Little is known about the mechanisms that give rise to spontaneous changes in the genome or epigenome and how this may lead, in somatic cells, to increased cancer risk and loss of organ and tissue function with age.
We study genome and epigenome instability as a function of age in various model organisms, including mouse and fruit fly, and its consequences in terms of alterations in tissue-specific patterns of gene regulation.
We developed transgenic reporter systems in mouse and fruit fly, which allow us to determine tissue-specific frequencies of various forms of genome instability, e.g., point mutations, deletions, translocations.
Similarly, by using knockdown approaches we assess the effect of specific genes implicated in longevity and healthy aging, e.g., SOD, FOXO, SIR2, on genome integrity.
More recently, we have begun to assess global gene mutation and epimutation loads in normal and disease tissues of both animal models and humans using massively parallel sequencing approaches.