Cellular and Molecular Neurobiology – Stem Cells

Rebecca Matsas | Department of Neurobiology

Head of Laboratory

Contact:

Tel:+30 2106478843 |  .img@.img|  CV

ABOUT

Our long-running research has focused on nervous system development and regeneration aiming at translational approaches for the treatment of neurodegenerative diseases and neurotrauma. We have been studying the biology of neural stem cells, especially mechanisms regulating proliferation versus differentiation, and have developed therapeutic cell transplantation approaches in pre-clinical animal models of neurodegeneration.

Our approaches integrate techniques of cell and animal modeling, histopathology, bioimaging, molecular biology and genetics, biochemistry, ex vivo and in vivo gene therapy with viral vectors.

We have established a microsurgery and neural stem cell/Schwann cell transplantation Unit for rodent models of neuropathology in conjunction with histopathology and behavioural suites to monitor anatomical and functional recovery.

We are closely connected and have contributed to the establishment of the Institute’s Bioimaging Unit through acquisition of new instrumentation and know-how development.

More recently our group has been using neural precursor cells and neurons derived from human embryonic stem cells and induced pluripotent stem cells to model human neural development and disease and has established the Institute’s Human Embryonic and Induced Pluripotent Stem Cell Unit.

RESEARCH PROJECTS

Human embryonic stem cells and induced pluripotent stem cells (iPSCs) for modeling neural development and neurological disease – Establishment of the Institute’s Human Stem Cell Unit

Understanding the mechanisms underlying human brain development and disease has long been hampered by limited access to the living brain and the inability to isolate and maintain live human neurons. The recent advent of human stem cells in combination with cellular reprogramming technologies has opened new avenues in the field of brain research. Human embryonic stem cells (HUES) and induced pluripotent stem cells (hiPSCs) generated by reprogramming of differentiated somatic cells to pluripotency, provide for the first time the opportunity to foster live human neurons in the laboratory. hiPSCs can be derived from adult cells of a healthy individual or a patient with neurological disease and then turned into neurons thus constituting an attractive biological system for modeling human brain development and disease. We have generated hiPSCs from healthy donors but also from patients with a familial form of Parkinson’s disease (PD), carrying the autosomal dominant point mutation G209S in the alpha synuclein gene SNCA, which results in the pathological p.A53T-αSyn protein. This mutation was first identified in families of Greek and Italian origin and is prevalent in Greece.

 

Development of an iPSC-based model for studying Parkinson’s disease pathogenesis: a platform for identification and testing of candidate disease-modifying compounds

α-Synuclein (αSyn) is the major gene linked to sporadic Parkinson’s disease (PD) while the G209A (p.A53T) αSyn mutation causes a familial form of PD characterized by early onset and a generally severe phenotype, including non-motor manifestations. Based on our garnered knowledge in brain development and regeneration, we launched a project for de novo generation of induced pluripotent stem cells (iPSCs) from fibroblasts of patients harboring the p. A53T mutation (provided by Prof. Stefanis at BRFAA). We developed a robust model that captures PD pathogenic processes at basal conditions. iPSC-derived mutant neurons displayed novel disease-relevant phenotypes, closely resembling those observed in brains of p. A53T-patients. Small molecules targeting αSyn, reverted the degenerative phenotype indicating a treatment strategy for PD and other synucleinopathies. Further, mutant neurons showed disrupted synaptic connectivity and widespread transcriptional alterations in genes involved in synaptic signaling, a number of which have been previously linked to mental disorders. Our findings raise intriguing implications for potentially converging pathological mechanisms in psychiatric and neurologic diseases, highlight a promising therapeutic strategy for PD and other synucleinopathies and provide a cellular platform to screen disease modifying drugs.

Members involved

Kouroupi, E. Taoufik, N. Antoniou, G. Athanasopoulou, F. Papastefanaki, R. Matsas (PI)

Relevant publication

  • Grudina C, Kouroupi G, Nonaka T, Hasegawa M, Matsas R, Zurzolo C. Human NPCs can degrade α-syn fibrils and transfer them preferentially in a cell contact-dependent manner possibly through TNT-like structures. Neurobiol Dis. 2019 Dec;132:104609. doi: 10.1016/j.nbd.2019.104609. Epub 2019 Sep 5.
  • Elkouris M, Kouroupi G, Vourvoukelis A, Papagiannakis N, Kaltezioti V, Matsas R, Stefanis L, Xilouri M and Politis PK. Long non-coding RNAs associated with neurodegeneration-linked genes are reduced in Parkinson’s Disease patients. Front Cell Neurosci. 2019 Feb 22;13:58. doi: 10.3389/fncel.2019.00058. eCollection 2019.
  • Taoufik E, Kouroupi G, Zygogianni O., Matsas R. Synaptic dysfunction in neurodegenerative and neurodevelopmental diseases: an overview of induced pluripotent stem cell-based disease models. Royal Society’s Open Biology, 2018.
  • Kouroupi G, Taoufik E, Vlachos IS, Tsioras K, Antoniou N, Papastefanaki F, Chroni-Tzartou D, Wrasidlo W, Bohl D, Stellas D, Politis PK, Vekrellis K, Papadimitriou D, Stefanis L, Bregestovski P, Hatzigeorgiou AG, Masliah E, Matsas R. Defective synaptic connectivity and axonal neuropathology in a human iPSC-based model of familial Parkinson’s disease. Proceedings of the National Academy of Sciences USA, 2017.

A human stem cell-based model of neurodevelopment for the identification of novel miRNAs controlling neurogenesis

Apart from the well known fully annotated protein-coding transcripts, non-coding RNAs are being vigorously researched for physiological and pathological implications, especially miRNAs. To identify signaling networks relevant for neural development, we performed whole transcriptome RNA-sequencing of coding and non-coding RNAs at distinct stages of neuronal differentiation of human embryonic stem (HUES) cells. Systematic analysis of RNA-Seq data on miRNA expression (in collaboration with A. Hatzigeorgiou, DIANA-Lab at HPI) is implemented to reveal novel miRNAs involved in neurogenesis and identify the underlying mechanisms using gain- and loss-of-function approaches.

Members involved

Prodromidou, G. Kouroupi, E. Taoufik, M. Gaitanou, R. Matsas (PI)

Relevant publication

  • Prodromidou K, Vlachos IS, Gaitanou M, Kouroupi G, Hatzigeorgiou AG, Matsas R. MicroRNA-934 is a novel primate-specific small non-coding RNA with neurogenic function during early development. Elife. 2020 May 27;9:e50561. doi: 10.7554/eLife.50561. Online ahead of print.

Col. Dr Regis Grailhe

High Content screening analysis for the identification of kinase inhibitors that enhance differentiation to dopaminergic neurons in an iPSC-based model of Parkinson’s disease

The purpose of this study is to identify small molecules that selectively enhance the survival and/or differentiation of dopaminergic neurons as a new therapeutic strategy. Since kinases are attractive targets for the treatment of various diseases, including degenerative diseases of the brain, we chose to test a library of kinase inhibitors, in collaboration with Dr. Regis Grailhe at the Technology Resource Center of the Institute Pasteur in Korea, on iPSC-derived neurons from p.A53T patients and healthy donors. Several hits were obtained and are being validated.

Members involved

Antoniou (PhD), E. Taoufik, G. Kouroupi, R. Matsas (PI)

In vivo modeling of p.A53T-aSyn pathology

The goal of this project is to study the properties of p.A53T iPSC-derived neural precursors in vivo after transplantation in a hemi-parkinsonian mouse model generated by stereotactic injection of 6-hydroxy-dopamine (6-OHDA) in the striatum of immunosupressed NOD-SCID mice. Ongoing analysis aims to determine the survival, differentiation and integration of transplanted cells in the host brain, using immunohistochemistry, confocal microscopy & image analysis and behavioural assessment.

Members involved

Zygogianni (PhD), E. Taoufik, G. Kouroupi, M.Kalomoiri, R. Matsas (PI)

Relevant publication

  • Zygogianni O, Kouroupi G, Taoufik E, Matsas R. Engraftable Induced Pluripotent Stem Cell-Derived Neural Precursors for Brain Repair. Methods Mol Biol. 2020;2155:23-39. doi: 10.1007/978-1-0716-0655-1_3.
  • Zygogianni O, Antoniou A, Kalomoiri M, Kouroupi G, Taoufik E, Matsas R. In vivo phenotyping of familial Parkinson’s disease with human induced pluripotent stem cells: a proof-of-concept study. Neurochem Res. 2019 Apr 15. doi: 10.1007/s11064-019-02781-w.

Modeling Primary Progressive Multiple Sclerosis with Induced Pluripotent Stem Cell-Derived Biological Systems

Multiple Sclerosis (MS) is the prototype immune-mediated neurodegenerative disease with current treatments targeting the inflammatory component of the disease whilst the progressive irreversible central nervous system (CNS) tissue damage, brain atrophy and neurological disability progress are not halted by current therapies. Today MS remains an incurable devastating neurological disorder with an unmet need for effective therapies. Current models do not adequately phenocopy MS pathology and fail to recapitulate the characteristics of the human disorder. To address this problem, we established hiPSC lines from Primary Progressive MS patients, in collaboration with Dr V. Fossati, NYSCF, to identify perturbations in neuronal function and synaptic homeostasis that could render hiPSC-derived neurons susceptible within an inflammatory environment.

Members involved

E. Taoufik (PI), G. Kouroupi, F. Papastefanaki, R. Matsas

Neurodevelopment: Signaling Pathways Controlling Cell Cycle Progression/Exit and Differentiation Of Neural Stem Cells

The transition of a proliferative neural precursor cell to a postmitotic neuron is a highly regulated process resulting in the generation of appropriate numbers of neurons at the right time and place. Key regulators of cell cycle progression influence neural cell fate and differentiation and conversely, cell fate determinants and differentiation factors regulate the cell cycle. Using in vitro and in vivo gain- and loss-of-function approaches in the chick and the mouse embryo we have identified novel molecular pathways that act in concert and contribute to this complex regulation, involving the neuronal-lineage specific modulator BM88/Cend1, RanBPM, Dyrk1B, the cellular prion protein PrP, Prox1 (in collaboration with P. Politis at BFRAA) and insulin-like growth factor I.

Over the past years we have documented the pivotal role of the protein BM88/Cend1 in the coordination of cell cycle exit and differentiation of neural stem cells. The negative influence of Cend1 on cell proliferation is mediated through the p53/cyclin D1/pRb pathway while its neuronal differentiation-promoting activity involves downregulation of Notch signaling and activation of proneural genes network, including neurogenin2 and ascl1. Further, we identified the signal transduction scaffolding protein Ran-binding protein M (RanBPM) as a Cend1 binding partner and showed a tripartite interaction between Cend1, RanBPM and the dual specificity tyrosine-phosphorylation regulated kinase 1B (Dyrk1B) in maintaining the balance between cellular proliferation and differentiation of neural precursor cells.

Selected relevant publications

  • Gaitanou M, Segklia K and Matsas R. (2019) Cend1, a story with many tales: From regulation of cell cycle progression/exit of neuralstem cells to brain structure and function. Stem Cells International, in Press.
  • Segklia K, Stamatakis A, Stylianopoulou F, Lavdas AA, Matsas R. (2019) Increased Anxiety-Related Behavior, Impaired Cognitive Function and Cellular Alterations in the Brain of Cend1-deficient Mice. Front Cell Neurosci. 12:497. doi: 10.3389/fncel.2018.00497. eCollection 2018
  • Prodromidou K, Papastefanaki F, Sklaviadis T, Matsas R. (2014) Functional cross-talk between the cellular prion protein and the neural cell adhesion molecule NCAM is critical for neuronal differentiation of neural stem/precursor cells. Stem Cells 32(6):1674-87.
  • Tsioras K, Papastefanaki F, Politis PK, Matsas R, Gaitanou M. (2013) Functional Interactions between BM88/Cend1, Ran-binding protein M and Dyrk1B kinase affect cyclin D1 levels and cell cycle progression/exit in mouse neuroblastoma cells. PLoS One. 8(11):e82172.
  • Kaltezioti V*, Kouroupi G*, Oikonomaki M*, Mantouvalou E, Charonis A, Rohrer H, Matsas R and Politis PK (2010) Prox1 suppresses Notch1 gene expression to regulate neurogenesis in the spinal cord, PLoS Biology, Dec 21;8(12):e1000565 *equal contribution
  • Kouroupi G, Lavdas AA, Gaitanou M, Thomaidou D, Stylianopoulou F, Matsas R. Lentivirus-mediated expression of insulin-like growth factor-I promotes neural stem/precursor cell proliferation and enhances their potential to generate neurons. J Neurochem. 2010 Oct;115(2):460-74.
  • Sergaki MC, Guillemot F and Matsas R (2010) Impaired cerebellar development and deficits in motor coordination in mice lacking the neuronal protein BM88/Cend1. Mol Cell Neurosci, 44:15–29.
  • Katsimpardi L, M Gaitanou, CE Malnou, PM Lledo, P. Charneau, R Matsas and D Thomaidou (2008) BM88/Cend1 expression levels are critical for proliferation and differentiation of subventricular zone-derived neural precursor cells. Stem Cells 26:1796-807.
  • Politis PK, Makri G, Thomaidou D, Geissen M, Rohrer H, Matsas R. (2007) BM88/CEND1 coordinates cell cycle exit and differentiation of neuronal precursors. Proc Natl Acad Sci U S A. 2104 (45):17861-6.
  • Georgopoulou N, Hurel C, Politis PK, Gaitanou M, Matsas R, Thomaidou D. (2006) BM88 is a dual function molecule inducing cell cycle exit and neuronal differentiation of neuroblastoma cells via cyclin D1 down-regulation and retinoblastoma protein hypophosphorylation. J Biol Chem. 281:33606-20.

Mirk/Dyrk1B kinase is a novel cell cycle regulator of neuronal progenitors inducing neuronal differentiation in vitro and in vivo

DYRKs constitute an evolutionarily conserved family of protein kinases participating in several signaling pathways with key roles in control of cell proliferation and differentiation. Dyrk1A is implicated in nervous system development, in Down syndrome pathology and in several neurodegenerative disorders, such as Alzheimer’s disease. Dyrk1B is characterized as a cell cycle regulator in skeletal muscle differentiation and has been implicated in carcinogenesis and in metabolic syndrome. Our study by Tsioras et al 2013 (PLoS One 2013 8(11):e82172) was the first to implicate Dyrk1B in cell cycle exit and differentiation of neuronal precursors. The mechanism by which Dyrk1B is involved in neurogenesis is under investigation in the early chick neural tube and the mouse embryonic brain using siRNAs/shRNAs, CrispR/Cas9 gene editing and small molecules that act as specific kinase inhibitors for Dyrk1B.

Members involved

Kokkorakis (PhD), R. Matsas, M. Gaitanou (PI)

Neuroregeneration: Novel Combinatorial Gene and Cell Therapy Approaches and Drug Delivery Systems for CNS Repair

The central nervous system (CNS) has limited capacity for regeneration after injury or disease. We have been studying the use of cell transplantation as a therapeutic strategy exploring the regenerative potential of neural stem/progenitor cells (NPCs) and promyelinating cells in mouse models of neurological disease or neurotrauma. To achieve better integration of the grafted cells within the CNS and enhance their potential to confer functional recovery, we have developed combinatorial approaches involving transplantation of ex vivo genetically modified cell populations for expression of regeneration-promoting molecules, such as growth factors, cell adhesion molecules or cell-fate inducers.

Novel combinatorial gene/cell therapy approaches and drug delivery systems in mouse models of brain and spinal cord neuropathology

Over the years we have assessed the regenerative potential of naïve or genetically modified NPCs in mouse models of brain injury or disease, including cortical or hippocampal mechanical injury, temporal lobe epilepsy and Parkinson’s disease. We have provided proof-of-principle that NPC transplantation is a beneficial approach that may be translated to future clinical applications. The high plasticity of transplanted NPCs, which can acquire injury-dependent phenotypes within the host CNS, supports that reciprocal interactions between transplanted cells and the host tissue are an important factor to be considered when designing prospective cell-based therapies for CNS degenerative conditions.

Spinal cord injuries (SCI) affecting mainly young individuals constitute a serious health problem and functional restoration remains a significant challenge. We have explored cell-based therapeutic interventions in mouse models of SCI using Schwann cells, the regeneration supporting myelinating glia of the peripheral nervous system. To improve their integration within the central nervous system we modified their surface properties by genetically altering the expression profile of neural cell adhesion molecules. In collaboration with Prof. M. Schachner (Rutgers USA) and Dr Igor Jakovcevski (DZNE Bonn/University Hospital of Cologne) we explored the potential of gold nanoparticles (AuNPs) conjugated to tissue-compatible reagents, such as polyethylene glycol (PEG), as promising candidates for drug delivery. We have proposed that PEG-AuNPs represent a favorable drug-delivery platform with therapeutic potential that could be further enhanced if PEG-AuNPs were used as carriers of regeneration-promoting molecules.

Relevant publications

  • Koutsoudaki PN, Stamatakis A, Papastefanaki F, Kouroupi G, Xingi E, Stylianopoulou F and Matsas R (2016) Neural stem/progenitor cells differentiate to oligodendrocytes, reduce inflammation and ameliorate learning deficits after transplantation in a mouse model of traumatic brain injury, GLIA 64(5):763-79.
  • Papastefanaki F, Jakovcevski I, Poulia N, Djogo N, Schulz F, Martinovic T, Ciric D, Loers G, Vossmeyer T, Weller H, Schachner M, Matsas R. (2015) Intraspinal Delivery of Polyethylene Glycol-coated Gold Nanoparticles Promotes Functional Recovery After Spinal Cord Injury. Mol Ther 23(6):993-1002.
  • Papastefanaki F, Matsas R. (2015) From demyelination to remyelination: The road toward therapies for spinal cord injury. GLIA 63(7):1101-25.
  • Miltiadous P*, Kouroupi G*, Stamatakis A, Koutsoudaki PN, Matsas R. and F. Stylianopoulou (2013) Subventricular zone-derived neural stem cell grafts protect against hippocampal degeneration and restore cognitive function in the mouse following intrahippocampal kainic acid administration. Stem Cells Transl Med. 2013 2:185-98.
  • Ziavra D, Makri G, Giompres P, Taraviras S, Thomaidou D, Matsas R, Mitsacos A,Kouvelas ED. Neural stem cells transplanted in a mouse model of Parkinson’sdisease differentiate to neuronal phenotypes and reduce rotational deficit. CNS Neurol Disord Drug Targets. 2012 Nov 1;11(7):829-35
  • Lavdas AA, Papastefanaki F, Thomaidou D, Matsas R. (2011) Cell adhesion molecules in gene and cell therapy approaches for nervous system repair. Curr Gene Ther. Apr;11(2):90-100. Review.
  • Makri G, Lavdas AA, Katsimpardi L, Charneau P, Thomaidou D and Matsas R (2010) Transplantation of embryonic neural stem/ precursor cells overexpressing BM88/Cend1 enhances the generation of neuronal cells in the injured mouse cortex. Stem Cells 28:127-39
  • Kouroupi G, Lavdas AA, Gaitanou M, Thomaidou D, Stylianopoulou F, Matsas R. Lentivirus-mediated expression of insulin-like growth factor-I promotes neural stem/precursor cell proliferation and enhances their potential to generate neurons. J Neurochem. 2010 Oct;115(2):460-74.
  • Lavdas AA, Chen J, Papastefanaki F, Chen S, Schachner M, Matsas R and Thomaidou D (2010) Schwann cells engineered to express the cell adhesion molecule L1 accelerate myelination and motor recovery after spinal cord injury. Exp Neurol 221:206-16.
  • Lavdas AA, Efrose R, Douris V, Gaitanou M, Papastefanaki F, Swevers L, Thomaidou D, Iatrou K, Matsas R. Soluble forms of the cell adhesion molecule L1 produced by insect and baculovirus-transduced mammalian cells enhance Schwann cell motility. J Neurochem. 2010 Dec; 115(5):1137-49.
  • Lavdas, AA and Matsas, R (2009) Towards personalized cell-replacement therapies for brain repair Personalized Medicine 6(3): 293-313.
  • Lavdas AA, Papastefanaki F, Thomaidou D, Matsas R (2008) Schwann cell transplantation for CNS repair. Curr Med Chem. 15:151-60.
  • Papastefanaki F, Chen J, Lavdas AA, Thomaidou D, Schachner M, Matsas R. (2007) Grafts of Schwann cells engineered to express PSA-NCAM promote functional recovery after spinal cord injury. Brain 130:2159-74. (featured article – editorial commentary in Brain (2007), 130:1978-1980)
  • Lavdas AA, Franceschini I, Dubois-Dalcq M, Matsas R. (2006) Schwann cells genetically engineered to express PSA show enhanced migratory potential without impairment of their myelinating ability in vitro. GLIA 53(8):868-78

COLLABORATIVE PROJECTS

Microbes and Brain (collaboration with Pauline Speder, Brain Plasticity in Response to the Environment, Institut Pasteur Paris)

The brain is exposed to pathogens that can ultimately cross its protective barriers and infect host cells. Recent data show that infection and associated inflammation can affect neural stem cells (NSC) and their supporting niche, leading to impaired neurogenesis. This could explain the late onset of infection-associated neurological disorders while also being a potentially potent shield to damage. Understanding how pathogens can reach and alter the neural stem cell microenvironment is key to devising antimicrobial and/or repair strategies. Our collaborators in Institut Pasteur Paris (Dr Pauline Speder and Dr Shaynoor Dramsi) have established an ex vivo Drosophila model of the blood brain barrier (BBB) to take advantage of Drosophila’s unrivaled genetics and offer a simple, fast and tractable model of brain infection. Many basic aspects of mammalian brain development are conserved in flies through the existence of a genuine NSC niche sharing neurogenic features and common players with the mammalian niche. Moreover, the Drosophila BBB exhibits conserved chemoprotective strategies with the mammalian BBB, ensuring brain homeostasis. The goal of this collaborative project is to shed light into (1) the mechanisms of BBB crossing by pathogens and (2) the pathways activated in the NSC niche during infection and their impact on neurogenesis. Our role in the project is to cross the data obtained in the Drosophila model with an in vivo approach in the mouse to identify core conserved mechanisms. We have currently focused on Streptococcus agalactiae (Group B Streptococcus), the major pathogen causing meningitis in newborns, the elderly and immunocompromised subjects that can be lethal. We have set up a hematogenous model of brain infection, in collaboration with Dr V. Miriagou (Laboratory of Bacteriology, Department of Microbiology) to explore pathogen entry and distribution in the brain and we study the effects on neurogenesis.

Members involved

Α. Segklia, F. Papastefanaki, R. Matsas

Mitochondrial Neurological Diseases (collaboration with E. Douni BSRC Al. Fleming & Agricultural University of Athens)

Following a forward genetics approach, Dr. Douni’s team at BSRC Fleming identified a loss-of-function mutation in the Slc25a46 gene that causes lethal neuropathology in mice. Mutations in nuclear genes encoding mitochondrial proteins have emerged as novel causalities in diseases affecting the nervous system. The mitochondrial protein SLC25A46 has been recently identified as a novel pathogenic cause in a wide spectrum of human neurological diseases, including inherited optic atrophy, Charcot-Marie-Tooth type 2, Leigh syndrome and progressive myoclonic ataxia. SLC25A46 is an outer membrane mitochondrial protein, member of the Solute Carrier 25 (SLC25) family of nuclear genes encoding mitochondrial carriers, with a role in mitochondrial dynamics. Our task in this project was to characterize the complex neurological phenotype displayed by the mouse model. In line with the main clinical features identified in patients, we demonstrated optic atrophy and cerebellar hypoplasia. Histopathological analysis revealed previously unseen cellular alterations in the retina and the optic nerve as well as disrupted cerebellar cytoarchitecture with severely compromised Purkinje cell dendritic growth and defective synaptic connectivity. Further, we observed significant astrogliosis and microgliosis in the spinal cord of mutant mice, indicating high levels of neuroinflammation and prominent abnormalities in the neuromuscular junctions of the diaphragm, indicative of a functional deficit that could be causal to early lethality. Our analysis confirmed that the Slc25a46 mutant mice constitute a valid model for mechanistic studies and further investigation of the associated human pathology.

Members involved

A. Segklia, F. Papastefanaki, R. Matsas

Relevant publications

  • Terzenidou Μ*, Segklia Α*, Kano Τ, Papastefanaki F, Karakostas A, Charalambous M, Ioakeimidis F, Papadaki M, Kloukina I, Chrysanthou-Piterou M, Samiotaki M, Panayotou G,  Matsas R#,  Douni E.# (2017) Novel Insights into SLC25A46 Related Pathologies in a Genetic Mouse Model. PLOS Genet. 13(4): e1006656. * equal first authors; # joint senior authors

FUNDING

Flagship Action for Research on Neurodegenerative Diseases on the Basis of Personalized Medicine. HPI coordinator, R. Matsas

Pasteur Joint International Research Unit Partnership within IPIN, PIU2020-2025: Creation of a Virtual Research Unit for Studies in Neurodegenerative Diseases. PIs Rebecca Matsas (HPI) and Chiara Zurzolo (IP-Paris)

Partnership Agreement for the Development Framework 2014-2020 for a 15-month project: Investigation of the effect of the microneurotrophin BNN-20 on Parkinson’s Disease patient induced pluripotent stem cell-derived neurons and on the success of stem cell transplantation in an animal model of the disease (Deputy Academic Advisor: G. Kouroupi)

Institut Pasteur Direction du Development, GRAND PROGRAMME FÉDÉRATEUR M&B, MICROBES & BRAIN PROJECTS 2016: SEEDS FOR INNOVATION 2017-2019: In vivo models of brain infection by Gram+ bacteria: from barrier crossing to neural stem cell (InFeSteR). PIs: Pauline Spéder-Murphy (coordinator); Shaynoor Dramsi; Rebecca Matsas.

Hellenic Foundation for Research and Innovation (HFRI) Project for Postdoctoral Researchers 2018-2021: Mechanisms of synaptic dysfunction in human induced pluripotent stem cell-based 2D- and 3D-models of familial Parkinson’s disease (PARKINSynapse). Principal Investigator: Georgia Kouroupi

Institut Pasteur Direction du Développement, GRAND PROGRAMME FÉDÉRATEUR M&B, MICROBES & BRAIN PROJECTS 2016: SEEDS FOR INNOVATION 2017-2018: In vivo models of brain infection by Gram+ bacteria: from barrier crossing to neural stem cell (InFeSteR). PIs: Pauline Spéder-Murphy (coordinator); Shaynoor Dramsi; Rebecca Matsas.

Stavros Niarchos Foundation Grant 2016-2020: Development of innovative biological products and services for infectious and neurodegenerative diseases Coordinated by R. Matsas and V. Miriagou

Institut Pasteur Transversal Research Program 2015-2018 PTR-523: Mechanisms of pathological A53T-alpha-synuclein transmission in human iPS-derived neurons. Coordinated by R. Matsas; Participants: C. Zurzolo, PM Lledo and F. Lazarini IP-Paris

Fondation Santé Grant 2014-2016: An integrated genome-wide miRNA-mRNA approach in a human stem cell-based model of neurodevelopment and disease.

Greek Ministry of Education 2012-2015: EXCELLENCE GRANT I-2272 – Modeling Parkinson’s disease by conversion of fibroblasts to dopaminergic neurons.

Greek General Secretariat for Research and Technology 2011-2015: Cooperation GRANT 09SYN-21–969 – Mechanisms of Induced Pluripotency: From Transcriptional Noise to Stem Cell Therapies.

Greek General Secretariat for Research and Technology 2013-2015 KRHPIS GRANT InfeNeuTra – MIS450598: Infectious and Neurodegenerative diseases: From study of basic mechanisms to development of translational research towards prevention and therapy.

Greek General Secretariat for Research and Technology 2013-2015: THALES GRANT KA3578 “Mitochondrial Dysfunction in Neurodegenerative Diseases”

Institut Pasteur Transversal Research Program Grant 2013-2015 PTR-417: Parkinsonian patient-derived dopaminergic neurons for disease modeling and drug discovery. Coordinated by R. Matsas; Participants: D. Bohl IP-Paris, R. Grailhe IP-Korea.

Empeirikion Foundation 2013-2014 Generation of patient-derived induced pluripotent stem cells

Fondation BNP Paribas 2010-2013: Use of human stem cells for the treatment of neurodegenerative diseases and injuries of the brain and spinal cord.

EU FP7 Program Grant 264083 NEUROSIGN 2010-2013: Development of a Centre of Excellence in Neurosignalling (raised by Tzartos – coordinator, Matsas and Probert).

Bodossaki Foundation Award, 2009-2010: Establishment of a Stem Cell and Transplantation Facility.

Wings for Life Foundation for Spinal Cord Research 2006-2007: Therapeutic potential of Schwann cells genetically engineered to express PSA after transplantation in the lesioned mouse spinal cord.

Greek General Secretariat for Research and Technology 2005-08: Development of infrastructure in cutting-edge technologies for innovative diagnostic and therapeutic strategies. (Matsas, Mamalaki, Probert and Soteriadou co-PIs)

Greek General Secretariat for Research and Technology Programme PENED, 2005-2007. Application of the neuroprotective factor IGF1 for the treatment of brain trauma and neurodegeneration (F. Stylianopoulou – coordinator)

Greek General Secretariat for Research and Technology Programme EPAN, 2004-2006 Neural Stem Cell Therapies for Neurodegenerative Diseases: Determination of a “molecular signature” for neuronal fate, YB26:

Greek General Secretariat for Research and Technology Programme EPAN, 2004-2006. Baculovirus Artificial Chromosomes (BVACs) and Technologies for Gene Therapy and Continuous High-Level Expression of Therapeutic Proteins in Insect Production Systems, YB11.

EU Training and Mobility Programme – Neurosciences, 2003-2005. Role of calcium mobilization in neuronal differentiation: novel aspects of single cell and organellar calcium signals. QLG2-CT-2002-51680:

EU Quality of Life Programme – Neurosciences, 2000-2003. Genes controlling neuronal specification and differentiation QLG3-CT-00072:

EU Quality of Life Programme – Neurosciences, 2000-2003 Engineering neural precursors for myelin repair. QLG3-CT-00911:

AWARDS

Matsas

2017 to date: Nominated member of the General Assembly of ELIDEK, the Greek Foundation for Research and Innovation

2015: Elected EMBO Member; Nominated by EMBO member of AcademiaNet

2015 to date: Member of the International Advisory Board of the Hellenic Pasteur Institute

2011-2014: Nominated by the Ministry of Education member of the Life Sciences Section of the National Scientific Council for Research and Technology

2010: Fulbright Foundation Award for Academic Excellence

2010-2014: Elected Member of the Schools Committee of the Federation of European Neuroscience Societies (FENS)

2005: Decorated Chevalier de l’Ordre National du Mérite by the French Republic

2002-2005: National Delegate in the 6th Framework Program: Life Sciences & Biotechnology for Health

2003-2005: Member of the Executive Bureau of the International Network of Pasteur Institutes and Regional Representative of the European Pasteur Institutes

1992: EMBO Research Fellow

1980-2005: Medical Research Council UK Research Fellow

1994 to date: National Delegate in the European Neuroglial Network

Taoufik

2016: Fulbright Visiting Scholar to Sanford Burnham Prebys Medical Discovery Institute, San Diego, USA and Dr. Fossati’s lab at the New York Stem Cell Institute

Papastefanaki

2017: Travel grant to attend the 2nd Croucher course on Advanced Imaging in Hong Kong.

2016: EMBO travel grant to attend the EMBO Workshop on Dendritic Anatomy, Molecules and Function

2013: Research Fellowship from the Theodore-Theochari Cozzika Foundation

2012: EMBO Short Term Fellowship to visit Mellita Schachner lab, Hamburg, Germany

Kouroupi

2018: Best Oral Presentation Award, ‘Impaired autophagy and synaptic defects in a human iPSC-based model of familial Parkinson’s disease’, 3rd Congress of the Hellenic Society of Gene Therapy and Regenerative Medicine, Thessaloniki, Greece

2017: Selected for the Neuroscience School of Advanced Studies: Neural Stem Cells and Brain Repair, 20-27 May 2017, Tuscany, Italy

2016: Best Poster Presentation Award ‘Rescue of the pathological phentoype using small molecules targeting α-synuclein in a patient-specific cell-based model of Parkinson’s disease’, Kouroupi G., Taoufik E., Vlachos I. S., Tsioras K., Antoniou N., Wrasidlo W., Vekrellis K., Stefanis L., Bregestovski P., Hatzigeorgiou A. G., Masliah E., Matsas R. 2nd Symposium of Postgraduate Students and Postdoctoral Researchers, Hellenic Pasteur Institute, Athens, Greece

2014: Travel Award, International Society for Stem Cell Research (ISSCR) for 12th Annual Meeting of the International Society for Stem Cell Research, Vancouver, Canada

2010: Best Oral Presentation Award, ‘Lentivirus-mediated expression of insulin-like growth factor-I promotes neural stem cell proliferation and enhances their potential to generate neurons’, Kouroupi G., Lavdas A. A., Gaitanou M., Thomaidou D., Stylianopoulou F., Matsas R. 5TH Meeting of the Hellenic Society for Bioscientists, Athens, Greece

2010: Best Oral Presentation Award, ‘Lentivirus-mediated expression of insulin-like growth factor-I promotes neural stem cell proliferation and enhances their potential to generate neurons’, Kouroupi G., Lavdas A. A., Gaitanou M., Thomaidou D., Stylianopoulou F., Matsas R. Neuroscience Days of the Hellenic Society for Neuroscience (HSfN), Athens, Greece

2009Travel Award, “Athinoula A. Martinos” Foundation for 41st Meeting of the European Brain and Behaviour Society (EBBS) and the 23rd Meeting of the Hellenic Society for Neuroscience (HSfN), Rhodes, Greece

Prodromidou

2018: ‘George Stamatoyannopoulos’ Award for best project ‘MicroRNA-934 is a novel regulator of early human neurogenesis with a prospective evolutionary role in brain development’, K. Prodromidou, I. S. Vlachos, M. Gaitanou, G. Kouroupi, A. G. Hatzigeorgiou, R. Matsas, 3rd Congress of the Hellenic Society of Gene Therapy and Regenerative Medicine, Thessaloniki, Greece

2016: ‘Athanasios Loukeris’ annual award for best oral presentation/project of a young researcher of Hellenic Pasteur Institute ‘mir-934 is a novel regulator of early human neurogenesis’ Kanella Prodromidou, Ioannis Vlachos, Georgia Kouroupi, Maria Gaitanou, Era Taoufik, Artemis Hatzigeorgiou and Rebecca Matsas.

2016: Travel grant for EMBO Workshop: Nuclear Function and Cell Fate, 18-22 September 2016

2011: Best Oral presentation Award at the 62nd Conference of the Hellenic Society for Biochemistry and Molecular Biology (HSBMB) ‘The cellular prion protein is required for NCAM-induced neuronal differentiation’ Prodromidou K., Papastefanaki F., Sklaviadis T., Matsas R.,

Segklia 

2015: ‘Athanasios Loukeris’ annual award for best oral presentation/project of a young researcher of Hellenic Pasteur Institute, “A nonsense point mutation in a novel SLC25 family member of mitochondrial carriers causes severe recessive neurological disease and epilepsy in mice”, Aikaterini Segklia, Maria-Eirini Terzenidou, Florentia Papastefanaki, Eleni Douni and Rebecca Matsas, 1st Young Scientists Forum, 24/09/2015, Hellenic Pasteur Institute

Antoniou

2017: Best Poster Award, 2nd Congress of Gene Therapy and Regenerative Medicine, Athens “High Content screening analysis in an induced pluripotent stem cell-based model of familial Parkinson’s disease reveals a kinase inhibitor that enhances the differentiation to dopaminergic neurons” Antoniou N, Kouroupi G, Taoufik E, Grailhe R, Matsas R

2016: Grant for participation in the Course: High Content Assay for Target Discovery Using RNAi technology, 9-13 May 2016, Institute Pasteur Korea

2015: Calmette-Yersin grant: Identification of therapeutic targets for Parkinson’s disease using a humaninduced pluripotent stem cell-based model. Collaborative proposal between IP-Hellenic and IP-Korea. Responsible Scientists: Rebecca Matsas and Regis Grailhe. Student mobility: Nasia Antoniou, September 2015-January 2016 and May 2016-August 2016

Zygogianni

2016: Calmette-Yersin grant to participate in the IP-Paris Course “Principles
and Applications of Fluorescence Microscopy” (22/02-04/03/2016).

2015: Best poster award in 2nd Young Scientists Forum with title: “Development of a chimeric brain model for the study of A53T-alpha-synuclein pathology” Zygogianni O., Papastefanaki F., Kouroupi G., Koronaiou M., Taoufik E., Matsas R., Hellenic Pasteur Institute (24/09/2015)

Group Award 

2014: “miStem”, a project for the development of a spin-off/start-up company for biomarker and drug discovery in the field of neurodegenerative diseases was selected among the top 10 projects (out of 205 submitted) in the “Innovation Project Disrupt, Startup, ScaleUp” competition organized by the Hellenic Association of Pharmaceutical Companies (SFEE)

http://2014.industrydisruptors.org/program/

The 10 finalist Startups:

  • miStem
  • Τhe Hellenic EyeBank Demokritos “Grigoris Georgariou”
  • WatchAngel
  • Mol-Ther
  • DermaSense
  • Proteomarkers Biotech
  • MeR Lab
  • Biomarket, Medical Physiology Lab
  • Amyndas Pharmaceuticals
  • OncoGen

TEACHING

The Laboratory of Cellular and Molecular Neurobiology has a track record in educational and training activities. In conjunction with the Biology Departments of the University of Athens and the University of Patras as well as the Medical School of the University of Athens, a large number of graduate students have performed their thesis towards an MSc or PhD degree. The researchers of the lab are actively involved in teaching in University post-graduate courses while they undertake undergraduate and post-graduate students for training and theses.

Faculty members of the lab are actively involved in the Athens International Master’s Programme in Neurosciences launched in 2017 as part of the Network of European Neuroscience Schools (NENS).

Also participation in the following Master’s Courses:

“Molecular Medicine – Neurobiology” of the Athens Medical School

“Applications of Biology in Medicine” of the Biology Department of the University of Athens

“Applied Neuroanatomy” of the Athens Medical School

ORGANIZATION OF SELECTED SCIENTIFIC MEETINGS AND WORKSHOPS

1998                3rd European Meeting on Glial Cell Function in Health and Disease Athens

2000                4th European Meeting on Glial Cell Function in Health and Disease,
Barcelona

2001                FEBS/EMBO Advanced Course “From differentiation to death of nerve cells”
Spetses

2002                5th European Meeting on Glial Cell Function in Health and Disease, Rome

2003                FENS/IBRO Winter School NEURAL STEM CELLS from specification and
nervous system patterning to therapies for neurodegenerative diseases,
Kitzbuhel, Austria

2004                Modern Light Microscopy Techniques In Biomedical Research HPI, Athens

2009                9th European Meeting on Glial Cell Function in Health and Disease, Paris

2009                60th Meeting of the Hellenic Society for Molecular Biology and Biochemistry
Athens.

2009                23rd Meeting of the Hellenic Society for Neuroscience Rhodes.

2011                10th European Meeting on Glial Cell Function in Health and Disease, Prague

2011                62nd Meeting of the Hellenic Society for Biochemistry and Molecular Biology

2011                International Society of Neurochemistry Meeting Athens

2013                11th European Meeting on Glial Cell Function in Health and Disease, Berlin

2012                REGPOT Neurosign Workshop “Animal models of neurodegeneration and
behavioral tests for assessment of motor and cognitive function” HPI,
Athens.

2013                REGPOT Neurosign Workshop “Live Cell Imaging and Electrophysiology”
HPI, Athens.

2013                26th Meeting of the Hellenic Neuroscience Society jointly with REGPOT
Neurosign

2015                12th European Meeting on Glial Cell Function in Health and Disease, Bilbao

OUTREACH ACTIVITIES AND MEDIA COVERAGE

Communicating science to the public is an important task of our lab. Here are some examples of open-to-the-public actions that we have participated in:

THE FOLLOWING OUTREACH ACTIVITIES ARE ONLY IN GREEK

  • The Hub Science Events-2020: “Νέα βιολογία και ιατρική: Μια ανατρεπτική σχέση” Ομιλητές Μανώλης Δερμιτζάκης και Ρεβέκκα Μάτσα
  • Τηλεοπτικά αφιερώματα για την επιστήμη: ΕΡΤ2 «Οι Δρόμοι της Ανάπτυξης» και κανάλι της Βουλής, αφιέρωμα για τα 100 χρόνια του ΕΙΠ στην εκπομπή Διαβουλεύσεις
  • Εκδήλώση Pint of Science-2019: “Μια κανάτα… βλαστοκύτταρα και… «καλά γεράματα”! Ρ. Μάτσα
  • Εγκέφαλοι μινιατούρες και θεραπείες του μέλλοντος. Διάλεξη Γ. Κουρούπη,
    Εκδήλωση “Εξερευνώντας τον Εγκέφαλο”, Κέντρο Πολιτισμού Ίδρυμα Σταύρος Νιάρχος, Μάρτιος 2018,  http://exploringthebrain.gr/
  • Επιδιορθώνοντας τον εγκέφαλο: βλαστικά κύτταρα. Διάλεξη Ρ. Μάτσα, Όμιλος Φίλων Παστέρ – Café Scientific Ίδρυμα Εικαστικών Τεχνών και Μουσικής Β&Μ Θεοχαράκη, Αθήνα 2016
  • Διερευνώντας τη νόσο Πάρκινσον με βλαστικά κύτταρα. Διάλεξη Ρ. Μάτσα, Megaron Plus 2014
  • Επιδιορθώνοντας τον εγκέφαλο: βλαστικά κύτταρα. Διάλεξη Ρ. Μάτσα, Όμιλος Φίλων Παστέρ Λιβαδειά, 2015
  • Βλαστικά κύτταρα: Μύθος και πραγματικότητα. Διάλεξη Ρ. Μάτσα, Megaron Plus 2014
  • Νέο Εθνικό Κέντρο Αριστείας για τις Νευροεπιστήμες. Καθημερινή 2014
  • Η χρήση των βλαστικών κυττάρων σε κυτταρικές θεραπείες νευροεκφυλιστικών ασθενειών. Διάλεξη Μ. Γαϊτάνου, Ναυτικό Νοσοκομείο Σαλαμίνας, 2012
  • Συνδυαστικές θεραπείες με γενετικά τροποποιημένα κύτταρα. Ημερησία 2009
  • Η έρευνα για την υγεία στην Ελλάδα. Βήμα Ιδεών, Νοέμβριος 2008
  • Θα μπορέσουμε να θεραπεύσουμε τις παθήσεις του εγκεφάλου; Βήμα Ιδεών, Ιούλιος 2008
  • Έχουν τον έλεγχο των πιο κρυφών κυττάρων σου. Ελεύθερος Τύπος 2008
  • Κύτταρα διασώστες στη σπονδυλική στήλη. Βήμα Science 2007
  • Λουί Παστέρ: Ο πατέρας της Μικροβιολογίας. «Ε» Ιστορικά 2007

PUBLICATIONS

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Zygogianni O, Kouroupi G, Taoufik E, Matsas R. Engraftable Induced Pluripotent Stem Cell-Derived Neural Precursors for Brain Repair. Methods Mol Biol. 2020;2155:23-39. doi: 10.1007/978-1-0716-0655-1_3.

Prodromidou K, Vlachos IS, Gaitanou M, Kouroupi G, Hatzigeorgiou AG, Matsas R. MicroRNA-934 is a novel primate-specific small non-coding RNA with neurogenic function during early development. Elife. 2020 May 27;9:e50561. doi: 10.7554/eLife.50561. Online ahead of print.

2020
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Grudina C, Kouroupi G, Nonaka T, Hasegawa M, Matsas R, Zurzolo C. Human NPCs can degrade α-syn fibrils and transfer them preferentially in a cell contact-dependent manner possibly through TNT-like structures. Neurobiol Dis. 2019 Sep 5:104609. doi: 10.1016/j.nbd.2019.104609.

Zygogianni O, Antoniou A, Kalomoiri M, Kouroupi G, Taoufik E, Matsas R. In vivo phenotyping of familial Parkinson’s disease with human induced pluripotent stem cells: a proof-of-concept study. Neurochem Res. 2019 Apr 15. doi: 10.1007/s11064-019-02781-w.

Elkouris M, Kouroupi G, Vourvoukelis A, Papagiannakis N, Kaltezioti V, Matsas R, Stefanis L, Xilouri M and Politis PK. Long non-coding RNAs associated with neurodegeneration-linked genes are reduced in Parkinson’s Disease patients. Front Cell Neurosci. 2019 Feb 22;13:58. doi: 10.3389/fncel.2019.00058. eCollection 2019.

Segklia K, Stamatakis A, Stylianopoulou F, Lavdas AA, Matsas R. (2019) Increased Anxiety-Related Behavior, Impaired Cognitive Function and Cellular Alterations in the Brain of Cend1-deficient Mice. Front Cell Neurosci. 12:497. doi: 10.3389/fncel.2018.00497. eCollection 2018

Gaitanou M, Segklia K and Matsas R. (2019) Cend1, a story with many tales: From regulation of cell cycle progression/exit of neuralstem cells to brain structure and function. Stem Cells International, in Press.

2019
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Taoufik E, Kouroupi G, Zygogianni O., Matsas R. Synaptic dysfunction in neurodegenerative and neurodevelopmental diseases: an overview of induced pluripotent stem cell-based disease models. Royal Society’s Open Biology, 2018.

2018
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Kouroupi G, Taoufik E, Vlachos IS, Tsioras K, Antoniou N, Papastefanaki F, Chroni-Tzartou D, Wrasidlo W, Bohl D, Stellas D, Politis PK, Vekrellis K, Papadimitriou D, Stefanis L, Bregestovski P, Hatzigeorgiou AG, Masliah E, Matsas R. (2017) Defective synaptic connectivity and axonal neuropathology in a human iPSC-based model of familial Parkinson's disease. Proc Natl Acad Sci USA, 114(18):E3679-E3688

Terzenidou Μ*, Segklia Α*, Kano Τ, Papastefanaki F, Karakostas A, Charalambous M, Ioakeimidis F, Papadaki M, Kloukina I, Chrysanthou-Piterou M, Samiotaki M, Panayotou G, Matsas R#, Douni E.# (2017) Novel Insights into SLC25A46 Related Pathologies in a Genetic Mouse Model. PLOS Genet. 13(4): e1006656. * equal first authors; # joint senior authors

Pallaki P., Georganta E., Serafimidis I., Papakonstantinou M., Papanikolaou V., Koutloglou S., Papadimitriou E., Agalou A., Tserga A., Simeonof A., Thomaidou D., Gaitanou M. and Georgoussi Z. (2017). A novel regulatory role of RGS4 in STAT5B activation, neurite outgrowth and neuronal differentiation Neuropharmacology (117):408-421.

2017
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Koutsoudaki PN, Stamatakis A, Papastefanaki F, Kouroupi G, Xingi E, Stylianopoulou F and Matsas R (2016) Neural stem/progenitor cells differentiate to oligodendrocytes, reduce inflammation and ameliorate learning deficits after transplantation in a mouse model of traumatic brain injury, GLIA 64(5):763-79.

2016
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Aravantinou-Fatorou K, Ortega F, Chroni-Tzartou D, Antoniou N, Poulopoulou C, Politis PK, Berninger B, Matsas R, Thomaidou D. (2015) Cend1 and Neurogenin2 Reprogram Mouse Astrocytes and Embryonic Fibroblasts to Induced Neural Precursors and Differentiated Neurons. Stem Cell Reports 5(3):405-18.

Papastefanaki F, Jakovcevski I, Poulia N, Djogo N, Schulz F, Martinovic T, Ciric D, Loers G, Vossmeyer T, Weller H, Schachner M, Matsas R. (2015) Intraspinal Delivery of Polyethylene Glycol-coated Gold Nanoparticles Promotes Functional Recovery After Spinal Cord Injury. Mol Ther 23(6):993-1002.

Papastefanaki F, Matsas R. (2015) From demyelination to remyelination: The road toward therapies for spinal cord injury. GLIA 63(7):1101-25.)

2015
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Prodromidou K, Papastefanaki F, Sklaviadis T, Matsas R. (2014) Functional cross-talk between the cellular prion protein and the neural cell adhesion molecule NCAM is critical for neuronal differentiation of neural stem/precursor cells. Stem Cells 32(6):1674-87.

Foka P, Karamichali E, Dalagiorgou G, Serti E, Doumba PP, Pissas G, Kakkanas A, Kazazi D, Kochlios E, Gaitanou M, Koskinas J, Georgopoulou U and Mavromara P. (2014). “Hepatitis C virus modulates lipid regulatory factor Angiopoietin-like 3 gene expression by repressing HNF-1α activity”. J. Hepatol. 60(1):30-8.

2014
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Miltiadous P*, Kouroupi G*, Stamatakis A, Koutsoudaki PN, Matsas R. and F. Stylianopoulou (2013) Subventricular zone-derived neural stem cell grafts protect against hippocampal degeneration and restore cognitive function in the mouse following intrahippocampal kainic acid administration. Stem Cells Transl Med. 2013 2:185-98. *equal contribution

Tsioras K, Papastefanaki F, Politis PK, Matsas R, Gaitanou M. (2013) Functional Interactions between BM88/Cend1, Ran-binding protein M and Dyrk1B kinase affect cyclin D1 levels and cell cycle progression/exit in mouse neuroblastoma cells. PLoS One. 8(11):e82172.

Georganta EM, Tsoutsi L, Gaitanou M and Georgoussi Z. (2013) “δ-opioid receptor activation leads to neurite outgrowth and neuronal differentiation via a STAT5B-Gαi/o pathway” J. Neurochem. 127(3):329-41.

2013
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Ziavra D, Makri G, Giompres P, Taraviras S, Thomaidou D, Matsas R, Mitsacos A,Kouvelas ED. Neural stem cells transplanted in a mouse model of Parkinson'sdisease differentiate to neuronal phenotypes and reduce rotational deficit. CNS Neurol Disord Drug Targets. 2012 Nov 1;11(7):829-35

2012
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Lavdas AA, Papastefanaki F, Thomaidou D, Matsas R. (2011) Cell adhesion molecules in gene and cell therapy approaches for nervous system repair. Curr Gene Ther. Apr;11(2):90-100. Review.

2011
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Kaltezioti V*, Kouroupi G*, Oikonomaki M*, Mantouvalou E, Charonis A, Rohrer H, Matsas R and Politis PK (2010) Prox1 suppresses Notch1 gene expression to regulate neurogenesis in the spinal cord, PLoS Biology, Dec 21;8(12):e1000565 *equal contribution

Makri G, Lavdas AA, Katsimpardi L, Charneau P, Thomaidou D and Matsas R (2010) Transplantation of embryonic neural stem/ precursor cells overexpressing BM88/Cend1 enhances the generation of neuronal cells in the injured mouse cortex. Stem Cells 28:127-39.

Lavdas AA, Chen J, Papastefanaki F, Chen S, Schachner M, Matsas R and Thomaidou D (2010) Schwann cells engineered to express the cell adhesion molecule L1 accelerate myelination and motor recovery after spinal cord injury. Exp Neurol 221:206-16.

Lavdas AA, Efrose R, Douris V, Gaitanou M, Papastefanaki F, Swevers L, Thomaidou D, Iatrou K, Matsas R. (2010) Soluble forms of the cell adhesion molecule L1 produced by insect and baculovirus-transduced mammalian cells enhance Schwann cell motility. J Neurochem. Dec; 115(5):1137-49.

Kouroupi G, Lavdas AA, Gaitanou M, Thomaidou D, Stylianopoulou F, Matsas R. (2010) Lentivirus-mediated expression of insulin-like growth factor-I promotes neural stem/precursor cell proliferation and enhances their potential to generate neurons. J Neurochem. Oct;115(2):460-74.

Sergaki MC, Guillemot F and Matsas R (2010) Impaired cerebellar development and deficits in motor coordination in mice lacking the neuronal protein BM88/Cend1. Mol Cell Neurosci, 44:15–29.

2010
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Lavdas A and Matsas R (2009). Schwann cell morphology In: New Encyclopedia of Neuroscience (L.R. Squire, Editor) Oxford: Academic Press, pp 475-484.

Roser M, Hurel C, Papastefanaki F, Georgopoulou N, Thomaidou D and Matsas R (2009) BM88/Cend1 regulates stimuli-induced calcium mobilization. Neuropharmacology, 56:598-609.

Lavdas, AA and Matsas, R (2009) Towards personalized cell-replacement therapies for brain repair Personalized Medicine 6(3): 293-313.

2009
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Katsimpardi L, M Gaitanou, CE Malnou, PM Lledo, P. Charneau, R Matsas and D Thomaidou (2008) BM88/Cend1 expression levels are critical for proliferation and differentiation of subventricular zone-derived neural precursor cells. Stem Cells 26:1796-807.

Politis PK, Akrivou S, Hurel C, Papadodima O, Matsas R. (2008) BM88/Cend1 is involved in histone deacetylase inhibition-mediated growth arrest and differentiation of neuroblastoma cells. FEBS Lett. 582:741-8.

Politis PK, Thomaidou D, Matsas R. (2008) Coordination of cell cycle exit and differentiation of neuronal progenitors. Cell Cycle. Mar 15;7(6):691-7.

Sidera K, Gaitanou M, Stellas D, Matsas R, Patsavoudi E. (2008) A critical role for HSP90 in cancer cell invasion involves interaction with the extracellular domain of HER-2. J Biol Chem. 283:2031-41.

Lavdas AA, Papastefanaki F, Thomaidou D, Matsas R (2008) Schwann cell transplantation for CNS repair. Curr Med Chem. 15:151-60.

2008
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Politis PK, Makri G, Thomaidou D, Geissen M, Rohrer H, Matsas R. (2007) BM88/CEND1 coordinates cell cycle exit and differentiation of neuronal precursors. Proc Natl Acad Sci U S A. 2104 (45):17861-6.

Papastefanaki F, Chen J, Lavdas AA, Thomaidou D, Schachner M, Matsas R. (2007) Grafts of Schwann cells engineered to express PSA-NCAM promote functional recovery after spinal cord injury. Brain 130:2159-74. (featured article - editorial commentary in Brain (2007), 130:1978-1980)

Politis PK, Rohrer H, Matsas R. (2007) Expression pattern of BM88 in the developing nervous system of the chick and mouse embryo. Gene Expr Patterns 7:165-77.

Gravvanis AI, Lavdas AA, Papalois A, Tsoutsos DA, Matsas R. (2007) The beneficial effect of genetically engineered Schwann cells with enhanced motility in peripheral nerve regeneration Acta Neurochir 100:51-6.

2007
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Lavdas AA, Franceschini I, Dubois-Dalcq M, Matsas R. (2006) Schwann cells genetically engineered to express PSA show enhanced migratory potential without impairment of their myelinating ability in vitro. GLIA 53(8):868-78.

Kenoutis C, Efrose RC, Swevers L, Lavdas AA, Gaitanou M, Matsas R, Iatrou K. (2006) Baculovirus-mediated gene delivery into Mammalian cells does not alter their transcriptional and differentiating potential but is accompanied by early viral gene expression. J Virol. 80:4135-46.

Georgopoulou N, Hurel C, Politis PK, Gaitanou M, Matsas R, Thomaidou D. (2006) BM88 is a dual function molecule inducing cell cycle exit and neuronal differentiation of neuroblastoma cells via cyclin D1 down-regulation and retinoblastoma protein hypophosphorylation. J Biol Chem. 281:33606-20.

2006
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Gravvanis AI, Lavdas A, Papalois AE, Franceschini I, Tsoutsos DA, Dubois-Dalcq M, Matsas R, Ioannovich JD. (2005) Effect of genetically modified Schwann cells with increased motility in end-to-side nerve grafting. Microsurgery 25:423-32.

Papadodima O, Sergaki M, Hurel C, Mamalaki A, Matsas R. (2005) Characterization of the BM88 promoter and identification of an 88 bp fragment sufficient to drive neurone-specific expression. J Neurochem. 95:146-59.

2005
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Koutmani Y, Hurel C, Patsavoudi E, Hack M, Gotz M, Thomaidou D, Matsas R. (2004) BM88 is an early marker of proliferating precursor cells that will differentiate into the neuronal lineage. Eur J Neurosci. 20(10):2509-23.

Meintanis S, Thomaidou D, Jessen KR, Mirsky R, Matsas R. (2004) Novel method for studying myelination in vivo reveals that EDTA is a potent inhibitor of myelin protein and mRNA expression during development of the rat sciatic nerve. Glia. 48(2):132-44.

2004
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Thomaidou D, Coquillat D, Meintanis S, Noda M, Rougon G, Matsas R. (2001) Soluble forms of NCAM and F3 neuronal cell adhesion molecules promote Schwann cell migration: identification of protein tyrosine phosphatases zeta/beta as the putative F3 receptors on Schwann cells. J Neurochem. 78(4):767-78.

Gaitanou M, Buanne P, Pappa C, Georgopoulou N, Mamalaki A, Tirone F, Matsas R. (2001) Cloning, expression and localization of human BM88 shows that it maps to chromosome 11p15.5, a region implicated in Beckwith-Wiedemann syndrome and tumorigenesis. Biochem J. 355(Pt 3):715-24.

Meintanis S, Thomaidou D, Jessen KR, Mirsky R, Matsas R. (2001) The neuron-glia signal beta-neuregulin promotes Schwann cell motility via the MAPK pathway. Glia. 34(1):39-51.

Boutou E, Matsas R, Mamalaki A. (2001) Isolation of a mouse brain cDNA expressed in developing neuroblasts and mature neurons. Brain Res Mol Brain Res. 86(1-2):153-67.

2001
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Boutou E, Hurel C, Matsas R. (2000) Early expression of the BM88 antigen during neuronal differentiation of P19 embryonal carcinoma cells. Int J Dev Neurosci. 18(2-3):321-8.

2000
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Gomez J, Boutou E, Hurel C, Mamalaki A, Kentroti S, Vernadakis A, Matsas R. (1998) Overexpression of the neuron-specific molecule BM88 in mouse neuroblastoma cells: altered responsiveness to growth factors. J Neurosci Res. 51(1):119-28.

1998
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Gaitanou M, Mamalaki A, Merkouri E, Matsas R. (1997) Purification and cDNA cloning of mouse BM89 antigen shows that it is identical with the synaptic vesicle protein synaptophysin. J Neurosci Res. 48(6):507-14.

Matsas R. (1997) Genes controlling neural fate and differentiation. Adv Exp Med Biol. ;429:3-17. Review.

1997
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Mamalaki A, Boutou E, Hurel C, Patsavoudi E, Tzartos S, Matsas R. (1995) The BM88 antigen, a novel neuron-specific molecule, enhances the differentiation of mouse neuroblastoma cells. J Biol Chem. 270(23):14201-8.

Kioussi C, Mamalaki A, Jessen K, Mirsky R, Hersh LB, Matsas R. (1995) Expression of endopeptidase-24.11 (common acute lymphoblastic leukaemia antigen CD10) in the sciatic nerve of the adult rat after lesion and during regeneration. Eur J Neurosci. 7(5):951-61.

Patsavoudi E, Merkouri E, Thomaidou D, Sandillon F, Alonso G, Matsas R. (1995) Characterization and localization of the BM88 antigen in the developing and adult rat brain. J Neurosci Res. 40(4):506-18.

1995
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Kioussi C, Crine P, Matsas R. (1992) Endopeptidase-24.11 is suppressed in myelin-forming but not in non-myelin-forming Schwann cells during development of the rat sciatic nerve. Neuroscience. 50(1):69-83.

1992
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Kioussi C, Matsas R. (1991) Endopeptidase-24.11, a cell-surface peptidase of central nervous system neurons, is expressed by Schwann cells in the pig peripheral nervous system. J Neurochem. 57(2):431-40.

Patsavoudi E, Hurel C, Matsas R. (1991) Purification and characterization of neuron-specific surface antigen defined by monoclonal antibody BM88. J Neurochem. 56(3):782-8.

1991
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Patsavoudi E, Hurel C, Matsas R. (1989) Neuron- and myelin-specific monoclonal antibodies recognizing cell-surface antigens of the central and peripheral nervous system. Neuroscience. 30(2):463-78.

1989

Faculty Members

Rebecca Matsas

Head of Laboratory
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Maria Gaitanou

Researcher
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Erasmia Taoufik

Researcher
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Florentia Papastefanaki

Research Staff Scientist
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Georgia Kouroupi

Researcher
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Post-doctoral fellows

Kanella Prodromidou

Post-doctoral fellow
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Aikaterini Segklia

Post-doctoral fellow
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PhD students

Nasia Antoniou

PhD Student
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Nikolaos Kokkorakis

PhD Student
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Research Technician

Georgia Athanasopoulou

Biologist
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COLLABORATORS

Ilias Kazanis, Department of Biology, University of Patras

Pauline Speder| Brain Plasticity in Response to the Environment, Institut Pasteur Paris

Shaynoor Dramsi| Laboratory: Biology of Gram-Positive Pathogens, Institut Pasteur Paris

Vivi Miriagou| Laboratory of Bacteriology, Department of Microbiology, Hellenic Pasteur Institute, Athens

Leonidas Stefanis| Biomedical Research Foundation, Academy of Athens

Maria Xilouri| Biomedical Research Foundation, Academy of Athens

Panagiotis Politis| Biomedical Research Foundation, Academy of Athens

Artemis Hatzigeorgiou| DIANA LAB, Hellenic Pasteur Institute, Athens

Ioannis Vlachos| Prof. Patsopoulos Laboratory, Ann Romney Center for Neurological Diseases, Brigham & Women’s Hospital,  Harvard Medical School, Boston, MA, USA

Piotr Bregestovski| Aix-Marseille Université, France

Eliezer Masliah| School of Medicine, UC San Diego, USA

Pierre-Marie Lledo| Department of Neuroscience, Institute Pasteur Paris

Chiara Zurzolo| Department of Cell Biology and Infection

Regis Grailhe| Technology Development Platform, Institute Pasteur Korea

Valentina Fossati| The New York Stem Cell Foundation, USA

Panos Douvaras| The New York Stem Cell Foundation, USA

Evan Snyder| Sanford Burham Prebys, Medical Discovery Institute, La Jolla, CA, USA

Melitta Schachner| W.M. Keck Center for Collaborative Neuroscience, Rutgers University, NJ, USA

Igor Jakovcevski| DZNE Bonn/University Hospital of Cologne, Germany

Eleni Douni| “Alexander Fleming” Biomedical Sciences Research Center, Athens

Fotini Stylianopoulou| Faculty of Nursing, University of Athens

Antonis Stamatakis| Faculty of Nursing, University of Athens

ALUMNI

Alexandros Lavdas| Researcher, Institute of Biomedicine, EURAC Research, Bolzano, Italy

Panagiotis Politis| Researcher, Biomedical Research Foundation, Academy of Athens

Lida Katsimpardi| Researcher, Department of Neuroscience, Institute Pasteur Paris

Georgia Makri| Post-Doc in Johns Hopkins University (2010-2015)

Maritina Sergaki| Post-Doc Research Institute of Molecular Pathology, Vienna

Konstantinos Tsioras| Post-Doc, Northwestern University Feinberg School of Medicine, Chicago IL, USA

Roser Masgrau| Group Leader, Institut de Neurociencies, Autonomous University of Barcelona

Olga Papadodima| Research Staff Scientist, Metabolic Engineering – Bioinformatics, National Hellenic Research Foundation, Athens

Yassemi Koutmani| Laboratory Technician, Biomedical Research Foundation, Academy of Athens

Chrissa Kioussi| Professor, College of Pharmacy, Oregon State University

Efrossini Merkouri|

Stathis Meintanis| High School Teacher

Efrosini Boutou| Thalassaemia Center, Laiko Hospital, University of Athens

Evangelia Patsavoudi| Professor, Technological Educational Institute of Athens

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