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                                            1. ISD Research
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                                            3. Gokce Lab

                                            Gokce Lab – Systems Neuroscience – Cell Diversity

                                            • Research Focus
                                            • Publications
                                            • Team
                                            Gokce Key Visual

                                            The immune and the nervous system evolved to respond to changes in the environment. Both systems recognize the outer world (by antibodies or sensory organs), learn (pathogens or food sources), and remember them. Back in 1967, Hood, Gray, & Dreyer proposed a genetic learning and memory mechanism for the immune and the nervous systems. Since then, site-specific somatic recombination and hypermutation in T and B cells have been well established as a genetic mechanism for learning and memory in the immune system but how the nervous system achieves learning and memory is still unclear. In the last ten years, revolutionary developments in high-throughput “-omics” measurements allowed us to characterize interactions between immune and nervous systems, which revealed surprising roles of immune mechanisms in shaping the nervous system in health and disease. Our group focuses on identifying shared mechanisms regulating nervous and immune systems and how these two systems regulate each other during aging and diseases.

                                            1. Role of white matter and cerebrovascular aging in neurodegeneration 

                                            White matter volume starts to decrease gradually from 50 years of age onwards. Electron microscopy studies performed in non-human primates have shown that the major changes observed during normal aging are not a loss of neurons, but rather changes in myelinated nerve fiber morphology. Our single-cell RNA-seq work showed that aging results in microglial activation in the white matter. We propose that age-related gliovascular changes induce myelindamage, which in turn affects microglia function in the white matter. Our group focuses on understanding how age-related gliovascular changes form and lead to the development neurodegenerative diseases.

                                            2. Emerging Roles of cytokines in neurological diseases 

                                            The highest expressed chemokine in neurons is macrophage migration inhibitory factor (MIF), which is also a newly identified nuclease. In collaboration with Prof. Bernhagen, we are studying MIF functions in the brain. We are testing if targeting MIF functions is a viable therapeutic strategy for neurodegenerative disorders. 

                                            Contact: Dr. Ozgun Gokce
                                            Tel: +49-89-4400-46149
                                            E-Mail: oezguen.goekce@med.uni-muenchen.de

                                            Gokce Key Visual

                                            Publications by Ozgun Gokce

                                            2021

                                            Besson-Girard S, Ji H, Gehring K, Bulut B, Kaya T, Usifo F, Simons M, Gokce O. Dissociation of microdissected mouse brain tissue for artifact free single-cell RNA sequencing. STAR Protoc. 2021 Apr https://doi.org/10.1016/j.xpro.2021.100590 

                                            Safaiyan S, Besson-Girard S, Kaya T, Cantuti-Castelvetri L, Liu L, Ji H, Schifferer M, Gouna G, Usifo F, Kannaiyan N, Fitzner D, Xiang X, Rossner MJ, Brendel M, Gokce O, Simons M. White matter aging drives microglial diversity. Neuron. 2021 Feb 11:S0896-6273(21)00073-8. doi: 10.1016/j.neuron.2021.01.027. Epub ahead of print. 

                                            2020

                                            Cantuti-Castelvetri L, Ojha R, Pedro LD, Djannatian M, Franz J, Kuivanen S, van der Meer F, Kallio K, Kaya T, Anastasina M, Smura T, Levanov L, Szirovicza L, Tobi A, Kallio-Kokko H, Österlund P, Joensuu M, Meunier FA, Butcher SJ, Winkler MS, Mollenhauer B, Helenius A, Gokce O, Teesalu T, Hepojoki J, Vapalahti O, Stadelmann C, Balistreri G, Simons M. Neuropilin-1 facilitates SARS-CoV-2 cell entry and infectivity. Science. 2020 Oct 20:eabd2985. 

                                            Stanley G, Gokce O, Malenka RC, Südhof TC, Quake SR. Continuous and Discrete Neuron Types of the Adult Murine Striatum. Neuron. 2020 Feb 19;105(4):688-699.e8. 

                                            2019

                                            Kapurniotu A, Gokce O, Bernhagen J. The Multitasking Potential of Alarmins and Atypical Chemokines. Front Med (Lausanne). 2019 Jan 23;6:3. 


                                            2018

                                            Zhang B, Gokce O, Hale WD, Brose N, Südhof TC. Autism-associated neuroligin-4 mutation selectively impairs glycinergic synaptic transmission in mouse brainstem synapses. J Exp Med. 2018 Jun 4;215(6):1543-1553. 

                                            Wang W, Penland L, Gokce O, Croote D, Quake SR. High fidelity hypothermic preservation of primary tissues in organ transplant preservative for single cell transcriptome analysis. BMC Genomics. 2018 Feb 13;19(1):140. 

                                            2017

                                            Chen LY, Jiang M, Zhang B, Gokce O, Südhof TC. Conditional Deletion of All Neurexins Defines Diversity of Essential Synaptic Organizer Functions for Neurexins. Neuron. 2017 May 3;94(3):611-625.e4. 


                                            2016

                                            Gokce O, Stanley GM, Treutlein B, Neff NF, Camp JG, Malenka RC, Rothwell PE, Fuccillo MV, Südhof TC, Quake SR. Cellular Taxonomy of the Mouse Striatum as Revealed by Single-Cell RNA-Seq. Cell Rep. 2016 Jul 26;16(4):1126-1137. 

                                            Zhang B, Seigneur E, Wei P, Gokce O, Morgan J, Südhof TC. Developmental plasticity shapes synaptic phenotypes of autism-associated neuroligin-3 mutations in the calyx of Held. Mol Psychiatry. 2017 Oct;22(10):1483-1491. 


                                            2015

                                            Fuccillo MV, Földy C, Gökce Ö, Rothwell PE, Sun GL, Malenka RC, Südhof TC. Single-Cell mRNA Profiling Reveals Cell-Type-Specific Expression of Neurexin Isoforms. Neuron. 2015 Jul 15;87(2):326-40. 

                                            Zhang B, Chen LY, Liu X, Maxeiner S, Lee SJ, Gokce O, Südhof TC. Neuroligins Sculpt Cerebellar Purkinje-Cell Circuits by Differential Control of Distinct Classes of Synapses. Neuron. 2015 Aug 19;87(4):781-96. 


                                            2014

                                            Rothwell PE, Fuccillo MV, Maxeiner S, Hayton SJ, Gokce O, Lim BK, Fowler SC, Malenka RC, Südhof TC. Autism-associated neuroligin-3 mutations commonly impair striatal circuits to boost repetitive behaviors. Cell. 2014 Jul 3;158(1):198-212. 

                                            Treutlein B, Gokce O, Quake SR, Südhof TC. Cartography of neurexin alternative splicing mapped by single-molecule long-read mRNA sequencing. Proc Natl Acad Sci U S A. 2014 Apr 1;111(13):E1291-9.

                                            Smith MR, Syed A, Lukacsovich T, Purcell J, Barbaro BA, Worthge SA, Wei SR, Pollio G, Magnoni L, Scali C, Massai L, Franceschini D, Camarri M, Gianfriddo M, Diodato E, Thomas R, Gokce O, Tabrizi SJ, Caricasole A, Landwehrmeyer B, Menalled L, Murphy C, Ramboz S, Luthi-Carter R, Westerberg G, Marsh JL. A potent and selective Sirtuin 1 inhibitor alleviates pathology in multiple animal and cell models of Huntington's disease. Hum Mol Genet. 2014 Jun 1;23(11):2995-3007. 


                                            2013

                                            Gokce O, Südhof TC. Membrane-tethered monomeric neurexin LNS-domain triggers synapse formation. J Neurosci. 2013 Sep 4;33(36):14617-28. 

                                            La Rosa S, Benicchi T, Bettinetti L, Ceccarelli I, Diodato E, Federico C, Fiengo P, Franceschini D, Gokce O, Heitz F, Lazzeroni G, Luthi-Carter R, Magnoni L, Miragliotta V, Scali C, Valacchi M. Fused 3-Hydroxy-3-trifluoromethylpyrazoles Inhibit Mutant Huntingtin Toxicity. ACS Med Chem Lett. 2013 Aug 8;4(10):979-84. 

                                            Gokce O, Südhof TC. Membrane-tethered monomeric neurexin LNS-domain triggers synapse formation. J Neurosci. 2013 Sep 4;33(36):14617-28. 

                                            La Rosa S, Benicchi T, Bettinetti L, Ceccarelli I, Diodato E, Federico C, Fiengo P, Franceschini D, Gokce O, Heitz F, Lazzeroni G, Luthi-Carter R, Magnoni L, Miragliotta V, Scali C, Valacchi M. Fused 3-Hydroxy-3-trifluoromethylpyrazoles Inhibit Mutant Huntingtin Toxicity. ACS Med Chem Lett. 2013 Aug 8;4(10):979-84. 


                                            2011

                                            Decreased striatal RGS2 expression is neuroprotective in Huntington's disease (HD) and exemplifies a compensatory aspect of HD-induced gene regulation. Seredenina T, Gokce O, Luthi-Carter R. PLoS One. 2011;6(7):e22231. 


                                            2010

                                            SIRT2 inhibition achieves neuroprotection by decreasing sterol biosynthesis. Luthi-Carter R, Taylor DM, Pallos J, Lambert E, Amore A, Parker A, Moffitt H, Smith DL, Runne H, Gokce O, Kuhn A, Xiang Z, Maxwell MM, Reeves SA, Bates GP, Neri C, Thompson LM, Marsh JL, Kazantsev AG. Proc Natl Acad Sci U S A. 2010 Apr 27;107(17):7927-32. 

                                            Diminished activity-dependent brain-derived neurotrophic factor expression underlies cortical neuron microcircuit hypoconnectivity resulting from exposure to mutant huntingtin fragments. Gambazzi L, Gokce O, Seredenina T, Katsyuba E, Runne H, Markram H, Giugliano M, Luthi-Carter R. J Pharmacol Exp Ther. 2010 Oct;335(1):13-22. 

                                            Decreased Lin7b expression in layer 5 pyramidal neurons may contribute to impaired corticostriatal connectivity in huntington disease. Zucker B, Kama JA, Kuhn A, Thu D, Orlando LR, Dunah AW, Gokce O, Taylor DM, Lambeck J, Friedrich B, Lindenberg KS, Faull RL, Weiller C, Young AB, Luthi-Carter R. J Neuropathol Exp Neurol. 2010 Sep;69(9):880-95. 


                                            2009

                                            Short-term striatal gene expression responses to brain-derived neurotrophic factor are dependent on MEK and ERK activation. Gokce O, Runne H, Kuhn A, Luthi-Carter R. PLoS One. 2009;4(4):e5292.

                                            Rudinskiy N, Kaneko YA, Beesen AA, Gokce O, Régulier E, Déglon N, Luthi-Carter R. Diminished hippocalcin expression in Huntington's disease brain does not account for increased striatal neuron vulnerability as assessed in primary neurons. J Neurochem. 2009 Oct;111(2):460-72. 


                                            2008

                                            Jan A, Gokce O, Luthi-Carter R, Lashuel HA. The ratio of monomeric to aggregated forms of Abeta40 and Abeta42 is an important determinant of amyloid-beta aggregation, fibrillogenesis, and toxicity. J Biol Chem. 2008 Oct 17;283(42):28176-89. 

                                            Runne H, Régulier E, Kuhn A, Zala D, Gokce O, Perrin V, Sick B, Aebischer P, Déglon N, Luthi-Carter R. Dysregulation of gene expression in primary neuron models of Huntington's disease shows that polyglutamine-related effects on the striatal transcriptome may not be dependent on brain circuitry. J Neurosci. 2008 Sep 24;28(39):9723-31.

                                            Gokce Team

                                            Peter Androvič, PhD / postdoc

                                            Simon Besson-Girard, MSc / GSN PhD student

                                            Buket Bulut, MSc / PhD student

                                            Elena Ernst / Master student

                                            Katrin Gehring / Master-PhD student

                                            Ozgun Gokce, PhD / PI

                                            Hao Ji, MD / MMRS PhD student

                                            Lu Liu, MD / MMRS PhD student

                                            Tuğberk Kaya, MSc / GSN PhD student

                                            Fumere Usifo, MSc / lab manager

                                            Yijing Wang, MD / PhD student

                                            Sabrina Lukanovic / team assistant



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                                            Institute for Stroke and Dementia Research (ISD)
                                            University Hospital, LMU Munich

                                            Director: Prof. Dr. med. Martin Dichgans

                                            Feodor-Lynen-Straße 17
                                            81377 Munich, Germany

                                            Phone: +49 (0)89 4400 46019
                                            www.isd-research.de
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                                            Neurologische Klinik und Poliklinik der Universität München

                                            DZNE – Deutsches Zentrum für Neurodegenerative Erkrankungen

                                            SyNergy – Munich Cluster for Systems Neurology

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