Molecular Mechanisms of Cancer and Aging
Our group has traditionally focused on the elucidation of molecular and biological mechanisms of tumorigenesis, focusing on myeloid leukemia and breast cancer. We have i) identified and characterized several AML-associated genetic alterations (PML-RARa; NPMc+); ii) defined biological mechanisms of tumorigenesis (for example their effect on chromatin) and iii) exploited our findings for the development of novel targeted treatments (retinoic acid, HDAC inhibitors, Lysine demethylase inhibitors). Furthermore, we have defined the underlying molecular (p53 and p21) and biological (symmetric vs asymmetric division) mechanisms contributing to CSC pool maintenance.
More recently, our group has been focusing on the analysis of intratumor heterogeneity, particularly on the study of adaptive responses, with the aim of defining its role during tumor progression and treatment resistance.
Major emphasis is given to explore mechanisms of accumulation of DNA damage in cancer cells.
A parallel line of investigation focuses on the role of the aging gene p66, which we discovered in 1999 as being involved in the regulation of oxidative stress response.
Most Relevant Publications
A rare subset of primary tumor cells with concomitant hyper-activation of extracellular matrix remodeling and dsRNA-IFN1 signaling metastasizes in breast cancer.
Cancer Res, 2023
High-resolution Nanopore methylome-maps reveal random hyper-methylation at CpG-poor regions as driver of chemoresistance in leukemias.
Commun Biol, 2023
Aberrant activation of p53/p66Shc-mInsc axis increases asymmetric divisions and attenuates proliferation of aged mammary stem cells.
Cell Death Differ, 2022
Release of paused RNA polymerase II at specific loci favors DNA double-strand-break formation and promotes cancer translocations.
Nat Genet, 2019
Alfredo Errico Provenzano
PhD Student Bioinformatician