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                                          1. ISD Research
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                                          3. GokceLab

                                          GokceLab – Systems Neuroscience – Cell Diversity

                                          • Research Focus
                                          • Publications
                                          • Team
                                          Gokce Key Visual

                                          Changes in the genome, called mutations, are the driving force of evolution. These mutations continue to shape us from the moment we begin life as a single cell to the end of our life by altering the genome of each cell. During development, these somatic mutations provide important benefits including fighting infections by developing B-cells antibody diversity, but they are also the underlying cause of almost all age-related diseases, particularly cancer and neurodegeneration. Yet, we do not know how many mutations accumulate in each cell and what the key mutagenic mechanisms are.

                                          Our group aims to characterize genomic changes at single cell resolution and to reveal mutagenic mechanisms leading to diseases. We primarily use single-cell sequencing technologies to characterize phenotypes and use molecular biology and animal models to understand the effects of somatic mutations on disease pathologies.

                                          Our major research focus is genomic instability in brain during post stroke pathologies and neurodegeneration. We use single-cell sequencing to measure the accumulation of genomic mutations in animal models. Our aim is to identify mechanisms leading to genomic instability in cell types of the brain and to develop therapies to slow genomic aging.

                                          We use a combination of single cell transcriptomics, live imaging and molecular approaches to elucidate the cellular and molecular mechanisms regulating the interconnected vascular-glial-neuron triad.

                                          Together with Jürgen Bernhagen, we also analyze B-cell development at the single-cell resolution, as they are a key player in cardiovascular disease and atherosclerosis which is the main risk factor for stroke. B-cell maturation involves somatic hypermutation and genetic recombination generating antibody diversity. We specifically study the role of atypical chemokines in B-cell development in order to reveal their function in the development and induction of the somatic mutations.

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

                                          Gokce Key Visual

                                          Publications by Ozgun Gokce

                                          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

                                          Gokce, Ozgun, PhD / PI

                                          Besson-Girard Simon, MSc / PhD student

                                          Bulut, Buket, MSc / PhD student

                                          Hao, Ji / PhD student

                                          Heisen, Christine / MD student

                                          Liu, Lu / PhD student

                                          Lukanovic, Sabrina / team assistant

                                          Usifo, Fumere, MSc / technician 

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