GokceLab – Systems Neuroscience – Cell Diversity
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
Bo Zhang, Ozgun Gokce, W Dylan Hale, Nils Brose, Thomas C Südhof (2018) Autism-associated neuroligin-4 mutation selectively impairs glycinergic synaptic transmission in mouse brainstem synapses. The Journal of experimental medicine 215: 6. 1543-1553 Jun.
Wanxin Wang, Lolita Penland, Ozgun Gokce, Derek Croote, Stephen R Quake (2018) High fidelity hypothermic preservation of primary tissues in organ transplant preservative for single cell transcriptome analysis. BMC genomics 19: 1. 02.
Lulu Y Chen, Man Jiang, Bo Zhang, Ozgun Gokce, Thomas C Südhof (2017) Conditional Deletion of All Neurexins Defines Diversity of Essential Synaptic Organizer Functions for Neurexins. Neuron 94: 3. 611-625.e4 May.
Ozgun Gokce, Geoffrey M Stanley, Barbara Treutlein, Norma F Neff, J Gray Camp, Robert C Malenka, Patrick E Rothwell, Marc V Fuccillo, Thomas C Südhof, Stephen R Quake (2016) Cellular Taxonomy of the Mouse Striatum as Revealed by Single-Cell RNA-Seq. Cell reports 16: 4. 1126-1137 Jul.
B Zhang, E Seigneur, P Wei, O Gokce, J Morgan, T C Südhof (2016) Developmental plasticity shapes synaptic phenotypes of autism-associated neuroligin-3 mutations in the calyx of Held. Molecular psychiatry Oct.
Marc V Fuccillo, Csaba Földy, Özgün Gökce, Patrick E Rothwell, Gordon L Sun, Robert C Malenka, Thomas C Südhof (2015) Single-Cell mRNA Profiling Reveals Cell-Type-Specific Expression of Neurexin Isoforms. Neuron 87: 2. 326-340 Jul.
Bo Zhang, Lulu Y Chen, Xinran Liu, Stephan Maxeiner, Sung-Jin Lee, Ozgun Gokce, Thomas C Südhof (2015) Neuroligins Sculpt Cerebellar Purkinje-Cell Circuits by Differential Control of Distinct Classes of Synapses. Neuron 87: 4. 781-796 Aug.
Patrick E Rothwell, Marc V Fuccillo, Stephan Maxeiner, Scott J Hayton, Ozgun Gokce, Byung Kook Lim, Stephen C Fowler, Robert C Malenka, Thomas C Südhof (2014) Autism-associated neuroligin-3 mutations commonly impair striatal circuits to boost repetitive behaviors. Cell 158: 1. 198-212 Jul.
Barbara Treutlein, Ozgun Gokce, Stephen R Quake, Thomas C Südhof (2014) Cartography of neurexin alternative splicing mapped by single-molecule long-read mRNA sequencing. Proceedings of the National Academy of Sciences of the United States of America 111: 13. E1291-E1299 Apr.
Marianne R Smith, Adeela Syed, Tamas Lukacsovich, Judy Purcell, Brett A Barbaro, Shane A Worthge, Stephen R Wei, Giuseppe Pollio, Letizia Magnoni, Carla Scali, Luisa Massai, Davide Franceschini, Michela Camarri, Marco Gianfriddo, Enrica Diodato, Russell Thomas, Ozgun Gokce, S J Tabrizi, Andrea Caricasole, Bernard Landwehrmeyer, Liliana Menalled, Carol Murphy, Sylvie Ramboz, Ruth Luthi-Carter, Goran Westerberg, J Lawrence Marsh (2014) A potent and selective Sirtuin 1 inhibitor alleviates pathology in multiple animal and cell models of Huntington's disease. Human molecular genetics 23: 11. 2995-3007 Jun.
Ozgun Gokce, Thomas C Südhof (2013) Membrane-tethered monomeric neurexin LNS-domain triggers synapse formation. The Journal of neuroscience : the official journal of the Society for Neuroscience 33: 36. 14617-14628 Sep.
Salvatore La Rosa, Tiziana Benicchi, Laura Bettinetti, Ilaria Ceccarelli, Enrica Diodato, Cesare Federico, Pasquale Fiengo, Davide Franceschini, Ozgun Gokce, Freddy Heitz, Giulia Lazzeroni, Ruth Luthi-Carter, Letizia Magnoni, Vincenzo Miragliotta, Carla Scali, Michela Valacchi (2013) Fused 3-Hydroxy-3-trifluoromethylpyrazoles Inhibit Mutant Huntingtin Toxicity. ACS medicinal chemistry letters 4: 10. 979-984 Oct.
Tamara Seredenina, Ozgun Gokce, Ruth Luthi-Carter (2011) Decreased striatal RGS2 expression is neuroprotective in Huntington's disease (HD) and exemplifies a compensatory aspect of HD-induced gene regulation. PloS one 6: 7. 07.
Ruth Luthi-Carter, David M Taylor, Judit Pallos, Emmanuel Lambert, Allison Amore, Alex Parker, Hilary Moffitt, Donna L Smith, Heike Runne, Ozgun Gokce, Alexandre Kuhn, Zhongmin Xiang, Michele M Maxwell, Steven A Reeves, Gillian P Bates, Christian Neri, Leslie M Thompson, J Lawrence Marsh, Aleksey G Kazantsev (2010) SIRT2 inhibition achieves neuroprotection by decreasing sterol biosynthesis. Proceedings of the National Academy of Sciences of the United States of America 107: 17. 7927-7932 Apr.
Luca Gambazzi, Ozgun Gokce, Tamara Seredenina, Elena Katsyuba, Heike Runne, Henry Markram, Michele Giugliano, Ruth Luthi-Carter (2010) Diminished activity-dependent brain-derived neurotrophic factor expression underlies cortical neuron microcircuit hypoconnectivity resulting from exposure to mutant huntingtin fragments. The Journal of pharmacology and experimental therapeutics 335: 1. 13-22 Oct.
Birgit Zucker, Jibrin A Kama, Alexandre Kuhn, Doris Thu, Lianna R Orlando, Anthone W Dunah, Ozgun Gokce, David M Taylor, Johann Lambeck, Bernd Friedrich, Katrin S Lindenberg, Richard L M Faull, Cornelius Weiller, Anne B Young, Ruth Luthi-Carter (2010) Decreased Lin7b expression in layer 5 pyramidal neurons may contribute to impaired corticostriatal connectivity in huntington disease. Journal of neuropathology and experimental neurology 69: 9. 880-895 Sep.
Ozgun Gokce, Heike Runne, Alexandre Kuhn, Ruth Luthi-Carter (2009) Short-term striatal gene expression responses to brain-derived neurotrophic factor are dependent on MEK and ERK activation. PloS one 4: 4. 04.
Nikita Rudinskiy, Yoshio A Kaneko, Ayshe Ana Beesen, Ozgun Gokce, Etienne Régulier, Nicole Déglon, Ruth Luthi-Carter (2009) Diminished hippocalcin expression in Huntington's disease brain does not account for increased striatal neuron vulnerability as assessed in primary neurons. Journal of neurochemistry 111: 2. 460-472 Oct.
Asad Jan, Ozgun Gokce, Ruth Luthi-Carter, Hilal A Lashuel (2008) The ratio of monomeric to aggregated forms of Abeta40 and Abeta42 is an important determinant of amyloid-beta aggregation, fibrillogenesis, and toxicity. The Journal of biological chemistry 283: 42. 28176-28189 Oct.
Heike Runne, Etienne Régulier, Alexandre Kuhn, Diana Zala, Ozgun Gokce, Valérie Perrin, Beate Sick, Patrick Aebischer, Nicole Déglon, Ruth Luthi-Carter (2008) 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. The Journal of neuroscience : the official journal of the Society for Neuroscience 28: 39. 9723-9731 Sep.
Ozlem Guzeloglu-Kayisli, Umit A Kayisli, Nduka M Amankulor, Jennifer R Voorhees, Ozgun Gokce, Michael L DiLuna, Maxwell S H Laurans, Guven Luleci, Murat Gunel (2004) Krev1 interaction trapped-1/cerebral cavernous malformation-1 protein expression during early angiogenesis. Journal of neurosurgery 100: 5 Suppl Pediatrics. 481-487 May.
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