LieszLab – Stroke-Immunology
We are interested in the interplay between the brain and the immune system after stroke. Acute brain lesions disturb the well-balanced interconnection between both systems. Hence, our research focuses on both directions of brain-immune interaction: The impact of immune mechanisms on neuronal damage and recovery and the systemic immunomodulation after stroke.
Our methodological spectrum covers diverse brain ischemia models, transgenic animal models, a broad spectrum of cutting-edge immunological techniques as well as histological, biomolecular and behavioral analysis tools. The lab has a strong translational research focus with the ultimate goal to develop novel diagnostic tools, therapies and mechanistic insights on the highly complex disease which stroke represents.
Currently, the laboratory focuses on the following main research topics within the area of brain-immune interaction:
Cerebral lymphocyte invasion: beyond the vasculature
One focus of our research is the migration of pro-inflammatory leukocytes to the ischemic brain (Brain, 2011). We are investigating pathophysiological mechanisms of leukocyte-endothelial interaction and novel therapeutic approaches for translational use (Science Translational Medicine, 2015). We have previously identified the choroid plexus as a previously unrecognized invasion pathways (Acta Neuropathologica, 2017) and are further striving to understand the differential role of alternative invasion routes to the injured brain.
An alarmin(g) consequence of stroke: Brain-released alarmins and sterile inflammation
A third research area investigates alarmin-driven mechanisms of peripheral immune alterations after brain ischemia. We aim to characterize alarmins—humoral mediators released by the necrotic brain tissue—as modulators of the systemic immune system (The Journal of Neuroscience, 2015). We previously described alarmins as key mediators leading to the exacerbation of vascular inflammation and atherosclerosis after stroke (Science Translational Medicine, 2018). Currently, we aim to expand our knowledge on the multicellular interaction in the systemic immune compartment after stroke and the role of circulating blood factors in modulating immune homeostasis.
Chronic neuroinflammation: friend or foe in post-stroke recovery?
We have recently identified that acute brain ischemia not only induces acute inflammation but results in long-lasting and profound neuroinflammation. These findings suggest either a deficiency in endogenous resolution mechanisms or a preponderance of currently unknown mechanisms driving chronic immune activation after stroke. We try to elucidate the underlying mechanism and study how chronic neuroinflammation affect the chronic recovery after stroke.
From mouse to patient … and back
A premise of our work is to address key unmet needs of stroke patients and make use of translationally relevant tools. For this we strive to constantly improve the translational relevance of our work by standardization, performing validation trials and close interaction with clinician-scientists. Access to stroke patients allows us to identify clinically relevant questions and utilize patient biosamples and clinical data together with our experimental models to answer these questions. Currently, we are working with human blood, brain, feces and CSF samples in order to study brain-immune interactions after stroke.
Contact: Arthur Liesz
Publications by Arthur Liesz
Asare Y, Campbell-James TA, Bokov Y, Yu LL, Prestel M, El Bounkari O, Roth S, Megens RT, Straub T, Thomas K, Yan G, Schneider M, Ziesch N, Tiedt S, Silvestre-Roig C, Braster Q, Huang Y, Schneider M, Malik R, Haffner C, Liesz A, Soehnlein O, Bernhagen J, Dichgans M. Histone Deacetylase 9 Activates IKK to Regulate Atherosclerotic Plaque Vulnerability. Circ Res. 2020 Jun 17. Epub ahead of print.
Sebastian Monasor L, Müller SA, Colombo AV, Tanrioever G, König J, Roth S, Liesz A, Berghofer A, Piechotta A, Prestel M, Saito T, Saido TC, Herms J, Willem M, Haass C, Lichtenthaler SF, Tahirovic S. Fibrillar Aβ triggers microglial proteome alterations and dysfunction in Alzheimer mouse models. Elife. 2020 Jun 8;9:e54083.
Sadler R, Cramer JV, Heindl S, Kostidis S, Betz D, Zuurbier KR, Northoff BH, Heijink M, Goldberg MP, Plautz EJ, Roth S, Malik R, Dichgans M, Holdt LM, Benakis C, Giera M, Stowe AM, Liesz A. Short-chain fatty acids improve post-stroke recovery via immunological mechanisms. J Neurosci. 2020 Jan 29;40(5):1162-1173.
Zhou Q, Mareljic N, Michaelsen M, Parhizkar S, Heindl S, Nuscher B, Farny D, Czuppa M, Schludi C, Graf A, Krebs S, Blum H, Feederle R, Roth S, Haass C, Arzberger T, Liesz A, Edbauer D. Active poly-GA vaccination prevents microglia activation and motor deficits in a C9orf72 mouse model. EMBO Mol Med. 2020 Feb 7;12(2):e10919.
Cserép C, Pósfai B, Lénárt N, Fekete R, László ZI, Lele Z, Orsolits B, Molnár G, Heindl S, Schwarcz AD, Ujvári K, Környei Z, Tóth K, Szabadits E, Sperlágh B, Baranyi M, Csiba L, Hortobágyi T, Maglóczky Z, Martinecz B, Szabó G, Erdélyi F, Szipőcs R, Tamkun MM, Gesierich B, Duering M, Katona I, Liesz A, Tamás G, Dénes Á. Microglia monitor and protect neuronal function via specialized somatic purinergic junctions. Science. 2020 Jan 31;367(6477):528-537.
Cai R, Pan C, Ghasemigharagoz A, Todorov MI, Förstera B, Zhao S, Bhatia HS, Parra-Damas A, Mrowka L, Theodorou D, Rempfler M, Xavier ALR, Kress BT, Benakis C, Steinke H, Liebscher S, Bechmann I, Liesz A, Menze B, Kerschensteiner M, Nedergaard M, Ertürk A. Panoptic imaging of transparent mice reveals whole-body neuronal projections and skull-meninges connections. Nat Neurosci. 2019 Feb;22(2):317-327.
Roth S, Singh V, Tiedt S, Schindler L, Huber G, Geerlof A, Antoine DJ, Anfray A, Orset C, Gauberti M, Fournier A, Holdt LM, Harris HE, Engelhardt B, Bianchi ME, Vivien D, Haffner C, Bernhagen J, Dichgans M, Liesz A. Brain-released alarmins and stress response synergize in accelerating atherosclerosis progression after stroke. Sci Transl Med. 2018 Mar 14;10(432).
Llovera G, Benakis C, Enzmann G, Cai R, Arzberger T, Ghasemigharagoz A, Mao X, Malik R, Lazarevic I, Liebscher S, Ertürk A, Meissner L, Vivien D, Haffner C, Plesnila N, Montaner J, Engelhardt B, Liesz A. The choroid plexus is a key cerebral invasion route for T cells after stroke. Acta Neuropathol. 2017 Dec;134(6):851-868.
Demuth HU, Dijkhuizen RM, Farr TD, Gelderblom M, Horsburgh K, Iadecola C, Mcleod DD, Michalski D, Murphy TH, Orbe J, Otte WM, Petzold GC, Plesnila N, Reiser G, Reymann KG, Rueger MA, Saur D, Savitz SI, Schilling S, Spratt NJ, Turner RJ, Vemuganti R, Vivien D, Yepes M, Zille M, Boltze J; ISN&N meeting contributors. Recent progress in translational research on neurovascular and neurodegenerative disorders. Restor Neurol Neurosci. 2017;35(1):87-103.
Tiedt S, Prestel M, Malik R, Schieferdecker N, Duering M, Kautzky V, Stoycheva I, Böck J, Northoff BH, Klein M, Dorn F, Krohn K, Teupser D, Liesz A, Plesnila N, Holdt LM, Dichgans M. RNA-Seq Identifies Circulating miR-125a-5p, miR-125b-5p, and miR-143-3p as Potential Biomarkers for Acute Ischemic Stroke. Circ Res. 2017 Sep 29;121(8):970-980.
Kumar V, Fleming T, Terjung S, Gorzelanny C, Gebhardt C, Agrawal R, Mall MA, Ranzinger J, Zeier M, Madhusudhan T, Ranjan S, Isermann B, Liesz A, Deshpande D, Häring HU, Biswas SK, Reynolds PR, Hammes HP, Peperkok R, Angel P, Herzig S, Nawroth PP. Homeostatic nuclear RAGE-ATM interaction is essential for efficient DNA repair. Nucleic Acids Res. 2017 Oct 13;45(18):10595-10613.
Friedländer F, Bohmann F, Brunkhorst M, Chae JH, Devraj K, Köhler Y, Kraft P, Kuhn H, Lucaciu A, Luger S, Pfeilschifter W, Sadler R, Liesz A, Scholtyschik K, Stolz L, Vutukuri R, Brunkhorst R. Reliability of infarct volumetry: Its relevance and the improvement by a software-assisted approach. J Cereb Blood Flow Metab. 2017 Aug;37(8):3015-3026.
Llovera G, Hofmann K, Roth S, Salas-Pérdomo A, Ferrer-Ferrer M, Perego C, Zanier ER, Mamrak U, Rex A, Party H, Agin V, Fauchon C, Orset C, Haelewyn B, De Simoni MG, Dirnagl U, Grittner U, Planas AM, Plesnila N, Vivien D, Liesz A. Results of a preclinical randomized controlled multicenter trial (pRCT): Anti-CD49d treatment for acute brain ischemia. Sci Transl Med. 2015 Aug 5;7(299):299ra121.
Mracsko E, Liesz A, Stojanovic A, Lou WP, Osswald M, Zhou W, Karcher S, Winkler F, Martin-Villalba A, Cerwenka A, Veltkamp R. Antigen dependently activated cluster of differentiation 8-positive T cells cause perforin-mediated neurotoxicity in experimental stroke. J Neurosci. 2014 Dec 10;34(50):16784-95.
Liesz A, Rüger H, Purrucker J, Zorn M, Dalpke A, Möhlenbruch M, Englert S, Nawroth PP, Veltkamp R. Stress mediators and immune dysfunction in patients with acute cerebrovascular diseases. PLoS One. 2013 Sep 19;8(9):e74839.
Stefan Roth, Postdoctoral fellow
I studied biology with majors in immunology, human genetics and virology at the University of Tübingen. After finishing my diploma on neurodegeneration in CAG-repeat disorders in 2013 in Tübingen, I joined the Liesz lab to study the impact of systemic sterile inflammation after stroke. I focus in my work particularly on the correlation between stroke and vascular inflammation. In my life outside the lab, I love to travel, play badminton and squash. I also have a great interest in historic cars and enjoy restoring them.
Gemma Llovera, Postdoctoral fellow
It all started in Barcelona (Spain) where a bachelor in Biology and a Master in Neuroscience gave me the tools to start the PhD in Munich in 2013. I graduated in March 2019 and continue since then my work on post-stroke neuroinflammation in the Liesz lab as a postdoctoral researcher. When I am not looking for new leukocyte invasion routes to the brain after stroke, you can find me playing with my twin boys in the park. In my free time I try to do some sports, such as running or basketball.
Alba Simats, Postdoctoral fellow
Being always fascinated by science, I studied Biochemistry and obtained a Master in Translational Biomedical Research in Barcelona. In 2018, I obtained my PhD in Biomedicine and Molecular Biology under the mentorship of Dr. Joan Montaner at the Vall d’Hebron Institute of Research (Barcelona) working on the field of stroke neuroprotection and biomarkers. There, I continued my work as a postdoctoral researcher until moving to Munich and joining the Liesz lab in October 2019. Besides science, I really enjoy hiking and skiing and when possible, I love traveling around the world visiting new places and cultures.
Daniel Varga, Postdoctoral fellow
I am a Hungarian scientist and obtained my PhD in Neuroscience at the University of Szeged, Hungary. I started my research activity as an undergraduate student in 2009 by studying neuroprotective strategies for acute ischemic stroke. Then I studied neurophysiology and cerebral hemodynamics during cortical spreading depolarization under the supervision of Dr Eszter Farkas. I came to Munich to join the Liesz lab to investigate interactions between post-stroke inflammatory responses and neurovascular dysfunction. My work heavily focuses on mesoscale imaging. When I am not in the imaging room you will find me outdoors. If it is summer then I go hiking if its winter then skiing or snowboarding. For endurance running weather cannot be an excuse. I am passionate about travelling and exploring new places. Also, I enjoy mixing music.
Tanima Bose, Postdoctoral fellow
I am originally from India and first came to Germany in the year of 2009. After obtaining my PhD from the Leibniz Institute for Neurobiology on the role of memory immune cells, I went to Singapore to further study the function of ion channels on immune cells. During this phase, I have worked on a collaborative project between Singapore, USA, and Australia and explored the role of the memory cell types and ion channels in ocular surface inflammatory disorder. I have been back in Munich since 2018, initially working with the memory B cells and later computational analysis of the ocular surface immune cells. I joined the Liesz lab in 2020 to explore the role of chronic neuroinflammation and memory T cells in stroke. When I am not working in the lab, I love writing both scientific and non-scientific articles and books (which you will be hopefully able to read soon). For fun, I like to do nature photography and love to explore different lakes and hiking areas around Bavaria.
Alessio Ricci, PhD student
I am originally from Tuscany and I obtained my Bachelor and Master in Neuroscience in Pisa. I started working on stroke since my Master Thesis, focusing on electrophysiological predictors for stroke recovery. During my studies I fell in love with the nervous system and its extraordinary complexity. I started my PhD in the Liesz lab in October 2019, where I have the opportunity to study another amazing topic: the immune system! In particular, I study the role of T cells in recovery after stroke. In my free time, I am a passionate cook and baker and enjoy any kind of outdoor activities.
Jie Zhu, PhD student
I have joined the Liesz lab after achieving my master's degree from Shanghai Jiaotong university. In my project I focus on mechanisms of microglia activation after stroke and their role in chronic post-stroke recovery. When I am outside the lab, I am still in the process of adapting to the Bavarian culture and I love to play basketball.
Steffanie Heindl, PhD student
I am from Passau, a small town near Munich. The question how to help people recover brought me to LMU in Munich, where I studied Pharmaceutical Sciences and Biology, focussing on Neuroimmunology and Neurobiology. I am currently doing my PhD in the Liesz lab trying to answer the question how microglia influence regeneration after stroke. When I’m not in the lab, music and art is what I spend my time on (playing guitar and ukulele).
Jiayu Cao, PhD student
I am a neurosurgical student from Shanghai, China. After obtaining my master degree at Shanghai Jiao Tong University, I joined the Liesz lab to start my PhD studies. In my work, I focus mainly on the systemic immune response after stroke and mechanisms of sterile immune activation. In my free time I love to do some sports such as running and badminton.
Philip Melton, MD Student
Born in Cologne, but originally American-Canadian, I started studying Medicine at the Ludwig-Maximilians-University Munich in 2015 and joined the Liesz lab in 2018 for my MD thesis. My project focuses mainly on the effect of tryptophan metabolites on the microbiom and gut immune response in the context of stroke. Outside the lab I enjoy literature, classical film and the occasional game of tennis.
Kerstin Thuß-Silczak, Lab technician
I was born in Dresden which was previously Eastern Germany. As the lab technician I take care of organizational issues, orders and routine tasks of the Lab. I enjoy manual techniques and am particularly fond of histology. In my private time you find me mostly in the mountains with my family, doing long hikes and photographing.
Yasemin Aydin, Team assistant
After having spend several years in different countries and cities, working in the free market economy, I have come to the conclusion, that there must be more then marketing and projects. The idea of being a part of something that might make an impact for stroke patients, was the driving force in deciding to join the Liesz lab as their project assistant. It’s a satisfaction to be part of this team, support the research projects and learn more about their topics.
I have been working on the topic of brain-immune interaction after acute brain injuries for more than 10 years and am fascinated by the interaction of these two highly complex super-organisms. My scientific goal is to make new discoveries that will lead to therapies for the benefit of stroke patients. Therefore, we try in my laboratory to combine the use of cutting-edge methodologies and innovative research ideas with a focus on the translational relevance.
Key research achievements include the first report on the neuroprotective role of regulatory T cells in stroke (Nat Med, 2009) which has been reproduced over 20 times. We provided the first description of a bi-directional link between the brain and gut microbiota via immune-mechanisms in acute brain injury (J Neurosci, 2016). Our work on blocking leukocyte brain invasion by Anti-CD49d antibodies (Brain, 2011 and Science Transl Med, 2015) has led to already two completed clinical Phase II studies.
2016 Habilitation on the topic “Immunological Mechanisms in Acute Brain Ischemia”
2010 - 2016 Residency in Clinical Neurology at the Department of Neurology in Heidelberg (Prof. Dr. W. Hacke) and Munich (Prof. Dr. M. Dieterich)
2006 - 2010 Medical thesis at the Department of Neurology (supervisor: Dr. R. Veltkamp), University Heidelberg, Germany (summa cum laude)
2006 - 2009 Training in Experimental Immunology, Department of Molecular Immunology (Dr. E. Suri-Payer), German Center for Cancer Research (DKFZ), Heidelberg
2003 - 2010 Medical studies at the Universities Würzburg and Heidelberg
Awards & honors
2004 - 2010 Scholar of the Klaus Murmann Fellowship Program
2013 Postdoctoral scholarship award, Daimler-Benz Foundation
2013 Independent group leader award - Clinician Scientist Program by the Cluster for Systems Neurology (SyNergy)
2015 Niels Lassen Award Finalist, International Society of Cerebral Blood Flow and Metabolism
2015 Young Investigator Award, European Stroke Organization
Stefan Roth, Vikramjeet Singh, Steffen Tiedt, Lisa Schindler, Georg Huber, Arie Geerlof, Daniel J Antoine, Antoine Anfray, Cyrille Orset, Maxime Gauberti, Antoine Fournier, Lesca M Holdt, Helena Erlandsson Harris, Britta Engelhardt, Marco E Bianchi, Denis Vivien, Christof Haffner, Jürgen Bernhagen, Martin Dichgans, Arthur Liesz (2018) Brain-released alarmins and stress response synergize in accelerating atherosclerosis progression after stroke. Science translational medicine 10: 432. Mar.
Gemma Llovera, Corinne Benakis, Gaby Enzmann, Ruiyao Cai, Thomas Arzberger, Alireza Ghasemigharagoz, Xiang Mao, Rainer Malik, Ivana Lazarevic, Sabine Liebscher, Ali Ertürk, Lilja Meissner, Denis Vivien, Christof Haffner, Nikolaus Plesnila, Joan Montaner, Britta Engelhardt, Arthur Liesz (2017) The choroid plexus is a key cerebral invasion route for T cells after stroke. Acta neuropathologica Jul.
Vikramjeet Singh, Stefan Roth, Gemma Llovera, Rebecca Sadler, Debora Garzetti, Bärbel Stecher, Martin Dichgans, Arthur Liesz (2016) Microbiota Dysbiosis Controls the Neuroinflammatory Response after Stroke. The Journal of neuroscience : the official journal of the Society for Neuroscience 36: 28. 7428-7440 Jul.
Gemma Llovera, Kerstin Hofmann, Stefan Roth, Angelica Salas-Pérdomo, Maura Ferrer-Ferrer, Carlo Perego, Elisa R Zanier, Uta Mamrak, Andre Rex, Hélène Party, Véronique Agin, Claudine Fauchon, Cyrille Orset, Benoît Haelewyn, Maria-Grazia De Simoni, Ulrich Dirnagl, Ulrike Grittner, Anna M Planas, Nikolaus Plesnila, Denis Vivien, Arthur Liesz (2015) Results of a preclinical randomized controlled multicenter trial (pRCT): Anti-CD49d treatment for acute brain ischemia. Science translational medicine 7: 299. Aug.
Arthur Liesz, Wei Zhou, Éva Mracskó, Simone Karcher, Henrike Bauer, Sönke Schwarting, Li Sun, Dunja Bruder, Sabine Stegemann, Adelheid Cerwenka, Clemens Sommer, Alexander H Dalpke, Roland Veltkamp (2011) Inhibition of lymphocyte trafficking shields the brain against deleterious neuroinflammation after stroke. Brain : a journal of neurology 134: Pt 3. 704-720 Mar.
Arthur Liesz, Elisabeth Suri-Payer, Claudia Veltkamp, Henrike Doerr, Clemens Sommer, Serge Rivest, Thomas Giese, Roland Veltkamp (2009) Regulatory T cells are key cerebroprotective immunomodulators in acute experimental stroke. Nature medicine 15: 2. 192-199 Feb.
Arthur Liesz, Sebastien Hagmann, Carolin Zschoche, Johanna Adamek, Wei Zhou, Li Sun, Andreas Hug, Markus Zorn, Alexander Dalpke, Peter Nawroth, Roland Veltkamp (2009) The spectrum of systemic immune alterations after murine focal ischemia: immunodepression versus immunomodulation. Stroke; a journal of cerebral circulation 40: 8. 2849-2858 Aug.
Road Trip to France
Christmas Market 2017
Octoberfest 2016 and 2017
The official group picture 2016
Lab outing 2015
Moving to the new lab at the Center for Stroke and Dementia Research.
We gratefully acknowledge support for our work by the following funding agencies:
Emmy-Noether-Grant by the German Research Foundation (DFG)
European Research Council (ERC) starting grant
The Munich Excellence Cluster for Systems Neurology (SyNergy)