Jürgen Bernhagen – Vascular Biology

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: Barbara Hönig
Tel: +49-89-4400-46149
Barbara.Hoenig@med.uni-muenchen.de

Dr. Omar El Bounkari, Senior staff scientist & Technical laboratory head

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.

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.

Maida Avdic, B.Sc., Technical assistant

I am originally from Bosnia and Herzegovina, where I received my Bachelor degree in Genetics and Bioengineering. In October 2021, I moved to Munich and joined the Bernhagen team as Technical Assistant. The position was very appealing to me because of my interest in biochemistry, vascular biology, and the mechanisms of cardiovascular diseases. I am excited to be in a top-class research institute where I can get trained in various technologies and methods. I am looking forward to share my gained knowledge with some other young scientists in the future. In my spare time, I like to spend time with my nieces and go for walks.

Dr. rer. nat. Markus Brandhofer, postdoctoral investigator & m4 team member

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, 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.

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 study the ‘atheroprotective role of the COP9 signalosome in atherogenesis’ using mouse models and cellular in vitro models. My PhD studies have been supported by a fellowship from IRTG1123, the graduate school of atherosclerosis SFB1123, and are funded by a current scholarship award from the Studienstiftung des deutschen Volkes. 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.

Yuan Tian, PhD, postdoctoral investigator

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.

Bishan Yang, PhD student

Originally from China, I obtained my Master degree from South China University of Technology in physiology. I finished my Master thesis on the topic of cell recruitment mechanisms at the Institute of Biomechanics, and I decided to do further studies related to inflammation. In 2019, I was accepted as a PhD student in the Bernhagen lab funded by an LMU/CSC scholarship for 4 years. Now I study for my PhD thesis in which I explore the relationship between MIF proteins and B lymphocytes in atherosclerosis. In my spare time, I love playing card games with my friends as well as playing badminton.

Lin Zhang, MD, PhD student

Originally from China, I studied Clinical Medicine at Zhengzhou University, where I got my medical Master’s degree. In the fall of 2019, I joined the Bernhagen lab to work on my PhD thesis. My research focuses on the role of MIF family proteins in the resolution of inflammatory processes, e.g. in Acute Respiratory Distress Syndrome, a project performed under the supervision of Dr. med. Adrian Hoffmann and in collaboration with the Department of Anesthesiology at LMU University Hospital. In my spare time, I enjoy hiking, traveling, and spending time with friends.

Kobra Moradzadeh Gavbazeh, PhD student

I am originally from Iran, where I received my bachelor’s and master’s degree in biotechnology and medical biotechnology, respectively. During my master’s study I worked in the Regenerative Medicine Research Center in the area of kidney diseases. My thesis project was mainly about the role of CXCL12 in the regeneration of acute kidney injury. It was part of a systems biology study, in which the prediction of a mathematical model on a hypoxia pathway, a common condition in acute kidney injury, was validated experimentally. After graduation, I shortly worked for a pharmaceutical company and then joined the Gene Therapy Research Center, in which I worked as a research assistant. Based on my scientific experience in the field of biomedicine I found myself interested in inflammation, regenerative medicine and systems biology. In 2022, I joined Bernhagen research group and the CRC1123 ‘atherosclerosis’ as a PhD student, to work on discovering the role and mechanisms of new MIF family members in atherosclerosis. My PhD study is supported by a fellowship from the Integrated Research Training Group (IRTG) of CRC1123 at LMU. In my spare time, I like doing yoga, mountain climbing, and reading.

Simon Ebert, PhD student

I am originally from Augsburg, a lovely city near Munich. I first did an apprenticeship as a chemical laboratory assistant at ratiopharm Ulm. Following I obtained my B.Sc. in Chemistry and Biochemistry at LMU Munich, where I was furthermore admitted to the Deutschlandstipendium. Because of my interest in cardiovascular disease and inflammation, I performed my Master's Thesis in the Bernhagen Lab from April-September 2022 on a novel CD74 ligand and have started my PhD thesis on the role of chemokine receptor mimics and their utility in cardiovascular diseases in the end of 2022. During my spare time, I like to play ice hockey, go backcountry snowboarding, and cycling.

Noor Ismail, cand. med., MD doctoral student

Growing up in Stuttgart, I started studying medicine at LMU Munich in 2018. For my MD doctoral thesis, I joined the Bernhagen lab in 2022, supported by a FöFoLe fellowship of Munich Medical Research School (MMRS). During my time here, I will work on 2 subtypes of so-called new MIFs, aiming to characterize their role and mechanisms in atherosclerosis, applying in vitro cell models and tissue specimens from carotid plaques. Outside the lab, I like reading, enjoying time in nature, and traveling.

Michael Kobina Otabil, M.Sc. student

Originally from Ghana, where I obtained a Bachelor in Biochemistry and Master in Pharmacology. I relocated to Munich, and enrolled in another master in Biochemistry studies at LMU, primarily to upgrade my research knowledge and skills in inflammation, ligand – receptor crosstalk and drug studies. I joined the Bernhagen research group for a practical course and master thesis. I am interested in studying the effect of MIF, an atypical chemokine and finding ways to modulate its receptor interactions helps to understand it chemotactic activity implicated in atherosclerosis and other inflammatory diseases, and also, how it signals through its receptor interaction.

Sara Mardazad, M.Sc. student

Being born to Persian parents in Munich, I obtained my Bachelor’s Degree in Chemistry and Biochemistry from the LMU Munich in 2020. Continuing with my Master Studies in Biochemistry, one of my major interests has been the scientific field of inflammation and immunity. Focusing on this topic, I had the chance to perform a research practical at the AG Bernhagen. My curiosity was teased and I started working on my Master Thesis here in the lab in June of 2022. For my Thesis I will focus on the regulatory role of MIF-2 in atherosclerosis. Outside of the lab I enjoy athletic occupations, music, and exploring different languages and cultures.

Carl-Christian Schäfer, cand. med., MD doctoral student

Growing up in the Frankfurt area, I moved to Munich to study Medicine in 2017. Now in my fourth year studying Medicine first at LMU and now TUM, I joined the Bernhagen Lab in March 2021 for my MD doctoral thesis. During my time here, I will work on the atypical cytokine MIF and its cognate receptor CD74 and its effect on T cells, in particular focusing on T-cell receptors. Outside of work, I like to spend time outdoors and do sports, such as tennis, hockey or soccer, or playing my guitar.

Chunfang Zan, PhD
Collaborative Innovation Center for Molecular Imaging of Precision Medicine, First Hospital of Shanxi Medical University, Taiyuan, China

Elina Bugar
Bernhagen Lab 2022

Ruben Ellesworth Galindo
Bernhagen Lab 2021

Christine Krammer
Scientist / QC Manager, Eurofins Biopharma Product Testing Munich GmbH
Bernhagen Lab 2016 - 2021

Priscila Bourilhon
Bernhagen Lab 2016 - 2021

Dr. med. Wang Sijia, MD
Resident in Neurology at Shenzhen People's Hospital, China
Bernhagen Lab (2017-2021)

Dr. med. Jonas Wagner
Junior Attending Physician and Clinician Scientist, University Medical Center Hamburg- Eppendorf (UKE),
Bernhagen Lab 2015-2020

Dr. Lisa Schindler
Postdoc, Department of Biochemistry and Molecular Cell Biology (IBMZ), University Medical Center Hamburg- Eppendorf (UKE)
Bernhagen Lab 2013-2020 (Aachen and Munich)

Dr. Dzmitry Sinitski
Scientist, Institute of Microbiology and Laboratory Medicine/WHO – Supranational Reference Laboratory of Tuberculosis
Bernhagen Lab 2016-2020

Dr. med. Valerie Exler
Junior Attending Physician, Chirurgie Spital Thun, Schweiz
Bernhagen Lab 2014-2018

Prof. Dr. Christian Stoppe, FAHA
Department of Anesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Würzburg, German
Bernhagen Lab 2010-2014

Dr. Corinna Schmitz
Postdoc, Institute for Molecular Cardiovascular Research (IMCAR), RWTH Aachen University
Bernhagen Lab 2012-2017

Dr. Christoph Emontzpohl
Postdoc, The University of Texas Health Science Center at Houston, McGovern Medical School
Bernhagen Lab2013-2018 (partial, shared with StoppeLab)

Dr. Josefine Soppert
Postdoc, Institute for Molecular Cardiovascular Research (IMCAR), RWTH Aachen University
Bernhagen Lab 2013-2018 (partial, shared with StoppeLab)

Dr. med. Luisa Averdunk
Junior Attending Physician, Institute for Genetics, Düsseldorf University
Bernhagen Lab 2013-2018 (partial, shared with StoppeLab)

Michael Lacy
PhD student, IPEK, LMU Munich
Bernhagen Lab2015-2017

Dr. med. Wibke Schulte
Junior Attending Physician, Charite Hospital, Berlin
Bernhagen Lab 2010-2016 (partial)

Dr. Pathricia Tilstam
Postdoc, Yale University
Bernhagen Lab 2010-2014 (partial, shared with NoelsLab)

Dr. Sandra Jumpertz
Postdoc, Department of Visceral Surgery, RWTH Aachen University
Bernhagen Lab 2011-2015

Dr. Thomas Hennes
Clinical Data Coordinator, CROMSOURCE
Bernhagen Lab 2011-2015

Priv.-Doz. Dr. med. Bong-Sung Kim
Senior Attending Physician, UniversitätsSpital Zürich
Bernhagen Lab 2009-2014 (partial)

Dr. Christina Klasen
Sales Manager Life Science EMEA, SYSMEX Deutschland GmbH
Bernhagen Lab 2010-2014

Dr. Setareh Alampour-Rajabi
Postdoc, Institute for Molecular Cardiovascular Research (IMCAR), RWTH Aachen University
Bernhagen Lab2010-2015

Dr. Yaw Asare
Postdoc, Institute for Stroke and Dementia Research (ISD, DichgansLab), LMU Munich
Bernhagen Lab2010-2014

Dr. med. Hongqi Lue
Senior Scientist, RWTH Aachen University
Bernhagen Lab 2000-2015

Priv.-Doz. Dr. med. Gerrit Grieb
Director, Clinic for Plastic and Hand Surgery, Havelhöhe Hospital Berlin
Bernhagen Lab2007-2013 (partial)

Dr. Daniel Heinrichs
Projektträger Jülich (PTJ), BMBF
Consulting Molecular Life Sciences
Bernhagen Lab2009-2015 (associated 2016-2020)

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

2021 – BioM m4 Award

2021 – () Associate Editor: The FASEB Journal

2018 – 2022 Member SFB1123 „Novel Targets in Atherosclerosis“

2017 – 2020 Member SFB-TRR57 “Organ Fibrosis”

2019 – () Editorial Board: Atherosclerosis; Scientific Reports (NPG); Associate Editor: The Quarterly Journal of Medicine (Oxford University Press); Conditioning Medicine

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, Guest editor Frontiers in Immunology (2014-2016)

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

Video microscopy and live imaging of single cell migration tracks

As a lab focusing on chemokines and atypical chemokines, immune cell migration studies are in the center of our interest to understand their roles in cardiovascular and inflammatory diseases. The lab is equipped with the premium class high power inverse fluorescence microscope, the Leica DMi8 that is equipped with a fully motorized video microscopy modality, a micro-incubator for mid- to -longterm tracking experiments and various high power, high resolution objectives to track leukocyte migration movements in real-time.

Features DMI8 life cell imaging microscope:

Fluorescence detection at broad wavelength range due to variety of filters and RFIP fluorescence revolver
Numerous colors/filters (excitation/emission: 350/460, 436/480, 480/535, 500/527, 546/585, 545/605)
Fully motorized
High-speed live tracking (XGA 1024x768 mit 30 fps)
sCMOS camera (Hamamatsu Orca Flash 4.0)
Various objectives including HC PL APO 63x/1.400.60 - OIL
LAS X Premium software and Huygens deconvolution software
Anti-vibration table
Incubator (heat, temperature, and CO2-O2 control)

Multi-Photon microscopy with 1300 nm pulsed IR laser an FLIM-FRET

We have one of the first new-generation Leica multiphoton microscopes, i.e. the Leica TCS SP8 DIVE with FLIM-FRET modality, in Germany and Europe. The instrument is primarily used for atherosclerosis and stroke research, but also is an important tool for various other cardiovascular, neuroscience, neurophysiology, and cell biology questions.

The advanced Leica TCS SP8 DIVE multiphoton microscope is equipped with spectrally tunable detection over the whole visible spectrum (380 – 800 nm) and a highly sophisticated Vario Beam Expander (VBE) combining maximum depth, high resolution and full color correction. Our system consists of both confocal and multiphoton units and is thereby perfectly suited for all standard applications including in vivo live imaging, ex vivo leukocyte adhesion, in vivo cell recruitment and homing, calcium imaging, dye separation and live time determination using Fluorescence Lifetime Imaging (FLIM), detection and imaging of both molecular interactions and molecular distance in vitro and in vivo using FLIM-FRET. The femto-second high power 1300 nm laser in combination with the three-photon excitation option allows imaging at high penetration depth of up to 800 µm.

SPECIFICATIONS:

Confocal lasers: 488 nm, 552 nm, and 638 nm (Vis. CW)
Confocal detectors: 2 internal detectors (1 HyD, 1 standard PMT)
Multiphoton lasers: extended IR spectrum tunable multiphoton laser (New InSight® X3™, Spectra-Physics) tunable in the range of 680-1300 nm (laser class 4) and 1045 nm fixed IR laser (pulsed)
Multiphoton detectors: 3 external Reflected Light Hybrid Detectors ((RLHyD)
Vario Beam Expander (VBE)
Ultra high-speed resonant scanner 8kHz (Maximal Frame Resolution: 1024x1024 pixel; scan-zoom: 1.3 - 48x)
Leica LAS X Navigator for the acquisition and review of large data sets
Long-working distance immersion objectives that can be used according to the experimental model and imaging needs are available, including cleared tissues
High-end fully motorized XY-stage
SP8 FALCON (FAstLifetime CONtrast) for Fluorescence Lifetime Imaging (FLIM)
LIGHTNING and Huygens Deconvolution Algorithms
PicoQuant FLIM-FRET module
3D visualization mode

Access to the imaging system, as well as design of experimental procedures including image data acquisition and analysis are possible. If you are interested in using our system, please don´t hesitate to contact the responsible person:

Dr. Omar El Bounkari

Tel.: +49 (0)89 4400 - 46152 
E-Mail: omar.el_bounkari@med.uni-muenchen.de

Single cell sorting and sequencing unit

The SH800 is a microfluidic chip-based sorter ideally suited for various single cell sorting and scRNAseq applications. It is run by the Bernhagen and Gokce labs at ISD and supports cell sorting experiments of the Bernhagen and Gokce labs, of other ISD investigators, users of the SyNergy excellence cluster, as well users from the DZNE, the DZHK, and the LMU/KUM campus. The SH800 sorter is associated with the SyNergy Transcriptomics technology hub.

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.

If you wish to use the SH800 sorter, please contact Prof. Jürgen Bernhagen or Dr. Ozgun Gokce to register, learn about user conditions, and get training. Registered and trained users please visit the booking site here: https://www.gokcelab.com/sony.

Research News
Group News

Yuan Tian and Markus Brandhofer successfully defended their doctoral theses
Sept-Oct 2022 – Congratulations to Yuan Tian and Markus Brandhofer, who successfully completed their doctoral theses entitled “Modulation of neuroinflammation and stroke outcome by the COP9 signalosome” and “Interactions between MIF-family proteins and the classical chemokine ligand/receptor network”, respectively. Yuan and Markus have been instrumental members of our team for several years and have made important contributions to several of our research lines and publications. Yuan wrote a full-size PhD script (“monography”), while Markus pursued the prestigious Dr. rer. nat. thesis line and concluded with a cumulative thesis based on three first/co-first authorship publications, accompanied by several flanking co-authorships. Congratulations again to both of you on your degree! We are happy that Markus will stay with us as part of our BioM m4 team SELECKREM, while Yuan has successful acquired a position abroad and is embarking on a postdoctoral scientist track in the UK as a next step in her career. We wish both of them a great start into their new positions.

CRC1123 “Atherosclerosis” approved for another 4 years

Jun 2022 – CRC1123 “Atherosclerosis” approved for another 4 years: The Collaborative Research Center CRC1123 “Atherosclerosis - Mechanisms and Networks of Novel Therapeutic Targets” (Speaker: Christian Weber, IPEK, LMU) was awarded a third funding period from the DFG for the years 2022-2026. The cluster encompasses 16 projects, 3 central projects, and a graduate school with a total funding volume of 14.5 mio. €. The ISD scientists Yaw Asare, Jürgen Bernhagen, Martin Dichgans, and Arthur Liesz contribute to 4 projects within the center: A2 (von Hundelshausen/Bernhagen), A3 (Bernhagen/Kapurniotu), B3 (Asare, Dichgans), B11 (Liesz/Sager). J. Bernhagen also is the Vice-Spokesperson of CRC1123. It is the aim of the multidisciplinary basic and clinical research projects in CRC1123 to elucidate the mechanisms and molecular networks driving atherosclerosis and to further the identification of potential therapeutic target candidates. The projects A2 and A3, in which the BernhagenLab is involved, address the roles of chemokines and their receptors in atherosclerosis and seek to identify novel therapeutic target candidates. In project A2, the BernhagenLab supports Philipp von Hundelshausen (IPEK, LMU) in efforts to study “Interactions of chemokines with heterologous effectors in atherosclerosis”. In A3, the BernhagenLab teams up with the peptide biochemistry lab of Aphrodite Kapurniotu at the TUM School of Life Sciences to explore “Differential mechanisms of MIF proteins in atherosclerosis and selective peptide-based strategies for intervention”.

Christine Krammer, PhD, successfully defended her thesis
Nov 2021 – We are happy to share the good news that Christine Krammer successfully completed her PhD Thesis entitled “MIF proteins and their receptors in atherogenesis: structure-activity relationships and novel cellular routes”. Christine has been an instrumental member of our team since 2017 and has made important contributions to several of our research lines. She successfully concluded an impressive cumulative thesis based on three first/co-first authorship publications, as well as a review article and several co-authorships. Congratulations again on your great thesis! Christine has decided to accept an attractive offer from industry and we wish her good luck, a successful career, and a good start at her new position at Eurofins.

Conference awards to Chunfang Zan and Markus Brandhofer
Oct 2021 – Chunfang Zan, PhD student in the BernhagenLab, won the Young Investigator Award at last week’s 9th Cardiac Regeneration and Vascular Biology Conference in San Servolo. At the same conference, Markus Brandhofer, a close to defense PhD student as well, was one of the four winners of a poster prize. The meeting was the first in-person conference for us in more than one-and-a-half years of COVID-19-related restrictions. The conference was co-organized by TUM-MRI (Christian Kupatt), the IRTG1123 graduate school of SFB1123 (Sabine Steffens, Christian Weber), and the DFG/ANR MIF-cross-kingdom consortium (Jürgen Bernhagen, Ralph Panstruga). It hosted more than 110 participants, including top-international speakers. Bishan Yang and Jelena Milic from our lab also presented posters at the conference.

m4 Award for project team of BernhagenLab together with KapurniotuLab at TUM
Oct 2021 – With their project idea SELECKREM “Preclinical development of peptide-based chemokine receptor mimetics as ligand-selective agents in atherosclerotic disease”, the team of Jürgen Bernhagen together with Aphrodite Kapurniotu and Christos Kontos (Division of Peptide Biochemistry, TUM), and Markus Brandhofer (ISD) is one of 5 winners of the 2021 pre-seed competition m4 award for innovative biomedical projects awarded by the Bavarian State Ministry of Economic Affairs, Regional Development and Energy. Despite significant medical advances, atherosclerotic diseases such as myocardial infarction and stroke remain the leading cause of death worldwide. A problem is the residual inflammatory risk in patients on lipid-lowering treatment and currently pursued anti-inflammatory approaches lack specificity and have side effects. With the m4 award, the team aims to develop chemokine receptor mimics as a new class of anti-inflammatory drug leads to selectively inhibit atherosclerosis-causing chemokines in cardiovascular diseases.

Bernhagen Lab contributes to studies on the role of MIF proteins in liver diseases

The papers comprehensively characterize the pathogenic role of MIF and its receptors in the entire cascade of liver pathologies from metabolic liver disease, to fibrosis/cirrhosis, and hepatocellular carcinoma. Specifically, MIF and its receptor CD74 were found to be causative in conditions such as non-alcoholic steatohepatitis (NASH), acute decompensation of cirrhosis, and hepatocellular carcinoma. Unraveled mechanisms encompass a shift in NKT cell populations, soluble CD74, and anti-apoptotic effects via CD74, respectively.

Sijia Wang, MD, successfully defended her thesis
May 2021 – Sijia Wang completed her MD Doctoral Thesis entitled “The role of MIF proteins in ischemic stroke”, a comprehensive and impressive MD thesis that actually is almost comparable to a full-size PhD thesis. Sijia successfully defended her doctoral thesis on 27 April 2021 and is currently preparing the corresponding original manuscript, on which she will be the first author. We are very proud of her big achievement and happy that Sijia was part of our laboratory for 4 years. We wish her best of success for her future carrier path in clinical neurology and biomedical science and hope that she will return to Munich soon.

New papers of the BernhagenLab reveal a role for the MIF/CXCR2 axis in neutrophil survival and identify novel cyclic peptides that inhibit MIF/CXCR2: implications for targeting strategies in inflammatory diseases

Nov 2020 / Feb 2021 – While the recruitment role of MIF and its chemokine receptors in atherosclerotic inflammation has been well described for monocytes, little is known about neutrophils, the first cells to arrive at inflammatory sites. Lisa Schindler, Leon Zwissler, and Christine Krammer together with our collaborators at the University of Otago in Christchurch, NZ, and the West-German Heart Center in Essen, now identify a role for the MIF/CXCR2 axis in neutrophil survival, a process governing the balance between the amplification of the inflammatory response and its resolution. In a second paper, Christine Krammer from our lab, together with collaborators from the KapurniotuLab at TUM and colleagues from the Institute for Cardiovascular Prevention (IPEK) of LMU, RWTH Aachen University, and Carolus/Moderna Therapeutics, report on novel, proteolytically stable, cyclic peptides that can block the MIF/CXCR2 axis. The studies are published in the Journal of Leukocyte Biology and ChemBioChem.

Schindler L, Zwissler L, Krammer C, Hendgen-Cotta U, Rassaf T, Hampton MB, Dickerhof N*, Bernhagen J*. Macrophage migration inhibitory factor inhibits neutrophil apoptosis by inducing cytokine release from mononuclear cells. J Leukoc Biol. 2021 Feb 10. doi: 10.1002/JLB.3A0420-242RRR. Online ahead of print.

Krammer C, Kontos C, Dewor M, Hille K, Dalla Volta B, El Bounkari O, Taş K, Sinitski D, Brandhofer M, Megens RTA, Weber C, Schultz JR, Bernhagen J*, Kapurniotu A*. A MIF-Derived Cyclopeptide that Inhibits MIF Binding and Atherogenic Signaling via the Chemokine Receptor CXCR2. Chembiochem. 2020 Oct 30. doi: 10.1002/cbic.202000574. Online ahead of print.

Jelena Milic received a prestigious fellowship (“Promotionsstipendium”) from Studienstiftung des deutschen Volkes.

July 2020 – Studienstiftung is Germany's oldest and most prestigious scholarship foundation. It awards fellowships to outstanding and particularly motivated doctoral students with distinguished personalities and well above-average degrees and scientifically excellent dissertation projects. Studienstiftung awards go to less than 0.5% of students pursuing their studies or doctoral projects in Germany. Jelena received the fellowship to pursue her doctoral thesis project on “The role of the COP9 signalosome in atherosclerosis”. Congratulations, Jelena, for receiving this fellowship award, best of success for your doctoral thesis, and enjoy the interactions with the other fellows at Studienstiftung’s wonderful academic program.

Young Investigator Award goes to Jelena Milic from Bernhagen Lab

March 2020 – Jelena Milic won the Gotthard Schettler Young Investigator Award at the Vascular Medicine and Atherosclerosis Conference (VMAC), held in Augsburg, 12-13th March, 2020. VMAC is organized by several leading German societies focusing on atherosclerosis and its sequelae, i.e. DGAF, DACH, and DGFF, as well as Working Group 41 (Atherosclerosis) of the German Cardiac Society (DGK). Jelena received the award for her lecture on “The Role of the COP9 Signalosome in Atherosclerosis” that she gave in the “Basic science – Young Investigator Award Session” of the VMAC conference. Congratulations, Jelena, for this very nice recognition of your research findings!

Feb 2020 – The BernhagenLab recently discovered that plant MIF proteins surprisingly have MIF-like chemokine activity. Dzmitry is the first author on this paper and did a great job in highlighting the X-Kingdom activity of MIF proteins with implications for both basics research (e.g. evolution of the innate immune system, structure-activity relationships of MIF/receptor interactions) to unexpected translational opportunities (e.g. smart foods or immune modulation). The paper is a collaborators with researchers from Aachen University and the University of Groningen, NL, and was published in the Journal of Biological Chemistry

Sinitski et al, JBC 2020; J Biol Chem. 2020 Jan 17;295(3):850-867.

and highlighted in Science Signaling

In collaboration with research from Zürich University and Yale University, we demonstrate a differential regulation of macrophage activation by the MIF cytokine superfamily members MIF and MIF-2 in adipose tissue during endotoxemia.

This study was just published in the FASEB Journal (Kim et al, FASEB J 2020; )

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

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

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“

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.

CSC-LMU fellowship awardees Chunfang Zan, Ying Gao, and Hao Ji start their PhD theses

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.

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