Carlo Vascotto, PhD

Group Leader

Laboratory of Mitochondrial Nucleic Acids
ORCID ID: 0000-0003-4431-029X

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Research interests

Mitochondria are the primary endogenous source of reactive oxygen species (ROS): highly reactive molecules that can modify proteins, lipids, and nucleic acids. To ensure the stability of mitochondrial DNA and the functionality of transcription and translation processes, cells have evolved repair mechanisms and signaling pathways to detect and respond to ROS production.

In the Laboratory of Molecular Biology, we study the molecular mechanisms responsible for the repair of mtDNA lesions, the degradation processes of damaged mitochondrial mRNAs, and the characterization of mitochondrial-nucleus crosstalk in the regulation of mitochondrial functions.

Members of the group

NameSurnameDegreeE-mail
SzymonBalińskis.balinski@imol.institute
VeronicaBazzaniPhDv.bazzani@imol.institute
MaraEquisoain Redinm.equisoainredin@imol.institute
EveHardinge.harding@imol.institute
JoshuaMcHalej.mchale@imol.institute
ŁukaszMilewskil.milewski@imol.institute
CarloVascottoPhDc.vascotto@imol.institute

Publications

2024
  • Xu, P., Yang, T., Kundnani, D. L., Sun, M., Marsili, S., Gombolay, A. L., Jeon, Y., Newnam, G., Balachander, S., Bazzani, V., Baccarani, U., Park, V. S., Tao, S., Lori, A., Schinazi, R. F., Kim, B., Pursell, Z. F., Tell, G., Vascotto, C., & Storici, F. (2024). Light-strand bias and enriched zones of embedded ribonucleotides are associated with DNA replication and transcription in the human-mitochondrial genome. Nucleic acids research, 52(3), 1207–1225. https://doi.org/10.1093/nar/gkad1204
2023
  • Sbai, O., Bazzani, V., Tapaswi, S., McHale, J., Vascotto, C., & Perrone, L. (2023). Is Drp1 a link between mitochondrial dysfunction and inflammation in Alzheimer’s disease?. Frontiers in molecular neuroscience, 16, 1166879. https://doi.org/10.3389/fnmol.2023.1166879
2022
  • Bazzani, V., Equisoain Redin, M., McHale, J., Perrone, L., Vascotto, C. Mitochondrial DNA Repair in Neurodegenerative Diseases and Ageing. Int J Mol Sci. 2022 Sep 27;23(19):11391. doi: 10.3390/ijms231911391.
  • Sbai, O., Djelloul, M., Auletta, A., Ieraci, A., Vascotto, C., Perrone, L. RAGE-TXNIP axis drives inflammation in Alzheimer’s by targeting Aβ to mitochondria in microglia. Cell Death Dis. 2022 Apr 19;13(4):368. doi: 10.1038/s41419-022-04840-7.

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2021
  • Bazzani, V., Pravisani, R., Baccarani, U., Vascotto, C. Hepatocellular Carcinoma: Diagnosis, Therapy and Molecular Investigations. pp.60-65. J Cancer Immunology. 2021 vol. 3 (1). doi:10.33696/cancerimmunol.3.042.
  • Barchiesi, A., Bazzani, V., Jabczynska, A., Borowski, L. S., Oeljeklaus, S., Warscheid, B., Chacinska, A., Szczesny R. J., Vascotto, C. (2021). DNA Repair Protein APE1 Degrades Dysfunctional Abasic mRNA in Mitochondria Affecting Oxidative Phosphorylation. Journal of Molecular Biology, 433(18):167125. DOI: 10.1016/j.jmb.2021.167125.
    • 2020
    • Barchiesi A, Bazzani V, Elancheliyan P, Wasilewski M, Chacinska A, Vascotto C. Mitochondrial oxidative stress induces IMS/matrix translocation of APE1 through TIM23/PAM complex. J Mol Biol. 2020 Dec 4;432(24):166713. doi: 10.1016/j.jmb.2020.11.012.
    • Bazzani V, Barchiesi A, Radecka D, Pravisani R, Guadagno A, Di Loreto C, Baccarani U, Vascotto C. Mitochondrial Apurinic/Apyrimidinic Endonuclease 1 enhances mtDNA repair contributing to cell proliferation and mitochondrial integrity in early stages of hepatocellular carcinoma. BMC-Cancer. 2020 Oct 7;20(1):969. doi: 10.1186/s12885-020-07258-6.
    2019
    • Barchiesi A and Vascotto C. Transcription, Processing, and Decay of Mitochondrial RNA in Health and Disease. Int J Mol Sci. 2019 May 6;20(9). pii: E2221. doi: 10.3390/ijms20092221. Review.
    2017
    • Barchiesi A, Baccarani U, Billack B, Tell G, Vascotto C. [Letter to the Editor] Isolation of mitochondria is necessary for precise quantification of mitochondrial DNA damage in human carcinoma samples. Biotechniques. 2017 Jan 1;62(1):13-17. doi: 10.2144/000114491.
    2016
    • Baldan F, Mio C, Allegri L, Conzatti K, Toffoletto B, Puppin C, Radovic S, Vascotto C, Russo D, Di Loreto C, Damante G. Identification of tumorigenesis-related mRNAs associated with RNA-binding protein HuR in thyroid cancer cells. Oncotarget. 2016 Sep 27;7(39):63388-63407. doi: 10.18632/oncotarget.11255.
    • Poletto M, Malfatti MC, Dorjsuren D, Scognamiglio PL, Marasco D, Vascotto C, Jadhav A, Maloney DJ, Wilson DM 3rd, Simeonov A, Tell G. Inhibitors of the apurinic/apyrimidinic endonuclease 1 (APE1)/nucleophosmin (NPM1) interaction that display anti-tumor properties. Mol Carcinog. 2016 May;55(5):688-704. doi: 10.1002/mc.22313.
    2015
    • Di Maso V, Mediavilla MG, Vascotto C, Lupo F, Baccarani U, Avellini C, Tell G, Tiribelli C, Crocè LS. Transcriptional Up-Regulation of APE1/Ref-1 in Hepatic Tumor: Role in Hepatocytes Resistance to Oxidative Stress and Apoptosis. PLoS One. 2015 Dec 1;10(12):e0143289. doi: 10.1371/journal.pone.0143289.
    • Barchiesi A, Wasilewski M, Chacinska A, Tell G, Vascotto C. Mitochondrial translocation of APE1 relies on the MIA pathway. Nucleic Acids Res. 2015 Jun 23;43(11):5451-64. doi: 10.1093/nar/gkv433.
    • Bortolussi G, Codarin E, Antoniali G, Vascotto C, Vodret S, Arena S, Cesaratto L, Scaloni A, Tell G, Muro AF. Impairment of enzymatic antioxidant defenses is associated with bilirubin-induced neuronal cell death in the cerebellum of Ugt1 KO mice. Cell Death Dis. 2015 May 7;6:e1739. doi: 10.1038/cddis.2015.113.
    2014
    • Avolio E, Gianfranceschi G, Cesselli D, Caragnano A, Athanasakis E, Katare R, Meloni M, Palma A, Barchiesi A, Vascotto C, Toffoletto B, Mazzega E, Finato N, Aresu G, Livi U, Emanueli C, Scoles G, Beltrami CA, Madeddu P, Beltrami AP. Ex vivo molecular rejuvenation improves the therapeutic activity of senescent human cardiac stem cells in a mouse model of myocardial infarction. Stem Cells. 2014 Sep;32(9):2373-85. doi: 10.1002/stem.1728
    • Domenis R, Bergamin N, Gianfranceschi G, Vascotto C, Romanello M, Rigo S, Vagnarelli G, Faggiani M, Parodi P, Kelley MR, Beltrami CA, Cesselli D, Tell G, Beltrami AP. The redox function of APE1 is involved in the differentiationprocess of stem cells toward a neuronal cell fate. PLoS One. 2014 Feb19;9(2):e89232. doi: 10.1371/journal.pone.0089232.
    • Londero AP, Orsaria M, Tell G, Marzinotto S, Capodicasa V, Poletto M, Vascotto C, Sacco C, Mariuzzi L. Expression and prognostic significance of APE1/Ref-1 and NPM1 proteins in high-grade ovarian serous cancer. Am J Clin Pathol. 2014Mar;141(3):404-14. doi: 10.1309/AJCPIDKDLSGE26CX.
    • Antoniali G, Lirussi L, D’Ambrosio C, Dal Piaz F, Vascotto C, Casarano E, Marasco D, Scaloni A, Fogolari F, Tell G. SIRT1 gene expression upon genotoxic damage is regulated by APE1 through nCaRE-promoter elements. Mol Biol Cell. 2014 Feb;25(4):532-47. doi: 10.1091/mbc.E13-05-0286.
    • Romanello M, Piatkowska E, Antoniali G, Cesaratto L, Vascotto C, Iozzo RV, Delneri D, Brancia FL. Osteoblastic cell secretome: a novel role for progranulin during risedronate treatment. Bone. 2014 Jan;58:81-91. doi:10.1016/j.bone.2013.10.003
    2013
    • Tell G, Di Piazza M, Kamocka MM, Vascotto C. Combining RNAi and in vivo confocal microscopy analysis of the photoconvertible fluorescent protein Dendra2 to study a DNA repair protein. Biotechniques. 2013 Oct;55(4):198-203. doi:10.2144/000114088.
    • Cesaratto L, Codarin E, Vascotto C, Leonardi A, Kelley MR, Tiribelli C, TellG. Specific inhibition of the redox activity of ape1/ref-1 by e3330 blocks TNF-α-induced activation of IL-8 production in liver cancer cell lines. PLoS One. 2013 Aug 15;8(8):e70909. doi: 10.1371/journal.pone.0070909.
    • Vascotto C, Lirussi L, Poletto M, Tiribelli M, Damiani D, Fabbro D, Damante G, Demple B, Colombo E, Tell G. Functional regulation of the apurinic/apyrimidinic endonuclease 1 by nucleophosmin: impact on tumor biology. Oncogene. 2013 Jul 8.doi: 10.1038/onc.2013.251.
    • Poletto M, Vascotto C, Scognamiglio PL, Lirussi L, Marasco D, Tell G. Role of the unstructured N-terminal domain of the hAPE1 (human apurinic/apyrimidinic endonuclease 1) in the modulation of its interaction with nucleic acids and NPM1 (nucleophosmin). Biochem J. 2013 Jun 15;452(3):545-57. doi: 10.1042/BJ20121277.
    • Marasco D, Ruggiero A, Vascotto C, Poletto M, Scognamiglio PL, Tell G,Vitagliano L. Role of mutual interactions in the chemical and thermal stability of nucleophosmin NPM1 domains. Biochem Biophys Res Commun. 2013 Jan11;430(2):523-8. doi: 10.1016/j.bbrc.2012.12.002.
    • Tell G, Vascotto C, Tiribelli C. Alterations in the redox state and liver damage: hints from the EASL Basic School of Hepatology. J Hepatol. 2013Feb;58(2):365-74. doi: 10.1016/j.jhep.2012.09.018.
    2012
    • Lirussi L, Antoniali G, Vascotto C, D’Ambrosio C, Poletto M, Romanello M, Marasco D, Leone M, Quadrifoglio F, Bhakat KK, Scaloni A, Tell G. Nucleolar accumulation of APE1 depends on charged lysine residues that undergo acetylation upon genotoxic stress and modulate its BER activity in cells. Mol Biol Cell. 2012Oct;23(20):4079-96. doi: 10.1091/mbc.E12-04-0299.
    • Li M, Vascotto C, Xu S, Dai N, Qing Y, Zhong Z, Tell G, Wang D. Human AP endonuclease/redox factor APE1/ref-1 modulates mitochondrial function after oxidative stress by regulating the transcriptional activity of NRF1. Free Radic Biol Med. 2012 Jul 15;53(2):237-48. doi: 10.1016/j.freeradbiomed.2012.04.002.
    2011
    • Vascotto C, Bisetto E, Li M, Zeef LA, D’Ambrosio C, Domenis R, Comelli M, Delneri D, Scaloni A, Altieri F, Mavelli I, Quadrifoglio F, Kelley MR, Tell G. Knock-in reconstitution studies reveal an unexpected role of Cys-65 in regulatingAPE1/Ref-1 subcellular trafficking and function. Mol Biol Cell. 2011Oct;22(20):3887-901. doi: 10.1091/mbc.E11-05-0391.

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    2010
    • Fantini D, Vascotto C, Marasco D, D’Ambrosio C, Romanello M, Vitagliano L, Pedone C, Poletto M, Cesaratto L, Quadrifoglio F, Scaloni A, Radicella JP, Tell G. Critical lysine residues within the overlooked N-terminal domain of human APE1 regulate its biological functions. Nucleic Acids Res. 2010 Dec;38(22):8239-56. doi: 10.1093/nar/gkq691.
    2009
    • Vascotto C, Fantini D, Romanello M, Cesaratto L, Deganuto M, Leonardi A, Radicella JP, Kelley MR, D’Ambrosio C, Scaloni A, Quadrifoglio F, Tell G. APE1/Ref-1 interacts with NPM1 within nucleoli and plays a role in the rRNA quality control process. Mol Cell Biol. 2009 Apr;29(7):1834-54. doi: 10.1128/MCB.01337-08.
    • Vascotto C, Cesaratto L, Zeef LA, Deganuto M, D’Ambrosio C, Scaloni A, Romanello M, Damante G, Taglialatela G, Delneri D, Kelley MR, Mitra S, Quadrifoglio F, Tell G. Genome-wide analysis and proteomic studies reveal APE1/Ref-1 multifunctional role in mammalian cells. Proteomics. 2009 Feb;9(4):1058-74. doi: 10.1002/pmic.200800638.
    2008
    • Codutti L, van Ingen H, Vascotto C, Fogolari F, Corazza A, Tell G, Quadrifoglio F, Viglino P, Boelens R, Esposito G. The solution structure of DNA-free Pax-8 paired box domain accounts for redox regulation of transcriptional activity in the pax protein family. J Biol Chem. 2008 Nov 28;283(48):33321-8. doi: 10.1074/jbc.M805717200.
    • Iannetti A, Pacifico F, Acquaviva R, Lavorgna A, Crescenzi E, Vascotto C, Tell G, Salzano AM, Scaloni A, Vuttariello E, Chiappetta G, Formisano S, Leonardi A. The neutrophil gelatinase-associated lipocalin (NGAL), a NF-kappaB-regulated gene, is a survival factor for thyroid neoplastic cells. Proc Natl Acad Sci U S A. 2008 Sep 16;105(37):14058-63. doi: 10.1073/pnas.0710846105.
    • Fantini D, Vascotto C*, Deganuto M, Bivi N, Gustincich S, Marcon G, Quadrifoglio F, Damante G, Bhakat KK, Mitra S, Tell G. APE1/Ref-1 regulates PTEN expression mediated by Egr-1. Free Radic Res. 2008 Jan;42(1):20-9. doi: 10.1080/10715760701765616. [*: co-first author author]
    2007
    • Avellini C, Baccarani U, Trevisan G, Cesaratto L, Vascotto C, D’Aurizio F, Pandolfi M, Adani GL, Tell G. Redox proteomics and immunohistology to study molecular events during ischemia-reperfusion in human liver. Transplant Proc. 2007 Jul-Aug;39(6):1755-60.
    • Cesaratto L, Calligaris SD, Vascotto C, Deganuto M, Bellarosa C, Quadrifoglio F, Ostrow JD, Tiribelli C, Tell G. Bilirubin-induced cell toxicity involves PTEN activation through an APE1/Ref-1-dependent pathway. J Mol Med (Berl). 2007 Oct;85(10):1099-112.
    • Pacifico F, Paolillo M, Chiappetta G, Crescenzi E, Arena S, Scaloni A, Monaco M, Vascotto C, Tell G, Formisano S, Leonardi A. RbAp48 is a target of nuclear factor-kappaB activity in thyroid cancer. J Clin Endocrinol Metab. 2007 Apr;92(4):1458-66.
    • Vascotto C, Salzano AM, D’Ambrosio C, Fruscalzo A, Marchesoni D, di Loreto C, Scaloni A, Tell G, Quadrifoglio F. Oxidized transthyretin in amniotic fluid as an early marker of preeclampsia. J Proteome Res. 2007 Jan;6(1):160-70.
    2006
    • Pines A, Bivi N, Vascotto C, Romanello M, D’Ambrosio C, Scaloni A, Damante G, Morisi R, Filetti S, Ferretti E, Quadrifoglio F, Tell G. Nucleotide receptors stimulation by extracellular ATP controls Hsp90 expression through APE1/Ref-1 in thyroid cancer cells: a novel tumorigenic pathway. J Cell Physiol. 2006 Oct;209(1):44-55.
    • Vascotto C, Cesaratto L, D’Ambrosio C, Scaloni A, Avellini C, Paron I, Baccarani U, Adani GL, Tiribelli C, Quadrifoglio F, Tell G. Proteomic analysis of liver tissues subjected to early ischemia/reperfusion injury during human orthotopic liver transplantation. Proteomics. 2006 Jun;6(11):3455-65.
    • Salzano AM, Paron I, Pines A, Bachi A, Talamo F, Bivi N, Vascotto C, Damante G, Quadrifoglio F, Scaloni A, Tell G. Differential proteomic analysis of nuclear extracts from thyroid cell lines. J Chromatogr B Analyt Technol Biomed Life Sci. 2006 Mar 20;833(1):41-50.
    2005
    • Risso A, Tell G, Vascotto C, Costessi A, Arena S, Scaloni A, Cosulich ME. Activation of human T lymphocytes under conditions similar to those that occur during exposure to microgravity: a proteomics study. Proteomics. 2005 May;5(7):1827-37.
    • Cesaratto L, Vascotto C, D’Ambrosio C, Scaloni A, Baccarani U, Paron I, Damante G, Calligaris S, Quadrifoglio F, Tiribelli C, Tell G. Overoxidation of peroxiredoxins as an immediate and sensitive marker of oxidative stress in HepG2 cells and its application to the redox effects induced by ischemia/reperfusion in human liver. Free Radic Res. 2005 Mar;39(3):255-68.
    2004
    • Cesaratto L, Vascotto C, Calligaris S, Tell G. The importance of redox state in liver damage. Ann Hepatol. 2004 Jul-Sep;3(3):86-92. Review.
    Book chapters
    • Vascotto C, Poletto M, Tell G. Understanding the basic for translating the base excision repair pathway from benchtop to bedside in cancer treatment. In: DNA Repair in Cancer Therapy: Molecular Targets and Clinical Applications. Second Edition, 2016. p. 83-114, ISBN: 978-0-12-803582-5.
    • Vascotto C*, Tiribelli C. Oxidative stress, antioxidant defenses and the liver. In: Studies on Hepatic Disorders. 2015. p. 41-64, ISBN: 9783319155388. [*: corresponding author]
    • Fishel M, Vascotto C, Kelley MR. Novel Base Excision Repair Therapeutics: APE1 focus and a brief summary of other BER targets. In: DNA Repair and Cancer: From Bench to Clinic. 2013. p. 233–287, ISBN: 1466577436.
    • Vascotto C, Fishel ML. Blockade of Base Excision Repair: Inhibition of Small Lesions Results in Big Consequences to Cancer Cells. In: DNA Repair in Cancer Therapy: Molecular Targets and Clinical Applications. 2011, p. 29-53, ISBN: 9780123849991.

    About Group Leader

    Dr. Carlo Vascotto received his PhD in Biomedical and Biotechnological Sciences at the University of Udine (Italy), where he studied the molecular mechanisms controlling the cellular response to oxidative stress. In 2006, he joined the laboratories of Prof. Sankar Mitra at the University of Texas Medical Branch (USA) as a visiting student, where he studied the mechanisms of genome damage, its repair and its impact on carcinogenesis and cancer. In 2011, he established an independent research group at the Department of Medicine of the University of Udine, focusing on the stability of the mitochondrial genome and its role in tumorigenesis and tumor progression. As a Visiting Professor from 2017 to 2019 at the Center of New Technologies of the University of Warsaw (Poland), he expanded his research interests in mitochondrial protein trafficking. In spring 2023, he joined IMol PAS as a group leader of the Laboratory of Molecular Biology.

    Memberships and awards

    2010
    • Fulbright Fellowship
    2017-2019
    • MSCA Fellowship

    Funding

    2022-2026
    • HE-MSCA-DN – Vascotto (Coordinator and PI), MITGEST – “Quality control of the mitochondrial gene expression system in health and disease”. (Total: ~2.7 MEuro; Vascotto Unit: ~700 KEuro)
    2022-2025
    • NCN-OPUS 22 – Vascotto (PI), “Inhibiting the Mitochondrial Intermembrane Space Assembly pathway as a new approach to prevent metabolic reprogramming of therapy-resistant leukemia”. (~620 KEuro);
    2023-2025
    • Premia na Horyzoncie – Support by MInistry of Education and Science for OLIGOMED project (Total: 139 338 PLN)
    2021-2024
    • H2020-MSCA-ITN – Vascotto (Unit Leader and PI), OLIGOMED – “Oligonucleotides for Medical Applications”. (Total: ~4.3 MEuro; Vascotto Unit: 530 KEuro)