Molecular Parasitology

Despina Smirlis | Department of Microbiology

Scientific Team Leader

Contact:

+30 210-6478841 | .img@.img,  |  CV

ABOUT

The main research activity of the group is focused on the study of the protozoan parasite Leishmania, the aetiological agent of the important disease leishmaniasis. The disease is characterized as anthropozoonotic and is transmitted by the bite of sandflies. Leishmaniasis is endemic in Greece, whereby the prevalence in dogs, the local reservoir host, is up to 34%. In humans leishmaniasis has different clinical manifestations, including cutaneous, mucocutaneous and visceral, the latter being the most severe form of disease, lethal if left untreated. Leishmaniasis is considered a major health problem with more than 1.5 million infections occurring each year, whereas current chemotherapy has important limitations including high toxicity and  emergence of drug resistance. Thus, there is an urgent need to discover new drugs. For contributing to the fight against leishmaniasis the first research axis of the group investigates the pathogen and host signal transduction pathways, aiming to expand the drug-discovery platforms for the treatment of the disease.  In this context, we use molecular and cellular biology techniques and systems approaches, to focus on the druggable genome and more specifically on kinases of the host implicated in inflammation (i.e. GSK-3, DYRK) and on parasitic kinases implicated in parasite viability, virulence and differentiation (i.e. GSK-3, Aurora, DYRK). Aiming towards the discovery of new antiparasitic drugs we have developed target- and cell- based screening assays, and we evaluate the efficacy of selected drugs in vivo, in animal models of leishmaniasis. The second research axis involves epidemiological studies of strains isolated in South-Eastern Europe for understanding parasite factors that determine the clinical outcome of leishmaniasis and factors that contribute to drug resistance.

CURRENT PROGRAMS

Α. Investigation of signal transduction pathways and of proteins involved in Leishmania cell-cycle progression, differentiation and virulence

To achieve our research objectives we use transgenic parasites, molecular and cellular biology techniques and systems approaches for investigating components and mechanisms of signal transduction pathways.

PUBLICATIONS

  • Leishmania dual-specificity tyrosine-regulated kinase 1 (DYRK1) is required for sustaining Leishmania stationary phase phenotype.Rocha VPC, Dacher M, Young SA, Kolokousi F, Efstathiou A, Späth GF, Soares MBP, Smirlis D. Mol Microbiol. 2020 May;113(5):983-1002. doi: 10.1111/mmi.14464.
  • The loss of virulence of histone H1 over-expressing Leishmania donovani parasites is directly associated with a reduction of HSP83 rate of translation. Alexandratos, J. Clos, M. Samiotaki, A. Efstathiou, G. Panayotou, K. Soteriadou, D. Smirlis. Mol. Microbiology. 2013 Jun;88(5):1015-31.
  • Trypanosomatid apoptosis: ‘Apoptosis’ without the canonical regulators. D. Smirlis, K. Soteriadou. Virulence. 2011 May 1;2(3).
  • Targeting essential pathways in trypanosomatids gives insights into protozoan mechanisms of cell death. D Smirlis, M. Duszenko, A. Jimenez-Ruiz, E. Scoulica, P. Bastien, N. Fasel, K. Soteriadou. Parasit Vectors. 2010 Nov 17;3:107. (Highly accessed)
  • Leishmania donovani RAN-GTPase interacts at the nuclear rim with linker histone H1. D. Smirlis, H. Boleti, M. Gaitanou, M. Soto, K. Soteriadou. Biochem. J. 2009 Dec 10;424(3):367-74 9.
  • Leishmania histone H1 over-expression delays parasite cell-cycle progression, parasites differentiation and reduces Leishmania infectivity in vivo. D. Smirlis, S. Bisti, E. Xingi, G. Konidou, M. Thiakaki, K. Soteriadou. Mol. Microbiology. 2006; 60(6): 1457-73

Β. Drug discovery efforts against leishmaniasis and trypanosomiasis and investigation of the mechanism of drug action

To achieve this objective we have developed medium throughput non-radioactive kinase assays for investigating the inhibitory potential of Leishmania kinases and we assess cell growth inhibition and mechanism of drug action (cell-cycle, mechanism of cell death). Finally we assess the toxicity of selected compounds and their in vivo efficacy in a murine model of leishmaniasis.

PUBLICATIONS

  • Indirubin Analogues Inhibit Trypanosoma brucei Glycogen Synthase Kinase 3 Short and T. brucei Growth. Efstathiou A, Gaboriaud-Kolar N, Myrianthopoulos V, Vougogiannopoulou K, Subota I, Aicher S, Mikros E, Bastin P, Skaltsounis AL, Soteriadou K, Smirlis D. Antimicrob Agents Chemother. 2019 May 24;63(6):e02065-18. doi: 10.1128/AAC.02065-18.
  • Indirubin analogues inhibit Typanosoma brucei Glycogen Synthase Kinase 3 short and T. brucei growth.. Efstathiou A, Gaboriaud-Kolar N, Myrianthopoulos V, Vougogiannopoulou K, Subota I, Aicher S, Mikros E, Bastin P, Skaltsounis AL, Soteriadou K, Smirlis D. Antimicrob Agents Chemother 2019 Mar 25. pii: AAC.02065-18. doi: 10.1128/AAC.02065-18. [Epub ahead of print]
  • Indirubin derivatives are potent and selective anti-Trypanosoma cruzi Efstathiou A, Meira CS, Gaboriaud-Kolar N, Bastos TM, Rocha VPC, Vougogiannopoulou K, Skaltsounis AL, Smirlis D, Soares MBP. Virulence. 2018;9(1):1658-1668. doi: 10.1080/21505594.2018.1532242. PMID: 30387370
  • Selection of molecular targets for drug development against trypanosomatids. D. Smirlis& M.B.P. Soares. In Proteins and Proteomics of Leishmania and Trypanosoma, Springer (Editor: dos Santos, A.L.S), Subcell Biochem. 2014;74:43-76. doi: 10.1007/978-94-007-7305-9_2. (Book Chapter)
  • 5-Me-6-BIO targeting the leishmanial short form affects cell-cycle progression and induces apoptosis like death: exploitation of GSK-3 for treating leishmaniasis. E. Xingi, D. Smirlis, V. Myrianthopoulos, P. Magiatis, K. M. Grant, L. Meijer, E. Mikros, A. -L. Skaltsounis, K. Soteriadou. Int. J. Parasitol. 2009;39(12):1289-303
  • In vitro activity of 10-deacetylbaccatin-III against Leshmania donovani promastigotes and intracellular amastigotes. K. Georgopoulou, D. Smirlis, S. Bisti, E. Xingi, L. Skaltsounis, K. Soteriadou. Planta Medica 2007 Aug;73(10):1081-8. Epub 2007 Aug 9

C. Epidemiological studies of strains isolated in South-Eastern Europe for understanding parasite factors that determine the clinical outcome of leishmaniasis and factors that contribute to drug resistance.

We use parasites MLMT typed that share the same genomic background to investigate distict phenotypes towards clinical outcome and drug resistance. By applying next generation sequencing or and other molecular biology approaches, we are trying to investigate on the mechanisms that contribute to the above phenotypes.

PUBLICATIONS

  • Genetic diversity and structure in Leishmania infantum populations from south-eastern Europe revealed by microsatellite analysis. E. Gouzelou, C. Haralambous, M. Antoniou, V. Christodoulou, F. Martinković, T. Živičnjak , D. Smirlis, F. Pratlong, J.P. Dedet, Y. Özbel, S.Ö. Toz, W. Presber, G. Schönian, K. Soteriadou. Parasit Vectors. 2013 Dec 5;6:342.doi: 10.1186/1756-3305-6-342. (Highly accessed)

 

D.Host-pathogen interactions.

We investigate host and pathogen mechanisms that can modify virulence and pathogenicity

PUBLICATIONS

  • SILAC-based quantitative proteomics reveals pleiotropic, phenotypic modulation in primary murine macrophages infected with the protozoan pathogen Leishmania donovani. Smirlis D, Dingli F, Pescher P, Prina E, Loew D, Rachidi N, Späth GF. J Proteomics. 2020 Feb 20;213:103617. doi: 10.1016/j.jprot.2019.103617.
  • Osteopontin in the host response to Leishmania amazonensis. Giraud E, Rouault E, Fiette L, Colle JH, Smirlis D, Melanitou E. BMC Microbiol. 2019 Feb 8;19(1):32. doi: 10.1186/s12866-019-1404-z.

GRANTS

2016-2017: IKY: Scholarship of Excellence for post-doctoral studies Siemens, (RecipientDr Antonia Efstathiou)

2014-2017: International Pasteur Network: LeisHield: A new collaborative action to determine prevalence, anticipate emergence and assess urbanization of cutaneous and visceral leishmaniasis in LeishRIIP partner countries (Coordinator: Gerald Spath, PI: PI)

2013-2015: ACIP 2013 International Pasteur Network: “Evaluation of Leishmania DYRK family of kinases as molecular targets for the development of antileishmanial drugs” (Hellenic Pasteur Institute, IP Paris, IP Montevideo, FIOCRUZ) (Coordinator: Despina Smirlis)

2011-2015: FP7-PEOPLE-2010-IRSES: Exploring Chemical Biodiversity with Innovative Approaches for Fighting Chagas and Leishmaniasis. PIRCES-GA-2010-269301 (Coordinator: A.-L. Skaltsounis, PI: Ketty Soteriadou, Member, Co-PI: Despina Smirlis)

2012-2015: General Secretariat of Research and Technology KRIPIS: Infectious and neurodegenerative diseases of the 21st Century: From the study of basic mechanisms to translational research and development of cutting-edge technologies aiming towards prevention, diagnosis and treatment (WP leader), (WP Leader)

2011-2012: Foundation for Education and European Culture (IPEP) award: “Evaluation of the anti-leishmanial action of new indirubin analogues” (Recipient of Grant: Despina Smirlis)

TEACHING ACTIVITIES

TEACHING ACTIVITIES

Invited lectures/ Courses/ Seminars

  1. Research seminar of the Biology Department of the National Kapodistrian University of Athens: The unusual lives of trypanosomatids, 19-12-2012.
  2. UMR8638 CNRS-Université Paris Descartes, “Novel drug targets and drugs for the treatment of leishmaniasis, 19-7-2013.
  3. Institute Pasteur Paris, Scientific Symposium of the Institut Pasteur International Network “Exploring the role of Leishmania infantumDYRK1 and Aurora kinases in the parasitic lifecycle for anti-leishmanial drug discovery”, 11-9-14.
  4. Institut Pasteur, Tehran, Iran: International Workshop “Leishmania and leishmaniasis immunology, vaccine and drug discovery-therapy” Speaker: Recent approaches in anti-leishmanial drug discovery, 9-13 November 2016.

Theses/ Final Year Projects

2012-now: Currently co-supervising with Dr Milena Soares (FIOCRUZ, Bahia, Brazil) Mr. Vinicius Pinto Rocha

2017: Foteini Kolokousi Dissertation supervisor (Biology, NKUA) in the project entitled “Exploring the role of Leishmania infantum DYRK1 for antileishmanial drug discovery”

2016: Garyfallia Loulou Dissertation supervisor (Technical University of Athens) in project entitled “Phenotypic characterisation of Leishmania infantum parasites knocked out or over-expressing the Leishmania dual specificity tyrosine regulated kinase 1 (DYRK1), for the study of its biological role”

2010-2014: Co-supervisor of Antonia’s Efstathiou PhD thesis entitled (Biology, National Kapodistrian University of Athens) entitled «Study of molecules implicated in the development of Leishmania and T.brucei parasites»

2010-2013: Co-supervisor of Alexandros Alexandratos PhD thesis (Chemistry, University of Ioannina) “Study of molecules important for cell-cycle progression in the protozoan parasite Leishmania

2009: Evangelos Nomikos BSc Final Year Project Supervisor (Technical University of Athens) in the final Year Project entitled “Expression and purification of a Leishmania RCC1 protein fragment”

2008: Irene’s Daoudadakis BSc Final Year Project Supervisor (Technical University of Athens) in a project entitled “Construction of targeted cassettes for the knockout of Leishmania protein Ran”

2007-2008: Anastasios Katopodis Final Year (Biology, National Kapodistrian University) Project Supervisor in a project entitled “Cloning and molecular characterisation of the Leishmania protein Ran”

AWARDS - HONORS

1997-2001: Welcome Trust Toxicology PhD Prize Studentship

09/2009: Recipient of the Short Mission Fellowship of the COST BM0802 Action for training in theTrypanosome Cell BiologyLaboratory – CNRS URA 2581, Institute Pasteur Paris (Dr P. Bastin)

2009-2012: Appointed Greek Management Committee substitute member of the BM0802 action- Life or death of protozoan parasites

4-8/2013: Recipient of the Programme Calmette and Yersin traineeship (International Pasteur Network) in the Molecular Parasitology and Signaling Unit of Institut Pasteur: “Generation of conditional Leishmhania Aurora null mutants for investigating the role of this kinase in the parasitic life-cycle and evaluating its potential as a putative drug target for anti-leishmanial chemotherapy”

2013-2015: Coordinator of Actions Concertées des Institut Pasteur (ACIP, 2013)

2015-2017: Appointed Greek Management Committee Substitute Member for Greece in the COST CM1307 ACTION “Targeted chemotherapy towards diseases caused by  endoparasites”

9-12/2015: Recipient of the Short Mission Fellowship of the COST CM1307 Action “Investigating regulatory& functional elements of Leishmania infantum Aurora kinase, and assessment of its role in parasite genomic adaptation”in the Molecular Parasitology and Signaling Unit of Institut Pasteur

11-02-2016: Unesco-Hellas Award for Scientific achievement

COURCES

LINKS

PUBLICATIONS

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Efstathiou A and Smirlis D. A Radioactive-free Kinase Inhibitor Discovery Assay Against the Trypanosoma brucei Glycogen Synthase Kinase-3 short (TbGSK-3s). Bio-protocol, January 20, 2020; 10(02): e3493. DOI:10.21769/BioProtoc.3493.

Martínez de Iturrate P, Sebastián-Pérez V, Nácher-Vázquez M, Tremper CS, Smirlis D, Martín J, Martínez A, Campillo NE, Rivas L, Gil C. Towards discovery of new leishmanicidal scaffolds able to inhibit Leishmania GSK-3. J Enzyme Inhib Med Chem. 2020 Dec;35(1):199-210. doi: 10.1080/14756366.2019.1693704.

Smirlis D, Dingli F, Pescher P, Prina E, Loew D, Rachidi N, Späth GF. SILAC-based quantitative proteomics reveals pleiotropic, phenotypic modulation in primary murine macrophages infected with the protozoan pathogen Leishmania donovani. J Proteomics. 2020 Feb 20;213:103617. doi: 10.1016/j.jprot.2019.103617.

Rocha VPC, Dacher M, Young SA, Kolokousi F, Efstathiou A, Späth GF, Soares MBP, Smirlis D. Leishmania dual-specificity tyrosine-regulated kinase 1 (DYRK1) is required for sustaining Leishmania stationary phase phenotype. Mol Microbiol. 2020 May;113(5):983-1002. doi: 10.1111/mmi.14464.

2020
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Hombach-Barrigah A, Bartsch K, Smirlis D, Rosenqvist H, MacDonald A, Dingli F, Loew D, Späth .GF, Rachidi N, Wiese M, Clos J. Leishmania donovani 90 kD Heat Shock Protein - Impact of Phosphosites on Parasite Fitness, Infectivity and Casein Kinase Affinity. Sci Rep. 2019 Mar 25;9(1):5074. doi: 10.1038/s41598-019-41640-0.

Efstathiou A, Gaboriaud-Kolar N, Myrianthopoulos V, Vougogiannopoulou K, Subota I, Aicher S, Mikros E, Bastin P, Skaltsounis AL, Soteriadou K, Smirlis D. Indirubin Analogues Inhibit Trypanosoma brucei Glycogen Synthase Kinase 3 Short and T. brucei Growth. Antimicrob Agents Chemother. 2019 May 24;63(6):e02065-18. doi: 10.1128/AAC.02065-18. Print 2019 Jun.

Giraud E, Rouault E, Fiette L, Colle JH, Smirlis D, Melanitou E. Osteopontin in the host response to Leishmania amazonensis. BMC Microbiol. 2019 Feb 8;19(1):32. doi: 10.1186/s12866-019-1404-z.

2019
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Bussotti G, Gouzelou E, Côrtes Boité M, Kherachi I, Harrat Z, Eddaikra N, Mottram JC, Antoniou M, Christodoulou V, Bali A, Guerfali FZ, Laouini D, Mukhtar M, Dumetz F, Dujardin JC, Smirlis D, Lechat P, Pescher P, El Hamouchi A, Lemrani M, Chicharro C, Llanes-Acevedo IP, Botana L, Cruz I, Moreno J, Jeddi F, Aoun K, Bouratbine A, Cupolillo E, Späth GF. Leishmania Genome Dynamics during Environmental Adaptation Reveal Strain-Specific Differences in Gene Copy Number Variation, Karyotype Instability, and Telomeric Amplification. mBio. 2018 Nov 6;9(6):e01399-18. doi: 10.1128/mBio.01399-18.

Agallou M, Pantazi E, Tsiftsaki E, Toubanaki DK, Gaitanaki C, Smirlis D, Karagouni E. Induction of protective cellular immune responses against experimental visceral leishmaniasis mediated by dendritic cells pulsed with the N-terminal domain of Leishmania infantum elongation factor-2 and CpG oligodeoxynucleotides. Mol Immunol. 2018 Nov;103:7-20. doi: 10.1016/j.molimm.2018.08.004.

Hombach-Barrigah A, Bartsch K, Smirlis D, Rosenqvist H, MacDonald A, Dingli F, Loew D, Späth GF, Rachidi N, Wiese M, Clos J. Leishmania donovani 90 kD Heat Shock Protein - Impact of Phosphosites on Parasite Fitness, Infectivity and Casein Kinase Affinity. Sci Rep. 2019 Mar 25;9(1):5074. doi: 10.1038/s41598-019-41640-0.

Efstathiou A, Meira CS, Gaboriaud-Kolar N, Bastos TM, Rocha VPC, Vougogiannopoulou K, Skaltsounis AL, Smirlis D, Soares MBP.Indirubin derivatives are potent and selective anti-Trypanosoma cruzi agents Virulence. 2018;9(1):1658-1668. doi:10.1080/21505594.2018.1532242.

2018
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Zoidis G, Tsotinis A, Tsatsaroni A, Taylor MC, Kelly JM, Efstathiou A, Smirlis D, Fytas G. Lipophilic conformationally constrained spiro carbocyclic 2,6-diketopiperazine-1-acetohydroxamic acid analogues as trypanocidal and leishmanicidal agents: An extended SAR study. Chem Biol Drug Des. 2018 Feb;91(2):408-421. doi: 10.1111/cbdd.13088. Epub 2017 Sep 18.

Kyriazis ID, Smirlis D, Papadaki A, Koutsoni O., Aligiannis N., Skaltsounis AL, Dotsika E. Leishmanicidal Activity of Oleuropein: Leishmania donovani Promastigote Cell Death through a Possibly ROS-Independent Mechanism. J Pharmacogn Nat Prod 2017, 3:2. DOI: 10.4172/2472-0992.1000141.

2017
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Azevedo L , Faqueti L., Kritsanida M., Efstathiou A., Smirlis D., Franchi Jr GC, Genta-Jouve G., Michel S., Sandjo LP, Grougnet R, Biavatti MW.Three New Trixane Glycosides Obtained From the Leaves of Jungia Sellowii Less. Using Centrifugal Partition Chromatography. Beilstein J Org Chem. 2016 Apr 12;12:674-83. doi: 10.3762/bjoc.12.68. eCollection 2016.

2016
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Papadaki A, Politou AS, Smirlis D, Kotini MP, Kourou K, Papamarcaki T, Boleti HThe Leishmania Donovani Histidine Acid Ecto-Phosphatase LdMAcP: Insight Into Its Structure and Function. Biochem J. 2015 May 1;467(3):473-86. doi: 10.1042/BJ20141371.

2015
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Smirlis D, Soares MB. Selection of molecular targets for drug development against trypanosomatids.. Subcell Biochem. 2014;74:43-76. doi: 10.1007/978-94-007-7305-9_2.

Stellas D, Souliotis VL, Bekyrou M, Smirlis D, Kirsch-Volders M, Degrassi F, Cundari E, Kyrtopoulos SA.Benzo[a]pyrene-induced cell cycle arrest in HepG2 cells is associated with delayed induction of mitotic instability. Mutat Res. 2014 Nov;769:59-68. doi: 10.1016/j.mrfmmm.2014.07.004. Epub 2014 Jul 19.

Efstathiou A, Gaboriaud-Kolar N, Smirlis D, Myrianthopoulos V, Vougogiannopoulou K, Alexandratos A, Kritsanida M, Mikros E, Soteriadou K, Skaltsounis AL. An inhibitor-driven study for enhancing the selectivity of indirubin derivatives towards leishmanial Glycogen Synthase Kinase-3 over leishmanial cdc2-related protein kinase 3. Parasit Vectors. 2014 May 20;7:234. doi: 10.1186/1756-3305-7-234.

Alexandratos A and Smirlis D. Protein Sample Preparation for Proteomic Analysis in Leishmania donovani. Bio-protocol . Vol 4, Iss 5, March 05, 2014. DOI: 10.21769/BioProtoc.1058.

2014
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Vassilaki N, Kalliampakou KI, Kotta-Loizou I, Befani C, Liakos P, Simos G, Mentis AF, Kalliaropoulos A, Doumba PP, Smirlis D, Foka P, Bauhofer O, Poenisch M, Windisch MP, Lee ME, Koskinas J, Bartenschlager R, Mavromara P.Low oxygen tension enhances hepatitis C virus replication.J Virol. 2013 Mar;87(5):2935-48. doi: 10.1128/JVI.02534-12.

Sacconnay L, Smirlis D, Queiroz EF, Wolfender JL, Soares MB, Carrupt PA, Nurisso A.Structural insights of SIR2rp3 proteins as promising biotargets to fight against Chagas disease and leishmaniasis. Mol Biosyst. 2013 Sep;9(9):2223-30. doi: 10.1039/c3mb70180h.

Gouzelou E, Haralambous C, Antoniou M, Christodoulou V, Martinković F, Živičnjak T, Smirlis D, Pratlong F, Dedet JP, Özbel Y, Toz SÖ, Presber W, Schönian G, Soteriadou K.Genetic diversity and structure in Leishmania infantum populations from southeastern Europe revealed by microsatellite analysis. Parasit Vectors. 2013 Dec 5;6:342. doi: 10.1186/1756-3305-6-342.

Alexandratos A, Clos J, Samiotaki M, Efstathiou A, Panayotou G, Soteriadou K, Smirlis D.The loss of virulence of histone H1 overexpressing Leishmania donovani parasites is directly associated with a reduction of HSP83 rate of translation. Mol Microbiol. 2013 Jun;88(5):1015-31. doi: 10.1111/mmi.12240.

2013
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Soares MB, Silva CV, Bastos TM, Guimarães ET, Figueira CP, Smirlis D, Azevedo WF Jr.Anti-Trypanosoma cruzi activity of nicotinamide. Acta Trop. 2012 May;122(2):224-9. doi: 10.1016/j.actatropica.2012.01.001.

Vassilaki N, Kalliampakou KI, Kotta-Loizou I, Befani C, Liakos P, Simos G, Mentis AF, Kalliaropoulos A, Doumba PP, Smirlis D, Foka P, Bauhofer O, Poenisch M, Windisch MP, Lee ME, Koskinas J, Bartenschlager R, Mavromara P.Low oxygen tension enhances hepatitis C virus replication.J Virol. 2013 Mar;87(5):2935-48. doi: 10.1128/JVI.02534-12.

Agallou M, Smirlis D, Soteriadou KP, Karagouni E. Vaccination with Leishmania histone H1-pulsed dendritic cells confers protection in murine visceral leishmaniasis.Vaccine. 2012 Jul 20;30(34):5086-93. doi: 10.1016/j.vaccine.2012.05.075. Epub 2012 Jun 13.

2012
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• Smirlis D, Soteriadou, K. Virulence. Trypanosomatid Apoptosis: 'Apoptosis' Without the Canonical Regulators. May-Jun 2011;2(3):253-6. doi: 10.4161/viru.2.3.16278. Epub 2011 May 1.DOI: 10.4161/viru.2.3.16278.

2011
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Smirlis D, Duszenko M, Ruiz AJ, Scoulica E, Bastien P, Fasel N, Soteriadou K.Targeting essential pathways in trypanosomatids gives insights into protozoan mechanisms of cell death. Parasit Vectors. 2010 Nov 17;3:107. doi: 10.1186/1756-3305-3-107.

Boleti H, Smirlis D, Dalagiorgou G, Meurs EF, Christoforidis S, Mavromara P.ER targeting and retention of the HCV NS4B protein relies on the concerted action of multiple structural features including its transmembrane domains. Mol Membr Biol. 2010 Jan;27(1):45-62. doi: 10.3109/09687680903426208.

2010
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Smirlis D, Boleti H, Gaitanou M, Soto M, Soteriadou K. Leishmania donovani Ran-GTPase interacts at the nuclear rim with linker histone H1. Biochem J. 2009 Dec 10;424(3):367-74. doi: 10.1042/BJ20090576.

Xingi E, Smirlis D, Myrianthopoulos V, Magiatis P, Grant KM, Meijer L, Mikros E, Skaltsounis AL, Soteriadou K. 6-Br-5methylindirubin-3'oxime (5-Me-6-BIO) targeting the leishmanial glycogen synthase kinase-3 (GSK-3) short form affects cell-cycle progression and induces apoptosis-like death: exploitation of GSK-3 for treating leishmaniasis. Int J Parasitol. 2009 Oct;39(12):1289-303. doi: 10.1016/j.ijpara.2009.04.005.

2009
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Georgopoulou K, Smirlis D, Sylvia Bisti, Xingi E, Skaltsounis L, Soteriadou K. In Vitro Activity of 10-deacetylbaccatin III Against Leishmania Donovani Promastigotes and Intracellular Amastigotes. Planta Med. 2007 Aug;73(10):1081-8. doi: 10.1055/s-2007-981579.

2007
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Edwards M, Wong SC, Chotpadiwetkul R, Smirlis D, Phillips IR, Shephard EA Transfection of Primary Cultures of Rat Hepatocytes. Methods Mol Biol. 2006;320:273-282. doi: 10.1385/1-59259-998-2:273.

Smirlis D, Bisti SN, Xingi E, Konidou G, Thiakaki M, Soteriadou KP. Leishmania histone H1 overexpression delays parasite cell-cycle progression, parasite differentiation and reduces Leishmania infectivity in vivo. Mol Microbiol. 2006 Jun;60(6):1457-73. doi: 10.1111/j.1365-2958.2006.05205.x.

2006
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Muangmoonchai R, Wong SC, Smirlis D, Phillips IR, Shephard EA.Transfection of Liver in Vivo by Biolistic Particle Delivery: Its Use in the Investigation of Cytochrome P450 Gene Regulation.Mol Biotechnol. 2002 Feb;20(2):145-51. doi: 10.1385/mb:20:2:145

2002
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Smirlis D, Muangmoonchai R, Edwards M, Phillips IR, Shephard EA. Orphan receptor promiscuity in the induction of cytochromes p450 by xenobiotics.J Biol Chem. 2001 Apr 20;276(16):12822-6. doi: 10.1074/jbc.M005930200.

Muangmoonchai R, Smirlis D, Wong SC, Edwards M, Phillips IR, Shephard EA. Xenobiotic induction of cytochrome P450 2B1 (CYP2B1) is mediated by the orphan nuclear receptor constitutive androstane receptor (CAR) and requires steroid co-activator 1 (SRC-1) and the transcription factor Sp1. Biochem J. 2001 Apr 1;355(Pt 1):71-8. doi: 10.1042/0264-6021:3550071.

2001

MEMBERS

Despina Smirlis

Researcher C of Molecular Parasitology
Biochemist (BSc)
Molecular Biologist (PhD)

Antonia Efstathiou

Post-doctoral scientist,
Chemist (BSc)
Biochemist (Msc)
Molecular Biologist and Biochemist (PhD)
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PAST MEMBERS

Stavroula Gouzelou

Post-doctoral Scientific Collaborator
Biologist- Parasitologist
Epidimiologist (PhD)
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