foto

Prof. E.M.A. Aronica

Position
Professor
Main activities
Patient care, Research, Teaching
Specialisation
Neuropathology
Focus of research
  • Epilepsy
  • Inflammation
  • Neurodevelopmental disorders
  • Brain development and ageing
  • Neuroncology
  • Neuromusculaire ziekten  

The research group headed by Aronica is involved in different research lines in neuropathology (neurodegenerative disorders, neuro-oncology and epilepsy), establishing national and international collaboration. In particular we focused on the role of neuron-glia interactions in brain function and pathology. We address three pivotal scientific objectives of current international interest: 1. Identifying and defining novel molecular and cellular pathways of bidirectional communication between neurons and glia in the developing and the adult brain 2. Defining alterations of neuron-glia interactions in the diseased brain using epilepsy as a central paradigm (complex brain disorder exhibiting a variety of pathological events also seen in other CNS diseases) 3. Developing better research instrumentation, novel drug screening and evaluation assays and disease models to reveal the diversity of neuron-glia interactions in the healthy and the epileptic brain. The research has been focused on the search for effective treatment for patients with epilepsy by delineating the biological and molecular pathways that contribute to development and progression of epilepsy (epileptogenesis) in patients with focal epilepsy, including patients with malformations of cortical development (MCD). The research group has contribute to the identification of key pathways involved in the pathogenesis of a large spectrum of MCD. Moreover, we provided evidence of a prominent and persistent activation of the innate immune response in various neurological disorders with different etiologies, but without a primary inflammatory pathogenesis. This response involves both astrocytes and microglial cells and is associated with the activation of several pathways which influence hyperexcitability and degeneration. Looking for an effective disease-modifying therapies targeting pathologic neuroinflammation, we studied the upstream control mechanism this process focusing on a family of non-coding RNAs (microRNAs) acting as key post-transcriptional modulators of the innate immune response and as novel disease biomarkers.

Key publications
  • van Scheppingen J, Iyer AM, Prabowo AS, Mühlebner A, Anink JJ, Scholl T, Feucht M, Jansen FE, Spliet WG, Krsek P, Zamecnik J, Buccoliero AM, Giordano F, Genitori L, Kotulska K, Jozwiak S, Jaworski J, Liszewska E, van Vliet EA, Aronica E, Expression of microRNAs miR21, miR146a, and miR155 in tuberous sclerosis complex cortical tubers and their regulation in human astrocytes and SEGA-derived cell cultures. GLIA 2016;64 (6):1066-1082 [PubMed]
  • Gorter JA, Iyer A, White I, Colzi A, van Vliet EA, Sisodiya S, Aronica E, Hippocampal subregion-specific microRNA expression during epileptogenesis in experimental temporal lobe epilepsy. NEUROBIOL DIS 2014;62:508-520 [PubMed]
  • Iyer A, Zurolo E, Prabowo A, Fluiter K, Spliet WGM, van Rijen PC, Gorter JA, Aronica E, MicroRNA-146a: A Key Regulator of Astrocyte-Mediated Inflammatory Response. PLOS ONE 2012;7 (9):e44789 [PubMed]
  • Aronica E, Bauer S, Bozzi Y, Caleo M, Dingledine R, Gorter JA, Henshall DC, Kaufer D, Koh S, Löscher W, Louboutin JP, Mishto M, Norwood BA, Palma E, Poulter MO, Terrone G, Vezzani A, Kaminski RM, Neuroinflammatory targets and treatments for epilepsy validated in experimental models. EPILEPSIA 2017;58 (Suppl. 3):27-38 [PubMed]
  • van Scheppingen J, Mills JD, Zimmer TS, Broekaart DWM, Iori V, Bongaarts A, Anink JJ, Iyer AM, Korotkov A, Jansen FE, van Hecke W, Spliet WG, van Rijen PC, Baayen JC, Vezzani A, van Vliet EA, Aronica E, miR147b: A novel key regulator of interleukin 1 beta-mediated inflammation in human astrocytes. GLIA 2018;66 (5):1082-1097 [PubMed]
All Publications
Curriculum Vitae

Eleonora Aronica completed her MD and Neurology residency at the University of Catania (Italy). After receiving a doctorate from the UvA (1993) she moved to the USA, where she had research associated appointments in Albany and New York. Subsequently, she moved to The Netherlands and joined the Department of Neuropathology of AMC at the UvA, where she completed the Neuropathology residence program. In 2012 she was appointed  Professor by Special Appointment of the Pathology of the Nervous System, focusing on epileptic conditions at the University of Amsterdam’s (UvA) Faculty of Science (FNWI).  In 2016 she was appointed  Professor of Neuropathology at at the University of Amsterdam's Faculty of Medicine (AMC-UvA).  She is actively involved in the different research lines, including neuro-oncology, neurodegeneration, developmental disorders and epilepsy. She leads a research group focused on translational research into Epilepsy and aiming to understand the pathogenesis, epileptogenesis and pharmacoresistance of human focal chronic pharmacoresistant epilepsy. Her research has been focused on the search for effective treatment for patients with epilepsy by delineating the biological and molecular pathways that contribute to development and progression of epilepsy (epileptogenesis) in patients with focal epilepsy, including patients with malformations of cortical development (MCD). She ILAE task force member. Her scientific honours include the Michael Prize (2011) for the best scientific and clinical research in the field of epilepsy.  She is the author of more than 300 peer-reviewed original articles.

 

 

 

 

 

 

 

 

 

Research programmes

Neuron-glia interactions in health and disease and inflammation

In 2007, international collaborations have been established to further investigate the role of astroglial and microglial cells in the initiation and persistence of the inflammatory response associated with neuronal degeneration and hyperexcitability (Grant of the European Union: HEALTH-2007-2.2.1-6:“ Neuron-glia interactions in health and disease”; www.neuroglia.eu ). This has been investigated in human brain and in well established animal models of epilepsy. 

2012-2015:. Grant of the European Union: HEALTH.2011.2.2.2-2 " Pathways common to brain development and ageing: defining strategies for preventive therapy and diagnostics “
Objectives
a. To examine neurodegeneration-related proteins during development: comparing early and postnatal developmental stages in developmental disorders
b. To examine the relationship between neurodegeneration-related proteins and specific developmental pathways
c. To study selected altered mRNAs, microRNAs and proteins in focal cortical malformations

 2012-2016: Characterization of genetic aberrations in pediatric low-grade glioneuronal tumors Stichting Kinderen Kankervrij (KiKa).
The aim of the study is to identify chromosomal changes in an international large series of GNT’s by genomic wide microarray based comparative genomic hybridization (aCGH), PCR and genomic sequencing. During the project these chromosomal changes will be investigated for their potential clinical relevance as related to prognosis, pathogenesis en epileptogenesis. The miRNA profile of GNT’s will be also evaluated. By investigating these biologic characteristics in relation to the clinical data, we can improve the diagnostics and therapy for GNT’s in children, as guided by the clinical biological risk profile of the tumor.

2013-2017: National Epilepsy Fonds (NEF): miRNA and inflammation: new opportunities for therapy in epilepsy associated pathologies. Recent clinical-neuropathological and experimental observations support the notion that a dysregulation of the astrocyte immune-inflammatory function represents a common factor, which may predispose or directly contribute to the generation of seizures and to seizure-related neuronal damage in epilepsy of various aetiologies.
Since specific miRNAs have been recently shown to regulate the immune/inflammatory responses, our strategy is devoted to identify key miRNAs that may act as regulators of specific pro-inflammatory/ pro-epileptogenic pathways and to study the effects of their modulation and its therapeutic potential in epilepsy, using a multidisciplinary approach. 

 2013-2017: National Epilepsy Fonds (NEF): Towards effective surgery in focal cortical dysplasias: histopathology, EEG and 7T MRI characteristics. The aim of this proposal is three-fold.First, we want to improve the prediction of postoperative outcome, by elucidating the clinico-pathological correlates of FCD subtypes.

 2013-2018: Grant of the European Union: FP7-HEALTH-2013-INNOVATION-(HEALTH.2013.2.2.1-4: Patho-physiology and therapy of epilepsy and epileptiform disorders): “Long-term, prospective study evaluating clinical and molecular biomarkers of epileptogenesis in a genetic model of epilepsy – tuberous sclerosis complex”. EPISTOP.

The aim of EPISTOP is to better understand the pathophysiology of epilepsy and its consequences, to develop a preventative strategy for epilepsy, to identify new biomarkers of epilepsy, and to develop new therapeutic targets to block or otherwise modify epileptogenesis in humans.
To achieve this aim, the risk factors and biomarkers of epilepsy will be identified by a multidisciplinary, systematic approach in three settings:
- a prospective study of epilepsy development in infants with TSC, using a wide range of clinical, neuroimaging, and genetic analyses, including a diverse set of cutting edge analyses of blood samples, that will be obtained at study entry, at the onset of epileptiform discharges on EEG, at seizure onset and at the age of 24 months.
- prospective clinical study of TSC infants treated with antiepileptic drugs at the onset of subclinical seizures in comparison to children treated only after clinical seizures appear, evaluating the benefit of preventative antiepileptic treatment and the possible mechanisms of epilepsy prevention
- analysis of biomarkers of epileptogenesis and drug-resistant epilepsy in epileptogenic brain specimens obtained from patients with TSC who underwent epilepsy surgery and TSC autopsy cases collected in the past.
 

 2013-2018: Grant of the European Union: FP7-HEALTH-2013-INNOVATION-(HEALTH.2013.2.2.1-4: Patho-physiology and therapy of epilepsy and epileptiform disorders): “Targets and biomarkers for antiepileptogenesis”. EPITARGET.

This multi- and transdisciplinary project is therefore focused on the processes leading to epilepsy (i.e. epileptogenesis) in adult brain. Epileptogenesis is a complex multifactorial pathologic process, characterized by the concomitant or sequential occurrence of multiple changes in the brain. A major conceptual originality of this project is to consider the underlying patho-physiologic mechanisms of epileptogenesis as temporally evolving multiple processes, even after the epileptic seizures occur and become recurrent.

Overall scientific objectives of  EPITARGET are:
Using multidisciplinary strategies of basic, preclinical and clinical research to:
1. identify novel biomarkers and their combinations that will characterize the different stages of epileptogenesis and predict/diagnose early and late stages of the evolution of the disease.
2. unravel the complex patho-physiology of epileptogenesis and to design new, disease-modifying combinatorial treatment strategies specifically targeted to the different stages of epileptogenesis.
3. translate the knowledge obtained in experimental models to patients in order to improve diagnosis, achieve better patient stratification, and develop new antiepileptogenic treatments and means to predict their efficacy.

Projects 2016-2017:

  1. The extracellular matrix in epileptogenesis  Innovative Training Networks (ITN) Call: H2020-MSCA-ITN-2014 “ECMED”: (642881; 2015-2018); National Epilepsy Fonds (NEF; 2016-2020).
  2. Joint Programme - Neurodegenerative Disease Research ”European research projects for Cross-Disease Analysis of Pathways related to Neurodegenerative Diseases” (2015-2018).
  3. Stichting Kinderen Kankervrij (KiKa): Multi-platform analysis of TSC Subependymal Giant Cell Astrocytoma (SEGA) to identify novel therapeutic approaches  (2016-2020).
  4. Ministero della Salute (sezione Ricerca Sanitaria): Project Type: Italian researcher abroad. PE-2013-02355126: Homer-mGlu5 scaffold as common abnormal mechanism and therapeutic target for Intellectual Disability (ID) and Autism (2016-2019).      Theme: Neurological and Psychiatric Disorders
  5. 2016-2020: Subsidie Stichting "Michelle" (Tuberous Sclerosis)
  6. 2016-2017: Stichting Koppie-AU: MeMo studie Medulloblastoom, moleculaire biologie voor een betere risicoclassificatie bij kinderen .
  7. 2017-2021: H2020-MSCA-ITN-2016; EU-GliaPhD: Training, Research and Raising of Public Awareness in Cell Biology and Pathology of Neuroglia (722053)
  8.  2016-2019: Neuro-MIG COST Action (European Cooperation in the field of Scientific and Technical Research): OC-2016-1-20862 European Network on Brain Malformations.
  9. 2017-2018: Stichting Knip: Epileptogene Glioneuronale tumoren: “Moleculaire biologie en classificatie”.
  10. 2017-2022: Gezamenlijk Programma Translationeel Onderzoek tussen ZonMw, Stichting LSH-TKI en de Samenwerkende Gezondheidsfondsen. Projecttitel: Molecular diagnostics for personalized epilepsy surgery evaluation and prognosis.
     

Societal impact activiteit:

Interview Develage interview: https://www.youtube.com/watch?v=yLvsv3fmER8 Interview ILAE: focal lesions and epilepsy. http://www.ilae.org/Visitors/MeetingProceedings/29thiecvideos.cfm New York Times: New Epilepsy Tactic: Fight Inflammation: http://www.nytimes.com/2012/06/05/health/research/new-epilepsy-tactic-fight-inflammation.html?pagewanted=all&_r=0
 Impact magazine: http://www.epistop.eu/index.php/news/137-impact-publication-epistop

Books (2011-2016):
Annamaria Vezzani, Stephan Auvin, Teresa Ravizza, Eleonora Aronica Glia-neuronal interactions in ictogenesis and epileptogenesis: role of inflammatory mediators. In: Noebels JL, Avoli M, Rogawski MA, Olsen RW, Delgado-Escueta AV, editors. Jasper's Basic Mechanisms of the Epilepsies. 4th edition. Bethesda (MD): National Center for Biotechnology Information (US); 2012
Eleonora Aronica, Werner Stenzel. Reactions of muscle to toxins and drugs. Muscle Disease: Pathology and Genetics - Second Edition. International Society of Neuropathology (ISN) Book Series, 2014.
Clinical Neuroembryology: Development and developmental disorders of the human central nervous system, second edition (2014). Chapter10.7.4 Disorders of Cortical Development and Epilepsy.
Eleonora Aronica and Angelika Mühlebner. Handbook of Clinical Neurology 3rd Series: Neuropathology of Epilepsy (2016).
Eleonora Aronica, Angelika Mühlebner, Erwin van Vliet and Jan GorterModels of Seizure and Epilepsy, Second Edition Technical and methodological issues. Characterization of pathology (2016) .
Nikolay Kuzmin, Sander Idema, Eleonora Aronica, Philip C. de Witt Hamer, Pieter Wesseling, Marie Louise Groot. Higher Harmonic Generation Imaging for NeuroPathology (Taylor & Francis) Neurophotonics (2016).
M. de Visser and E. Aronica. Histopathological Features of Idiopathic Inflammatory Myopathies Myositis (Oxford Rheumatology Library, 2016).
Heidrun Potschka and Eleonora Aronica. Pathophysiology of drug refractoriness. The Atlas of Epilepsies. Springer-Verlag Berlin Heidelberg. DOI: 10.1007/SpringerReference_188157 2011-05-09 09:18:39 UTC, 2011.
Eleonora Aronica and Pitt Niehusmann. Gangliogliomas: molecular pathogenesis and epileptogenesis. Tumors Of The Central Nervous System. Ed. M. A. Hayat, Springer, 2011.
Çiğdem Özkara and Eleonora Aronica. Hippocampal sclerosis. Handbook of Clinical Neurology (3rd Series). Elsevier, Handb Clin Neurol.108:621-39, 2012.
 

1. Commissielid: International League Against Epilepsy (ILAE)Task Force of the Diagnostic Methods Commission, Task Force on FCD.

2. Tutor/Trekker: neuropathology teaching course aimed at colleagues engaged in the diagnostic evaluation of patients with drug-resistant focal epilepsy. http://www.ilae.org/Visitors/Congress/Ed-INES.cfm 

3. Contribution to the 193rd ENMC (European Neuromuscluar center) workshop on pathology diagnosis of idiopathic inflammatory myopathies.

4. Contribution to EURO-CNS CME Course, Developmental Neuropathology 2018


 

Faculty
Prof. E.M.A. Aronica

Postdocs
Dr. L. Mesarosova
Dr. J.D. Mills
Dr. A. Mühlebner
Dr. E.A. van Vliet

PhD Students
A. Bongaarts MSc
D.W.M. Broekaart
N.L. Fransen
A. Korotkov
H. Meeusen
T.S. Zimmer
T.J. Veersema MD (UMCU)

Others
J.J. Anink
C. Mijnsbergen

Other research related activities
  • Membership of medical or scientific committee, Netherlands Society of Neuropathology (NVVNP)
  • Membership of medical or scientific committee, Federation of European Neuroscience Societies
  • Membership of medical or scientific committee, American Society for Neuroscience
  • Membership of medical or scientific committee, British Neuropathological society
  • Contribution to guidelines and protocols, International League Against Epilepsy (ILAE)Task Force of the Diagnostic Methods Commission
  • Membership of medical or scientific committee, Scientific Research Section (SWO) of the Dutch League against Epilepsy
  • Membership of medical or scientific committee, Graduate School Neurosciences Amsterdam Rotterdam (ONWAR)
  • Membership of editorial board / Editorship, NEUROSCIENCE
  • Membership of editorial board / Editorship, FRONTIERS IN NEUROLOGY
Current research funding
  • AMC
  • AMC (Vrijgesteld)
  • Europese Unie
  • Life Sciences Health TKI
  • Nationaal Epilepsie Fonds
  • New York University School of Medicine
  • NWO
  • RWTH Aachen University Hospital
  • Stichting ALS Nederland
  • Stichting AMC Foundation (Vrijgesteld)
  • Stichting KIKA
  • Stichting Margaret Olivia Knip
  • Stichting Michelle
  • Stichting Parkinson Fonds
  • UCB Biopharma SPRL
  • ZonMw