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CHIARA RAMPAZZO

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Position

Professoressa Associata

Structure

Dipartimento di Biologia - DiBio

Address

VIALE GIUSEPPE COLOMBO, 3 - VIA UGO BASSI, 58/B - PADOVA

Telephone

0498276456

E-mail

chiara.rampazzo.1@unipd.it


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.


Notices

Office hours

  • Tuesday from 10:30 to 12:30
    at Dipartimento di Biologia 5° piano sud

Teachings

Publications

Publications (last 10 years)

G Santinon, I Brian I, A Pocaterra, P Romani, E Franzolin, C Rampazzo, A Bicciato, and S. Dupont (2018) “dNTP metabolism links YAP/TAZ and mechanical cues to cell growth and oncogene-induced senescence” EMBO Journal. e97780.

D Pajalunga, E Franzolin, M Stevanoni, S Zribi, N Passaro, A Gurtner, S Donsante, D Loffredo, L Losanno, V Bianchi, A Russo, C Rampazzo and M Crescenzi (2017) “A defective dNTP pool hinders DNA replication in cell cycle-reactivated terminally differentiated muscle cells.” Cell Death and Differentiation, 24(5):774-784.

C Rampazzo, MG Tozzi, C Dumontet, L P Jordheim (2016) “The druggability of intracellular nucleotide degrading enzymes”. Cancer Chemotherapy and Pharmacology 77: 883-893.

E Franzolin, C Salata, V Bianchi, C Rampazzo (2015) “The Deoxynucleoside Triphosphate Triphosphohydrolase Activity of SAMHD1 Protein Contributes to the Mitochondrial DNA Depletion Associated with Genetic Deficiency of Deoxyguanosine Kinase”. Journal of Biological Chemistry 290:25986-96.

C Miazzi, P Ferraro, G Pontarin, C Rampazzo, P Reichard, and V Bianchi (2014) “Allosteric regulation of the human and mouse deoxyribonucleotide triphosphohydrolase sterile α-motif /histidine-aspartate domain containing protein 1 (SAMHD1)” Journal of Biological Chemistry 289: 18339-18346.

E. Franzolin, G. Pontarin, C. Rampazzo, C. Miazzi, P Ferraro, E. Palumbo, P. Reichard and V. Bianchi (2013) “The deoxynucleotide triphosphohydrolase SAMHD1 is a major regulator of DNA precursor pools in mammalian cells” Proceedings of the National Academy of Sciences of the United States of America 110:14272-7.

M. Frangini, E. Franzolin, F. Chemello, P. Laveder, C. Romualdi, V. Bianchi and C. Rampazzo (2013) “Synthesis of mitochondrial DNA precursors during myogenesis, an analysis in purified C2C12 myotubes” Journal of Biological Chemistry 288: 5624-5635.

E. Franzolin, C. Miazzi, M. Frangini, E. Palumbo, C. Rampazzo, V. Bianchi (2012) “The pyrimidine nucleotide carrier PNC1 and mitochondrial trafficking of thymidine phosphates in cultured human cells”. Experimental Cell Research 318: 2226-2236.

G. Pontarin, P. Ferraro, C. Rampazzo, G. Kollberg, E. Holme, P.Reichard, V. Bianchi (2011) “Deoxyribonucleotide metabolism in cycling and resting human fibroblasts with a missense mutation in p53R2, a subunit of ribonucleotide reductase”. Journal of Biological Chemistry 286:11132-40.

C. Rampazzo, C. Miazzi, E. Franzolin, G. Pontarin, P. Ferraro, M. Frangini, P. Reichard, V Bianchi. (2010) “Regulation by degradation, a cellular defence against deoxyribonucleotide pool imbalances”. Mutation Research 703: 2-10.

M. Frangini, C. Rampazzo, E. Franzolin, MC. Lara, MR. Vilà, R. Martí, V. Bianchi. (2009) “Unchanged thymidine triphosphate pools and thymidine metabolism in two lines of thymidine kinase 2-mutated fibroblasts”. FEBS Journal. 276: 1104-1113.

G. Pontarin, A. Fijolek, P. Pizzo, P. Ferraro, C. Rampazzo, T. Pozzan, L. Thelander, P. Reichard, V. Bianchi (2008) “ Ribonucleotide reduction is a cytosolic process in mammalian cells independently of DNA damage” Proceedings of the National Academy of Sciences of the United States of America 105: 17801-17806.

C. Rampazzo, S. Fabris, E. Franzolin, K. Crovatto, M Frangini, and V. Bianchi “ Mitochondrial thymidine kinase and the enzymatic network regulating thymidine triphosphate pools in cultured human cells” (2007) Journal of Biological Chemistry 282: 3

Research Area

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.

Thesis proposals

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.