Unsere Webseite nutzt Cookies, damit die User-Experience gesteigert wird. Bitte beachten Sie, dass ohne Cookies einige Funktionalitäten nicht mehr ausführbar sind (z.B. Formulare). Ausführlichere Hinweise zu Cookies
Ok
LMU Munich University Hospital
  • Research Groups
      DichgansLab
        BernhagenLab
          DueringLab
            LieszLab
              EwersLab
                PaquetLab
                  PlesnilaLab
                    ErturkLab
                      BenakisLab
                        Franzmeier Lab
                          GokceLab
                            JäkelLab
                              TiedtLab
                            • News
                            • Publications
                            • Support
                            • About us
                                Contact
                                  How to get there
                                    Management
                                      Scientific Advisory Board
                                        Imprint
                                          Privacy Policy
                                            Media
                                          • Jobs
                                          • For Patients
                                          1. ISD Research
                                          2. Research Groups
                                          3. PaquetLab

                                          Dominik Paquet – iPSC-models of brain diseases

                                          • Research Focus
                                          • Publications
                                          • Team
                                          • PI
                                          • News
                                          • Lab
                                          • Funding
                                          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, 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:

                                          Ihr Browser unterstützt das Video nicht, bitte laden Sie sich die neueste Version herunter und versuchen es erneut.

                                          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

                                          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

                                          PaquetLab Team 2019.jpg
                                          ☺︎


                                          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


                                          Isabel Weisheit

                                          Isabel Weisheit, GSN graduate student

                                          Isabel grew up in Augsburg, Germany. She obtained her BSc in Biochemistry from the University of Ulm and her MSc from LMU Munich. For her master’s thesis she joined the group of Prof. Jernej Ule at the Francis Crick Institute in London, where she studied the RNA-binding properties of TDP-43. Isabel started in the PaquetLab in April 2017 as a graduate student and is focusing on using CRISPR/Cas9-edited iPSCs to establish in vitro models of vascular dysfunction.

                                          E-Mail: Isabel.Weisheit@med.uni-muenchen.de
                                          Phone: +49 89 4400 46224


                                          Dennis Crusius, BTA

                                          Dennis is from Munich, where he also obtained his BTA degree. He joined the PaquetLab as a research assistant in November 2017 and is involved in several projects from stem cell differentiation to CRISPR/Cas9 genome editing. He also contributes to a functional lab environment and supports the entire team in multiple ways.

                                          E-Mail: Dennis.Crusius@med.uni-muenchen.de
                                          Phone: +49 89 4400 46224


                                          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


                                          Joseph Kroeger

                                          Joseph Kroeger, GSN graduate student, collaboration with Dichgans Lab, ISD

                                          Joseph grew up in the U.S. state of North Carolina. He earned a BSc in mathematics and chemistry with minors in physics and philosophy from Wingate University. After graduating from Wingate University, he moved to Munich and became a master’s student with the GSN. For his master’s thesis, he is working on approaches to apply CRISPR/Cas genomic editing to investigate the role of stroke-associated genes in iPSC-derived models.

                                          E-Mail: Joseph.Kroeger@med-uni-muenchen.de
                                          Phone: +49 89 4400 46224


                                          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

                                          Sophie Robinson

                                          Sophie Robinson, GSN graduate student, collaboration with Haass Lab, DZNE

                                          Sophie is from the Bay Area in California, USA. She received her BSc in Psychology and Biological Sciences from Carnegie Mellon University. In high school, she had internships at Stanford University with Dr. Tony Wyss-Coray studying AD. During her Bachelor's, she worked with Dr. Stephen Strittmatter at Yale University investigating a Fyn kinase inhibitor as a potential treatment in AD mouse models, which has subsequently made it into clinical trials. After graduating from college, she worked in a cancer immunotherapy lab under Dr. Ron Levy at Stanford University and in clinical operations at Roche Genentech. Sophie is a GSN Fast-Track student and started a rotation at the PaquetLab in February 2019. She is interested in studying microglia in homeostatic and disease-associated states, co-supervised by Christian Haass and Dominik Paquet.

                                          E-Mail: Sophie.Robinson@med-uni-muenchen.de
                                          Phone: +49 89 4400 46225


                                          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


                                          annika

                                          Annika Wagener, Master student

                                          Annika grew up near Konstanz, Germany, after which she moved to Scotland to obtain a B.Sc. Hons in Neuroscience from the University of Glasgow. Currently, she is pursuing a master’s degree in Molecular Biosciences with a major in Neuroscience from the University of Heidelberg. As part of her studies, she carried out research at the Department of Neurobiology and the Spinal Cord Injury Center in Heidelberg, and has spent a semester working with Prof. Per Nilsson at the Karolinska Institute in Stockholm to characterise a novel protease involved in APP cleavage in a triple KI mouse model of AD. For her master’s thesis, Annika has joined the PaquetLab to work on improving CRISPR/Cas9 mediated genome editing in iPSC models of neurodegeneration. ​

                                          E-Mail: Annika.Wagener@med.uni-muenchen.de
                                          Phone: +49 89 4400 46225


                                          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

                                          Katja Salbaum, Master student

                                          Katja Salbaum was born in Vilsbiburg and obtained her B. Sc. in Molecular Biotechnology at the TU Munich. During that time, she spent one term abroad at Aston University studying Chemical Engineering and completed additional internships at the Fraunhofer IVV, Leibniz Institute for Plant Genetics and Crop Plant Research and worked as a research assistant at new diagnostics GmbH. In the course of the elite master’s programme Biomedical Neuroscience, she completed a lab rotation at the Pennington Biomedical Research Center in Baton Rouge, Louisiana, supported by a scholarship from the Bavarian Ministry for Science and Art. For her master’s thesis she joined the PaquetLab to establish an efficient system for generating knockouts of disease-relevant genes in human iPSC-derived cortical neurons using CRISPR base editing. Katja’s work was awarded as best Master thesis of the elite master program Biomedical Neuroscience by the German Society for Biochemistry and Molecular Biology (GBM). Congratulations!


                                          Samantha Ho, Undergraduate researcher

                                          Samantha was born in Vancouver, Canada and raised partially in Taiwan. She obtained her BSc in Neuroscience from the University of Alberta in 2018. During her undergraduate studies, she completed her Bachelor's thesis in Dr. Ian Winship's laboratory, investigating endogenous pleiotrophin expression after photothrombotic stroke in a mouse model. In October 2018, she became a master's student at the Graduate School of Systemic Neurosciences (GSN). From January to April 2020, she worked in the PaquetLab to establish CRISPR-Cas9 gene-edited iPS cell lines to study differentiated human microglia under homeostatic and disease-associated states. 


                                          Ioanna Emmanouilidis, GSN undergraduate researcher, ISD

                                          Ioanna was born and raised in Athens, Greece. She received her BSc on Life Sciences from Pierre and Marie Curie University in Paris in 2018. During her undergraduate studies, she spent a semester at Karolinska Institut in Stockholm where she did a research internship on insulin signaling and genetic risk factors related to Alzheimer’s disease. Currently, she is a first-year master’s student at the Graduate School of Systemic Neurosciences (GSN-LMU) and works on the role of stroke-associated genes in iPSC-derived models.


                                          Andrea Stüven, Team Assistant

                                          Andrea joined the PaquetLab in 2018 and supported the research team as Team Assistant until 2019. When not at work she enjoyed going to the opera and concerts, visiting art exhibitions, working in her garden and swimming. She also stays connected with family and friends from across the world as much as possible.


                                          Sarah Hübner, Undergraduate researcher

                                          Sarah was born in Augsburg, Germany. After completing her BSc in Chemistry and Biochemistry at LMU Munich, she did a research internship at University of California Berkeley. There, she worked with Prof. Evan W. Miller on voltage-sensitive fluorescent dyes and also joined the lab of Prof. Christopher J. Chang developing fluorescent copper(I) sensors. Subsequently, she continued her master studies at LMU Munich and joined PaquetLab in April 2018 to study CRISPR/Cas9 edited iPSCs as a model system for neurovascular diseases.


                                          Johannes Heim, Undergraduate researcher

                                          Johannes is from a small town in the south of Munich. He studied medicine at LMU Munich. During the preclinical stage of his studies, he did an internship in molecular neurophysiology in Prof. Michael Meyers Lab at LMU Munich. With an intrinsic interest in neurology and vascular medicine, he gained experience in these fields during clinical electives. Johannes worked on a collaborative project between the Dichgans Lab and PaquetLab to investigate the role of endothelial cells in ischemic stroke.

                                          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

                                          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

                                          Bild und Ausschnitt jetzt in den Widget-Eigenschaften auswählen

                                          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


                                          Follow us on Twitter

                                          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

                                          Redakteurs Log-In
                                          • Imprint
                                          • Privacy Policy
                                          © Institute for Stroke and Dementia Research (ISD)
                                        • LMU Munich
                                        • University Hospital

                                          ISD Research

                                          • Research Groups
                                            • DichgansLab
                                            • BernhagenLab
                                            • DueringLab
                                            • LieszLab
                                            • EwersLab
                                            • PaquetLab
                                            • PlesnilaLab
                                            • ErturkLab
                                            • BenakisLab
                                            • Franzmeier Lab
                                            • GokceLab
                                            • JäkelLab
                                            • TiedtLab
                                          • News
                                          • Publications
                                          • Support
                                          • About us
                                            • Contact
                                            • How to get there
                                            • Management
                                            • Scientific Advisory Board
                                            • Imprint
                                            • Privacy Policy
                                            • Media
                                          • Jobs
                                          • For Patients