Vascular Biology – PI: Jürgen Bernhagen

We are interested in the molecular and cellular mechanisms of cardiovascular disease and inflammation. A focus is on the role of atypical chemokines, inflammatory signaling pathways, and leukocyte recruitment processes in atherosclerosis, a chronic inflammatory condition of arterial vessels and the main underlying condition of ischemic stroke. We study these mechanisms from basic vascular biology to clinical translation.

We have discovered the cytokine MIF in inflammatory and vascular disease and have characterized it as a protagonistic member of the class of ‘atypical chemokines’. Relying on biochemical and vascular biology methodologies in combination with transgenic mouse models and clinical approaches, we broadly study the MIF protein family (i.e. MIF, MIF-2/D-DT, CXCR2, CXCR4, CXCR7, CD74, sCD74) and related classical chemokines in atherosclerosis, ischemic stroke, and myocardial infarction. This involves deciphering the receptor complexes and pathways driving atherogenic recruitment of leukocyte sub-populations, but we also focus on site- and disease-specific oxidized iso-forms as encountered under ischemic/oxidative stress as well as on chemokine-like alarmins such as HMGB1.

Another focus is on atheroprotective signaling pathways maintained by the COP9 signalosome (CSN) in atherogenic endothelium. The CSN is a multi-functional protein complex that regulates SCF cullin-RING E3-ligase (CRL) NEDDylation status, controlling ubiquitin/26S-proteasome-mediated degradation of cell-regulatory proteins. Based on our discovery of a link between CSN5/JAB1 and inflammation, we currently study atheroprotective effects of CSN5 via NFκB signaling.

We are also interested in cardioprotective mechanisms of some of these mediators and how they compare with corresponding effects in ischemic stroke and cerebral-/(micro)vascular pathogenesis but also other inflammatory diseases. Lastly, capitalizing on various collaborations, we increasingly pursue links between inflammation and neurodegeneration, i.e. inflammasome and amyloid/chaperone-type mechanisms.

Contact:

Prof. Dr. rer. nat. Jürgen Bernhagen
Tel: +49-89-4400-46151
juergen.bernhagen@med.uni-muenchen.de

Secretary: Sabrina Lukanovic
Tel: +49-89-4400-46149
sabrina.lukanovic@med.uni-muenchen.de

See all publications by Jürgen Bernhagen

Dr. Omar El Bounkari, Senior staff scientist & Technical laboratory headRead more about the PI

Following my Biochemistry studies at the University of Hannover, I pursued my PhD degree at the Institute of Biochemistry at the Medical School of Hannover (MHH) under the supervision of Prof. Tamura-Niemann focusing on the interplay between tyrosine kinase signaling and the mRNA export machinery (THO complex). After a brief postdoc fellowship in the same group, I joined the lab of Prof. Bernhagen at RWTH Aachen University in 2010 first as a post-doc and then junior group leader, focusing on the characterization of heteromeric cytokine¬/chemokine receptor complexes MIF proteins, and their function in immune and inflammatory diseases. I followed the lab when it moved to LMU Munich in the end of 2015, where I am now a senior staff scientist, junior group, leader, and technical laboratory head. My research aims at decrypting the role of the MIF protein family and their receptors in immune cells, in particular B lymphocytes, and the related mechanisms that drive inflammatory processes in cardiovascular or autoimmune disease. In my leisure time, I like horse riding and hiking.

Dr. Dzmitry Sinitski, Postdoc

Originally from Belarus, I graduated from Belarusian State University in the field of Biology. After gaining experience in Microbiology and Molecular Biology at the same University, I worked in the field of fungal genetics at the Institute of Food and Biobased Research, Wageningen University, The Netherlands. Thereafter, I did my PhD at the University of Münster in the area of vascular and infection biology. In 2016, I joined the ISD and the research group of Prof. Bernhagen. My research interests are lying particularly in the area of atherosclerosis and vascular immunity. Additionally, I´m highly interested in specific questions of the evolutionary development of immune system regulation with a focus on inter-species cross-talk between immune system elements. When I am not in the lab, I am a passionate mushroom picker.

Chunfang Zan, MD, PhD trainee

Originally from Datong, China, I have majored in Clinical Medicine (Surgery) at Jilin University in Changchun, China. From September 2018 on, and joined the Bernhagen Lab at ISD for my PhD study, which is supported by a prestigious LMU-CSC Scholarship. I am also a candidate to be admitted to the Munich Medical Research School at LMU. My thesis topic focusses on MIF-2/D-DT-mediated recruitment mechanisms of lymphocytes in the cardiovascular diseases such as atherosclerosis and stroke. In my spare time, I enjoy travelling and exploring the world.

Priscila Bourilhón, M.Sc., Technical assistant

Originally from Argentina, I obtained my M.Sc. degree in Biotechnology and after working in a private company, I decided that an academic institution would be a better fit for me. I glad to now be a part of the Bernhagen lab team as a Lab Technician. I take care of organizational issues, and routine experiments, run and develop receptor-specific bacterial, yeast and mammalian assay systems, and support the group with genotyping and general biological assays.

Simona Gerra, M.Sc., Technical assistant

I am originally from Italy, where I finished my Master’s studies in Biology at the University of Milano Bicocca. Working as Environmental Educator and Hiking Guide, I had the opportunity to share the basic ecological principles and evolutionary forces that affect wildlife and their associated habitats. I developed activities about topics such as forest, stream ecology and wildlife science. In August 2018, I joined the Bernhagen research group as Laboratory Technical Assistant. I perform bacterial culturing, protein purification, cell culture and immunoassays, as well as maintaining the lab supplies and equipment. In my spare time, I enjoy hiking and reading books.

Marlies Tursch, VD, doctoral student

I moved to Munich in 2005 and started an apprenticeship as a Veterinary Assistant which I passed 2 years later and then worked in a large Animal Clinic close to Munich. After some years in this job, I could started to study Veterinary Medicine at LMU Munich. I have recently concluded my curricular program and currently work on veterinary medical doctoral thesis. The focus here is on a cytokine/chemokine called D-dopachrome tautomerase or MIF-2 in the context of atherosclerotic mouse models.

Markus Brandhofer, M.Sc., PhD student

Originally from the Munich area, I obtained a Bachelor and Master in Biotechnology from FH Aachen University of Applied Sciences and first joined the Bernhagen Lab – back then located at RWTH Aachen University – for my Master thesis, working on effects of the proinflammatory cytokine MIF and alarmins in liver inflammation. In 2016, I followed the lab to the ISD and returned to Munich. Here, working on my PhD, I’m interested in the role of MIF family proteins as atypical chemokines and investigate their crosstalk with classical chemokines. When I’m not busy in the lab, I enjoy visiting friends, trying different kinds of craft beer, going geocaching or just relaxing and reading a nice book.

Christine Krammer, M.Sc., PhD student

I studied Molecular Biotechnology at TU München(TUM). After finishing my masters, I joined the Bernhagen lab to start my PhD in 2017. My scientific research focuses on the structure-activity relationships and novel cellular routes of MIF family member proteins and their receptors in atherogenesis. One emphasis is on the connection between MIF proteins and B lymphocytes and their role in atherosclerosis. Outside of the lab I like to do sports, hiking and biking in the mountains, reading books and spending time with family and friends. To inspire other students for Life Sciences, I joined the ”Biotechnologische Studenteninitiative (btS)” Munich in 2015. We are organizing different local and nationwide events to connect students with industry and academia.

Lisa Schindler, M.Sc., PhD student

Originally from Magdeburg, I studied Biotechnology at the University of Applied Science in Hamburg and at the RWTH Aachen, where I joined the Bernhagen lab for my master thesis. In 2015, the Bernhagen lab moved from Aachen to Munich, where I started my PhD in the beginning of 2016 investigating the potential role of posttranslational modifications of MIF family members in cardio vascular diseases. When I´m not doing experiments for my future nature publication – I love traveling to new places, do any kind of sport, read books and searching for new adventures.

Jelena Milic, M.Sc., PhD student

I am originally from Serbia, where I finished my Master’s studies in Molecular Biology and Physiology, as well as specialist academic studies in Criminalistics and Forensic Identification. In March 2017, I joined the Bernhagen research group as a PhD student (Munich Medical Research School of LMU). After some initial training in atherosclerosis and inflammation research, I am currently holding an IRTG1123 fellowship to study the ‘atheroprotective role of the COP9 signalosome in atherogenesis’. In order to support students on the path of their professional and personal development, I am volunteering as a mentor in the Mentoring Program of LMU Munich. Outside of the lab, I enjoy playing my guitar, go to a nice concert, and do sports or travel.

Tian Yuan, PhD student

Originally from Beijing, China, while working in a Neurology Department of my University Hospital, I decided that Neuroscience is what I want to be doing. And here I finally am, a PhD student focusing on neuroinflammation and stroke. I was able to obtain a 3-year LMU / CSC scholarship and got accepted as a PhD student in the Bernhagen lab and at Munich Medical Research School (MMRS) which made it possible for me to not only live my dream in the lab, but it also gives me the opportunity to enjoy exploring this beautiful city and making new friends.

Ying Gao, PhD student

I am originally from China, where in 2015, I got my Bachelor degree in Medicine from Central South University in Changsha. After that, I chose to continue my studies in the Department of Neurology affiliated to Shanghai Jiao Tong University. With an enquiring mind to explore the sustainable links between basic scientific research and clinical translation and to get scientific training abroad, I applied with the Chinese Scholarship Council (CSC)/LMU PhD program and got awarded a prestigious CSC/LMU fellowship to perform my PhD thesis in the Bernhagen Lab at ISD in Munich. Since October 2018, I am working on my thesis concerned with a novel class of chemokine peptide inhibitors with potential utility in cardiovascular disease and stroke. When not working at lab, I like spending time to do workout or some outdoor activities, such as traveling, climbing.

Leon Zwißler, cand. med., MD doctoral student

I am a fourth year medical student at LMU and joined the Bernhagen lab in February 2018 for my MD doctoral dissertation. My research interests focus on modifications of MIF family members by neutrophil-derived oxidants in the progression of atherosclerosis. In August 2018 I was admitted into the International Research Training Group (IRTG) program of the Collaborative Research Center (CRC) 1123 Atherosclerosis for a 6-month fellowship. During leisure time, I passionately follow and play tennis, soccer and other sports, listen to music, or enjoy spending time with friends.

Alexander Harjung, Student assistant

I obtained a Bachelor’s degree in Chemistry and Biochemistry from the University of Munich, doing my undergrad-research on the total synthesis of Wickerol in the group of Prof. Dirk Trauner. After graduating, I enrolled in the Master of Biochemistry program, also at LMU, with majors in Biochemistry and Organic chemistry. I joined the Bernhagen lab as student assistant some 2 years ago. My responsibilities in the lab are genotyping and the preparation of buffers and solutions, as well as taking over smaller parts of some of the research projects.

Verena Bolini, Student assistant

I am from Munich, where I went to school and finished my Bachelor degree in Biology at LMU. Currently, I am in the Biology Master program of LMU, focusing on the areas of human biology and cell biology. I previously worked as a student assistant in a molecular genetics lab for medical diagnostics and disease at the MGZ Munich. In August 2018, I joined the Bernhagen lab to support the scientific work as student assistant in various projects. I love travelling around the world and spending a lot of time outdoors. On the other hand, I also enjoy the city life in Munich with the Isar, Englischer Garten and bars and the beautiful nature around Munich with the numerous mountains and hiking opportunities.

Jürgen was appointed Professor and Chair of Vascular Biology at LMU and Principal Investigator at ISD in 2015. Grown up east of Cologne, Germany, he is a biochemist and immunologist by training, who obtained his Diploma (Master) degree and PhD from the University of Tübingen, Germany, and the Picower Institute for Medical Research, Manhasset, NY, USA.

He previously held positions in basic and applied biomedical research as a Postdoc and Senior Scientist at the Picower Institute for Medical Research, where he worked with Professors Richard Bucala and Anthony Cerami, and as a Group Leader and Department Head at the University of Stuttgart and the Fraunhofer Institute in Stuttgart. Before moving to Munich, he was a Professor of Biochemistry at RWTH Aachen University, where he headed the Institute of Biochemistry and Molecular Cell Biology.

His research centers around the molecular and cellular mechanisms driving inflammation and cardiovascular disease with a focus on cytokines, chemokines, their receptors, and cellular signaling platforms. He (re)-discovered MIF proteins, showing that they are central players in inflammatory pathologies, and identified the MIF/chemokine receptor axis as a driving force of atherosclerotic disease. The larger MIF family of proteins and their receptors as well as the COP9 signalosome continue to be a major focus in the lab due to their unique molecular properties and key position in cell physiology and disease processes including atherosclerosis and ischemic stroke.

Jürgen published >185 papers in this area, and his work has been cited >13000 times and is flanked by numerous patents. The research has been funded by the Deutsche Forschungsgemeinschaft (DFG), several Foundations, the SyNergy Excellence Cluster, the BMBF and Fraunhofer, the Munich Heart Alliance, and industry.

Personal Data

Jürgen Bernhagen, PhD

Date of birth: 24 February 1964

Place of birth: Wuppertal-Elberfeld

Professor, Ludwig-Maximilians-University (LMU), Munich

Chair of Vascular Biology (W3), Institute for Stroke and Dementia Research

PI, Institute for Stroke and Dementia Research

Scientific vita

2015 – Chair of Vascular Biology (W3), Institute for Stroke and Dementia Research (ISD), Klinikum der Universität München, Ludwig-Maximilians-University (LMU), Munich, Germany

2015 – Professor of Vascular Biology, Ludwig-Maximilians-University (LMU), Munich, Germany

2010 – 2015 Director (W3) of the Institute of Biochemistry and Molecular Cell Biology, RWTH Aachen University, Aachen, Germany

2009 – 2015 Chair of Biochemistry and Molecular Cell Biology, RWTH Aachen University, Aachen, Germany

2002 – 2009 Professor of Biochemistry (C3), Head of Division of Biochemistry and Molecular Cell Biology, Institute of Biochemistry and Molecular Biology, RWTH Aachen University, Aachen, Germany

2000 – 2005 Head of Department of Molecular Biotechnology at the Fraunhofer Institute of Interfacial Engineering and Biotechnology, Stuttgart (part time appointment), Stuttgart, Germany

2000 – 2001 Assistant Professor (C2) and Head of Laboratory of Biochemistry, IGVT, University of Stuttgart, Germany

2000 Habilitation in Biochemistry, University of Tübingen, Tübingen, Germany

1995 – 1999 Senior scientist/group leader, Laboratory of Biochemistry, IGVT, University of Stuttgart, Germany

1994 – 1995 Postdoctoral Investigator and Senior Scientist at the Picower Institute for Medical Research, Manhasset, NY, USA, with A. Cerami & R. Bucala

1992 – 1994 PhD thesis in Biochemistry (Dr. rer. nat.), Picower Institute for Medical Research, Manhasset, NY, USA, and Biochemical Institute of the University of Tübingen, Germany

1988 – 1989 Visiting Research Fellow in molecular arthritis research Queen Mary & Westfield College, University of London, England

1985 – 1991 Study of Biochemistry (Diplom/Master), University of Tübingen, Germany

Coordinating Functions, Editorial Roles, Honors, and Awards

2018 – 2022 Member SFB1123 „Novel Targets in Atherosclerosis“

2017 – 2020 Member SFB-TRR57 “Organ Fibrosis”

2019 – () Editorial Board, The FASEB Journal; Associate Editor, The Quarterly Journal of Medicine, Oxford University Press

2015 – () Member Munich Cluster of Systems Neurology (SyNergy)

2015 – () Member, Munich Heart Alliance (MHA) within German Center for Cardiovascular Research (DZHK)

2014 – 2018 Member SFB1123 „Novel Targets in Atherosclerosis“

2014 – 2015 Vice-Spokesman, IZKF Aachen, Cardiovascular Cluster

2014 – () Editorial board Frontiers in Cardiovascular Medicine and Mediators of Inflammation, Guest editor Frontiers in Immunology (2014-2016)

2014 – 2016 Guest editor Front. Immunol.

2013 – 2018 Permanent Member of the Referee Panel of the Studienstiftung des Deutschen Volkes for PhD fellowships

2010 – 2014 Spokesman of the International DFG Graduate School GRK1508/EuCAR “Arterial Remodeling”

2009 W3 Professorship offers for Chairs in Biochemistry at Ruhr-University, Bochum and Heinrich-Heine-University Düsseldorf (rejected)

2009 Editorial board Open Atheroscl. J

2009 – 2016 Member SFB-TRR57 “Organ Fibrosis”

2009 – 2015 IZKF Aachen, Vice-Spokesman Cardiovascular Cluster (2014-2015), Member of Executive Board (2009-2015)

2008 Paul-Martini-Award for Clinical Pharmacology and Achievements in Drug Discovery

2007 – () Founding Member and Member of Executive Board, International MIF Consortium

2007 – 2014 Deputy Spokesman of the DFG Collaborative Research Center FOR809

2007 Member Fellowship Selection Board (‘Hochschulauswahl’) of the German National Academic Foundation (‘Studienstiftung des Deutschen Volkes’)

2004 – 2005 Guest Editor, Antioxid. Redox Signal

2002 – 2011 Member SFB 542 „Molecular Mechanisms of Inflammation“

2000 – 2005 Member of the Institutional Steering Committee of the Fraunhofer Institute IGB

1994 Fellowship (“Promotionsstipendium“) award of the Studienstiftung des Deutschen Volkes

1988 – 1991 Study Scholarship of the Friedrich-Ebert-Foundation

Fields of Interest

Cytokines, chemokines, atypical chemokines, atherosclerosis, ischemic stroke, myocardial infarction and remote ischemic preconditioning, inflammation and inflammatory diseases, receptor mechanisms, signal transduction, and the COP9 signalosome

For information on Currently Funded Projects see ISD Research Support

Training of medical students as part of the ‘FöFoLe’ graduate program
Training of medical students as part of the ‘BVMD Mobility’ program of LMU
MD and PhD theses within the MMRS graduate program
Training of medical students during their MD thesis and within ‘MeCuM Module 6’
Contribution to lectures, within the LMU master course ‘Innate Immunity & Inflammation’ of the ‘Master of Biochemistry’ program
Contribution to seminars within the LMU master course ‘Innate Immunity & Inflammation’ of the ‘Master of Biochemistry’ program
Practical course within the LMU ‘Biochemistry Master’ program
Training of PhD graduate students within the ‘Integrated Research Training Group’ (IRTG) ‘Atherosclerosis – Mechanisms and Networks of Novel Therapeutic Targets’ within CRC1123
Bachelor and master theses in Biochemistry, Chemistry, Biotechnology, Biology, and related disciplines

Contact:

Prof. Dr. rer. nat. Jürgen Bernhagen

Tel: +49-89-4400-46151

juergen.bernhagen@med.uni-muenchen.de

Secretary: Sabrina Lukanovic

Tel: +49-89-4400-46149

sabrina.lukanovic@med.uni-muenchen.de

Single cell sorting and sequencing unit

The area of single cell analysis and single cell RNAseq/transcriptomics currently is exploding and revolutionizes biomedical research. Understanding the genetic, functional, and compository heterogeneity of healthy and pathogenic tissue specimens has become a major challenge in our efforts to decipher human diseases.

The Bernhagen and Gokce labs together with SyNergy recently acquired an SH800S Cell Sorter from Sony Instruments. The sorter is a key component of our pipeline to isolate and study cell populations from various tissues and animal models of cardiovascular and neurodegenerative diseases including atherosclerosis, ischemic stroke, and Alzheimer disease. With this sorter we can sort a wide range of cells, from B and T lymphocytes to microglial cells, pericytes, and neurons.

Sorting uses the 70μm, 100μm, and 130μm microfluidic sorting chips. We are able to perform bulk as well as single cell sorting into tubes and 96- and 384-well plates for high-throughput analyses. The SH800S sorter is equipped with four lasers (488 nm, 405nm, 561nm and 638nm) and eight fluorescence filters. Apart from that, the user-friendly design and software and the high level of automation allows for easy handling, even with beginners.

Research News

A novel link between the chemokine MIF and B lymphocytes in atherosclerosis

23 Mar 2018 – The Bernhagen lab uncovered a previously unrecognized connection between the atherogenic chemokine-like cytokine MIF and B cell function in atherosclerosis. Previously already implicated in controlling monocyte and T cell recruitment in atherogenesis, the current study (Schmitz et al., FASEB J. 2018) using an atherogenic ApoE-/- mouse model suggests that MIF also controls pro-atherogenic B cell activities in this disease. Mif-deficient mice which are protected from lesion development have a B cell development defect and exhibit atheroprotective natural IgM-containing antibody profile. The mechanism of generation of these anti-oxidized LDL antibodies needs to be explored in future work, the current study also supports recent evidence on a critical role for B cells in atherosclerosis. The study was conducted in collaboration with researchers from the Institute of Cardiovascular Prevention (IPEK) at LMU, RWTH Aachen University, the Peptide Biochemistry lab at WZW/TUM, Yale University, and the University of Düsseldorf.

A second paper by the same lab gave further mechanistic insight into how MIF regulates the receptor expression on B cell. Omar El Bounkari and his team unveil a connection between the pro-proliferative activity of MIF/CD74 signaling in B cells and inflammation (Klasen et al., Cell Signal 2018) uThis study was performed in collaboration with RWTH Aachen University and the Peptide Biochemistry lab at WZW/TUM.

Dositej Obradović fellowship award

27 Nov 2017 – Jelena Milic, first year PhD student in the Bernhagen lab at ISD, was awarded the Dositej Oradovic scholarship. This prize is awarded by the Fund for Young Talents of the Ministry of Youth and Sports of the Republic of Serbia for the best students from Serbia at EU Member State and European Free Trade Association (EFTA) universities and the world's leading universities and it encompasses a prize money of 4,600.85,- € to stimulate the outstanding achievements of the young talents of Serbia in various fields in terms of their further theoretical and professional development. Jelena performs her PhD thesis under the supervision of Jürgen Bernhagen and in the framework of the Munich Medical Research School (MMRS) of LMU. Her thesis focuses on elucidating the mechanisms underlying the protective role of the COP9 signalosome (CSN) signaling complex in atherosclerosis.

"MIF Family Cytokines in Innate Immunity and Homeostasis“

10 Dec 2017 – Jürgen Bernhagen, Chair of Vascular Biology at ISD, has edited a comprehensive book in the field of inflammation research. The book is titled: "MIF Family Cytokines in Innate Immunity and Homeostasis“ and was published within the Springer series "Progress in Inflammation Research“ (Progress in Inflammation Research; ISBN 978-3-319-52352-1; ISBN 978-3-319-52354-5 (eBook); DOI 10.1007/978-3-319-52354; Springer International Publishing AG 2017; Editors: J. Bernhagen, R. Bucala). Jürgen co-edited the book together with Prof. Richard Bucala, a Professor of Medicine at Yale University School of Medicine. The book covers recent advances in our understanding on the inflammatory mechanisms of MIF family proteins and their role in various inflammatory diseases, including promising MIF-based therapeutic avenues.

Group News

On 1 Oct 2018, Chunfang Zan and Ying Gao joined the Bernhagen Lab. Chunfang holds a master degree in Clinical Medicine from Jilin University, Changchun, China, and Ying holds a master in Neurology from Shanghai Jiao Tong University, China. Both received a prestigious Chinese Scholarship Council (CSC)-LMU fellowship following competitive selection among hundreds of applicants. The fellowship allows them to pursue a 3-4 year PhD project at LMU. Together with Ji Hao, another successful CSC scholar and PhD candidate in the neighboring Gokce Lab, they just successfully passed the exam concluding the LMU-CSC introductory training in September 2018. The photos were taken at the opening ceremony of the 2018 CSC-LMU program, which took place on 10 Oct at LMU Biomedical Center (BMC) and was led by LMU Vice President Professor van Ess, the Chinese General Consulate, LMU Vice President Prof. Conrad, and Drs. Lauterbach and Zhang from the LMU International Office. The PhD candidates were awarded their training certificates and notably, Hao delivered one of the welcome addresses.

Vascular Biology – PI: Jürgen Bernhagen

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