The transcriptional programs triggered by p53 during tumor suppression and in response to DNA damage remain to be clarified. Using whole genome mapping of p53 binding and gene expression profiling, we investigated the transcriptional circuitry induced by p53 in suppressing cancer development and in response to genotoxic injury. We studied the progression of Myc-induced lymphomas in Eμ-myc transgenic mice, as well as the regression of these lymphomas following restoration of p53 function, by either pharmacological or genetic means. In parallel, we determined the p53-dependent transcriptional program in splenic cells from mice exposed to ionizing radiation. We thus expanded our understanding of the p53 response to oncogenic and genotoxic stress and identified a set of novel components of the p53 transcriptional program. Currently, we are testing the impact of these new p53 target genes on tumorigenesis using an RNA interference (RNAi)-based functional genetic screen. Altogether our data represent an extensive characterization of the p53-regulated network in response to different stimuli and will hopefully highlight new tumor suppressive mechanisms, paving the way for their therapeutic application.

GENOME-WIDE ANALYSIS OF P53-DEPENDENT PROGRAMS IN TUMOR SUPPRESSION / C. Tonelli ; added supervisor: S. Campaner ; internal advisor: G. Natoli; external advisor: K.H. Vousden. - : . UNIVERSITA' DEGLI STUDI DI MILANO, 2015 Mar 18. ((26. ciclo, Anno Accademico 2014. [10.13130/tonelli-claudia_phd2015-03-18].

GENOME-WIDE ANALYSIS OF P53-DEPENDENT PROGRAMS IN TUMOR SUPPRESSION

C. Tonelli
2015

Abstract

The transcriptional programs triggered by p53 during tumor suppression and in response to DNA damage remain to be clarified. Using whole genome mapping of p53 binding and gene expression profiling, we investigated the transcriptional circuitry induced by p53 in suppressing cancer development and in response to genotoxic injury. We studied the progression of Myc-induced lymphomas in Eμ-myc transgenic mice, as well as the regression of these lymphomas following restoration of p53 function, by either pharmacological or genetic means. In parallel, we determined the p53-dependent transcriptional program in splenic cells from mice exposed to ionizing radiation. We thus expanded our understanding of the p53 response to oncogenic and genotoxic stress and identified a set of novel components of the p53 transcriptional program. Currently, we are testing the impact of these new p53 target genes on tumorigenesis using an RNA interference (RNAi)-based functional genetic screen. Altogether our data represent an extensive characterization of the p53-regulated network in response to different stimuli and will hopefully highlight new tumor suppressive mechanisms, paving the way for their therapeutic application.
AMATI, BRUNO
p53; tumor suppression; NGS technologies
Settore BIO/11 - Biologia Molecolare
GENOME-WIDE ANALYSIS OF P53-DEPENDENT PROGRAMS IN TUMOR SUPPRESSION / C. Tonelli ; added supervisor: S. Campaner ; internal advisor: G. Natoli; external advisor: K.H. Vousden. - : . UNIVERSITA' DEGLI STUDI DI MILANO, 2015 Mar 18. ((26. ciclo, Anno Accademico 2014. [10.13130/tonelli-claudia_phd2015-03-18].
Doctoral Thesis
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/257874
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