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Prof. Andreas Grabrucker

MSc Biology PhD

Biography

CAREER PROFILE


Education
  • 2000-2005 TU Munich, Germany, Diploma in Biology, Major: Genetics, Minor: Neurobiology and Zoology
  • 2005-2009 University Ulm, Germany, PhD, international PhD program in molecular medicine

Employment
  • 2009-2011 Postdoctoral fellow, Stanford University, USA, Dept. of Psychiatry and Behavioral Sciences, Stanford School of Medicine
  • 2011-2016 Assistant Professor, University Ulm, Germany, Dept. of Neurology
  • 2011-2016 Executive Director of the Neurocenter of Ulm University
  • 2017- Lecturer in Cell Biology, University of Limerick, Ireland, Dept. of Biological Sciences, School of Natural Sciences

Scientific Activities - My research focuses on synaptopathies as a key feature of neurodevelopmental diseases. Disruptions in synaptic structure leading to abnormal circuit formation and function are potentially the major determinant of such brain diseases. My work aims to understand how genetic and non-genetic factors contribute to neuronal dysfunction and to develop novel research and treatment strategies using nanotechnology.

Research Interests

My research is interested in the underlying components able to modify synaptic plasticity and transmission in the Central Nervous System (CNS) in health and disease. Thereby, synaptopathy defines key features of neurodegenerative and psychiatric diseases. It implies that disruptions in synaptic structure and function are potentially the major determinant of such brain diseases.

Using a combination of biochemical, cellular, molecular and behavioral approaches, we have investigated proteins of excitatory postsynapses focusing on their deregulation in neurodevelopmental and neuropsychiatric disorders such as Autism Spectrum Disorders, Alzheimer’s disease and Schizophrenia. We are especially interested in the functional interaction of biometals and synaptic proteins in mechanisms such as synapse formation and maturation in health and disease. Given that dysregulation of trace metals is reported in many brain disorders, their role in the modification of synaptic function needs to be investigated in more detail. Especially since many brain disorders seem to not only have a genetic but also an environmental component triggering the disease. To investigate the role of biometals in disorders of the CNS, we use several approaches. For example, targeted manipulation of biometal levels in animal models and cells derived from human induced pluripotent stem cells is a major goal in our research. To that end, the development of novel drug carriers (i.e. Nanoparticles) and assays designed to evaluate their potency to influence synapse formation, maturation and plasticity has become an important part of our research. On the other hand, we investigate human patients with selected disorders and perform a state of the art assessment of their trace metal status and clinical phenotype to define subgroups with biometal abnormalities, which can be associated with specific clinical presentations. Understanding how environmental and genetic factors contribute to synaptic function will hopefully allow the development of research strategies to normalize function in individuals with synaptopathies.

Professional Activities

Association

  • 2012 Member, International Society for Zinc Biology
  • 2007 Member, Society for Neuroscience

Language

  • German
  • English

Publications

Book

Book Chapter

2020

Metals and amyloid gain-of-toxic mechanisms in neurodegenerative diseases
Joana S. Cristóvão, Guilherme G. Moreira, Andreas M. Grabrucker, Cláudio M. Gomes
Protein Homeostasis Diseases. DOI: 10.1016/B978-0-12-819132-3.00009-9

2019

The Role of Trace Metals in Alzheimer’s Disease
Chiara A. De Benedictis, Antonietta Vilella, Andreas M. Grabrucker
Alzheimer's Disease DOI: 10.15586/alzheimersdisease.2019

2017

Animal models of ASD – Extracerebral dysfunction
Hill-Yardin, EL; McKeown, SJ; Novarino, G; Grabrucker, AM
Advances in Anatomy, Embryology and Cell Biology, Translational anatomy and cell biology of autism spectrum disorders DOI: 10.1007/978-3-319-52498-6_9

2017

Neurodegenerative Diseases: Anatomy and Pathology
Sarowar, T; Grabrucker, AM
Frontiers in Nanomedicine: Nanomedicine and Neuroscience.

2017

Zinc and autism
Grabrucker, S; Grabrucker AM
Biometals in Neurodegenerative Diseases: Mechanisms and Therapeutics

2016

Zinc in the developing brain
Grabrucker, AM
Nutrition and the developing brain

2016

Zinc Deficiency
Sauer, AK; Hagmeyer, S; Grabrucker, AM
Nutritional Deficiency DOI: 10.5772/63203

2014

Ursachen
Grabrucker, AM; Schmeisser, MJ
Handlexikon Autismus-Spektrum: Schlüsselbegriffe aus Forschung, Theorie, Praxis und Betroffenen-Sicht

2013

Nanoparticles as Blood–Brain Barrier Permeable CNS Targeted Drug Delivery Systems
Grabrucker, AM; Chhabra, R; Belletti, D; Forni, F; Vandelli, MA; Ruozi, B; Tosi,G
Topics in Medicinal Chemistry DOI: 10.1007/7355_2013_22

Other Publication

2017

Molecular and Cellular Mechanisms of Synaptopathies
Ardiles, AO; Grabrucker, AM; Scholl, FG; Rudenko, G; Borsello, T
Neural Plasticity DOI: 10.1155/2017/2643943

Peer Reviewed Journal

2020

Autism-associated SHANK3 mutations impair maturation of neuromuscular junctions and striated muscles.
Lutz AK;Pfaender S;Incearap B;Ioannidis V;Ottonelli I;Föhr KJ;Cammerer J;Zoller M;Higelin J;Giona F;Stetter M;Stoecker N;Alami NO;Schön M;Orth M;Liebau S;Barbi G;Grabrucker AM;Delorme R;Fauler M;Mayer B;Jesse S;Roselli F;Ludolph AC;Bourgeron T;Verpelli C;Demestre M;Boeckers TM;
Science Translational Medicine DOI: 10.1126/scitranslmed.aaz3267

2020

Drug delivery across the blood-brain barrier: recent advances in the use of nanocarriers
Mulvihill J.;Cunnane E.;Ross A.;Duskey J.;Tosi G.;Grabrucker A.
Nanomedicine (London, England) DOI: 10.2217/nnm-2019-0367

2020

Comparing nanoparticles for drug delivery: The effect of physiological dispersion media on nanoparticle properties
Ross A.M.;Kennedy T.;McNulty D.;Leahy C.I.;Walsh D.R.;Murray P.;Grabrucker A.M.;Mulvihill J.J.E.
Materials Science & Engineering C-Materials For Biological Applications DOI: 10.1016/j.msec.2020.110985

2020

Synthesis, Characterization, and In Vitro Studies of an Reactive Oxygen Species (ROS)-Responsive Methoxy Polyethylene Glycol-Thioketal- Melphalan Prodrug for Glioblastoma Treatment
Oddone N, Boury F, Garcion E, Grabrucker AM, Del Carmen Martinez M, Da F, Janaszewska A, Forni F, Vandelli MA, Tosi G, Ruozi B, Duskey JT
Frontiers In Pharmacology DOI: 10.3389/fphar.2020.00574

2019

Shank3 Transgenic and Prenatal Zinc-Deficient Autism Mouse Models Show Convergent and Individual Alterations of Brain Structures in MRI
Schoen M.;Asoglu H.;Bauer H.;Müller H.;Abaei A.;Sauer A.;Zhang R.;Song T.;Bockmann J.;Kassubek J.;Rasche V.;Grabrucker A.;Boeckers T.
Frontiers In Neural Circuits DOI: 10.3389/fncir.2019.00006

2019

Nanomedicine against Aβ aggregation by β–sheet breaker peptide delivery: In vitro evidence
Pederzoli F.;Ruozi B.;Duskey J.;Hagmeyer S.;Sauer A.;Grabrucker S.;Coelho R.;Oddone N.;Ottonelli I.;Daini E.;Zoli M.;Vandelli M.;Tosi G.;Grabrucker A.
Pharmaceutics DOI: 10.3390/pharmaceutics11110572

2019

ROS-responsive “smart” polymeric conjugate: Synthesis, characterization and proof-of-concept study
Oddone N.;Pederzoli F.;Duskey J.;De Benedictis C.;Grabrucker A.;Forni F.;Angela Vandelli M.;Ruozi B.;Tosi G.
International journal of pharmaceutics DOI: 10.1016/j.ijpharm.2019.118655

2019

Distribution and relative abundance of S100 proteins in the brain of the APP23 Alzheimer’s disease model mice
Hagmeyer S.;Romão M.;Cristóvão J.;Vilella A.;Zoli M.;Gomes C.;Grabrucker A.
Frontiers In Neuroscience DOI: 10.3389/fnins.2019.00640

2019

Altered Intestinal Morphology and Microbiota Composition in the Autism Spectrum Disorders Associated SHANK3 Mouse Model
Sauer A.;Bockmann J.;Steinestel K.;Boeckers T.;Grabrucker A.
International Journal Of Molecular Sciences DOI: 10.3390/ijms20092134

2018

Brain Lateralization in Mice Is Associated with Zinc Signaling and Altered in Prenatal Zinc Deficient Mice That Display Features of Autism Spectrum Disorder
Grabrucker, S,Haderspeck, JC,Sauer, AK,Kittelberger, N,Asoglu, H,Abaei, A,Rasche, V,Schon, M,Boeckers, TM,Grabrucker, AM
Frontiers In Molecular Neuroscience DOI: 10.3389/fnmol.2017.00450

2018

Hybrid nanoparticles as a new technological approach to enhance the delivery of cholesterol into the brain
Belletti, D; Grabrucker, AM; Pederzoli, F; Menrath, I; Vandelli, MA; Tosi, G; Duskey, TJ; Forni, F; Ruozi, B;
International journal of pharmaceutics DOI: 10.1016/j.ijpharm.2018.03.061

2018

Zinc Binding to S100B Affords Regulation of Trace Metal Homeostasis and Excitotoxicity in the Brain
Hagmeyer, S,Cristovao, JS,Mulvihill, JJE,Boeckers, TM,Gomes, CM,Grabrucker, AM
Frontiers In Molecular Neuroscience DOI: 10.3389/fnmol.2017.00456

2017

Reduced plaque size and inflammation in the APP23 mouse model for Alzheimer's disease after chronic application of polymeric nanoparticles for CNS targeted zinc delivery.
Vilella, A; Belletti, D; Sauer, AK; Hagmeyer, S; Sarowar, T; Masoni, M; Stasiak, N; Mulvihill, JJE; Ruozi, B; Forni, F; Vandelli, MA; Tosi, G; Zoli, M; Grabrucker, AM
Journal Of Trace Elements In Experimental Medicine DOI: 10.1016/j.jtemb.2017.12.006

2017

Novel Curcumin loaded nanoparticles engineered for Blood-Brain Barrier crossing and able to disrupt Abeta aggregates
Ruozi, B; Belletti, D; Pederzoli, F; Masoni, M; Keller, J; Ballestrazzi, A; Vandelli, MA; Tosi, G; Grabrucker, AM
International Journal Of Pharmaceutics DOI: 10.1016/j.ijpharm.2017.05.015

2017

De Novo Mutations in Protein Kinase Genes CAMK2A and CAMK2B Cause Intellectual Disability
Küry, S; van Woerden, GM; Besnard, T; Proietti Onori, M; Latypova, X; Towne, MC; Cho, MT; Prescott, TE; Ploeg, MA; Sanders, S; Stessman, HAF; Pujol, A; Distel, B; Robak, LA; Bernstein, JA; Denommé-Pichon, AS; Lesca, G; Sellars, EA; Berg, J; Carré, W; Busk, ØL; van Bon, BWM; Waugh, JL; Deardorff, M; Hoganson, GE; Bosanko, KB; Johnson, DS; Dabir, T; Holla, ØL; Sarkar, A; Tveten, K; de Bellescize, J; Braathen, GJ; Terhal, PA; Grange, DK; van Haeringen, A; Lam, C; Mirzaa, G; Burton, J; Bhoj, EJ; Douglas, J; Santani, AB; Nesbitt, AI; Helbig, KL; Andrews, MV; Begtrup, A; Tang, S; van Gassen, KLI; Juusola, J; Foss, K; Enns, GM; Moog, U; Hinderhofer, K; Paramasivam, N; Lincoln, S; Kusako, BH; Lindenbaum, P; Charpentier, E; Nowak, CB; Cherot, E; Simonet, T; Ruivenkamp, CAL; Hahn, S; Brownstein, CA; Xia, F; Schmitt, S; Deb, W; Bonneau, D; Nizon, M; Quinquis, D; Chelly, J; Rudolf, G; Sanlaville, D; Parent, P; Gilbert-Dussardier, B; Toutain, A; Sutton, VR; Thies, J; Peart-Vissers, LELM; Boisseau, P; Vincent, M; Grabrucker, AM; Dubourg, C; Tan, WH; Verbeek, NE; Granzow, M; Santen, GWE; Shendure, J; Isidor, B; Pasquier, L; Redon, R; Yang, Y; State, MW; Kleefstra, T; Cogné, B; Petrovski, S; Retterer, K; Eichler, EE; Rosenfeld, JA; Agrawal, PB; Bézieau, S; Odent, S; Elgersma, Y; Mercier, S
American Journal Of Human Genetics DOI: http://dx.doi.org/10.1016/j.ajhg.2017.10.003

2017

Object phobia and altered RhoA signaling in amygdala of mice lacking RICH2
Sarowar, T; Grabrucker, S; Boeckers, TM; Grabrucker, AM
Frontiers In Neuroscience DOI: 10.3389/fnmol.2017.00180

2017

Characterization of zinc amino acid complexes for zinc delivery in vitro using Caco-2 cells and enterocytes from hiPSC
Sauer, AK,Pfaender, S,Hagmeyer, S,Tarana, L,Mattes, AK,Briel, F,Kury, S,Boeckers, TM,Grabrucker, AM
Biometals DOI: 10.1007/s10534-017-0033-y

2017

Zinc deficiency and low enterocyte zinc transporter expression in human patients with autism related mutations in SHANK3
Pfaender, S; Sauer, AK; Hagmeyer, S; Mangus, K; Linta, L; Liebau, S; Bockmann, J; Huguet, G; Bourgeron, T; Boeckers, TM; Grabrucker, AM
Scientific Reports DOI: 10.1038/srep45190

2016

Activity and circadian rhythm influence synaptic Shank3 protein levels in mice
Sarowar, T; Chhabra, R; Vilella, A; Boeckers, TM; Zoli, M; Grabrucker, AM
Journal Of Neurochemistry DOI: 10.1111/jnc.13709

2016

Enlarged dendritic spines and pronounced neophobia in mice lacking the PSD protein RICH2
Sarowar, T; Grabrucker, S; Föhr, K; Mangus, K; Eckert, M; Bockmann, J; Boeckers, TM; Grabrucker, AM
Molecular Brain DOI: 10.1186/s13041-016-0206-6

2016

EXPLOITING THE VERSATILITY OF CHOLESTEROL IN NANOPARTICLES FORMULATION
Belletti, D; Grabrucker, AM; Pederzoli, F; Menrath, I; Cappello, V; Vandelli, MA; Forni, F; Tosi, G; Ruozi, B
International Journal Of Pharmaceutics DOI: 10.1016/j.ijpharm.2016.07.022

2016

Gender Dependent Evaluation of Autism like Behavior in Mice Exposed to Prenatal Zinc Deficiency
Grabrucker, S; Boeckers, TM; Grabrucker, AM
Frontiers In Behavioral Neuroscience DOI: 10.3389/fnbeh.2016.00037

2016

Cellular Zinc Homeostasis Contributes to Neuronal Differentiation in Human Induced Pluripotent Stem Cells
Pfaender, S; Föhr, K; Lutz, AK; Putz, S; Achberger, K; Linta, L; Liebau, S; Boeckers, TM; Grabrucker, AM
Neural plasticity DOI: 10.1155/2016/3760702

2015

N-Cadherin-mediated cell adhesion is regulated by extracellular Zn(2+)
Heiliger, E; Osmanagic, A; Haase, H; Golenhofen, N; Grabrucker, AM; Weth, A; Baumgartner, W
Metallomics DOI: 10.1039/c4mt00300d

2015

Application of Polymeric Nanoparticles for CNS Targeted Zinc Delivery In Vivo
Chhabra, R; Ruozi, B; Vilella, A; Belletti, D; Mangus, K; Pfaender, S; Sarowar, T; Boeckers, TM; Zoli, M; Forni, F; Vandelli, MA; Tosi, G; Grabrucker, AM
Cns & Neurological Disorders-Drug Targets

2015

Effects of trace metal profiles characteristic for autism on synapses in cultured neurons
Hagmeyer, S; Mangusm K; Boeckers, TM; Grabrucker, AM
Neural plasticity DOI: 10.1155/2015/985083

2015

Zinc in gut-brain interaction in autism and neurological disorders
Vela, G; Stark, P; Socha, M; Sauer, AK; Hagmeyer, S; Grabrucker, AM
Neural plasticity DOI: 10.1155/2015/972791

2015

Emerging Use of Nanotechnology in the Treatment of Neurological Disorders
Chhabra, R; Tosi, G; Grabrucker, AM
Current Pharmaceutical Design

2014

Zinc deficiency dysregulates the synaptic ProSAP/Shank scaffold and might contribute to autism spectrum disorders
Grabrucker, S; Jannetti, L; Eckert, M; Gaub, S; Chhabra, R; Pfaender, S; Mangus, K; Reddy, PP; Rankovic, V; Schmeisser, MJ; Kreutz, MR; Ehret, G; Boeckers, TM; Grabrucker, AM
Brain DOI: 10.1093/brain/awt303

2014

Characterization of lysosome-destabilizing DOPE/PLGA nanoparticles designed for cytoplasmic drug release
Chhabra, R; Grabrucker, AM; Veratti, P; Belletti, D; Boeckers, TM; Vandelli, MA; Forni, F; Tosi, G; Ruozi, B
International Journal Of Pharmaceutics DOI: 10.1016/j.ijpharm.2014.05.054

2014

Insight on the fate of CNS-targeted nanoparticles. Part I: Rab5-dependent cell-specific uptake and distribution
Vilella, A; Tosi, G; Grabrucker, AM; Ruozi, B; Belletti, D; Vandelli, MA; Boeckers, TM; Forni, F; Zoli, M
Journal Of Controlled Release DOI: 10.1016/j.jconrel.2013.11.023

2014

Behavioral impairments in animal models for zinc deficiency
Hagmeyer, S; Haderspeck, JC; Grabrucker, AM
Frontiers In Behavioral Neuroscience DOI: 10.3389/fnbeh.2014.00443

2014

Insight on the fate of CNS-targeted nanoparticles. Part II: Intercellular neuronal cell-to-cell transport
Tosi, G; Vilella, A; Chhabra, R; Schmeisser, MJ; Boeckers, TM; Ruozi, B; Vandelli, MA; Forni, F; Zoli, M; Grabrucker, AM
Journal Of Controlled Release DOI: 10.1016/j.jconrel.2014.01.004

2014

The PSD protein ProSAP2/Shank3 displays synapto-nuclear shuttling which is deregulated in a schizophrenia-associated mutation
Grabrucker, S; Proepper, C; Mangus, K; Eckert, M; Chhabra, R; Schmeisser, MJ; Boeckers, TM; Grabrucker, AM.
Experimental Neurology DOI: 10.1016/j.expneurol.2013.12.015

2013

The Nedd4-binding protein 3 (N4BP3) is crucial for axonal and dendritic branching in developing neurons
Schmeisser, MJ; Kühl, SJ; Schoen, M; Beth, NH; Weis, TM; Grabrucker, AM; Kühl, M; Boeckers, TM
Neural Development DOI: 10.1186/1749-8104-8-18

2012

Autistic-like behaviours and hyperactivity in mice lacking ProSAP1/Shank2
Schmeisser, MJ; Ey, E; Wegener, S; Bockmann, J; Stempel, AV; Kuebler, A; Janssen, AL; Udvardi, PT; Shiban, E; Spilker, C; Balschun, D; Skryabin, BV; Dieck, St; Smalla, KH; Montag, D; Leblond, CS; Faure, P; Torquet, N; Le Sourd, AM; Toro, R; Grabrucker, AM; Shoichet, SA; Schmitz, D; Kreutz, MR; Bourgeron, T; Gundelfinger, ED; Boeckers, TM
Nature DOI: 10.1038/nature11015

2012

Grabrucker AM. Environmental factors in autism
Grabrucker, AM
Frontiers in psychiatry DOI: 10.3389/fpsyt.2012.00118

2012

Autism-associated mutations in ProSAP2/Shank3 impair synaptic transmission and neurexin-neuroligin-mediated transsynaptic signaling
Arons, MH; Thynne, CJ; Grabrucker, AM; Li, D; Schoen, M; Cheyne, JE; Boeckers, TM; Montgomery, JM; Garner, CC
Journal Of Neuroscience DOI: 10.1523/JNEUROSCI.2215-12.2012

2011

Amyloid beta protein-induced zinc sequestration leads to synaptic loss via dysregulation of the ProSAP2/Shank3 scaffold
Grabrucker, AM; Schmeisser, MJ; Udvardi, PT; Arons, M; Schoen, M; Woodling, NS; Andreasson, KI; Hof, PR; Buxbaum, JD; Garner, CC; Boeckers, TM
Molecular Neurodegeneration DOI: 10.1186/1750-1326-6-65

2011

Development of novel Zn2+ loaded nanoparticles designed for cell-type targeted drug release in CNS neurons: in vitro evidences
Grabrucker, AM; Garner, CC; Boeckers, TM; Bondioli, L; Ruozi, B; Forni, F; Vandelli, MA; Tosi, G
Plos One DOI: 10.1371/journal.pone.0017851

2011

Postsynaptic ProSAP/Shank scaffolds in the cross-hair of synaptopathies
Grabrucker, AM; Schmeisser, MJ; Schoen, M; Boeckers, TM
Trends In Cell Biology DOI: 10.1016/j.tcb.2011.07.003

2011

Concerted action of zinc and ProSAP/Shank in synaptogenesis and synapse maturation
Grabrucker, AM; Knight, MJ; Proepper, C; Bockmann, J; Joubert, M; Rowan, M; Nienhaus, GU; Garner, CC; Bowie, JU; Kreutz, MR; Gundelfinger, ED; Boeckers, TM
Embo Journal DOI: 10.1038/emboj.2010.336

2009

ynaptic cross-talk between N-methyl-D-aspartate receptors and LAPSER1-beta-catenin at excitatory synapses
Schmeisser, MJ; Grabrucker, AM; Bockmann, J; Boeckers, TM
Journal Of Biological Chemistry DOI: 10.1074/jbc.M109.020628

2009

Small-molecule XIAP inhibitors enhance gamma-irradiation-induced apoptosis in glioblastoma
Vellanki, SH; Grabrucker, A; Liebau, S; Proepper, C; Eramo, A; Braun, V; Boeckers, T; Debatin, KM; Fulda, S
Neoplasia

2009

Synaptogenesis of hippocampal neurons in primary cell culture
Grabrucker, A; Vaida, B; Bockmann, J; Boeckers, TM
Cell And Tissue Research DOI: 10.1007/s00441-009-0881-z