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                                                    3. Paquet Lab

                                                    Dominik Paquet – iPSC-models of brain diseases

                                                    • iPSC derived astrocytes

                                                      The PaquetLab aims to build human tissue models recapitulating major brain diseases. To establish these models, we apply and combine cutting-edge technologies, such as CRISPR/Cas genome editing, induced pluripotent stem cells (iPSCs), differentiation of iPSCs into human brain cells, and brain tissue engineering. Using these models, we want to understand the molecular and cellular mechanisms leading to nerve cell damage and death, and subsequent cognitive decline in patients with neuropsychiatric disorders, such as Alzheimer’s disease and frontotemporal dementia, and neurovascular impairments including stroke and vascular cognitive impairment.

                                                      Due to the inaccessibility of human brain cells for molecular research, neurodegenerative diseases have mostly been studied in animal and simple cellular models. These have significantly broadened our knowledge, but due to their drawbacks also limit successful translational research. We address this gap by developing human disease models using a powerful combination of CRISPR genome editing – which allows altering most genes in the human genome – and iPSC technology – which allows generating and studying somatic brain cells in the laboratory that are directly affected by disease. The disease-relevant cell types we study include neurons, astrocytes, microglia, oligodendrocytes, smooth muscle cells and endothelial cells, and the research projects in our lab focus on three major areas:

                                                      CRISPR genome editing in iPSCs

                                                      We believe that efficient and reliable genetic access to the patient cells we study is crucial to investigate the role of disease-associated genes, genetic variations such as SNPs, and to induce or modify disease symptoms in our models. In a set of fundamental studies (Paquet et al. Nature 2016; Kwart et al. Nat Prot 2017; Kwart et al. Neuron 2019) we revealed simple principles of efficient CRISPR/Cas9 genome editing in human iPSCs. We also demonstrated the potential of studying Alzheimer’s disease-causing mutations in isogenic sets of CRISPR-edited, iPSC-derived human cortical neurons. Recent work in our lab focused on improving the reliability and specificity of the CRISPR system e.g., by revealing frequent on-target effects in human iPSCs after editing and providing the field with simple detection tools to characterize and avoid these deleterious consequences of CRISPR genome editing (Weisheit et al. Cell Reports 2020).

                                                      Featured Publication:

                                                      Weisheit I, Kroger JA, Malik R, Wefers B, Lichtner P, Wurst W, Dichgans M, Paquet D. CRISPR-induced on-target effects by qgPCR and SNP genotyping. Nat Prot 2021

                                                      Weisheit I, Kroeger J, Malik R, Klimmt J, Crusius D, Dannert A, Dichgans M, Paquet D. Detection of Deleterious On-Target Effects after HDR-Mediated CRISPR Editing. Cell Rep. 2020 
                                                      Figure Cell Reports

                                                      Watch our video abstract on Youtube:

                                                      Taming widespread collateral damage of CRISPR editing

                                                      CRISPR-Cas9 has revolutionized disease-research, as it greatly simplifies targeted genome editing. However, CRISPR systems are not entirely accurate and can introduce potentially harmful additional mutations, called on-target effects. In a collaborative study with the DichgansLab, the PaquetLab identified widespread prevalence of on-target effects in clinically relevant CRISPR-edited iPS cells and describes broadly applicable tools to detect these unintended alterations. The new method improves the reliability of CRISPR editing. [read more...]

                                                      Brain cell differentiation from iPSCs and brain tissue engineering to study neurodegenerative diseases

                                                      3D Tissue

                                                      Recent work in the field has indicated that major aspects of the complex pathological processes underlying human neurodegenerative disease depend on the interplay between multiple cell types, such as neurons, microglia, astrocytes and oligodendrocytes. We therefore believe that optimal investigation of such disease processes will not only require human cells, but also complex, 3-dimensional tissue models containing the major disease-relevant cell types. In a recent review article, we discussed the current status of the field and strategies to design the next generation of iPSC-based models of brain diseases (Klimmt*, Dannert*, Paquet, Curr Opin Neurobiol 2020). A major focus of our lab is therefore to establish technologies for the optimized differentiation of all major brain cell types relevant for neurodegenerative disease, and to combine them in a 3-dimensional human brain tissue model. In this model, we aim to elicit and study disease phenotypes and investigate underlying pathomechanisms. In addition, because such models are accessible for genetic manipulation and amenable to drug development, we plan to apply them for translational studies to accelerate the identification of novel therapeutic approaches and targets. 

                                                      Human models of brain vessels to investigate the biology of the blood-brain-barrier and mechanisms of neurovascular disease

                                                      3D-vessel

                                                      Increasing evidence points to a major role of brain vasculature not only in neurovascular diseases, such as stroke, small vessel disease, etc., but also in a broad group of other brain diseases including Alzheimer’s. At the same time, genetic studies from our institute and others revealed many genetic loci associated with neurovascular impairment in patients. Using the above-mentioned combination of CRISPR editing and iPSC-based tissue engineering, we are setting up modular systems of human brain vessels that allow investigating mechanisms of human neurovascular disorders and the underlying genetic causes and associations.

                                                      Contact:

                                                      Dominik Paquet
                                                      Professor of Neurobiology

                                                      Institute for Stroke and Dementia Research (ISD), University Hospital, LMU Munich
                                                      Room 8G 02 144

                                                      Feodor-Lynen-Straße 17
                                                      D-81377 Munich, Germany

                                                      Phone: +49 89 4400 46123
                                                      E-Mail: dominik.paquet@med.uni-muenchen.de

                                                    • iPSC derived endothelial cells

                                                      Publications by Dominik Paquet

                                                      Key Publications

                                                      > All Publications

                                                      2022

                                                      Scotto Rosato A, Krogsaeter EK, Jaślan D, Abrahamian C, Montefusco S, Soldati C, Spix B, Pizzo MT, Grieco G, Böck J, Wyatt A, Wünkhaus D, Passon M, Stieglitz M, Keller M, Hermey G, Markmann S, Gruber-Schoffnegger D, Cotman S, Johannes L, Crusius D, Boehm U, Wahl-Schott C, Biel M, Bracher F, De Leonibus E, Polishchuk E, Medina DL, Paquet D, Grimm C. TPC2 rescues lysosomal storage in mucolipidosis type IV, Niemann-Pick type C1, and Batten disease. EMBO Mol Med. 2022 Sep 7;14(9):e15377. doi: 10.15252/emmm.202115377. Epub 2022 Aug 5. 

                                                      Reifschneider A, Robinson S, van Lengerich B, Gnörich J, Logan T, Heindl S, Vogt MA, Weidinger E, Riedl L, Wind K, Zatcepin A, Pesämaa I, Haberl S, Nuscher B, Kleinberger G, Klimmt J, Götzl JK, Liesz A, Bürger K, Brendel M, Levin J, Diehl-Schmid J, Suh J, Di Paolo G, Lewcock JW, Monroe KM, Paquet D, Capell A, Haass C. Loss of TREM2 rescues hyperactivation of microglia, but not lysosomal deficits and neurotoxicity in models of progranulin deficiency. EMBO J. 2022 Feb 15;41(4):e109108. doi: 10.15252/embj.2021109108. Epub 2022 Jan 12. 

                                                      2021

                                                      Weisheit I, Kroeger JA, Malik R, Wefers B, Lichtner P, Wurst W, Dichgans M, Paquet D. Simple and reliable detection of CRISPR-induced on-target effects by qgPCR and SNP genotyping. Nat Protoc. 2021 Feb 17. doi: 10.1038/s41596-020-00481-2. Epub ahead of print. 

                                                      2020

                                                      Weisheit I, Kroeger J, Malik R, Klimmt J, Crusius D, Dannert A, Dichgans M, Paquet D. Detection of Deleterious On-Target Effects after HDR-Mediated CRISPR Editing. Cell Rep. 2020 

                                                      Klimmt J, Dannert A, Paquet D. Neurodegeneration in a dish: advancing human stem-cell-based models of Alzheimer's disease. Curr Opin Neurobiol. 2020;61:96–104. 

                                                      2019

                                                      Kwart D, Gregg A, Scheckel C, Murphy E, Paquet D, Duffield M, Fak J, Olsen O, Darnell R, Tessier-Lavigne M. A Large Panel of Isogenic APP and PSEN1 Mutant Human iPSC Neurons Reveals Shared Endosomal Abnormalities Mediated by APP β-CTFs, Not Aβ. Neuron. 2019 Oct 23;104(2):256-270.e5. 

                                                      Martín-Maestro P, Sproul A, Martinez H, Paquet D, Gerges M, Noggle S, Starkov AA. Autophagy Induction by Bexarotene Promotes Mitophagy in Presenilin 1 Familial Alzheimer's Disease iPSC-Derived Neural Stem Cells. Mol Neurobiol. 2019 Dec;56(12):8220-8236. 

                                                      2017

                                                      Kwart D, Paquet D, Teo S, Tessier-Lavigne M. Precise and efficient scarless genome editing in stem cells using CORRECT. Nat Protoc. 2017 Feb;12(2):329-354. 

                                                      2016

                                                      Paquet D, Kwart D, Chen A, Sproul A, Jacob S, Teo S, Olsen KM, Gregg A, Noggle S, Tessier-Lavigne M. Efficient introduction of specific homozygous and heterozygous mutations using CRISPR/Cas9. Nature. 2016 May 5;533(7601):125-9

                                                      Engerer P, Plucinska G, Thong R, Trovò L, Paquet D, Godinho L. Imaging Subcellular Structures in the Living Zebrafish Embryo. J Vis Exp. 2016 Apr 2;(110):e53456. 

                                                      2014

                                                      Paquet D, Plucińska G, Misgeld T. In vivo imaging of mitochondria in intact zebrafish larvae. Methods Enzymol. 2014;547:151-64. 

                                                      Giustiniani J, Chambraud B, Sardin E, Dounane O, Guillemeau K, Nakatani H, Paquet D, Kamah A, Landrieu I, Lippens G, Baulieu EE, Tawk M. Immunophilin FKBP52 induces Tau-P301L filamentous assembly in vitro and modulates its activity in a model of tauopathy. Proc Natl Acad Sci U S A. 2014 Mar 25;111(12):4584-9.

                                                      2012

                                                      Plucińska G, Paquet D, Hruscha A, Godinho L, Haass C, Schmid B, Misgeld T. In vivo imaging of disease-related mitochondrial dynamics in a vertebrate model system. J Neurosci. 2012 Nov 14;32(46):16203-12.

                                                      2010

                                                      Fett ME, Pilsl A, Paquet D, van Bebber F, Haass C, Tatzelt J, Schmid B, Winklhofer KF. Parkin is protective against proteotoxic stress in a transgenic zebrafish model. PLoS One. 2010 Jul 30;5(7):e11783. 

                                                      van Bebber F, Paquet D, Hruscha A, Schmid B, Haass C. Methylene blue fails to inhibit Tau and polyglutamine protein dependent toxicity in zebrafish. Neurobiol Dis. 2010 Sep;39(3):265-71. 

                                                      Paquet D, Schmid B, Haass C. Transgenic zebrafish as a novel animal model to study tauopathies and other neurodegenerative disorders in vivo. Neurodegener Dis. 2010;7(1-3):99-102.

                                                      2009

                                                      Paquet D, Bhat R, Sydow A, Mandelkow EM, Berg S, Hellberg S, Fälting J, Distel M, Köster RW, Schmid B, Haass C. A zebrafish model of tauopathy allows in vivo imaging of neuronal cell death and drug evaluation. J Clin Invest. 2009 May;119(5):1382-95.

                                                      2007

                                                      Exner N, Treske B, Paquet D, Holmström K, Schiesling C, Gispert S, Carballo-Carbajal I, Berg D, Hoepken HH, Gasser T, Krüger R, Winklhofer KF, Vogel F, Reichert AS, Auburger G, Kahle PJ, Schmid B, Haass C. Loss-of-function of human PINK1 results in mitochondrial pathology and can be rescued by parkin. J Neurosci. 2007 Nov 7;27(45):12413-8.

                                                      See all publications by Dominik Paquet

                                                    • Paquet Lab

                                                      Dominik Paquet

                                                      Dominik Paquet, Principal investigator

                                                      Dominik established the PaquetLab at ISD in 2017, after he was appointed Professor for Neurobiology at LMU Munich and became a member of the Munich Cluster for Systems Neurology (SyNergy). He received his BSc and MSc from the Eberhard-Karls-University Tübingen, Germany. During his MSc Dominik worked with Henry Roehl at the MRC Centre for Developmental Genetics in Sheffield, UK. For his PhD, Dominik developed the first Tau-transgenic zebrafish model to study mechanisms of Tau-related neurodegeneration with Christian Haass at LMU Munich. After working with Thomas Misgeld at TU Munich for 2 years on in vivo imaging to study mitochondrial transport defects in neurodegenerative diseases, Dominik joined the lab of Marc Tessier-Lavigne at The Rockefeller University in NYC as a New York Stem Cell Foundation Druckenmiller Fellow. There, he pioneered the use of CRISPR/Cas9 gene editing in induced pluripotent stem cells to study diseases of the human brain.

                                                      E-Mail: Dominik.Paquet@med.uni-muenchen.de
                                                      Phone: +49 89 4400 46123

                                                      Read more on PI tab

                                                      Julien Klimmt, GSN graduate student

                                                      Julien was born and raised in Chemnitz, Germany. He received his BSc in Human Biology from the University of Greifswald in 2014 and a MSc in Molecular Biosciences with a major in neurosciences at the University of Heidelberg. During his Master’s he worked at Harvard Medical School with Dr. Matthew J. LaVoie on the cytosolic function of Parkin. In 2017 he finished his Master’s degree working on epigenetic mechanisms in memory formation and then joined the PaquetLab as a graduate student. He is now working on complex cell culture systems using CRISPR/Cas9-edited, iPSC-derived brain cells to model AD.

                                                      E-Mail: Julien.Klimmt@med.uni-muenchen.de
                                                      Phone: +49 89 4400 46223



                                                      Angelika Dannert

                                                      Angelika Dannert, GSN graduate student

                                                      Angelika grew up near Ulm in Germany. She studied Molecular Medicine and obtained her BSc from the University of Tübingen, and her MSc from the University of Göttingen, Germany. During her studies she did international research internships at Free University Amsterdam, University of Zürich, and Stanford University. During her master’s she worked on iPSC-based models of depression followed by her thesis on prevention of vascular stiffening. She joined the PaquetLab in December 2018 and is working on the development of complex in vitro models of FTD using CRISPR/Cas9-edited iPSC-derived brain cells.

                                                      E-Mail: Angelika.Dannert@med.uni-muenchen.de
                                                      Phone: +49 89 4400 46223


                                                      Judith Gonzales

                                                      Judit Gonzalez Gallego, GSN graduate student, collaboration with Dichgans Lab, ISD

                                                      Judit is a native of Spain. She obtained her BSc in biochemistry from the Autonomous University of Barcelona. After completing her bachelors degree, she worked for one year at the Center of Neurobiology of Hamburg University with Dr. Marina Mikhaylova in protein neuronal transport. Currently, she is a fast-track student in the Graduate School of Systemic Neuroscience (GSN) and after performing a research internship in PaquetLab on CRISPR/Cas9 genome editing she decided to join the ISD in October 2018 for a PhD project in neurovascular disorders co-supervised by Martin Dichgans and Dominik Paquet.

                                                      E-Mail: Judit.Gonzalez@med.uni-muenchen.de
                                                      Phone: +49 89 4400 46177


                                                      Liliana Pedro

                                                      Liliana Pedro, GSN graduate student, collaboration with Simons Lab, DZNE

                                                      Liliana was born in Portugal. She received her BSc in Biochemistry (2011) and her MSc in Molecular Biotechnology (2013) from the University of Aveiro, Portugal. For her Master Thesis she worked to establish the role of trace elements in the structure and metabolism of connective tissues at the Medical Research Council in Cambridge, UK. After her Master, she remained in Cambridge working as a research assistant applying her expertise in the optical emission spectroscopy analysis of biological samples. In 2015 she joined Prof. Ulrike Gaul lab at the Gene Center in Munich investigating the blood brain barrier development in Drosophila melanogaster. At the moment she doing her PhD in Prof. Mikael Simons group, studying oligodendrocyte myelination in development and adults, in a collaborative project with the PaquetLab.

                                                      E-Mail: Liliana.Pedro-Domingues@dzne.de
                                                      Phone: +49 89 4400 46480



                                                      Marvin Reich, GSN graduate student, collaboration with Haass Lab, DZNE

                                                      Marvin grew up near Tübingen in Germany. He obtained both his BSc and his MSc in Life Science at the University of Konstanz. During his master’s, he spent one year at Uppsala University in Sweden on an Erasmus scholarship focusing on biotechnology and protein biochemistry. He studied oxidative stress pathways in an in vitro model for Parkinson’s disease as a research intern at Roche in Basel, Switzerland before he worked on the embryonal development of neuronal signaling using murine cortical organoids in the group of Andreas Hierlemann at ETH Zurich. During his master’s thesis, he developed a microglia differentiation protocol from iPSCs for drug screening purposes and the investigation of TREM2 biology at Roche in Basel. For his PhD, he joined the lab of Christian Haass in March 2020 to study microglial phenotypes and cellular interaction in the context of frontotemporal dementia. In collaboration with the PaquetLab, he will employ CRISPR/Cas genomic editing and iPSC differentiation into neural cell types as a system to model and investigate frontotemporal dementia. 

                                                      E-Mail: Marvin.Reich@mail03.med.uni-muenchen.de
                                                      Phone: +49-89 4400-46539


                                                      Carolina Cardoso Goncalves, GSN graduate student

                                                      Carolina grew up in a small town near Coimbra, Portugal. She obtained her BSc in Biochemistry and her MSc in Cellular and Molecular Biology from the University of Coimbra, Portugal. During her studies she did internships at Centre Hospitalier Universitaire Vaudois in Lausanne, Karolinska Institute in Stockholm and University of Lausanne. For her master´s thesis she joined the group of Prof. Paola Bezzi at the University of Lausanne, Switzerland, where she studied the mechanisms underlying the control of dopamine homeostasis in astrocytes from the prefrontal cortex. After her Masters she worked as a Junior Research Fellow investigating the role of astrocyte-induced neural microenvironment remodeling in neural 3D cell models at the Animal Cell Technology Unit of iBET and ITQB-NOVA in Lisbon, Portugal. Carolina joined the PaquetLab in September 2019 and is currently working on the development of dynamic 3D cell cultures to model AD.

                                                      E-Mail: Carolina.Cardoso@med.uni-muenchen.de
                                                      Phone: +49 89 4400 46222


                                                      Merle Bublitz, Master student

                                                      Merle grew up in Hannover, Germany, after which she moved to Iowa, USA, to become a student athlete at Morningside University and obtain her BSc in Biology and Mathematics. During her Bachelor’s she worked with Dr. Chad Leugers investigating the role of tau protein and abnormal MAPK signaling pathways in Alzheimer’s disease. She also spent one semester at Griffith University in Australia with a focus on computational biology. In 2019, Merle became a master’s student with the GSN. After a research internship with Prof. David Franklin, where she investigated the impact of positive reinforcement learning in dual adaptation, she joined the PaquetLab for a research internship in October 2020. For her master’s thesis she is studying CRISPR/Cas9-edited iPSCs as a model system for AD.

                                                      E-Mail: Merle.Bublitz@med.uni-muenchen.de
                                                      Phone: +49 89 4400 46226

                                                      Jennifer Sandrina Yilmaz, Lab manager

                                                      Jenny was born in Rosenheim, Germany. She graduated in 2015 as a chemistry lab technician and worked as a laboratory lubricant assistant for several years. After travelling for one year, she wanted to change to the clinical field and joined the PaquetLab in October 2019, where she supports the team in a variety of ways in organizing and structuring the laboratory and actively participates in stem cell differentiation and molecular biological methods. 

                                                      E-Mail: Jennifer.Chmiel@med.uni-muenchen.de
                                                      Phone: +49 89 4400 46026

                                                      Alumni

                                                      Melanie Falke, Masterstudentin

                                                      Patricia Yuste, Postdoc

                                                      Sophie Robinson, GSN-Doktorandin

                                                      Joseph Kroeger, GSN graduate student

                                                      Dennis Crusius, BTA

                                                      Bérenice Horlacher, master student

                                                      Isabel Weisheit, GSN graduate student

                                                      Annika Wagener, Master student

                                                      Katja Salbaum, master student

                                                      Samantha Ho, Undergraduate researcher

                                                      Ioanna Emmanouilidis, GSN undergraduate researcher, ISD

                                                      Andrea Stüven, Team Assistant

                                                      Sarah Hübner, Undergraduate researcher

                                                      Johannes Heim, Undergraduate researcher

                                                    • Dominik Paquet, PI

                                                      I have a long-standing interest in elucidating the molecular mechanisms leading to degeneration of the human brain in Alzheimer’s disease (AD), frontotemporal dementia (FTD), stroke and related neurodegenerative and neurovascular disorders. One of the major research goals of my lab is to develop model systems that recapitulate central features of human disease and apply these models to investigate the molecular players leading to malfunction and demise of neurons. I started my scientific career as a graduate student with Christian Haass at LMU Munich, where I developed the first transgenic zebrafish model of AD and FTD that showed neurodegeneration and protein aggregation. I a follow-up study with Thomas Misgeld at TU Munich we performed the first in vivo imaging of axonal transport, a cellular pathway involved in disease progression, in an intact vertebrate animal. Both studies opened the field for human disease modelling in transgenic zebrafish, served as models for several subsequent studies in other labs, were highly cited (Publications in JCI and J Neuroscience), and received several research awards.

                                                      After focusing on animal models during my PhD, I moved closer to the human patient during my Postdoc with Marc Tessier-Lavigne at The Rockefeller University in NYC. There, I developed induced pluripotent stem cell (iPSC) based models of Alzheimer’s disease (AD) and Tauopathies in collaboration with scientists at the New York Stem Cell Foundation. At this point, first studies had described the use of patient iPSCs for AD disease modelling, but there was no technology available allowing efficient genetic access, to introduce or correct mutations. I developed robust techniques for genome editing of iPSCs using CRISPR/Cas9 and demonstrated for the first time the formation of disease-relevant, zygosity-dependent phenotypes by knock-in two early-onset AD mutations (Publications in Nature and Nature Protocols).

                                                      Based on this work, my lab at ISD Munich is now focussing on building advanced human in vitro model systems recapitulating neurodegenerative and neurovascular diseases using iPSCs and genome editing with CRISPR/Cas9.


                                                      Scientific vita | Dominik Paquet

                                                      2011 – 2016 Postdoctoral Fellow, Laboratory for Brain Development and Repair, The Rockefeller University, New York, USA; Mentor: Marc Tessier-Lavigne

                                                      2009 – 2011 Postdoctoral Fellow, German Center for Neurodegenerative Diseases (DZNE), Munich, Germany; Mentors: Thomas Misgeld, Christian Haass

                                                      2005 – 2009 PhD Thesis (summa cum laude), Department of Biochemistry, Adolf-Butenandt-Institute, Ludwig-Maximilians University (LMU), Munich, Germany; Mentor: Christian Haass

                                                      2004 – 2005 Diploma Thesis, MRC Centre for Developmental Genetics, University of Sheffield, United Kingdom; Mentor: Henry Roehl

                                                      1999 – 2004 Studies of Biology (summa cum laude), University of Tuebingen, Germany

                                                      Fellowships

                                                      • Druckenmiller Postdoctoral Fellowship, The New York Stem Cell Foundation

                                                      • Postdoctoral Fellowship, German Academy of Sciences Leopoldina

                                                      • PhD-Fellowship, Universität Bayern e.V. (Graduiertenförderung nach dem Bayerischen Eliteförderungsgesetz)

                                                      • Diploma Thesis Fellowship, German academic exchange service (DAAD)

                                                      • Diploma Thesis Fellowship, Department of Biomedical Sciences, University of Sheffield, UK

                                                      Awards

                                                      • Best poster award, The New York Stem Cell Foundation Innovators Retreat 2016

                                                      • Best talk award, The New York Stem Cell Foundation Innovators Retreat 2015

                                                      • Award for 'Intelligible Science’, Helmholtz Zentrum Geesthacht, 2010

                                                      • Finalist at Deutscher Studienpreis 2010, Körber-Stiftung, 2010

                                                      • Best talk award, Interact-Meeting Munich 2009

                                                      • International Leda-Hanin-Award of the Cornelli Foundation, AD/PD-Meeting 2009

                                                      • International Verum Award of the Verum Foundation, 2009

                                                      • 1st Young Investigator Award of the Universität Bayern e.V., 2008

                                                      • Travel award, The Lindau Nobel Laureate Meeting, 2007

                                                    • Lab News

                                                      15 Mar 2021

                                                      NYAS.jpg

                                                      Isabel was selected for one of only two short talks at The New York Academy of Sciences - CRISPR: New Frontiers March 2021 meeting. Congratulations!

                                                      10 Mar 2021

                                                      ADPD-Posters.jpg

                                                      Julien and Angelika presented a virtual poster about their projects on human brain tissue models of AD and Tauopathies at ADPD 2021.

                                                      08 Mar 2021

                                                      Keystone.jpg

                                                      Isabel and Dominik presented a virtual short talk at Keystone Precision engineering of the Genome, Epigenome and Transcriptome.

                                                      04 Mar 2021

                                                      Nature-Protocols

                                                      Our newest Nature protocols paper was selected by Nature protocols editors to be presented as #Featured Protocol on the main page!

                                                      17 Feb 2021

                                                      Nature-Protocols

                                                      Our newest paper was just published at Nature Protocols: Simple and reliable detection of CRISPR-induced on-target effects by qgPCR and SNP genotyping. See paper here, and Tweetorial summary here.

                                                      17 Dec 2020

                                                      Virtual Christmas

                                                      We had a great virtual Christmas party with a cooking kit, dinner by zoom, and virtual games. Thanks lab for the nice evening!

                                                      11 Dec 2020

                                                      Neuronus

                                                      Dominik presented our recent work at the virtual Neuronus conference to a large (>100) audience of international young neuroscientists.

                                                      08 Dec 2020

                                                      Katja Award

                                                      We are very proud of Katja Salbaum, who won the award of the GBM (German Society for Biochemistry and Molecular Biology) for the best master thesis in Biomedical Neuroscience at TUM for her work on CRISPR base editing in iPSCs! Congratulations!

                                                      07 Dec 2020

                                                      NCL Meeting

                                                      Dominik gave the keynote lecture at the virtual 6th JNCL Young Investigator Symposium. Was a pleasure the learn more about NCL and related diseases and present our relevant work for this field. 

                                                      01 Dec 2020

                                                      TUM Course

                                                      Dominik taught his first ‚socially distanced‘ lab course on molecular biology at TUM‘s Biomedical Neuroscience Master program. This was quite different to previous years, but worked quite well overall and made the students happy, as they could meet in person for the first time since they started their MSc studies.

                                                      23 Sep 2020

                                                      GSCN

                                                      Isabel was selected for a talk at the German Stem Cell Network (GSCN) Conference and presented this virtually to the audience, with lots of good questions afterwards.
                                                      Read more...

                                                      10 Jun 2020

                                                      Lenggries

                                                      We use the nice weather and end of the lockdown to make a ‚socially distanced‘ lab hike to the mountains around Lenggries near Munich. Really nice warm day with lots of wildflowers!

                                                      01 Jun 2020

                                                      Sanofi Logo

                                                      We are delighted to be selected for an iAward of the Sanofi Innovation Awards Europe Program 2020 for our work on iPSC models of Neurodegenerative diseases. Many thanks to Sanofi for the support, we look forward to working with you! 

                                                      26 May 2020

                                                      Cell Reports Figure

                                                      Taming widespread collateral damage of CRISPR editing

                                                      CRISPR-Cas9 has revolutionized disease-research, as it greatly simplifies targeted genome editing. However, CRISPR systems are not entirely accurate and can introduce potentially harmful additional mutations, called on-target effects. In a collaborative study with the DichgansLab, the PaquetLab identified widespread prevalence of on-target effects in clinically relevant CRISPR-edited iPS cells and describes broadly applicable tools to detect these unintended alterations. The new method improves the reliability of CRISPR editing. [read more...]

                                                      [Watch Tweetorial] 

                                                      19 Feb 2020

                                                      ibidi

                                                      Judit presented our work on iPSC models of neurovascular disorders at the ibidi International Cell Culture Under Flow Meeting 2020. 

                                                      20 Dec 2019

                                                      Christmas-party-2019

                                                      Our traditional PaquetLab Christmas party took place again - with Raclette and drinks! Looks like everyone had a good time...

                                                      15 Dec 2019

                                                      Chinesicher Turm

                                                      Very nice lab tour to the Christmas Market at Chinesischer Turm in Munich!

                                                      10 Dec 2019

                                                      CSHL

                                                      Julien and Dominik attended the CSHL 3D human brain modeling meeting in Cold Spring Harbor, NY. It was a very exciting meeting with great science, and Julien’s poster attracted quite some attention.

                                                      29 Oct 2019

                                                      Drachensee

                                                      We made a nice small lab hike to Drachensee in the Austrian Alps with beautiful fall weather.

                                                      01 Aug 2019

                                                      Bright Focus Foundation

                                                      We are delighted and honored to receive a research grant from BrightFocus Foundation for our project on studying Alzheimer’s disease in our human brain tissue models. If successful it could advance our understanding of human-specific aspects of the disease including the connection between Abeta and Tau. Many thanks from the entire team to

                                                      BrightFocus Foundation and your donors for believing in the success of this project and supporting our ideas!


                                                      17 Jul 2019

                                                      B2 Run Team Paquet

                                                      Go PaquetLab! Again we had great fun this year at the Munich b2run with 30.000 other runners at the Olympic stadium in Munich! The PaquetLab running team is growing.


                                                      11 Jul 2019

                                                      Retreat 2019 Photo by Antonia Weingart
                                                      ☀︎

                                                      We spent two great days of science at our annual ISD Research Retreat at lake Ammersee with great talks, posters discussion, barbecue and sunshine.


                                                      17 Jun 2019

                                                      Moose

                                                      Dominik attended the Keystone Neurodegeneration meeting in Keystone, Colorado, USA to discuss our newest results with colleagues from the field and learn about their work. Dominik’s postdoc mentor Marc Tessier-Lavigne from Stanford presented a Keynote lecture with some of Dominik’s earlier work and follow-up studies. 


                                                      3 Jun 2019

                                                      New York Stem Cell Foundation Research Institute Alumni

                                                      Dominik visited the New York Stem Cell Foundation Research Institute in NYC for the inaugural NYSCF Fellowship alumni meeting and enjoyed discussing our work with stem cell colleagues from around the world. 


                                                      30 May 2019

                                                      German Stem Cell Network

                                                      Our stem cell images are on the cover and on many pages of the GSCN-German Stem Cell Network Annual Magazine. Thanks for selecting them!


                                                      15 May 2019

                                                      NCL Grant 

                                                      Very happy to receive a funding award by NCL Stiftung to support a collaborative project with Christian Grimm on NCL, a group of lysosomal storage disorders also know as childhood dementia. The NCL project is co-supported by philanthropy funds from Werner Reichenberger Stiftung and IQVIA Germany. Thanks for your support!


                                                      25 Feb 2019

                                                      Very happy to welcome Sophie Robinson from the Bay Area in California as intern in the lab! Sophie is a GSN fast track student and will work on iPSC-derived microglia. See tab "Team" for details.


                                                      07 Jan 2019

                                                      Very happy to welcome Joseph Kroger from North Carolina as intern in the lab! Joey is part of GSN and will work on CRISPR genome editing in iPSCs. See tab "Team" for details.


                                                      22 Dec 2018

                                                      Christmas Paquet Group

                                                      We had some nice lab events over Christmas: a Munich Christmas market visit, a lab party at my house and a fancy dinner with our GSN PhD students. Merry Christmas and happy new year to everyone!


                                                      01 Dec 2018

                                                      Angelika und Dominik

                                                      Very happy to welcome Angelika as a new grad student in the PaquetLab. Angelika is member of the GSN – Graduate School of Systemic Neurosciences and works on Tau biology and iPSC-based models of Tauopathies. We look forward to working with you!


                                                      01 Dec 2018

                                                      Wilhelm Vaillant Stiftung

                                                      We are thrilled to receive research grants from VERUM and Wilhelm-Vaillant Foundations to support our work on building an iPSC-derived brain tissue model for Frontotemporal Dementia and similar Tauopathies. Many thanks for your support!


                                                      01 Nov 2018

                                                      Rockefeller University in NYC

                                                      Happy to see that Rockefeller University in NYC (where Dominik did his postdoc with Marc Tessier-Lavigne) selected one of his images of stem-cell derived brain neurons as banner image for their Twitter Account


                                                      22 Oct 2018

                                                      Brecherspitze

                                                      We used the great fall weather for a lab hiking trip to Brecherspitze in the Bavarian Alps. It was a great day, and everyone had a lot of fun.


                                                      11 Oct 2018

                                                      Institut für Mikrobiologie

                                                      Dominik visited Dirk Busch and colleagues at TUM Institute for Immunology in Munich for a talk and discussions about CRISPR genome editing.


                                                      29 Sep 2018

                                                      Paquet Team Octoberfest

                                                      We had a great night at the Oktoberfest in Munich - everyone had a lot of fun!


                                                      20 Sep 2018

                                                      Molecular-Neurobiology

                                                      Dominik joined the Meeting of the German Society for Biochemistry and Molecular Biology in Marburg to talk about our most recent work in CRISPR genome editing and iPSC disease modeling! Thanks GBM for the invitation!


                                                      4 Aug 2018

                                                      Images by Paquet

                                                      We just finished our first molecular neurobiology course for the GSN - Graduate school of Systemic Neurosciences. The students learned how to turn human iPSCs into cortical neurons and took a couple of cool pictures of their cells. Looking forward to next year!


                                                      3 Aug 2018

                                                      BBQ Paquet Team

                                                      We had our first PaquetLab barbecue! It was a great night with steaks, drinks and star-gazing :-)


                                                      18 Jul 2018

                                                      B2 Run

                                                      Go @PaquetLab! We had great fun with 40.000 other runners at the Olympic stadium in Munich at b2run, one of the biggest running events for company teams in Germany, and we supported the winning team of our LMU University hospital.


                                                      11 Jul 2018

                                                      Images Paquet Group

                                                      Isabel and Julien received awards for the beautiful images they submitted to the photo competition at the ISD retreat in Herrsching, Germany. Congrats!


                                                      26 Jun 2018

                                                      GSN Logo

                                                      Congratulations to Isabel on her selection for the GSN – Graduate School of Systemic Neurosciences



                                                      1 May 2018

                                                      Lisbon

                                                      Dominik visited the Instituto de Technologia Quimica e Biologica in Lisbon to help with a PhD defense and give a talk about CRISPR genome editing. Many thanks to Catarina Brito and Claudia Almeida for the kind invitation! 


                                                      30 Apr 2018

                                                      Sarah and Johannes in Paquet Group

                                                      Sarah and Johannes joined the PaquetLab for research projects on neurodegenerative and neurovascular disorders, welcome!


                                                      15 Apr 2018

                                                      CTERP Event

                                                      Dominik our work on genome editing and Alzheimer disease modeling in iPSCs at the CTERP translational research in cell therapy meeting in Moscow, Russia.


                                                      15 Jan 2018

                                                      Judith in Paquet Lab

                                                      Judit joined the PaquetLab for an undergraduate research project on CRISPR/Cas9 genome editing, welcome! 


                                                      19 Dec 2017

                                                      Dominik invited the whole team to his place for the annual Christmas party. Everybody was so busy eating and drinking that we didn’t take any pictures.


                                                      12 Dec 2017

                                                      PaquetLab goes Christmas Market! We had a great time (and great Glühwein and food) at the traditional market in Haidhausen.


                                                      01 Nov 2017

                                                      Dennis starting in Paquet Lab

                                                      Dennis joins the PaquetLab as BTA and will support us in multiple ways in the cell culture and general lab. Welcome aboard Dennis!


                                                      27 Oct 2017

                                                      Paquet Group in Eibsee

                                                      Dominik presented our work at the The seventeenth Eibsee Meeting on Cellular Mechanisms of Neurodegeneration.

                                                      Read more...


                                                      05 Sep 2017

                                                      CTERP Event

                                                      Our work on improving HDR efficiency for CRISPR Editing is featured on the Addgene Blog. Thanks to Dylan Kwart at The Rockefeller University and Tyler Ford at Addgene for the nice collaboration.

                                                      Read more...


                                                      01 Sep 2017

                                                      After several weeks of construction, we opened our new stem cell research facility at the CSD building. The new lab provides ideal conditions to grow and characterize novel human brain tissue models derived from patient stem cells, to investigate molecular mechanisms of dementia, stroke and related diseases.


                                                      16 Jun 2017

                                                      Paquet Group Heidelberg

                                                      Dominik presents our work at the EMBO Mechanisms of Neurodegeneration Meeting in Heidelberg, Germany.

                                                      Read more... 


                                                      16 Jun 2017

                                                      GSN Logo

                                                      Congratulations to Julien on his selection for the GSN – Graduate School of Systemic Neurosciences.


                                                      16 Jun 2017

                                                      Dominik presents our work at Evotec AG in Hamburg, Germany.

                                                      Read more...


                                                      03 Apr 2017

                                                      Julien in Paquet-lab

                                                      Welcome to Julien, who also joined the lab as a graduate student - we look forward to working with you!



                                                      03 Apr 2017

                                                      Isabel in Paquet Lab

                                                      Welcome to Isabel, who joined the lab as a graduate student - we look forward to working with you!


                                                      31 Mar 2017

                                                      Vienna

                                                      Dominik presents our work at the 13th International Conference on Alzheimer’s & Parkinson’s Diseases (ADPD) 2017 in Vienna, Austria.

                                                      Read more...


                                                      01 Dec 2016

                                                      Dominik Paquet, PI

                                                      Dominik Paquet

                                                      Coming from The Rockefeller University (New York, USA), Dominik Paquet has joined the ISD. He was appointed Professor for Neurobiology and is a member of the Munich Cluster for Systems Neurology (SyNergy). Following his PhD at the LMU Munich, Prof. Paquet worked as a New York Stem Cell Foundation Druckenmiller Fellow in the laboratory of Marc Tessier-Lavigne, where he pioneered the use of CRISPR/Cas9 gene editing in induced pluripotent stem cells to study diseases of the human brain. His research at the ISD will center on the molecular and cellular mechanisms leading to neuronal death and cognitive decline in patients with neuropsychiatric disorders (e.g. Alzheimer’s disease and Frontotemporal dementia) and neurovascular impairments (stroke and vascular cognitive impairment). He plans to build advanced human in vitro model systems based on patient-derived cells that recapitulate major disease hallmarks, and thus facilitate molecular studies and accelerate the identification of novel therapeutic approaches.

                                                      Read more...

                                                    • The Lab

                                                      Center for Stroke and Dementia Research Building at Night 

                                                      The PaquetLab is part of the Institute for Stroke and Dementia Research (ISD) and located on the 2nd floor of the new CSD building on the high-tech campus Grosshadern / Martinsried, one of the biggest European centers combining basic and clinical life science research and technological innovation. The campus houses the LMU Klinikum, one of the biggest University hospitals in Europe, several research institutes of the LMU in medical and natural sciences, the Max Planck Institutes for Biochemistry and Neurobiology, as well as the Innovation and Start Up Center for Biotechnology.


                                                      Photo: Center for Stroke and Dementia Research © Stefan Müller-Naumann


                                                      Paquet Lab Writing Area

                                                      The CSD building was opened in 2014 and houses research labs of the ISD, the Chair of Metabolic Chemistry of the Medical Faculty of the LMU, the Technical University Munich and the German Center for Neurodegenerative Diseases (DZNE) , an outpatient clinic for stroke and dementia patients, as well as lecture halls, seminar rooms etc. It provides home to over 200 basic and clinician scientists, technical and support stuff.


                                                      PaquetLab writing area


                                                      Paquet Lab

                                                      PaquetLab wetlab


                                                      Paquet Lab

                                                      Gel area and confocal microscope


                                                      iPS

                                                      Stem cell culture


                                                      Breakroom in the ISD

                                                      Break Room


                                                    • Funding

                                                      The PaquetLab gratefully acknowledges research funding by:

                                                      Institute for Stroke and Dementia (ISD) Logo

                                                      SyNergy - Munich Cluster for Systems Neurology


                                                      Sanofi Logo
                                                      wilhelm-vaillant-stiftung

                                                      Verum-Foundation


                                                    Dominik Paquet

                                                    Dominik Paquet
                                                    Professor of Neurobiology
                                                    +49 89 4400 46123
                                                    dominik.paquet@med.uni-muenchen.de

                                                    Follow us on Twitter: @PaquetLab

                                                    Contact

                                                    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
                                                    Send a Mail

                                                    Partners

                                                    Neurologische Klinik und Poliklinik der Universität München

                                                    DZNE – Deutsches Zentrum für Neurodegenerative Erkrankungen

                                                    SyNergy – Munich Cluster for Systems Neurology

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