Efthimios Skoulakis Skoulakis

Efthimios M. C. Skoulakis, PhD Research Professor Director, Institute for Fundamental Biomedical Research BSRC Alexander Fleming Biomedical Sciences Research Centre “Alexander Fleming” 34 Fleming Str Vari 16672, Greece Ph: 210-9656-311xt188 skoulakis@fleming.gr EDUCATION AND DEGREES AWARDED 1990 The Ohio State University, Columbus, Ohio. Ph. D. Molecular Genetics, 1983 The University of Toledo, Toledo, Ohio. B. S. Biology/Chemistry minor Other education and Postdoctoral training 1993-1997 Baylor College of Medicine, Houston, Texas. 1991-1993 Cold Spring Harbor Laboratory, Cold Spring Harbor, New York. 1990-1991 Baylor College of Medicine, Houston, Texas. RESEARCH INTERESTS Efthimios MC Skoulakis is a trained Molecular Geneticist and a Behavioural Neurobiologist with a strong background in Chemistry. The long-term research goal of the Skoulakis laboratory is to define molecular mechanisms employed by neurons to receive and transduce signals essential for acquisition, storage and retrieval of information and how these are altered in cognitive, neurodegenerative diseases and dementia. A significant effort focuses on the molecular biology of habituation, an endophenotype linked to psychiatric conditions such as Schizophrenia, Attention Deficit Disorders and Autism Spectrum Disorders. His work on olfactory mechanisms has contributed to the emerging field of Quantum Biology Professional and Scientific Societies Genetics Society of America (GSA). Society for Neuroscience (SfN) Federation of European Neuroscience Societies (FENS) Hellenic Society for Neuroscience (HSN) Hellenic Society for Biochemistry and Molecular Biology British Biochemical Society (Ambassador in Greece) International Hellenic Initiative Against Alzheimer's Disease/HIAAD MENTORSHIP LAB ALUMNI: CURRENT MEMBERS: Postdocs. 9 4 Ph.D. 13 3 M.Sc. 14 4 B.Sc. Thesis 36 3 Practical training 16 2 SERVICE Administrative and Positions of Responsibility Director, Institute for Fundamental Biomedical Research Fleming Governing Board member (2019-current) Chair Biomedical Science Grant evaluation Hellenic Foundation for Research and Innovation HIADD Basic Science Board Member Institutional Fleming Scientific Council member (2015-2018) Scientific Officer, Fleming Technology Transfer Office Biological, Chemical and Refuge Safety Supervising Scientific Officer Editorial Associate Editor, Frontiers in Neuroscience-Neurodegeneration Associate Editor, Frontiers in Cell and Developmental Biology for Molecular Medicine Academic Editor, PLoS ONE Academic Editor, International Journal of Molecular Sciences Review Editor, Frontiers in Neurodegerative Diseases Editorial Board, Current Topics in Toxicology DISSEMINATION I am deeply interested in science dissemination. To that end I have organised meetings for scientists working in invertebrate models in Greece, organised monthly meetings of Behavioral Neuroscientists in the greater Athens area where students and postdoc present their work to colleagues. I was the main organizer and fundraiser two international Drosophila Neurobiology meetings in Greece and two International meetings on Tauopathies in Britain. In addition, I was the main organizer of the Final meeting of the EU program COST Action BM1307. I have taught in International Neuroscience and Quantum Biology Schools in Japan and India. He is a lecturer in four different Graduate programs in the greater Athens area and a founding member of the only International Neuroscience Graduate Program in the greater Athens area. I routinely participate in outreach activities to the general public in events such as “Brain week”, the annual “Athens Science Festival”, the monthly school visits to the Centre and visits to local high schools. Conference and meetings organization Learning and Memory workshop at Genetic Society of America Annual Drosophila Meeting. Chicago 2003 “Small Brains, Big Gains. Memory and movement in flies and bees”. Symposium at Federation of European Neuroscience Societies meeting in Vienna July 2006. First Hellenic Invertebrate Researchers meeting (BRFAA, Athens. 2005) Hellenic Drosophila Meeting (BRFAA, Athens. 2005, 2007) The Biology and Pathology of Tau and its role in Tauopathies Robinson College Cambridge UK (Jan 7-8 2010). Joint effort with Dr A. Mudher (University of Southampton) Sponsored by the British Biochemical Society Competitively renewed for Jan 2012 2014 and 2016. European Neurobiology of Drosophila meeting (Neurofly). Lead organizer. Conference organizer and Management Committee Member [BM1307 EL] to COST Action BM1307 European network to integrate research on intracellular proteolysis pathways in health and disease Lead organizer Final COST Action BM1307 Proteostasis meeting. “ Proteostatic mechanisms in Health and Disease” Feb 2018 Athens Greece Organizer “Quantum Biology” (QUEBS) meeting Crete, Greece 2021 Invited Lectures (Selected) 2019: Plenary speaker. Fondation Sante Symposium, Athens, Greece 2017: Plenary speaker Hellenic Society for Neuroscience, Athens 2017: QUEBS invited speaker, Jerusalem, Israel 2016: QUEBS invited speaker, Durban South Africa 2015: eLife Invited lecture KU and VIB Leuven Belgium 2015: Deans Lecture George Mason University Virginia USA 2014: Learning and memory meeting Janelia campus USA 2013: QUEBS invited speaker, Vienna Austria 2013: Plenary speaker Hellenic Society for Neuroscience, Athens 2013: Plenary speaker Quantum Biology School, IIT Jodhpur, India 2011: QUEBS invited speaker, Ulm Germany 2011: Learning and memory meeting Janelia campus USA 2011: International Summer School on Neurochemistry, Delfi, Greece 2009: Invited talk Queen Mary university London UK 2008: Learning and memory meeting Janelia campus USA 2008: Plenary speaker, Tohoku University Symposium, Sendai Japan 2006: Invited Speaker, Society for Experimental Biology, Kent UK PEER-REVIEWED PUBLICATIONS: In reverse chronological order 1. Georganta, E-M, Moressis, A. and Skoulakis, EMC (2021). "Associative learning requires Neurofibromin within a novel neuronal circuit to modulate GABAergic inputs to Drosophila Mushroom Bodies. J Neurosci. (In Press). 2. Keramidis, I., Vourkou, E., Papanikolopoulou, K. and Skoulakis, EMC. (2020). "Functional Interactions of Tau Phosphorylation sites that Mediate Toxicity and Deficient Learning in Drosophila melanogaster". Front Mol. Neurosci. 13:569520 3. Semelidou O, Acevedo SF, Skoulakis EMC (2019). Accessing Olfactory Habituation in Drosophila melanogaster with a T-maze Paradigm.Bio Protoc. 2019 Jun 5;9(11):e3259. 4. Roussou, I.G., Papanikolopoulou, K., Savvakis, C., and Skoulakis EMC (2019). " Drosophila Bruton's Tyrosine Kinase regulates habituation latency and facilitation in distinct mushroom body neurons." J Neurosci. 39(44):8730-8743 5. Papanikolopoulou, K., Roussou, I.G., Gouzi JY., Samiotaki, M. Panayotou, G., Τurin, L. and Skoulakis E.M.C. (2019) "Drosophila Tau negatively regulates translation and olfactory Long-Term Memory, but facilitates footshock habituation and cytoskeletal homeostasis." J Neuroscience 39(42):8315-8329 6.Tzortzopoulos, T., Thomaidou, D., Gaitanou, M., Matsas, R. and Skoulakis EMC. (2019) "Expression of mammalian BM88/CEND1 in Drosophila affects nervous system development by interfering with precursor cell formation". Neuroscience Bulletin May 11. doi: 10.1007/s12264-019-00386-5 7.Semelidou O, Acevedo SF and Skoulakis EMC (2018) "Temporally specific engagement of distinct neuronal circuits regulating olfactory habituation in Drosophila" Elife. 21;7. pii: e39569. 8. Crittenden JR, Skoulakis EMC, Goldstein ES, Davis RL. (2018). Drosophila mef2 is essential for normal mushroom body and wing development». Biol Open 7(9) pii: bio035618. 9. Kadas D, Papanikolopoulou K, Xirou S, Consoulas C and Skoulakis EMC. (2018). "Human Tau isoform-specific presynaptic deficits in a Drosophila Central Nervous system circuit" Neurobiol Dis. 124:311-321. 10. Gouzi JY, Bouraimi M, Roussou IG, Moressis A and Skoulakis EMC. (2018) "The Drosophila Receptor Tyrosine Kinase Alk Constrains Long-Term Memory Formation". J Neurosci. 29;38(35):7701-7712. 11. Papanikolopoulou K, Grammenoudi S, Samiotaki M and Skoulakis EMC. (2018). "Differential effects of 14-3-3 dimers on Tau phosphorylation, stability and toxicity in vivo." Hum Mol Genet. 27(13):2244-2261. 12. Maniati, K., Haralambous, KJ., Turin, L. and Skoulakis, E. M. C. (2017) "Vibrational detection of odorant functional groups by Drosophila melanogaster." eNeuro.Oct 31;4(5). pii: ENEURO.0049-17.2017. 13. Kotoyla, V., Moressis, A., Semelidou O. and Skoulakis, E. M. C. (2017) "Drk signaling to Rho kinase is required for Anesthesia Resistant Memory in Drosophila" Proc Natl Acad Sci U S A. 114(41): 10984-10989 14. Paoli, M., Münch, D., Haase, A., Skoulakis, E.M.C., Turin, L. and Galizia, CG. (2017) "Minute impurities contribute significantly to olfactory receptor ligand studies: tales from testing the vibration theory." eNeuro Jun 19;4(3). pii: ENEURO.0070-17.2017. doi: 10.1523/ENEURO.0070-17. 15. Sealey MA, Vourkou E, Cowan CM, Bossing T, Quraishe S, Grammenoudi S, Skoulakis EMC, Mudher A. (2017). Distinct phenotypes of three-repeat and four-repeat human tau in a transgenic model of tauopathy. Neurobiol Dis. 2017 105:74-83 16. Mansilla A, Chaves-Sanjuán A, Campillo N E, Semelidou O, Martínez-González L, Infantes L, González-Rubio J M, Gil C, Conde S, Skoulakis EMC, Ferrús A, Martínez A, Sánchez-Barrena M J. (2017) “Phenothiazines regulate synaptic function by interfering the NCS-1/Ric8a complex: a novel approach for Fragile X Syndrome” Proc Natl Acad Sci U S A. 114(6):E999-E1008. doi: 10.1073/pnas.1611089114. 17. Drimyli E, Gaitanidis A, Maniati K, Turin L, Skoulakis EMC (2016). "Differential electrophysiological responses to odorant isotopologues in Drosophilid antennae" eNeuro. 0152-15.2016. doi:10.1523 18. Papanikolopoulou K, Skoulakis EM. (2014) Temporally distinct phosphorylations differentiate Tau-dependent learning deficits and premature mortality in Drosophila. Hum Mol Genet. 24(7):2065-77 19. Turin, L., Skoulakis, E.M.C., Horsfield, A.P. (2014) Electron spin changes during general anesthesia in Drosophila. Proc Natl Acad Sci U S A. 111(34):E3524-33. 20. Kosmidis, S., Missirlis, F., Botella, J.A., Schneuwly, S., Rouault, T.A., Skoulakis, E.M.C. (2014). Behavioral decline and premature lethality upon pan-neuronal ferritin overexpression in Drosophila infected with a virulent form of Wolbachia. Front Pharmacol. 4; 5:66. 21. Lalle, M., Leptourgidou, F., Camerini, S., Pozio, E. and Skoulakis, E.M.C (2013) "Interkingdom complementation reveals structural conservation and functional divergence of 14-3-3 proteins." PLoS One. 2013;8(10):e78090. doi: 10.1371/journal.pone.0078090. 22. Gane, S., Georganakis, D., Maniati, K., Vamvakias, M., Ragoussis, N., Skoulakis, E.M.C, Turin L. (2013) "Molecular vibration-sensing component in human olfaction." PLoS One. 2013;8(1):e55780. doi: 10.1371/journal.pone.0055780. 23. Kanellopoulos, K. A., Semelidou, O, Anezaki, M., Kotini, A. G., and Skoulakis, E. M. C. (2012) "Learning and memory deficits consequent to FMRP reduction result from mGluR-mediated inhibition of cAMP signaling in Drosophila" 2012, J. Neurosci. 32(38):13111-13124. 24. Tsigkari, K., Acevedo, S. F, and Skoulakis, E. M. C. (2012) "14-3-3 ε is required for germline migration in Drosophila" PLoS One 7(5): e36702. doi:10.1371/journal.pone.0036702 25. Kadas, D., Tzortzopoulos, A., Skoulakis, E. M. C. and Consoulas, C. (2012) "Constitutive activation of Ca2+/Calmodulin-dependent Protein Kinase II during development impairs central cholinergic transmission and motor behavior in Drosophila." J. Neurosci., 32(1):170-82 26. Gouzi, J. Y., Moressis, A ., Walker, J. A., Apostolopoulou, A. A., Palmer, R. H., Bernards, A. and Skoulakis, E. M. C. (2011) "Drosophila Alk Tyrosine Kinase Controls Neurofibromin dependent Growth and Learning" PLoS Genet ,7(9): e1002281 27. Memos N, Kataki A, Chatziganni E, Nikolopoulou M, Skoulakis E, Consoulas C, Zografos G, Konstadoulakis M (2011). "Alternations of 14-3-3 θ and β protein levels in brain during experimental sepsis". J Neurosci Res. 2011 May 26. doi: 10.1002/jnr.22673 28. Shandala, T., Woodcock, J. M., Ng,Y., Biggs, L., Skoulakis, E.M.C., Brooks, D. A., and Lopez, A. F. (2011) "Innate immunity is regulated in Drosophila by 14-3-3ε's function in vesicular assembly and anti-microbial peptide secretion." J Cell Sci. 124(Pt 13):2165-74. 29. Kosmidis, S., Botella J. A., Mandilaras, K. Schneuwly, S., Skoulakis, E. M. C., Rouault, T. A. and Missirlis, F. (2011) "Ferritin overexpression in Drosophila glia leads to iron deposition in the optic lobes and late onset behavioural effects". Neurobiol Dis 43(1): 213-219 30. Franco MI, Turin L, Mershin A, Skoulakis E.M.C. (2011). "Molecular vibration-sensing component in Drosophila melanogaster olfaction." Proc Natl Acad Sci U S A. 108(9) :3797-802 31. Papanikolopoulou K., Kosmidis S., Grammenoudi S., Skoulakis E. M. C. (2010). "Phosphorylation differentiates tau-dependent neuronal toxicity and dysfunction. Biochem Soc Trans. 38(4):981-7. 32. Kosmidis, S., Grammenoudi, S. Papanikolopoulou, K. and Skoulakis, E. M. C (2010). "Differential effects of Tau on the integrity and function of neurons essential for learning in Drosophila". J. Neurosci. 30(2): 464-477. 33. Messaritou G, Grammenoudi, S. and Skoulakis EMC (2010) "Dimerization is essential for Drosophila 14-3-3ζ protein stability and function in vivo". J. Biol. Chem. 285(3):1692-700. 34. Messaritou G, Leptourgidou F. Franco, M and Skoulakis EMC. (2009) "A third functional isoform enriched in mushroom body neurons is encoded by the Drosophila 14-3-3ζ gene" FEBS Lett. 583: 2934-2938 35. Moressis, A., Friedrich, A. R., Pavlopoulos E., Davis, R. L. and E. M.C. Skoulakis. (2009) "A dual role for the adaptor protein DRK in Drosophila olfactory learning and memory." J. Neurosci. 29:2611-2625. 36. Pavlopoulos, E., Anezaki, M. and Skoulakis, E. M. C. (2008) "Neuralized is expressed in the α/β lobes of adult Drosophila Mushroom Bodies and facilitates olfactory Long-Term Memory formation". Proc Natl Acad Sci USA. 105(38):14674-9. 37. Tzortzopoulos, A, and Skoulakis E. M. C. (2007). Paternally and maternally transmitted GAL4 transcripts contribute to UAS transgene expression in early Drosophila embryos. Genesis. 45: 737-743 38. Acevedo, S. F., Tsigkari, K., Grammenoudi, S. and Skoulakis, E. M. C. (2007) "14-3-3 functional specificity and redundancy of 14-3-3 proteins in Drosophila melanogaster". Genetics. 177 (1): 239-253 39. Missirlis, F, Kosmidis, S., Brody, T., Mavrakis, M., Holmberg, S., Odenwald, W. F., Skoulakis, E.M.C., and Rouault T. A. (2007) "Multiple homeostatic mechanisms for iron storage revealed by genetic manipulations of Drosophila ferritin" Genetics. 177 (1): 89-100 40. Tsichitzis, T., Gaentzsch, P., Kosmidis, S., Brown, A. E., Skoulakis, E. M. C., Ligoxygakis, P., and Mosialos, G. (2007) "A Drosophila ortholog of the cylindromatosis tumor suppressor regulates triglyceride content and antibacterial defense" Development 134(14): 2605-2614 41. Acevedo, S. F, Froudarakis, E., Tsiorva, A-A., and Skoulakis E. M. C. (2007). "Distinct neuronal circuits mediate experience dependent, non-associative osmotactic responses in Drosophila". Mol. Cell. Neurosci. 34(3): 378-389 42. Acevedo, S. F., Froudarakis, E. I., Kanellopoulos, A. and Skoulakis, E. M. C. (2007) "Protection from premature habituation requires functional mushroom bodies in Drosophila" Learn. Mem. 14(5): 376-384 43. Grammenoudi S., Kosmidis, S. and Skoulakis, E. M. C. "Cell type-specific processing of human Tau proteins in Drosophila" (2006). FEBS Lett. 580(19): 4602-6. 44. Mershin, A., Pavlopoulos, E., Fitch, O., Braden, B. C., Nanopoulos, D. V. and Skoulakis, E. M. C. (2004) "Learning and memory deficits upon TAU accumulation in Drosophila mushroom body neurons." Learn. Mem. 11: 277-287 45. Chen, H-K., Fernandez-Funez,P., Lam, Y. C., Kaytor, M. D., Fernandez, M. H., Acevedo, S. F., Aitken, A., Skoulakis, E. M. C., Orr, H. T., Botas, J. and Zoghbi , H.Y. (2003). "Akt phosphorylation-dependent association of ataxin-1 with 14-3-3 mediates neurodegeneration in spinocerebellar ataxia type 1". Cell 113, 457-468 46. Sathyanarayana, P., Barthwal, M. K., Lane, M. E., Acevedo, S. F., Skoulakis, E. M. C., Bergman, A., Rana, A. (2003) Drosophila Mixed Lineage Kinase, a missing biochemical Link in Drosophila JNK signaling. Biochem. Biophys. Acta. 1640, 77-84. 47. Philip, N. Acevedo, S. and Skoulakis, E. M. C. (2001) Conditional rescue of olfactory learning and memory defects in mutants of the 14-3-3 gene leonardo . J. Neurosci 21 (21), 8417-8425. 48. Crittenden, J. R. , Skoulakis, E. M. C., K.-A. Han, Kalderon, D. and Davis, R. L. (1998).Tripartite Mushroom Body architecture revealed by antigenic markers. Learn. Mem. 5 (1 and 2), 38-51. 49. Li, W., Skoulakis, E. M. C. , Davis, R. L. and Perrimon, N. (1997) The Drosophila 14-3-3 protein Leonardo enhances Torso signaling through D-Raf in a Ras1-dependent manner. Development, 124, 4163-4171. 50. Broadie, K., Rushton, E., Skoulakis, E. M. C. and Davis, R. L. (1997) Leonardo, a Drosophila 14-3-3 protein involved in learning regulates presynaptic function. Neuron, 19, 391-402. 51. Skoulakis, E. M. C. and Davis, R. L. (1996) Olfactory learning deficits in mutants for leonardo, a Drosophila gene encoding a 14-3-3 protein. Neuron, 17, 931-944. 52. Skoulakis, E. M. C., Kalderon, D. and Davis, R. L. (1993). Preferential Expression in Mushroom Bodies of the Catalytic Subunit of Protein Kinase A and its Role in Learning and Memory. Neuron 11, 197-208. 53. Leicht, B., Skoulakis, E., Sites, C, Lyckegaard, E, Clark A. (1991). Identification of cis-regulatory elements involved in alternative splicing of the MLK-ALK pre-messenger-RNA of Drosophila. Am. J. Human Genetics 49(4), 430 Other (Reviews and book chapters): 54. Semelidou O and Skoulakis, EMC. One size does not fit all in Drosophila olfactory habituation.(2020). Proc Natl Acad Sci U S A. 117(34):20372 55. Papanikolopoulou K and Skoulakis EMC "Altered Proteostasis in Neurodegerative Tauopathies" (2020). Adv Exp Med Biol. 1233:177-194 56. Papanikolopoulou K, Mudher A, Skoulakis E. "An assessment of the translational relevance of Drosophila in drug discovery." Expert Opin Drug Discov. 2019 Mar;14(3):303-313. 57. Turin L and Skoulakis EMC. (2018) "Electron Spin Resonance (EPR) in Drosophila and General Anesthesia" Methods Enzymol. 2018;603:115-128. 58. Sotiropoulos I, Galas M-C, Silva JM, Skoulakis EMC, et al (2017). Atypical novel functions of the microtubule-associated Tau protein Acta Neuropathologica Comm. 5(1):91 doi: 10.1186/s40478-017-0489-6. 59. Turin L, Gane S, Georganakis D, Maniati K, Skoulakis EM. "Plausibility of the vibrational theory of olfaction." Proc Natl Acad Sci U S A. 2015 Jun 23;112(25):E3154. doi: 10.1073/pnas.1508035112. 60. Skoulakis EM, Mudher A. "Twice is better: Highlights of the second meeting focused on tau biology and pathology". Biochem Soc Trans. 2012 Aug 1;40(4):641-3. 61. Morales D, Skoulakis E.M.C. and Acevedo, SF. (2012) "14-3-3s are potential biomarkers for HIV-related neurodegeneration." J Neurovirol. 18(5):341-53 62. Franco MI, Turin L, Mershin A, Skoulakis E.M.C. (2011). "Olfaction is a physical and a chemical sense in Drosophila." Proc Natl Acad Sci U S A. 108(31): E350 63. Papanikolopoulou K. and Skoulakis, E. M. C. (2011) "The Power and Richness of modelling Tauopathies in Drosophila" Molecular Neurobiology 44(1):122-3318 64. Skoulakis E. M. C., Mudher A. "Two days of tau: a meeting focused on its biology and pathology." Biochem Soc Trans. 2010 Aug 1;38(4):953-4. 65. Grammenoudi, S., Anezaki, M. Kosmidis, S. and Skoulakis E. M. C. (2008). "Modeling Cell and Isoform type specificity of Tauopathies in Drosophila". In Drosophila: A Toolbox for the study of Neurodegenerative Disease. SEB Exp Biol Ser 60: pp 39-56. A. Mudher and T. Newman eds. Taylor & Francis group. 66. Skoulakis E. M. C. and Grammenoudi, S. (2006) "Dunces and DaVincis; The Genetics of Learning and Memory in Drosophila" Cellular and Molecular Life Sciences, 63, 975-988. 67. Mershin, A., Sanabria, H., Miller, J. H., Nawarathna, D., Skoulakis, E. M. C., Mavromatos, N. E., Kolomenskii, A. A. Schuessler, H. A., Luduena, R. F., Nanopoulos, D. V. (2005) "Towards experimental tests of quantum effects in Cytoskeletal proteins." In "The Emerging Physics of Consciousness" pp 89-148. Jack Tuszynski, ed. Springer-Verlag 68. Skoulakis, E. M. C. and Davis, R. L. (1998) 14-3-3 proteins in Neuronal development and function. Molecular Neurobiology, 16, 269-284. 69. Davis, R. L., Cherry, J., Dauwalder, B., Han, P.–L. and Skoulakis, E. M. C. (1995). The Cyclic AMP System and Drosophila Learning. Molecular and Cellular Biochemistry. 149/150:271-278 70. Skoulakis, E. M. C. , Han, P.-L. and Davis, R. L. (1993). Learning and memory in Drosophila. Novo Nordisk Foundation Symposium #7. Memory concepts. Basic and Clinical aspects. Elsevier Science Publishers. pg 99-111.

Researcher A and Director, Institute for Fundamental Biomedical Research

Biomedical Sciences Research Centre "Alexander Fleming"

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