Curriculum Vitae Ioannis V. Zaganas, MD, PhD Heraklion, Crete, November 2010 Personal Information http://www.neurologycrete.gr/index.php/el/zaganasioannis Date of birth: Address: Tel: Ε-mail: May 16th, 1973 Voutes, 70013, Heraklion, Crete, Greece +30-2810721493, +30-6946060360 johnzag@med.uoc.gr, johnzag@yahoo.com Education 1991-1997: University of Crete, Medical School (MD Degree) Postgraduate training and professional appointments (1) (2) (3) (4) (5) Doctoral Dissertation (1999-2005): «Glutamate dehydrogenase in the biology of the mammalian nervous system». Medical School, University of Crete (Advisor: Professor A. Plaitakis) Postdoctoral Fellow (2004-2005): Mount Sinai School of Medicine, Department of Psychiatry and Neurobiology (New York, USA), on Genetics and Neurobiology of Alzheimer’s Disease (Supervisor: Professor N. Robakis) Neurology Residency (2005-2008): Neurology Department, University Hospital of Heraklion, Crete (Neurology Certification on October 2010) Internal Medicine Residency (1999): Internal Medicine Department, University Hospital of Heraklion, Crete Psychiatry Residency (2000): Psychiatry Department, University Hospital of Heraklion, Crete 1 (6) (7) Neurology Consultant, Neurology Department, University Hospital of Heraklion, Crete (2010) Rural Service, Kastelli Health Center, Crete (1997-1999) Faculty appointments (1) (2) Temporary Lecturer of Neurology (Law PD407), University of Crete, Medical School (2009-2010) Temporary Assistant Professor of Neurology (Law PD407), University of Crete, Medical School (2008-2009) Scholarships (1) (2) (3) (4) (5) Scholarship from the “A. Onassis” foundation for training in Mount Sinai Hospital, New York (2004-2005) Scholarship “M. Manassaki” (University of Crete) for postgraduate studies (2001-2003) Scholarships from the Association for Research and Treatment of Neurological Disorders of Crete “EY ZHN” (1999-2009) Scholarship from the Erasmus program (pre-graduate training in Pediatrics in Lyon, France) (1996) Greek State Scholarships (IKY) for being within the top students in Medical School (19921994) Molecular Biology Techniques and other skills (1) (2) Cell cultures (mammalian and insect cells) Cloning, mutagenesis, protein expression in bacteria, insect cells, mammalian cells (EGFP, retroviral and Baculovirus systems, etc) (3) Enzyme kinetics, protein purification (chromatography systems), structural modeling software (Pymol, Swiss PDB viewer, etc) (4) SDS PAGE, Western blot, Immuno-fluorescence, Confocal microscopy, Coimmunoprecipitation (5) Cellular biology studies (cell survival pathways, apoptosis studies, kinase pathways, etc) (6) Mouse neuronal primary cultures (7) Production and characterization of polyclonal antibodies (8) PCR, Sequencing (ABI 3100 etc), Fragment Analysis (9) Genetic studies: Linkage analysis, Association studies (10) Statistical software (Origin, SPSS, Excel, etc) (11) English, French (fluently) 2 Publications in peer-reviewed journals: (1) Zaganas I, Plaitakis A. Single amino acid substitution (G456A) in the vicinity of the GTP binding domain of human housekeeping glutamate dehydrogenase markedly attenuates GTP inhibition and abolishes the cooperative behaviour of the enzyme. J Biol Chem 277: 26422-26428, 2002. (2) Zaganas I, Spanaki C, Karpusas M, Plaitakis A. Substitution of Ser for Arg443 in the regulatory domain of human housekeeping (GLUD1) glutamate dehydrogenase virtually abolishes basal activity and markedly alters the activation of the enzyme by ADP and Lleucine. J Biol Chem 277: 46552-46558, 2002. (3) Spanaki C*, Zaganas I*, Kleopa K, Plaitakis A. Human GLUD2 glutamate dehydrogenase is expressed in neural and testicular supporting cells. J Biol Chem 2010 (in press). *equal contribution (4) Xu J, Litterst C, Georgakopoulos A, Zaganas I, Robakis NK. Peptide EphB2/CTF2 generated by the gamma-secretase processing of EphB2 receptor promotes tyrosine phosphorylation and cell surface localization of N-methyl-D-aspartate receptors. J Biol Chem 284: 27220-27228, 2009. (5) Zaganas I, Waagepetersen HS, Georgopoulos P, Sonnewald U, Plaitakis A, Schousboe A. Differential expression of glutamate dehydrogenase in cultured neurons and astrocytes from mouse cerebellum and cerebral cortex. J Neurosci Res 66: 909-913, 2001. (6) Zaganas I, Prinianakis G, Xirouchaki N, Mavridis M. Opsoclonus-myoclonus syndrome associated with Cytomegalovirus encephalitis. Neurology 68: 1636, 2007. (7) Zaganas Ι, Latsoudis Η, Papadaki Ε, Vorgia P, Spilioti M, Plaitakis A. A8344G tRNALys Mutation Associated with Recurrent Brain Stem Stroke-like Episodes. J Neurol 256: 271273, 2009. (8) Zaganas I, Kanavouras K, Mastorodemos V, Latsoudis H, Spanaki C, Plaitakis A. The human GLUD2 glutamate dehydrogenase: localization and functional aspects. Neurochem Int 55: 52-63, 2009. (9) Plaitakis A, Zaganas I. Regulation of Human Glutamate Dehydrogenases: Implications for Glutamate, Ammonia and Energy Metabolism in Brain. J Neurosci Res 66: 899-908, 2001. (10) Plaitakis A, Spanaki C, Mastorodemos V, Zaganas I. Study of Structure-Function Relationships in Human Glutamate Dehydrogenases Reveals Novel Molecular Mechanisms for the Regulation of the Nerve Tissue-Specific (GLUD2) Isoenzyme. Neurochem Int 43: 401-410, 2003. (11) Mastorodemos V, Zaganas I, Spanaki C, Bessa M, Plaitakis A. Molecular basis of human glutamate dehydrogenase regulation under changing energy demands. J Neurosci Res 79: 65-73, 2005. (12) Saloustros E, Zaganas I, Mavridis M, Vamvakas L, Plaitakis A, Georgoulias V, Mavroudis D. Anti-CV2 associated cerebellar degeneration after complete response to chemoradiation of head and neck carcinoma. J Neurooncol 97: 291-294, 2010. 3 (13) Mastorodemos V, Kotzamani D, Zaganas I, Arianoglou G, Latsoudis H, Plaitakis A. Human GLUD1 and GLUD2 glutamate dehydrogenase localize to mitochondria and endoplasmic reticulum. Biochem Cell Biol 87: 505-516, 2009. (14) Kanavouras K, Borompokas N, Latsoudis H, Stagourakis A, Zaganas I, Plaitakis A. Mutations in human GLUD2 glutamate dehydrogenase affecting basal activity and regulation. J Neurochem 109 (Sup. 1): 167-173, 2009. (15) Plaitakis A, Latsoudis H, Kanavouras K, Ritz B, Bronstein JM, Skoula I, Mastorodemos V, Papapetropoulos S, Borompokas N, Zaganas I, Xiromerisiou G, Hadjigeorgiou GM, Spanaki C. Gain-of-function variant in GLUD2 glutamate dehydrogenase modifies Parkinson's disease onset. Eur J Hum Genet 18: 336-341, 2010. (16) Plaitakis A, Viskadouraki K, Tzagournissakis M, Zaganas I, Verghese-Nikolakaki S, Karagiorgis V, Panagiotides I, Kilindireas C, Patsouris E, Haberler C, Budka H, Sklaviadis T. Increased incidence of Sporadic Creutzfeldt-Jakob disease on the island of Crete associated with a high rate of PRNP 129 methionine homozygosity in the local population. Ann Neurol 50: 227-233, 2001. (17) Kofteridis DP, Karabekios S, Repa A, Zaganas I, Anastasopoulos T, Barbounakis E, Gikas A. A case of human immunodeficiency virus infection disclosed by cytomegalovirus encephalitis. Int J Infect Dis. 11:373-5, 2007. (18) Borompokas N, Papachatzaki MM, Kanavouras K, Mastorodemos V, Zaganas I, Spanaki C, Plaitakis A. Estrogen modification of human glutamate dehydrogenases is linked to enzyme activation state. J Biol Chem, 285: 31380-7, 2010. (19) Papapanagiotou P, Iacovidou N, Spengos K, Xanthos T, Zaganas I, Aggelina A, Alegakis A, Vemmos K. Temporal trends and associated factors for prehospital and in hospital stroke-related delay over a 16-year period: the Athens Study. Cerebrovasc Dis (in press), 2010. Selected abstracts (1) (2) (3) Zaganas I, Halpin AP, Oleink A, Kotzamani D, Chlapoutaki C, Tsimoulis D, Zafiris S, Giannakoudakis E, Alegakis A, Papadaki E, Furie KL, Greenberg SM, Plaitakis A. A Comparison of Acute Hemorrhagic Stroke Outcomes in Two Populations: The Crete-Boston Study. International Stroke Conference 2010, San Antonio, Texas (February 24-26, 2010). Stroke 41 (4): e13. Zaganas I, Latsoudis H, Papadaki E, Vorgia P, Spilioti M, Plaitakis A. Mitochondrial DNA A8344G tRNALys mutation associated with recurrent migratory brainstem stroke-like episodes. 132nd Annual Meeting of the American Neurological Association, 7-10 October 2007, Washington DC, United States. Ann Neurol 62 (suppl. 11): S47, 2007. Zaganas I, Saloustros E, Vamvakas L, Mavridis M. Paraneoplastic cerebellar degeneration associated with tongue cancer and anti-CV2 auto-antibodies. Poster Presentation at the 18th 4 Meeting of the European Neurological Society (7 - 11 June 2008, Nice, France). J Neurol 255 (suppl. 2): S153, 2008. (4) Zaganas I, Latsoudis H, Spilioti M, Tzagournissakis M, Amoiridis G, Plaitakis A. Title: Novel spastin mutation (IVS14+5G > A) in a Greek family with hereditary spastic paraplegia. Poster Presentation at the 18th Meeting of the European Neurological Society (20 - 24 June 2009, Milan, Italy). J Neurol 256 (suppl. 2): S156, 2009. (5) Plaitakis A, Viskadouraki A, Tzagournissakis M, Zaganas JV, Panayiotides J, Manousis T, Verghese-Nikolakaki S, Patsouris E, Haberler C, Budka H, Sklaviadis T. Increased incidence of sporadic Creutzfeldt-Jacob disease on the Island of Crete associated with a reduced rate of codon 129 Methionine/Valine heterozygosity in the local population. 52nd American Academy of Neurology Annual Congress 2000, San Diego, CA, United States. Neurology 2000; 54 (suppl 3): A285. (6) Spanaki C, Zaganas I, Plaitakis A. Frequent familial occurrence of late onset, Dopa responsive Parkinson’s disease on the island of Crete. 52nd American Academy of Neurology Annual Congress 2000, San Diego, CA, United States. Neurology 2000; 54 (suppl 3): A263 (7) Plaitakis A, Zaganas I. Allosteric regulation of human glutamate dehydrogenase, derived from the GLUD1 (housekeeping) and the GLUD2 genes (nerve tissue specific), and its implications for glutamate metabolism under changing energy demands. 5th International Conference on Brain Energy Metabolism. Trondheim, Norway, 19-22/5/2001. (8) Plaitakis A, Zaganas I. Gly456 and Arg443 are essential for allosteric regulation of human GLUD1 glutamate dehydrogenase. 33rd Annual Meeting of the American Society for Neurochemistry, 22-26 June 2002, Palm Beach, Florida, United States. J Neurochem 81 (suppl 1): 26, 2002. (9) Tzifa G, Kalikakis G, Zaganas I, Spilioti M, Kofteridis D, Daraki V, Petkova V, Tzoutzouraki P, Papavasileiou S. Secondary hypothalamic amenorrhea as the initial manifestation of HIV infection. 9th European Congress of Endocrinology, 28 April - 2 May 2007, Budapest, Hungary. (10) Zaganas I, Spanaki C, Plaitakis A. Structure-function relationship of brain-specific glutamate dehydrogenase, as studied by site-directed mutagenesis, reveals that Ser443 and Ala456 are critical for enzyme regulation in nerve tissue. 17th meeting of the Greek Society for Neuroscience: “Brain, Mind and Behavior”, 4-6 October 2002, Rethimnon, Crete, Greece. (11) Spanaki C, Mastorodemos V, Zaganas I, Plaitakis A. Purified nerve tissue-specific glutamate dehydrogenase has properties adapted to the metabolism of excitatory neurotransmitter glutamate. 17th meeting of the Greek Society for Neuroscience: “Brain, Mind and Behavior”, 4-6 October 2002, Rethimnon, Crete, Greece. (12) Evangeliou A, Varakis N, Spilioti M, Michailidou H, Sofokleous C, Frysira H, Zaganas I, Tzoufi M, Nikolaidou P. Autism and inborn errors of metabolism. Are we effective with the diagnosis? 1st Aegean Meeting on Neurologic Therapeutics, September 11-15, 2004, Heraklion, Crete, Greece. 5 (13) Mastorodemos V, Zaganas I, Petsakou A, Plaitakis A. Subcellular localisation of human GLUD1 and GLUD2-derived glutamate dehydrogenase. 2nd Aegean Meeting on Neurologic Therapeutics, May 20-23, 2006, Heraklion, Crete, Greece. (14) Kanavouras K, Spanaki C, Zaganas I, Plaitakis A. Substitution of Serine 445 by Alanine in the GLUD2-gene encoding neural tissue specific glutamate dehydrogenase associated with early onset Parkinson’s disease in male hemizygotic carriers. 2nd Aegean Meeting on Neurologic Therapeutics, May 20-23, 2006, Heraklion, Crete, Greece. Invited speaker in meetings (1) (2) Clinical picture and pathophysiology of Dementia: Nuclear Medicine / Neurology Conference, Heraklion (November 24th, 2007). Human glutamate dehydrogenases: structure and function: Glutamate in the tripartite synapse: functional and metabolic relations in norm and pathology Conference, Wierzba (Mazurian lakes, Poland) (23-27 August 2008). 6