Molecular Virology

Niki Vassilaki | Department of Microbiology

Scientific Team Leader

Contact:

+30 210-6478875 | .img@.img">.img@.img, .img@.img">.img@.img |  CV

ABOUT

The main activity of the Molecular Virology research team of Dr. Niki Vassilaki is the study of the life cycle of Hepatitis C virus (HCV) and other Flaviviridae viruses, as well as their defeat by the discovery of broad-spectrum anti-virals.

Viruses belonging to the Flaviviridae family constitute major causes of severe human disease (hepatitis, hemorrhagic fever, encephalitis) and mortality worldwide and often produce simultaneous outbreaks with serious co-infections. The importance of the development of new broad-spectrum drugs is widely regarded as a first-line defense against the spread of emerging viruses and as a means of protection against viral co-infections, while mitigating risks of resistance and reducing costs.

The team focuses on the study of molecular mechanisms regulating the proliferation of HCV and the flaviviruses Dengue (DENV), Yellow fever (YFV) and Zika (ZIKV), at the level of basic and applied research. For this purpose, the team has implemented viral subgenomic and infectious cell-culture based systems and has developed infectious models simulating normoxic and metabolic conditions of tissues. More specifically, the main goal of the team is to understand the role of glycolytic and lipid metabolism of the host cell in the interaction between intracellular oxygen tension and viral replication as well as the role of this interaction in viral pathogenesis. A secondary objective is to discover broadly effective small molecule inhibitors against Flaviviridae viruses and the characterization of their molecular mechanisms of action. By including the Hepatitis B virus (HBV) in its research portfolio, the team has additionally expanded the above studies to an important hepatotropic virus belonging to another family (Hepadnaviridae).

CURRENT RESEARCH PROJECTS (UNITS)

Α. Studying the metabolic basis of the interaction between intracellular oxygen tension and replication of hepatotropic viruses HCV, DENV, YFV and HBV, as well as the role of this interaction in viral pathogenesis

Developing hepatocyte culture-based infection models adapted at the median oxygen tension of liver microenvironment (3% v/v O2) and simulating the metabolic conditions of natural infection: a) we investigate the influence of low oxygen (liver normoxia) on viral replication, and b) we study the cellular metabolic pathways of glycolysis, creatine kinase B and lipid-metabolism implicated in this interaction in order to understand important determinants of infection outcome and identify new therapeutic targets.

PUBLICATIONS

  • Low oxygen tension enhances hepatitis C virus replication. Vassilaki N.*, Kalliampakou I., Kotta-Loizou I., Befani C., Liakos P., Simos G., Mentis A.F., Kalliaropoulos A., Doumba P.P., Smirlis D., Foka P., Bauhofer O., Poenisch M., Windisch M.P., Lee M.E., Koskinas J., Bartenschlager R. and Mavromara P.* J Virol. 2013, 87, 2935-48. doi: 10.1128/JVI.02534-12.
    * Corresponding authors
  • Virus-host interactions under hypoxia. Special issue: Effects of hypoxia on infection and host immune control. Vassilaki N.* and Frakolaki E. Microbes Infect. 2017, 19, 193-203. doi: 10.1016/j.micinf.2016.10.004.
    * Corresponding author
  • The Role of Tissue Oxygen Tension in Dengue Virus Replication. Frakolaki E., Kaimou P., Moraiti M., Kalliampakou K. I., Karampetsou K., Dotsika E. Liakos P., Vassilacopoulou D., Mavromara P., Bartenschlager R. and Vassilaki N.* Cells. 2018, 7(12), 241; doi: 10.3390/cells7120241. Special Issue Gene Regulation by HIFs during Hypoxia
    * Corresponding author

PRESENTATIONS in CONFERENCES

  • Institut Pasteur International Network Symposium 2016, “From basic science to biomarkers and tools in Global Health”. Paris, France, 29 Nov. – 2 Dec. 2016

Poster presentation: The interplay between hepatotropic viruses and liver normoxia determines viral levels and response to therapeutics

Frakolaki E., Giannakopoulou E., Feuillette-Cadenne Ν., Kaimou P., Niotis G., Bartenschlager R., Mavromara P., Zoidis G., Windisch M., Neuveut C. and Vassilaki N.

  • 68th Congress of the Hellenic Society of Biochemistry and Molecular Biology. Athens, Greece, 10-12 Nov. 2017
    Oral presentation: Developing a novel infectious cell model of Flaviviridae viruses that simulates in vivo normoxic and metabolic microenvironment for the characterization of broadly effective antivirals
    Frakolaki E., Kaimou P., Niotis G., Dimitriou M., Giannakopoulou E., Pardali V., Myrianthopoulos V., Mikros E., Bartenschlager R., Mavromara P., Zoidis G. and Vassilaki N.

Β. Identifying new, safe and broadly effective inhibitors, synthetic or naturally-derived, against the Flaviviridae viruses HCV, DENV, YFV and ZIKV, as well as against HBV, and characterizing their molecular mechanism of action. We evaluate two chemical libraries: a) A series of lipophilic heterocyclic compounds, derivatives of the fungal metabolite flutamide (2,6-diketopiperazines) and acetohydroxamic acid analogues, structurally related to broad-spectrum chelators that have intrinsic selectivity for two-metal ions in the active site of nucleic acid-processing enzymes of HCV, HIV and influenza virus b) A group of natural products, including terpenes, steroids, alkaloids (indoles) and flavonoids, isolated from plants of Greek and Mediterranean that we have been previously identified as active against HCV replication, as well as synthetic derivatives. For this purpose, we employ efficient cell culure-based infectious and subgenomic viral systems and we have established infection models simulating normoxic and metabolic conditions of tissues. Collaboration with Prof. G. Zoidis and A. L. Skaltsounis (Faculty of Pharmacy, University of Athens).

C. Studying the activity and mode of action of novel tricyclic nucleosides against HCV RNA replication. Collaboration with Prof. P. Marakos and N. Pouli (Faculty of Pharmacy, University of Athens).

D. Evaluating a series of novel organic molecules, rationally designed to target the HCV non-structural protein NS5A, against different virus genotypes, in order to discover highly potent inhibitors with pangenotypic activity and improved profile. Collaboration with Prof. Dr. Ashraf H. Abadi (Faculty of Pharmacy and Biotechnology, German University in Cairo, Egypt).

PUBLICATIONS

  • # Novel indole-flutimide heterocycles with activity against influenza PA endonuclease and hepatitis C virus. Zoidis G., Giannakopoulou E., Stevaert A., Frakolaki E., Myrianthopoulos V., Fytas G., Mavromara P., Mikros E., Bartenschlager R., Vassilaki Ν.* and Naesens L.* Chem. Comm. 2016, 7, 447-456. doi:10.1039/C5MD00439J.

* Principal investigators

     # Featured as: New Talent Europe, 2016 MedChemComm Hot Article, Front cover

  • Novel nucleoside analogues targeting HCV replication through an NS5A-dependent inhibition mechanism. Lougiakis N., Frakolaki E., Karmou P., Pouli N.*, Marakos P., Madan V., Bartenschlager R., Vassilaki N.* Chem Biol Drug Des. 2017, 90(3), 352-367.
    * Corresponding authors
  • Expanding the chemical space of anti-HCV NS5A inhibitors by stereochemical exchange and peptidomimetic approaches. Ramsis T.M., Abdel Karim S.E., Vassilaki N., Frakolaki E., Kamal A.A.M., Zoidis G., Ahmed N.S. and Abadi A.H. Arch Pharm (Weinheim). 2018, 351(7):e1800017. doi: 10.1002/ardp.201800017.

PRESENTATIONS in CONFERENCES

  • 67th Panhellenic Conference of the Hellenic Society for Biochemistry and Molecular Biology. Ioannina, Greece, 25-27 Nov. 2016

Oral presentation: Mechanism of action of broadly effective inhibitors targeting hepaci- and flavivirus replication: Validation under liver normoxic conditions

Frakolaki E., Kaimou P., Kelepouras K., Giannakopoulou E., Myrianthopoulos V., Niotis G., Mikros E., Bartenschlager R., Mavromara P., Zoidis G. and Vassilaki N.

 

  • International Symposium on Hepatitis C Virus and Related Viruses. Dublin, Ireland, 8-11 Oct. 2018

Αναρτημένη παρουσίαση: Novel acetohydroxamic metal-chelators targeting the replication of Flaviviridae viruses.

Frakolaki E., Niotis G., Karakostas C., Giannakopoulou E., Pardali V., Windisch M., Bartenschlager R., Papageorgiou N., Canard B., Zoidis G. and N. Vassilaki.

  • 31st International Conference on Antiviral Research (ICAR). Porto, Portugal, 11-15 June 2018

Αναρτημένη παρουσίαση: Acetohydroxamic Metal-Chelators against Hepatitis C Virus and Flaviviruses

Giannakopoulou E., Pardali V., Frakolaki E., Myrianthopoulos V., Mikros E., Bartenschlager R., Vassilaki N. and Zoidis G.

  • 23rd International Symposium on Hepatitis C Virus and Related Viruses. Kyoto, Japan, 11-15 Oct. 2016

Poster presentation: Broadly active antivirals with a naturally derived chelating moiety targeting hepaci- and flavivirus replication; further evaluation under liver normoxic conditions

Frakolaki E., Giannakopoulou E., Myrianthopoulos V., Dimitriou M., Madan V., Mikros E., Bartenschlager R., Mavromara P., Zoidis G. and Vassilaki N.

  • 29th International Conference on Antiviral Research (ICAR). La Jolla, California, United States, 17- 21 April 2016

Poster presentation: Novel indole-flutimide Heterocycles with Activity Against Influenza PA Endonuclease and Hepatitis C Virus

Zoidis G., Giannakopoulou E., Stevaert A., Frakolaki E., Myrianthopoulos V., Fytas G., Mavromara P., Mikros E., Bartenschlager R., Vassilaki N. and Naesens L.

  • 66th Panhellenic Conference of the Hellenic Society for Biochemistry and Molecular Biology. Eugenides Foundation, Athens, Greece, 11-13 Dec. 2015

Oral presentation: Developing a novel infectious cell culture system of Hepatitis C virus that simulates liver normoxia for the characterization of broadly effective inhibitors targeting the viral polymerase.

Frakolaki E., Giannakopoulou E., Myrianthopoulos V., Dimitriou M., Madan V., Bartenschlager R., Mavromara P., Zoidis G. and Vassilaki N.

E. Investigating the role of the HCV core+1/ARFP (alternative reading frame) protein in viral pathogenesis. We and others have previously discovered the expression of an alternative open reading frame that overlaps the core encoding sequence at +1 nucleotide (core+1 ORF). Different core+1 ORF products, derived from frameshifting or internal translation initiation, have been reported. We study the mRNA/miRNA expression profile of human hepatoma cells and immortalized hepatocytes infected with core+1 mutant viruses of HCV JFH1 isolate (genotype 2a), carrying non-sense mutations that abolish the translation of the core+1 open reading frame, as compared to cells infected with wild-type virus, employing the technology of Real-Time PCR arrays of the Molecular Virology lab obtained through the program ARISTEIA (P.I. Prof. P. Mavromara).

F. Studying the role of an alternative IRES element embedded within the core coding sequence of HCV genome in modulating translation initiation of the core+1 open reading frame. Core RNA stem-loops SL47 and SL87 of the HCV genome, in addition to their role in the translation of viral polyprotein, are also important for driving the expression of the short isoform of the core+1 alternative reading frame protein, via internal translation initiation at core+1 codons 85/87, in hepatocytes transfected with core RNA as well as in the context of the viral genome.

PRESENTATIONS in CONFERENCES

  • 22nd International Symposium on Hepatitis C Virus and Related Viruses. Strasbourg, France, 9-13 Oct. 2015

Poster presentation: Expression and functional properties of the short Core+1/ARF protein in the HCV life cycle

Vassilaki N., Frakolaki E., Kazazi D., Karakasiliotis I., Moustafa S., Bartenschlager R. and Mavromara P.

  • 10th Conference of the Hellenic Society of Virology. Athens, Greece, 27-28 Feb. 2015

Oral presentation: Phenotypic evaluation of mutations that disrupt the core+1 ORF or alter the core aminoacid sequence of Hepatitis C Virus

Vassilaki N., Frakolaki E., Samaras A., M. Dimitriou, Kotta-Loizou I., Karakasiliotis I., Bartenschlager R. and Mavromara P.

  • Scientific Symposium of the Institut Pasteur International Network 2014. Paris, 10-13 Sep. 2014
  • 21st International Symposium on Hepatitis C Virus and Related Viruses. Banff, Canada, 7-11 Sep. 2014

Poster presentation: Mutations introducing stop codons in HCV core+1 ORF and a single aminoacid substitution in core which is present in clinical isolates impair viral infectivity

Vassilaki N., Frakolaki E., Samaras A., Kotta-Loizou I., Karakasiliotis I., Bartenschlager R. and Mavromara P.

  • 64o Panhellenic Conference of the Hellenic Society for Biochemistry and Molecular Biology. Athens, Greece, 6-8 Δεκ. 2013

Oral presentation: An IRES-like element identified within the HCV core-coding region mediates internal translation initiation of the core+1/Short protein in the HCV replicon.

Vassilaki N., Kotta-Loizou I., Sakellariou P., Frakolaki E., Bartenschlager R. and Mavromara P.

RESEARCH GRANTS (SERVICES)

2019-2020       Asklepios Gilead Sciences Hellas grant 2018

Title: “Aromatic L-aminoacid decarboxylase: A new metabolic factor associated with Hepatitis C virus infection and the development of Hepatocellular Carcinoma”
Principal Investigator:  Dr N. Vassilaki
Collaborators: Dr D. Vassilacopoulou (Faculty of Biology, University of Athens, Greece), Prof. J. Koskinas (2nd Department of Internal Medicine of Athens University Medical School and Hippokration General Hospital) Prof. N. Pouli and P. Marakos (Faculty of Pharmacy, University of Athens, Greece), Dr H. Boleti (HPI, Light Mocroscopy Unit)

 2018-2019       Empeirikeion Foundation Research grant 2016 

Title: “Design, synthesis and biological characterization of novel broadly active inhibitors against Hepatitis C virus and the related re-emerging Flaviviruses Zika, Dengue and Yellow Fever. Validation in a cell-based infectious model simulating in vivo conditions of the tissue”

Principal Investigators: Dr N. Vassilaki (Molecular Virology Lab, Hellenic Pasteur Institute, Athens, Greece) and Prof. G. Zoidis (Faculty of Pharmacy, University of Athens, Greece).

Collaborators: Dr V. Myrianthopoulos (Faculty of Pharmacy, University of Athens, Greece), Prof. R. Bartenschlager (Department of Infectious Diseases, Heidelberg, Germany)

2017-2018       Asklepios Gilead Sciences Hellas grant 2016

Title: “Characterization of new synthetic and natural compounds with broad-spectrum anti-viral activity as inhibitors of Hepatitis B virus in a cell culture model simulating the in vivo normoxic microenvironment. Importance of liver normoxia for HBV replication and the efficiency of inhibitors”

Principal Investigator: Dr N. Vassilaki

Collaborators: Prof. A. L. Skaltsounis, Prof. G. Zoidis and Dr V. Myrianthopoulos (Faculty of Pharmacy, University of Athens, Greece), Dr C. Neuveut (IP Paris, Unité des Hépacivirus et Immunité Innée), Dr M. Windisch (IP Korea, Applied Molecular Virology).

2017-2019       IKY (State Scholarships Foundation) Doctoral Grant for the research project “Evaluation of novel inhibitors of Hepatitis C and related viruses and biomarkers of response to anti-viral therapeutics”,

Thesis project of the PhD student Efseveia Frakolaki
IKY and the European Social Fund (ESF) and the Public Investments Program, in the framework of the Operational Program “Education and Life Long Learning” within the National Strategic Reference Framework (NSRF) 2007-2013

Principal Investigator: Niki Vassilaki/ IKY and the European Social Fund (ESF) and the Public Investments Program, in the framework of the Operational Program “Education and Life Long Learning” within the National Strategic Reference Framework (NSRF) 2007-2013

Jan-May 2018       Erasmus+ EU funding for traineeship of the Biologist Giorgos Niotis in the laboratory Architecture et Fonctions des Macromolécules Biologiques (AFMB), UMR 7257 du CNRS et de l’Université Aix-Marseille (France), in the context of the research project “Lipophilic heterocyclic chelating agents (acetohydroxamic acids) that are broadly active against Flaviviridae viruses. Evaluation in enzymatic assays for viral metallo-enzymes from Flaviviruses and Arenaviruses; Co-relation with inhibitory activities determined in sub-genomic replicon transfected cells”

Principal Investigator: Niki Vassilaki (Molecular Virology, HPI) and Bruno Canard – Prof. Nicolas Papageorgiou (AFMB, UMR 7257 du CNRS et de l’Université Aix-Marseille, France)

 

2018-2019       Subproject of action Development grants for research institutions – KRIPIS IΙ (Greek General Secretariat for Research and Technology)

Program Title: “Infectious, autoimmune and neurodegenerative diseases: Study of pathogenetic mechanisms and development of diagnostic, prognostic and therapeutic approaches”.

Coordinator:  Dr E. Karagouni (Hellenic Pasteur Institute)

Subproject EE1.5: “Identification of broadly effective inhibitors against Flaviviridae viruses and Hepatitis B virus (HBV)”

Principal Investigator of subproject EE1.5: Dr N. Vassilaki

2019-2021       Subproject of the action ESFRI- European Strategy Forum for Research Infrastructures, National Research & Innovation Infrastructures EATRIS-GR: Infrastructure for Preclinical and Early-Phase Clinical Development of Drugs, Therapeutics and BioMedical Devices.

Coordinator: Paschalis Sideras (Biomedical Research Foundation Academy of Athens)

Title of subproject: “Application of advanced in vitro viral models for the preclinical evaluation of small molecule inhibitors and other drugs against Flaviviruses (Dengue, Yellow Fever, Zika)”

Principal Investigator of subproject: Dr N. Vassilaki

 

2018-2020       Participation in Single RTDI State Aid Action RESEARCH – CREATE – INNOVATE (EPAnEK, Greek General Secretariat for Research and Technology): “Development of peptide-based nanovaccines against Leishmanasis (NanoVacLeish)”.

Principal Investigator: Dr E. Karagouni

Participants:  Hellenic Pasteur Institute (Coordinator), Centre for Research and Technology Hellas, Gerolymatos International S.A.

2015-2017:      International Pasteur Network grant ACIP (Actions Concertées Inter-Pasteuriennes) 2015

Title: “Identification of broad-spectrum naturally derived inhibitors against hepatotropic viruses (DENV, YFV, HBV) under culture conditions simulating liver normoxic and metabolic microenvironment. The interplay between virus and hepatic normoxia as a possible disease determinant”.

Principal Investigator/Coordinator: Dr N. Vassilaki

Collaborating Institut Pasteur (IP) Network partners: C. Neuveut (IP Paris, Unité des Hépacivirus et Immunité Innée), M. Windisch (IP Korea, Applied Molecular Virology). Other collaborators: Prof. R. Bartenschlager (Department of Infectious Diseases, University of Heidelberg, Germany), Prof. A. L. Skaltsounis, Prof. Zoidis and Dr V. Myrianthopoulos (Faculty of Pharmacy, University of Athens, Greece)

2017                Subproject of Asklepios Gilead Sciences Hellas grant 2017

Program title: “Design, synthesis and biological evaluation of new bivalent inhibitors of NS5A with selective anti-HCV activity”.

Coordinator: Prof. G. Zoidis, Faculty of Pharmacy, University of Athens

Principal Investigator of the biological evaluation of the inhibitors against HCV: Dr N. Vassilaki

2016-2017       Subproject of Asklepios Gilead Sciences Hellas program 2015 concerning the evaluation against HCV of novel lipophilic heterocyclic chelating agents

Program title: “Design, synthesis and biological evaluation of novel lipophilic heterocyclic chelating agents against Hepatitis C virus”

Coordinator: Prof. G. Zoidis, Faculty of Pharmacy, University of Athens

Principal Investigator of the study on HCV: Dr N. Vassilaki

2013-2014       LATSIS Public Benefit Foundation grant:

Title: ‘Development and exploitation of a more true-to-life novel infectious cell culture system for HCV growth for the characterization of new anti-HCV drugs’.

Principal Investigator/Coordinator: Dr N. Vassilaki

National collaborations: Prof. P. Mavromara (Democritus University of Thrace, Hellenic Pasteur Institute), Prof. J. Koskinas (2nd Department of Internal Medicine, Medical School of Athens, Hippokration Hospital, Athens), Prof. A. L. Skaltsounis, Prof. N. Aligiannis and Dr A. Argyropoulou (Faculty of Pharmacy, University of Athens, Department of Pharmacognosy and Chemistry of Natural Compounds), Prof. G. Zoidis (Faculty of Pharmacy, University of Athens, Department of Pharmaceutical Chemistry), Prof. M. Hatzopoulou-Cladaras and Dr I. Vallianou (School of Biology, Aristotle University of Thessaloniki, Department of Genetics, Development and Molecular Biology)

International collaboration: Prof. R. Bartenschlager (Department of Infectious Diseases, Heidelberg University, Germany)

2013-2015:      Subprojects of action Development grants for research institutions – KRIPIS I (Greek General Secretariat for Research and Technology)

Program title: “Infectious and neurodegenerative diseases in the 21st century: From the study of basic mechanisms to the development of translational research and cutting-edge methodologies targeting diagnosis, prevention and treatment”.

Coordinator: Dr E. Karagouni (Hellenic Pasteur Institute)

Subproject EE2.2: “Development and exploitation of a more true-to-life novel infectious cell culture system for HCV growth”. Subproject EE4.2: “Role of circulating microRNAs as prognostic biomarkers for HCV-associated hepatocellular carcinoma’.

Principal Investigator of subprojects EE2.2 and EE4.2: Dr N. Vassilaki

2013-2015       Subproject of National Grant BIONIAN, Greek Life Sciences Cluster (Greek General Secretariat for Research and Technology), where H.P.I. has participated as a subcontractor of the company Institute for Clinical Investigation

Subproject title: “Novel inhibitors of HCV growth and biomarkers related to HCV pathogenesis and response to therapeutics. A) A set of novel inhibitors of Hepatitis C Virus growth. B) Evaluation of microRNAs as biomarkers for HCV pathogenesis and response to anti-virals”. Principal Investigator of subproject: Dr N. Vassilaki

2013-2015       Subproject of program ARISTEIA Oncohepcvir (Greek General Secretariat for Research and Technology)

Program title: “The role of oncogenic viruses in the pathogenesis of hepatocellular carcinoma: From the HCV core/core+1 protein/ host interactions to HCV-associated liver cancer”.

Principal Investigator: Prof. P. Mavromara (Hellenic Pasteur Institute)

Subproject title: Investigating the role of HCV core+1/ARFP/F protein in viral pathogenesis by analyzing the mRNA/miRNA profiles of hepatocytes supporting the replication of wild-type of core+1 mutant viruses (carrying non-sense mutations abolishing the translation of core+1 open reading frame)

Principal Investigator of subproject: Dr N. Vassilaki

2013-2015       Participation in program THALΕS (Ministry of Education)

Program title: STAGECAR “Μechanisms of signal transduction and gene expression in hepatocellular carcinoma”.

Coordinator: Prof. G. Mosialos, Collaborators: Prof. M. Hatzopoulou-Cladaras and Dr I. Vallianou (School of Biology, Aristotle University of Thessaloniki, Department of Genetics, Development and Molecular Biology).

Study title: Hepatitis C virus suppresses HNF4alpha, a key regulator of hepatocellular carcinogenesis

2006-2007       DAAD, German Academic Exchange Post-doctoral Research grant:

Title: “Role of hepatitis C virus core+1 open reading frame and core cis-acting RNA elements in hepatitis C virus life cycle”

The post-doctoral research of Dr N. Vassilaki was performed at the Department of Molecular Virology of Heidelberg University (Germany), which is headed by Prof. Ralf Bartenschlager, in collaboration with the Molecular Virology lab of H.P.I.

TEACHING ACTIVITIES (TRAINING)

Undergraduate diploma theses

  • “Characterizing the biological function of the Hepatitis C virus core/core+1 protein” Panagiotis Sakellariou, Diploma thesis 2013, Faculty of Biology, University of Athens, Department of Biochemistry and Molecular Biology
  • “Evaluating novel inhibitors of Hepatitis C virus proliferation” Marios Dimitriou, Diploma thesis 2015, Faculty of Biology, University of Athens, Department of Biochemistry and Molecular Biology
  • Study of natural and semisynthetic compounds for their inhibitory activity against the proliferation of Hepatitis C Virus and related Flaviviruses” Konstantinos Kelepouras, Diploma thesis 2017, Faculty of Biology, University of Athens, Department of Biochemistry and Molecular Biology
  • “Evaluation of replication inhibitors against viruses of the Flaviviridae family and characterization of their mechanisms of action by analysis of resistance mutations””Έλεγχος αναστολέων της αντιγραφής ιών της οικογένειας Flaviviridae και χαρακτηρισμός του μηχανισμού δράσης τους με μελέτη ανάπτυξης μεταλλαγών ανθεκτικότητας”, Giorgos Niotis, Diploma thesis 2016- 2017 , Faculty of Biology, University of Athens, Department of Genetics and Biotechnology
  • “Evaluating broadly active inhibitors of viral replication and characterizing their mechanism of action at the genetic level through the study of adaptive changes in the virus genome and the host cell” Christos Caracostas, Diploma thesis 2017- , Faculty of Biology, University of Athens, Department of Genetics and Biotechnology
  • “Study of the interaction between viral replication and cellular metabolism under conditions of tissue normoxia (low oxygen) and in relation to L-Dopa decarboxylase”. Nikolaos Kolaitis, Diploma thesis 2017-, Faculty of Biology, University of Athens, Department of Biochemistry and Molecular Biology
  • “Association between hepatotropic viruses and tissue normoxia: studying the implicated cellular factors, including L-Dopa decarboxylase, and the impact on the efficiency of anti-virals” Vassilis Siozos, Diploma thesis 2018- , Faculty of Biology, University of Athens, Department of Biochemistry and Molecular

Master theses

  • “Studying cellular energetic metabolism and viral replication in cultured cells infected with Flaviviridae viruses under conditions of liver normoxia and in relation to Dopa decarboxylase”, Panagiota Kaimou, Master thesis 2016- , Faculty of Biology, University of Athens, Department of Biochemistry and Molecular Biology, Postgraduate studies program Clinical Biochemistry – Molecular Diagnostics (Molecular Basis of Human Diseases)
  • “Molecular mechanisms determining the relationship among viral infection, tissue normoxia and L-Dopa decarboxylase for hepatotropic viruses” Maria Moraiti, Master thesis 2017- , Faculty of Biology, University of Athens, Department of Biochemistry and Molecular Biology, Postgraduate studies program Clinical Biochemistry – Molecular Diagnostics (Molecular Basis of Human Diseases)
  • “The importance of L-Dopa decarboxylase as a metabolic determinant of viral replication and pathogenesis”
    Anna Chalari, Master thesis 2018- , Faculty of Biology, University of Athens, Department of Biochemistry and Molecular Biology, Postgraduate studies program Clinical Biochemistry – Molecular Diagnostics (Molecular Basis of Human Diseases)

PhD theses

  • “Evaluation of novel inhibitors of Hepatitis C virus and biomarkers of response to anti-viral therapeutics” Efseveia Frakolaki, PhD thesis 2014 -, Faculty of Biology, University of Athens, Department of Genetics and Biotechnology, 3-member advisory committee: Prof. A. M. Pappas, Dr N. Vassilaki, Prof. P. Mavromara

Teaching in Postgraduate studies programs

  • 2015-current: Lectures “Molecular basis of viral diseases and their treatment”, Inter-University Postgraduate studies program CLINICAL BIOCHEMISTRY – MOLECULAR DIAGNOSTICS, in the context of the course Molecular Basis of Human Diseases, Faculty of Biology, University of Athens
  • 2015-current: Lectures “Viruses as tools for vaccine construction, diagnosis and drug discovery”, Postgraduate studies program MICROBIAL BIOTECHNOLOGY, Faculty of Biology, University of Athens

Teaching in laboratory exercises, courses

  • 2001-2005: Participation as assistant in undergraduate laboratory exercises of Biochemistry, Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Athens
  • 04/2005: Teaching at practical exercises of the course Modern Methods of Light Microscopy and Applications in Biomedical Research and Diagnosis (Hellenic Pasteur Institute)

 

SCIENCE AND SOCIETY

Teaching high school students at Hellenic Pasteur Institute with lectures and practical exercises in Molecular Biology and Virology techniques

AWARDS (REGULATIONS)

Reviewer in the international journals ‘Journal of General Virology’, ‘Virus Research’, ‘Biochimie’, ‘International Journal of Molecular Sciences’, ‘International Journal of Environmental Research and Public Health’ and ‘IUBMB Life’.

2018               Invited Co-Chair at the 25th International Symposium on Hepatitis C Virus and Related Viruses (HCV2018, Dublin, Ireland). Session: Emerging and Related Viruses

2018                Best Oral Presentation Award, 4th Meeting of Postgraduate and Postdoctoral Researchers of Hellenic Pasteur Institute. “Interaction between tissue normoxia and Dengue Virus replication“. Moraiti M., Frakolaki E., Kolaitis N., Kaimou P., Kalliampakou A., Karampetsou K., Dotsika E., Vassilacopoulou D., Mavromara P., Bartenschlager R. and Vassilaki N.

2016     The article “Novel indole-flutimide heterocycles with activity against influenza PA endonuclease and hepatitis C virus”, in Med. Chem. Comm. 2016, Vol.7, No3, p.447-456, of Zoidis G., Giannakopoulou E., Stevaert A., Frakolaki E., Myrianthopoulos V., Fytas G., Mavromara P., Mikros E., Bartenschlager R., Vassilaki Ν. and Naesens L., was featured as: a) New Talent Europe, b) 2016 MedChemComm Hot Article and c) Front cover

2016     International Pasteur Network traineeship grant Calmette & yersin 2016 awarded for training of the PhD student E. Frakolaki in Institut Pasteur Paris on the research topic: “Evaluation of broadly active anti-virals for their activity against Hepatitis B Virus in a cell culture model adapted at liver normoxic conditions”.

2016     Two awards for best trainees’ performance during the course ‘High Content Assay for Drug Screening and Target discovery Using RNAi Technology’ (Institut Pasteur Korea, 9-13 May)

2012     Poster presentation award from the 63rd Conference of the Hellenic Society for Biochemistry and Molecular Biology (HSBMB) 2012 for the study: “Low Oxygen Tension Enhances Hepatitis C Virus Replication”, of Vassilaki N., Kalliampakou K.I., Kotta-Loizou I., Befani C., Liakos P., Simos G., Mentis A.F., Kalliaropoulos A., Doumba P.P., Smirlis D., Bauhofer O., Poenisch M., Windisch M.P., Lee M.E., Koskinas J., Bartenschlager R. and Mavromara P.

2011     Federation of European Microbiological Societies (FEMS) Young Scientist Meeting Grant 2010 for oral presentation at the 4th European Congress of Virology (Cernobbio, Italy, 7-11 Apr. 2010): “Oxygen tension modulates hepatitis C virus proliferation”, of Vassilaki N., Kalliampakou K.I., Kotta-Loizou I., Smirlis D., Bartenschlager R. and Mavromara P.

2008     Federation of European Microbiological Societies (FEMS) Young Scientist Meeting Grant 2008 for presentation at the 14th International Congress of Virology of International Union of Microbiological Societies (Istanbul, Turkey, 10-15 Aug. 2008): “Exploring the importance of the hepatitis C virus core RNA secondary structure and core+1 reading frame expression for viral RNA translation and replication”, of Vassilaki N., Friebe P., Paranhos-Baccalà G., Mavromara P. and Bartenschlager R.

 

ΤΕCHNOLOGY

Real-Time PCR Array technology of the Molecular Virology lab at H.P.I. is available to scientists of H.P.I. and other Research Institutes/ Universities and integrates standard real-time PCR applications like nucleic acid quantification, detection of single nucleotide polymorphisms (SNPs), and copy number variation detection with others that include high-resolution melting (HRM), protein analysis with proximity ligation technology (Taqman protein assays), and gene expression analysis performed directly from cultured cells without RNA purification.

Responsible contact person: Niki Vassilaki (.img@.img">.img@.img)

PATENTS (COURCES)

Mavromara P. and Vassilaki N. “Novel HCV core+1 protein, methods for diagnosis of HCV infections, prophylaxis and for screening of anti-HCV agents, nucleic acids and new polypeptides associated with and/or overlapping with HCV core gene products”
U.S. Patent Office, Patent No. US 7,838,002 B2, Application No. 11/322,374, Issue date 23/11/2010

Mavromara P. and Vassilaki N. “In vitro expression of the HCV ARFP/F/CORE+1 coding open reading frame”
U.S. Provisional Patent Application No. 60/614,610

LINKS

  1. Κείμενο 01
  2. Κείμενο 02

PUBLICATIONS

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L-Dopa decarboxylase interaction with the major signaling regulator ΡΙ3Κ in tissues and cells of neural and peripheral origin. Vassiliou A.G., Siaterli M.Z., Frakolaki E., Gkogkosi P., Paspaltsis I., Sklaviadis T., Vassilacopoulou D.* and Vassilaki N.* Biochimie. 2019, 160:76-87. doi: 10.1016/j.biochi.2019.02.009. * Corresponding authors

2019
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Comparison of DCs activation by virus-based vaccine delivery vectors emphasises the transcriptional downregulation of the oxidative phosphorylation pathway. Tsitoura E., Kazazi D., Oz-Arslan D., Sever E. A., Khalili S., Vassilaki N., Aslanoglou E., Dérian N, Six A., Sezerman O. U., Klatzmann D. and Mavromara P. Hum Gene Ther. 2019, 30(4):429-445. doi: 10.1089/hum.2018.161

2019
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The Role of Tissue Oxygen Tension in Dengue Virus Replication. Frakolaki E., Kaimou P., Moraiti M., Kalliampakou K. I., Karampetsou K., Dotsika E. Liakos P., Vassilacopoulou D., Mavromara P., Bartenschlager R. and Vassilaki N.* Cells. 2018, 7(12), pii: E241. doi: 10.3390/cells7120241. Special Issue Gene Regulation by HIFs during Hypoxia. * Corresponding author

2018
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Expanding the chemical space of anti-HCV NS5A inhibitors by stereochemical exchange and peptidomimetic approaches. Ramsis T.M., Abdel Karim S.E., Vassilaki N., Frakolaki E., Kamal A.A.M., Zoidis G., Ahmed N.S. and Abadi A.H. Arch Pharm (Weinheim). 2018, 351(7):e1800017. doi: 10.1002/ardp.201800017.

2018
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Novel nucleoside analogues targeting HCV replication through an NS5A-dependent inhibition mechanism. Lougiakis N., Frakolaki E., Karmou P., Pouli N.*, Marakos P., Madan V., Bartenschlager R., Vassilaki N.* Chem Biol Drug Des. 2017, doi: 10.1111/cbdd.12966 * Corresponding authors

Virus-host interactions under hypoxia. Special issue: Effects of hypoxia on infection and host immune control. Vassilaki N.* and Frakolaki E. Microbes Infect. 2017, 19, 193-203. doi: 10.1016/j.micinf.2016.10.004. * Corresponding author

2017
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# Novel indole-flutimide heterocycles with activity against influenza PA endonuclease and hepatitis C virus. Zoidis G., Giannakopoulou E., Stevaert A., Frakolaki E., Myrianthopoulos V., Fytas G., Mavromara P., Mikros E., Bartenschlager R., Vassilaki Ν.* and Naesens L.* Med. Chem. Comm. 2016, 7, 447-456. doi: 10.1039/C5MD00439J. * Principal investigators # Featured as: New Talent Europe (top research from emerging investigators from Europe), 2016 MedChemComm Hot Article (particularly interesting or significant research), Front cover in MedChemComm

Hepatitis C virus suppresses Hepatocyte Nuclear Factor 4 alpha, a key regulator of hepatocellular carcinoma. Vallianou I., Dafou D., Vassilaki N., Mavromara P. and Hadzopoulou-Cladaras M. Int J Biochem Cell Biol. 2016, 78, 315-26. doi: 10.1016/j.biocel.2016.07.027.

2016
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Expression of the novel HCV core+1/ARF protein in the context of JFH1-based replicons. Kotta-Loizou I., Karakasiliotis I., Vassilaki N., Sakellariou P., Bartenschlager R. and Mavromara P. J Virol. 2015, 89:5164-70. doi: 10.1128/JVI.02351-14.

2015
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Viral Hepatitis. Robotis J.F.* and Vassilaki N.* In Reference Module in Biomedical Sciences, 2014, edited by M. Caplan, Elsevier. doi: 10.1016/B978-0-12-801238-3.05401-5. * Corresponding authors

2014
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Low oxygen tension enhances hepatitis C virus replication. Vassilaki N.*, Kalliampakou K.I., Kotta-Loizou I., Befani C., Liakos P., Simos G., Mentis A.F., Kalliaropoulos A., Doumba P.P., Smirlis D., Foka P., Bauhofer O., Poenisch M., Windisch M.P., Lee M.E., Koskinas J., Bartenschlager R. and Mavromara P.* J Virol. 2013, 87, 2935-48. doi: 10.1128/JVI.02534-12. * Corresponding authors

Hepatitis C virus core+1/ARF protein decreases hepcidin transcription through an AP1 binding site. Kotta-Loizou I., Vassilaki N.*, Pissas G., Kakkanas A., Bakiri L., Bartenschlager R. and Mavromara P.* J Gen Virol. 2013, 94, 1528-34. doi: 10.1099/vir.0.050328-0 * Corresponding authors

2013
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High Levels of HCV core+1 Antibodies in HCV Patients with Hepatocellular Carcinoma. Dalagiorgou G., Vassilaki N., Foka P., Boumlic A., Kakkanas A., Kochlios E., Khalili S., Aslanoglou E., Veletza S., Orfanoudakis G., Vassilopoulos D., Hadziyannis S., Koskinas J., Mavromara P. J Gen Virol. 2011, 92: 1343-51. doi: 10.1099/vir.0.023010-0.

Synonymous mutations in the core gene are linked to unusual serological profile in hepatitis C virus infection. Budkowska A., Kakkanas A., Nerrienet E., Kalinina O., Maillard P., Horm S.V., Dalagiorgou G., Vassilaki N., Georgopoulou U., Martinot M., Sall A.Α., and Mavromara P. PLoS One. 2011, 6:e15871. doi: 10.1371/journal.pone.0015871.

Internal translation initiation stimulates expression of the ARF/core+1 open reading frame of HCV genotype 1b. Boumlic A., Vassilaki N., Dalagiorgou G., Kochlios E., Kakkanas A., Georgopoulou U., Markoulatos P., Orfanoudakis G., Mavromara P. Virus Res 2011, 155, 213-20. doi: 10.1016/j.virusres.2010.10.007.

2011
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Prevalence of intrinsic disorder in the hepatitis C virus ARFP/Core+1/S protein. Boumlic A., Nominé Y., Charbonnier S., Dalagiorgou G., Vassilaki N., Kieffer B., Travé G., Mavromara P., Orfanoudakis G. FEBS J 2010, 277, 774-89. doi: 10.1111/j.1742-4658.2009.07527.x

2010
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The HCV ARFP/F/core+1 protein: production and functional analysis of an unconventional viral product. Vassilaki N.* and Mavromara P.* IUBMB Life 2009, 61, 739-52. doi: 10.1002/iub.201 * Corresponding authors

2009
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Role of hepatitis C virus core+1 open reading frame and core cis-acting RNA elements in viral RNA translation and replication. Vassilaki N., Friebe P., Meuleman P., Kallis S., Kaul A., Paranhos-Baccalà G., Leroux-Roels G., Mavromara P. and Bartenschlager R. J Virol 2008, 82, 11503-15. doi: 10.1128/JVI.01640-08.

Expression studies of the HCV-1a core+1 open reading frame in mammalian cells. Vassilaki N., Boleti H. and Mavromara P. Virus Res 2008, 133, 123-135. doi: 10.1016/j.virusres.2007.10.019.

Differences in the expression of the hepatitis C virus core+1 open reading frame between a nuclear and a cytoplasmic expression system. Vassilaki N., Kalliampakou K.I. and Mavromara P. J Gen Virol 2008, 89, 222-231. doi: 10.1099/vir.0.83260-0

2008
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Expression studies of the core+1 protein of the hepatitis C virus 1a in mammalian cells. The influence of the core protein and proteasomes on the intracellular levels of core+1. Vassilaki N., Boleti H., Mavromara P. FEBS J. 2007, 274, 4057-4074. doi: 10.1111/j.1742-4658.2007.05929.x

2007
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HCV-associated hepatocellular carcinoma. Vassilaki N., Khalili S. and Mavromara P. In Viral Oncogenesis 2006 (Tognon M, eds), pp 145-181. Research Signpost Press, Kerala, India.

2006
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Two alternative mechanisms are responsible for the synthesis of HCV ARFP/F/core+1. Vassilaki N. and Mavromara P. J Biol Chem 2003, 278, 40503−40513. doi: 10.1074/jbc.M305504200

2003
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Alternate translation occurs within the core-coding region of the hepatitis C viral genome. Varaklioti A., Vassilaki N., Georgopoulou U., and Mavromara P. J Biol Chem 2002, 277, 17713-17721. doi: 10.1074/jbc.M201722200

2002

MEMBERS

Niki Vassilaki

Researcher C’ of Molecular Virology
Biologist (BSc)
Molecular Virologist (PhD)
Scientific Team Leader
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Efseveia Frakolaki

Biologist (BSc, MSc)
PhD Student
Research contract with HPI 2013-2015 (IKY Doctorate Fellowship, Programs KRIPIS, Latsis)
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Panagiota Kaimou

Nursing Faculty (BSc)
Master Student in Clinical Biochemistry and Molecular Diagnostics
Diploma thesis (MSc)
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Marios Dimitriou

Biologist (BSc)
Practical exercise
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Giorgos Niotis

Biologist (BSc)
Diploma thesis BSc
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Όνομα Ερευνητή

Ιδιότητα – Επάγγελμα
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