CHIARA RAMPAZZO Associate Professor of Cell Biology Department of Biology, University of Padova Academic Positions 2017–present: Associate Professor of Cell Biology, University of Padova 2004–2017: Researcher in Cell Biology, University of Padova 1999–2003: Research Fellow, University of Padova Education and Fellowships 1996–1998: PhD in Evolutionary Biology, University of Padova 1995: Erasmus Fellowship, Department of Genetics, University of Stockholm, Sweden 1994: Laurea in Biological Sciences, University of Padova 1997 & 1998: EMBO Short-Term Fellowships, Department of Biochemistry, Karolinska Institute, Stockholm, Sweden Scientific Profile CR developed an interest in the regulation of DNA precursors (dNTPs) in mammalian cells during her Erasmus fellowship at Stockholm University. Her early work focused on the enzymes involved in dNTP de novo synthesis and salvage during the cell cycle, before turning to the study of 5′-nucleotidases. In 1999, she discovered the first known mitochondrial deoxynucleotidase (mdN), which functions within an intramitochondrial substrate cycle to regulate dTTP synthesis. She later demonstrated that the susceptibility of nucleotide analogs to dephosphorylation by 5′-nucleotidases serves as a predictive factor of their efficacy in anticancer and antiviral therapies. Her research has since explored the mechanisms that maintain dNTP pool balance in both the cytosol and mitochondria of proliferating and quiescent cells. In studies on muscle cell differentiation, she found that de novo thymidylate synthesis is markedly downregulated, suggesting that tight control of dTTP production is essential for maintaining the non-proliferative state of differentiated cells. Over the past decade, she has focused on SAMHD1, the most recently identified dNTP-catabolizing enzyme. Although nuclear, SAMHD1 influences cytosolic and mitochondrial dNTP pools through its triphosphohydrolase activity. Using fibroblasts from patients with Aicardi–Goutières syndrome and SAMHD1-deficient cancer cell lines, she demonstrated that loss of SAMHD1 causes dNTP imbalances that promote genome instability in non-transformed cells and affect telomere homeostasis—unveiling a novel link between nucleotide metabolism and genome maintenance.

Curriculum PDF File

Regulation of DNA precursors in mammalian cells during proliferation and quiescence: implications for the stability of the nuclear and mitochondrial genomes in health and disease. Disturbances of the relative concentrations and the dynamics of DNA precursor (dNTP) pools affect the accuracy and efficiency of DNA synthesis. Main effects are increased frequency of mutations, structural alterations of chromosomes, destabilization or depletion of the mitochondrial genome. We study the mechanisms that keep dNTP pools in tune with the needs of nuclear and mitochondrial DNA replication and repair. The enzyme network includes both synthetic and catabolic enzymes and we analyze their functional interactions in cultured mammalian cells.

Relationships between telomere metabolism and dNTP pool sizes. The aim of the project is to examine the effect of dNTP imbalance on telomere length by quantitative fluorescence in situ hybridization (Q-FISH) and quantitative PCR. Deoxynucleotide imbalance and mtDNA stability in mammalian cells. The aim of the project is to understand cellular mechanisms for the maintenance of mtDNA integrity and copy number by Next Generation Sequencing and quantitative PCR.

Last update: 02/07/2025