Obiettivo Background: Our recent studies implicate p53 in gut tissue homeostasis - suppressing epithelial invasion. This function is tightly linked to suppression of a gene cluster (PSIS- p53-Suppressed Invasiveness Signature), which requires Wnt activation and other cues, yet is only expressed upon loss of p53. The invasive signature explains a broad spectrum of the invasiveness property, from the loss of enterocyte polarity to matrix degradation, pointing to a concerted action. We documented a tight association between invasiveness and coexpression of several PSIS genes in different mouse models and showed that PSIS expression is essential in mediating epithelial cell invasiveness following p53 depletion.Goal: Elucidate functions of p53 activation which are of particular importance for epithelial tissues. Understand how WT p53 contributes to preserving epithelial boundaries, prohibiting invasion and abnormal cell mixture and controlling stem cell dynamics under tissue stress.Methodology: We will investigate the epithelial role of p53 and the invasive signature genes in several mouse models of inflammatory bowel diseases and intestinal cancer. These models will incorporate p53-modulating switchable genetic elements and cell-tracking genetic markers for monitoring tissue dynamics. Analyses of relevant human pathology samples will complement the mouse studies.Significance: Invasion is a defining hallmark of malignancy and understanding early invasion of tumor cells is of fundamental importance in designing future therapies for cancer - targeting PSIS is an example. PSIS database may also be used to develop biomarkers for distinguishing malignant tumors from benign ones, a critical determinant of therapeutic options in several types of cancers, currently solely based on morphologic assessment. A molecular definition of early invasive lesions may allow early implementation of curative treatments while withholding patient overtreatment which often results in serious morbidity. Campo scientifico medical and health sciencesclinical medicinegastroenterologyinflammatory bowel diseasemedical and health sciencesmedical biotechnologycells technologiesstem cellsmedical and health sciencesclinical medicineoncologymedical and health sciencesbasic medicinepathologymedical and health sciencesbasic medicinephysiologyhomeostasis Programma(i) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Argomento(i) ERC-AG-LS4 - ERC Advanced Grant - Physiology, Pathophysiology and Endocrinology Invito a presentare proposte ERC-2011-ADG_20110310 Vedi altri progetti per questo bando Meccanismo di finanziamento ERC-AG - ERC Advanced Grant Istituzione ospitante THE HEBREW UNIVERSITY OF JERUSALEM Contributo UE € 2 499 999,60 Indirizzo EDMOND J SAFRA CAMPUS GIVAT RAM 91904 Jerusalem Israele Mostra sulla mappa Tipo di attività Higher or Secondary Education Establishments Contatto amministrativo Hani Ben-Yehuda (Mr.) Ricercatore principale Yinon Ben Neriah (Prof.) Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Costo totale Nessun dato Beneficiari (1) Classifica in ordine alfabetico Classifica per Contributo UE Espandi tutto Riduci tutto THE HEBREW UNIVERSITY OF JERUSALEM Israele Contributo UE € 2 499 999,60 Indirizzo EDMOND J SAFRA CAMPUS GIVAT RAM 91904 Jerusalem Mostra sulla mappa Tipo di attività Higher or Secondary Education Establishments Contatto amministrativo Hani Ben-Yehuda (Mr.) Ricercatore principale Yinon Ben Neriah (Prof.) Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Costo totale Nessun dato
