Dipartimento
Oncologia
Ente di appartenenza
UNITO
Cognome e Nome Marchio Serena
Qualifica RU tipo A
Dipartimento Oncologia
Ente di appartenenza Unito

PERSONALE NON STRUTTURATO

Cognome e Nome
Noghero Alessio
Qualifica Assegnista di ricerca
Dipartimento
Oncologia
Ente di appartenenza UNITO
Cognome e Nome Napione Lucia
Qualifica Borsista
Dipartimento
Scienze Oncologiche
Ente di appartenenza Fondazione Piemontese per la Ricerca sul Cancro- Onlus
Cognome e Nome
Noghero Alessio
Qualifica
Assegnista di ricerca
Dipartimento
Oncoligia
Ente di appartenenza UNITO
Cognome e Nome
Astanina Elena
Qualifica
assegnista
Dipartimento
Oncologia
Ente di appartenenza UNITO
Cognome e Nome Doronzo Gabriella
Qualifica
Assegnista
Dipartimento
Oncologia
Ente di appartenenza UNITO
Cognome e Nome
Comunanza Valentina
Qualifica Assegnista di ricerca
Dipartimento
Oncologia
Ente di appartenenza UNITO
Cognome e Nome Napione Lucia
Qualifica Assegnsita
Dipartimento Oncologia
Ente di appartenenza UNITO

LINEE DI RICERCA

The Unit focuses its research in deciphering the molecular circuits between cancer and stroma cells with the final aim to understand the role of stroma in regulating cancer progression and the response to therapy.

Four projects are in progress.

  1. ROLE OF TFEB IN TUMOR PROGRESSION AND ANGIOGENESIS. TFEB belongs to the microphtalmia  family of bHLH-leucine zipper transcription factors. TFEB was originally described to be translocated in a juvenile subset of renal carcinoma. TFEB on chromosome 6 is fused to the non-protein encoding Alpha gene (MALAT1) on chromosome 11. This results in dramatic increase of expression of the whole molecule in tumour cells due to promoter substitution and efficient nuclear translocation.  Besides its oncogenic activity, TFEB controls the autophagy-lysosomal pathway by recognizing a recurrent motif present in the promoter regions of more than 400 genes that participate to lysosome biogenesis and autophagy.We have generated conditional mice models to overexpress or delete Tfeb in vasculature to study its role in vascular development and in tumor progression and angiogenesis. Furthermore more we set-up in vitro and in vivo models to modify Tfeb expression in epicardial cells to investigate its role in epithelial – mesenchymal transition (EMT) in heart development and more in general physiopatological processes characterized by this mechanism.
  2. ROLE OF NEUROLOGIN-2 IN PROGRESSION OF PANCREATIC DUCTAL CARCINOMA. Taking advantages from our previous observations of the role of axon guidance cues in tumor angiogenesis (reviewed in doi: 10.1016/j.molmed.2014.07.005) and based on recent observations showing that axon guidance and synaptogenic  cues are altered in PDAC (Nature 491, 399, 2012), we performed a whole transcriptomic analysis of the early in situ carcinomas (PanIn) isolated by laser capture microdissection from a genetic engineered mouse model characterized by the expression of KRASG12V in acinar cells through the use of the elastase promoter (Elas-K-RasG12V).  By analysing the expression of the 5 neuroligins (Nlgs) we found that Nlg2 is overexpressed in the early lesions.  In vitro loss-of-function experiments showed that Nlg-2 ablation halted acinar-ductal metaplasia and contributes in loss of cell polarity , supporting the concept that Nlg-2 is necessary in the early phase of PDAC.  The aim of the project  is the whole investigation of this molecule in the pathogenesis of PDAC and its identification as early biomarker of disease.
  3. THE GLOBAL NETWORK ANALYSIS OF REGULATORY RNAs IN SPROUTING ANGIOGENESIS. This project aims at decoding  networks of regulatory RNAs supporting sprouting angiogenesis, which is the most relevant process in vascular tree formation during embryonic and adult life.This goal is reached by realizing a biological platform constituted by 3D tissue cultures of vascular cells alone or in the presence of cancer cells realized by means of scaffolds and microfluidic channels with capability to tune physical, chemical and mechanical properties.  The platform is  implemented by endothelial cells genetically modified to follow their specification into tip and stalk cells bearing distinct morphologies and functional properties in sprouting angiogenesis. RNAseq analysis performed in specific cell subtypes by different bioinformatics and systems biology methods will generate data to design mixed gene regulatory circuits involving transcriptional, microRNA-mediated post-transcriptional interactions as well as long non-coding RNA. Molecular data are  dynamically correlated with the cell phenotypes. Validation of specific nodes or hubs identified in the mixed regulatory network are  exploited by gain-of-function and loss-of-function approaches.
  4. SELECTION OF RESPONDER PATIENTS TO ANTI-ANGIOGENIC COMPOUND BY INVESTIGATIONAL STUDIES WITH PATIENT- DERIVED  XENOGRAFTS (in collaboration with Prof. Livio Trusolino and Dr. Andrea bertotti, Department of Oncology-UniTo).Undoubted anti-angiogenic regimens have significantly contributed to extending the survival of cancer patients worldwide. However, in spite of the strong and widely accepted concept that tumour progression   and metastatic diffusion require angiogenesis and in the face of promising preclinical results,  only a fraction of patients receives a clinical benefit. This evidence calls for the identification of novel biomarkers for a more precise use of anti-angiogenic compounds. To tackle this urgent clinical need, this proposal exploits an extensive collection of colorectal cancers molecularly annotated and serially propagated in immunocompromized mice (patient-derived xenografts). Patient-derived xenografts conserve the interindividual diversity and the genetic heterogeneity typical of the tumours of origin, combining the flexibility of preclinical analysis with the informative value of population-based studies. The clinical and vascular responses to anti-angiogenic regimens and their dependence on colorectal cancer genotype will be investigated by designing two clinical trials that reproduce the known pharmacodynamic activities of these compounds. The first evaluates the standard dose of anti-angiogenic regimens, which induces the tumour vascular shrinking, influences the tumour burden and the time to disease relapse. The second will consider the emerging concept that low doses of anti-angiogenic regimens normalize the function of tumour capillaries, ameliorate blood flow thus favouring the uptake of chemomotherapeutic agents. The transcriptomic analysis by massive next-generation sequencing approaches of responder patient-derived xenografts allows setting an integrated data set to discovery putative surrogate end-points to monitor the anti-angiogenic response in patients in the future.  The analysis   of these trials will permit to identify colorectal cancer molecular subtypes that best predict therapeutic responsiveness to anti-angiogenic regimens.

TECNOLOGIE IN POSSESSO DELL'U. O.

  • Phage display screening
  • Manipulation of murine ES cells
  • Culture of endothelial cells and smooth muscle cells isolated form different animal species and tissues.
  • Protein-protein intraction by FRET and FRAP technolgies
  • Murine models of transgenic oncogenesis
  • Genetic manipulation of chick embryo by retroviral and lentiviral vectors.
  • In silico modeling and cellular and sub-cellular scale
  • Technologies to study endocytosis
  • Quantitative and qualitative instruments to study in vitro and in vivo angiogenesis.
  • Assays to study cellular migration (video-lapse migration, chemotaxis, chemiokinesis, chemioinvasion)
  • Bioinformatic skills

STRUMENTAZIONE

Denominazione
Struttura ove la strumentazione è allocata
Responsabile della strumentazione
Confocal microscopy; FRET, video-lapse microscopy
Dipartimento di Scienze Oncologiche
Direttore del Dipartimento
FACS sorter facility
Dipartimento di Scienze Oncologiche
Direttore del Dipartimento
Cell culture facility BS3/P3 level
Dipartimento di Scienze Oncologiche
Direttore del Dipartimento

PUBBLICAZIONI

Bartolini A, Di Paolo D, Noghero A, Murgia D, Sementa AR, Cilli M, Pasqualini  R, Arap W, Bussolino F, Ponzoni M, Pastorino F, Marchiò S. The NeuronalPentraxin-2 Pathway Is an Unrecognized Target in Human Neuroblastoma, Which Also Offers Prognostic Value in Patients. Cancer Res. 2015 Oct 15;75(20):4265-71.

 

Armando Gagliardi P, Puliafito A, di Blasio L, Chianale F, Somale D, Seano G,  Bussolino F, Primo L. Real-time monitoring of cell protrusion dynamics by impedance responses. Sci Rep. 2015 May 15;5:10206.

 

di Blasio L, Gagliardi PA, Puliafito A, Sessa R, Seano G, *Bussolino F, *Primo L. PDK1 regulates focal adhesion disassembly by modulating endocytosis of αvβ3integrin. J Cell Sci. 2015 Mar 1;128(5):863-77.

 

Seano G, Chiaverina G, Gagliardi PA, di Blasio L, Puliafito A, Bouvard C, Sessa R, Tarone G, Sorokin L, Helley D, Jain RK, Serini G, Bussolino F, Primo L. Endothelial podosome rosettes regulate vascular branching in tumour angiogenesis. Nat Cell Biol. 2014 Oct;16(10):931-41,

 

Corà D, Astanina E, Giraudo E, Bussolino F. Semaphorins in cardiovascular medicine. Trends Mol Med. 2014 Oct;20(10):589-98.

 

Gagliardi PA, di Blasio L, Puliafito A, Seano G, Sessa R, Chianale F, Leung T,Bussolino F, Primo L. PDK1-mediated activation of MRCKα regulates directional cell migration and lamellipodia retraction. J Cell Biol. 2014 Aug

4;206(3):415-34.

 

Samarelli AV, Riccitelli E, Bizzozero L, Silveira TN, Seano G, Pergolizzi M, Vitagliano G, Cascone I, Carpentier G, Bottos A, Primo L, *Bussolino F, *Arese M. Neuroligin 1 induces blood vessel maturation by cooperating with the α6 integrin.J Biol Chem. 2014 Jul 11;289(28):19466-76.

 

Seano G, Chiaverina G, Gagliardi PA, di Blasio L, Sessa R, Bussolino F, Primo  L. Modeling human tumor angiogenesis in a three-dimensional culture system. Blood. 2013 May 23;121(21):e129-37.

 

Marchiò S, Soster M, Cardaci S, Muratore A, Bartolini A, Barone V, Ribero D, Monti M, Bovino P, Sun J, Giavazzi R, Asioli S, Cassoni P, Capussotti L, Pucci P, Bugatti A, Rusnati M, Pasqualini R, Arap W, Bussolino F. A complex of α6 integrin and E-cadherin drives liver metastasis of colorectal cancer cells through hepatic angiopoietin-like 6. EMBO Mol Med. 2012 Nov;4:1156-75.

 

Rissone A, Foglia E, Sangiorgio L, Cermenati S, Nicoli S, Cimbro S, Beltrame  M, *Bussolino F, Cotelli F, *Arese M. The synaptic proteins β-neurexin and neuroligin synergize with extracellular matrix-binding vascular endothelial growth factor a during zebrafish vascular development. Arterioscler Thromb Vasc Biol. 2012 Jul;32(7):1563-72.

 

Napione L, Pavan S, Veglio A, Picco A, Boffetta G, Celani A, Seano G, Primo L, Gamba A, Bussolino F. Unraveling the influence of endothelial cell density on  VEGF-A signaling. Blood. 2012 Jun 7;119(23):5599-607

 

Maione F, Capano S, Regano D, Zentilin L, Giacca M, Casanovas O, Bussolino F, Serini G, Giraudo E. Semaphorin 3A overcomes cancer hypoxia and metastatic dissemination induced by antiangiogenic treatment in mice. J Clin Invest. 2012 May;122(5):1832-48.

 

Meda C, Molla F, De Pizzol M, Regano D, Maione F, Capano S, Locati M, Mantovani A, Latini R, *Bussolino F, *Giraudo E. Semaphorin 4A exerts a proangiogenic effect by enhancing vascular endothelial growth factor-A expression in macrophages. J Immunol. 2012 Apr 15;188(8):4081-92.

 

Bottos A, Martini M, Di Nicolantonio F, Comunanza V, Maione F, Minassi A,Appendino G, *Bussolino F, *Bardelli A. Targeting oncogenicserine/threonine-protein kinase BRAF in cancer cells inhibits angiogenesis and abrogates hypoxia. Proc Natl Acad Sci U S A. 2012 Feb 7;109(6):E353-9.

 

Serio G, Margaria V, Jensen S, Oldani A, Bartek J, Bussolino F, Lanzetti L. Small GTPase Rab5 participates in chromosome congression and regulates localization of the centromere-associated protein CENP-F to kinetochores. Proc Natl Acad Sci U S A. 2011 Oct 18;108(42):17337-42.

BOLD: people belonging to the U.O.

*: equally contributed


DOTTORATI DI RICERCA

Componente U.O. Dottorato di Ricerca Coordinatore Sede
Federico Bussolino
Complexity in post genomic biology
F Bussolino
UNITO
Marco Arese
Biochimica e Biotecnologia cellulare
Dario Ghigo
UNITO

CONGRESSI C.I.B.

Congressi Partecipazione
CNB4

CNB5

CNB6

CNB7

CNB8

CNB9
CNB10