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Complete profile
Carlo VASCOTTO
DMED
Dipartimento di medicina
Ricercatore Universitario
BIOS-08/A
Biologia molecolare
- DMED Dipartimento di medicina
- Ricercatore Universitario
- BIOS-08/A Biologia molecolare
Curriculum vitae
Publications
Research
My research activities are focused on the role of mitochondria in tumorigenesis and tumor resistance.
One line of research is aimed at studying the mitochondrial nature of the DNA repair protein APE1. This protein has been primarily described as key component of the base excision repair (BER) pathway which is involved in maintenance of the genome stability. It is the only cellular protein that can process apurinic/apyrimidinic (AP) sites generated by DNA glycosylases. The localization of APE1 protein is eminently nuclear as it plays a key role in the repair of DNA via the BER pathway. However, it is also present within the mitochondrial matrix, as an essential component of the mtBER pathway. Importantly, APE1 translocates into mitochondria in response to oxidative stress, increasing the mtDNA repair rate and therefore promoting cell survival. Our studies are aimed at characterize the molecular mechanisms involved in its the translocation and how accumulation within the mitochondrial compartment correlate with tumor resistance.
A second line of research is focused on the characterization of the mitochondrial import pathway MIA. This pathway is responsible for the translocation of proteins within the inner membrane space and it has been described to be upregulated in tumors. So far, the majority of studies on MIA pathway have been done in yeast; we are currently characterizing the pathway and its substrates in human cell lines and developing a peptide-based approach to inhibit it functionality.
A third line of research recently activated is aimed at the characterization of the molecular mechanisms involved in the degradation processes of damaged mitochondrial RNA. As DNA, also RNA is subjected to oxidative damages that can compromise the functionality of these molecules. Mitochondria is the major cellular source of reactive oxygen species (ROS) that react and damage biological molecules such as nucleic acids, proteins and lipids. Damage of mitochondrial RNA led at the stall of ribosome compromising mitochondrial encoded protein translation. We are currently investigating which are the proteins involved in the recognition of damaged RNA, and the mechanisms of RNA degradation. Moreover, we are also characterizing which are the signals that change the mitochondrial translation and the cytosolic translation and import of the nuclear-encoded subunits of the respiratory chain to balance the absence of the mitochnodrial-encoded subunits.
Research groups
- Group member: Biologia molecolare e cellulare del cancro
- Group member: Biochimica, ormoni e cancro