The Grieshaber-Bouyer Laboratory
(c) SIMOarts / Simone Kessler
About
We are a systems immunology laboratory in the Department of Internal Medicine 3 – Rheumatology and Immunology at Erlangen University Hospital.
Our group investigates the mechanisms driving immune cell heterogeneity in tissues and inflammatory conditions and the links to disease variation across individuals. Our approach is characterized by a combination of high dimensional discovery in patient samples (in particular in the context of innovative therapies such as CAR-T cells) with in vitro systems, CRISPR-mediated genetic perturbations and murine models. We also develop novel analysis tools for high dimensional data.
In published work, we demonstrated that neutrophils in homeostasis are organized a chronologically ordered main sequence, termed neutrotime. In experimental inflammation, neutrophils reach distinct polarization states driven by timepoint, tissue and stimulus.
To apply this principle to human immune-mediated disease, we developed a method to jointly analyze murine and human transcriptomic data. Thereby, we identified a transcriptional program which characterizes neutrophils in the arthritic joint in both mice and humans. Functionally, this program was highly enriched for interferon gamma response genes, which we validated on the protein level and using in vitro models.
Team
Principal Investigator
Prof. Dr. med. Ricardo Grieshaber-Bouyer
Professor of Clinical Systems Immunology
Head of the Clinical Trial Unit
Director, Center of Systems Immunology (CSI) Erlangen (FOCIS Center of Excellence)
Lab Members – Erlangen
Dr. Kirill Anoshkin, PhD
Postdoctoral fellow
Sebastian Böltz, MD
Physician scientist
Laura Bucci, MD
Physician scientist
Elaine Degen
Dr. med. candidate
Sonia Dresel
Dr. med. candidate
Dr. Panagiotis Garantziotis, PhD
Physician scientist
Sanjukta Gubbi
Dr. rer. nat. candidate
Dr. med. Melanie Hagen
Physician scientist
Head of the Clinical Trial Unit
Nicolas J. Nitsche
M.Sc. student
Dr. rer. nat. Tobias Rothe
Postdoctoral fellow
Peter Scheuerlein
Research technician
Liang Zhang
Dr. rer. nat. candidate
Lab Members – Heidelberg
Dr. med. Tarik Exner
Postdoctoral fellow/PhD candidate in the HBIGS MD/PhD program
Frederic S. Pohl
Dr. med. candidate
Alumni
Dr. med. Cassian M. Afting
Rotation student
Now HBIGS fellow in Prof. Dr. Joachim Wittbrodt’s Lab
Selina Belghalem
Research technician
Dr. med. Frank Y. Huang
Dr. med. candidate and Boehringer Ingelheim Fonds fellow
Now HBIGS fellow in Prof. Dr. Andreas Trumpp’s Lab
Mareike de Groot
Dr. med. candidate
Peter-Scriba fellow (German Society of Internal Medicine)
Nicolaj S. Hackert
Dr. med. candidate
Boehringer Ingelheim Fonds fellow
Niklas R. Junker
Dr. med. candidate
Sophie E. Leonhardt
Research technician
Now Medical Student at Saarland University
Görkem Osmanusta
Dr. med. candidate
Felix A. Radtke
Dr. med. candidate and Boehringer Ingelheim Fonds fellow
Now DPhil Student in Professor Paresh Vyas’ Group at University of Oxford
Julia T. Schnell
Dr. med. candidate
PROMOS fellow (German Academic Exchange Service, DAAD)
Open Positions
We welcome applications by enthusiasts across wet and dry immunology, bioinformatics and data science enthusiasts!
Publications
2024
Bispecific T cell engager therapy for refractory rheumatoid arthritis
Bucci L, Hagen M, Rothe T, Raimondo MG, Fagni F, Tur C, Wirsching A, Wacker J, Wilhelm A, Auger JP, Pachowsky M, Eckstein M, Alivernini S, Zoli A, Krönke G, Uderhardt S, Bozec A, D’Agostino MA, Schett G, Grieshaber-Bouyer R
Nature Medicine 2024
CD19 CAR T-Cell Therapy in Autoimmune Disease — A Case Series with Follow-up
Müller F, Taubmann J, Bucci L, Wilhelm A, Bergmann C, Völkl S, Aigner M, Rothe T, Minopoulou I, Tur C, Knitza J, Kharboutli S, Kretschmann S, Vasova I, Spoerl S, Reimann H, Munoz L, Gerlach RG, Schäfer S, Grieshaber-Bouyer R, Korganow AS, Farge-Bancel D, Mougiakakos D, Bozec A, Winkler T, Krönke G, Mackensen A, Schett G
New Engl J Med 2024
Selective CAR-T cell mediated B cell depletion suppresses interferon signature in SLE
Wilhelm A, Chambers D, Müller F, Bozec A, Grieshaber-Bouyer R, Winkler T, Mougiakakos D, Mackensen A, Schett G, Krönke G
JCI Insight 2024
CAR T-cell therapy in rheumatology-What we know so far?
Hagen M, Wirsching A, Bohr D, Taubmann J, Müller F, Mackensen A, Grieshaber-Bouyer R*, Schett G*
Z Rheumatol 2024
2023
Human and mouse neutrophils share core transcriptional programs in both homeostatic and inflamed contexts
Hackert NS*, Radtke FA*, Exner T*, Lorenz HM, Mueller-Tidow C, Nigrovic PA, Wabnitz G, Grieshaber-Bouyer R
Nature Communications 2023
CD19 CAR-T cell treatment: Unraveling the role of B cells in Systemic Lupus Erythematosus
Taubmann J, Müller F, Mutlu MY, Völkl S, Aigner M, Bozec A, Mackensen A, Grieshaber-Bouyer R*, Schett G*
Arthritis Rheumatol 2023
Distinct Functional States of Neutrophils by Actin Disassembly and NF-kB/STAT3 Signaling
Heineken N, Schumacher JC, Exner T, Neuenfeldt F, Habicht J, Kahlich F, Platzer H, Merle U, Renkawitz T, Samstag Y, Grieshaber-Bouyer R, Autenrieth S, Wabnitz GH
bioRxiv 2023
2022
Ageing and interferon gamma response drive the phenotype of neutrophils in the inflamed joint
Grieshaber-Bouyer R#, Exner T, Hackert NS, Radtke FA, Jelinsky SA, Halyabar O, Wactor A, Karimizadeh E, Brennan J, Schettini J, Jonsson AH, Rao DA, Henderson LA, Mueller-Tidow C, Lorenz HM, Wabnitz G, Lederer JA, Hadjipanayis A, Nigrovic PA#. #Corresponding authors
Ann Rheum Dis 2022
Inflammation induces pro-NETotic neutrophils via TNFR2 signaling
Neuenfeldt F*, Schumacher JC*, Grieshaber-Bouyer R, Habicht J, Schröder-Braunstein J, Gauss A, Niesler B, Heineken N, Dalpke A, Gaida MM, Giese T, Meuer S, Samstag Y, Wabnitz G
Cell Reports 2022
Neutrophil transit time and localization within the megakaryocyte define morphologically distinct forms of emperipolesis
Huang FY*, Cunin P*, Radtke FA, Darbousset R, Grieshaber-Bouyer R, Nigrovic PA
Blood Advances 2022
2021
The neutrotime transcriptional signature defines a single continuum of neutrophils across biological compartments
Grieshaber-Bouyer R, Radtke FA, Cunin P, Stifano G, Levescot A, Vijaykumar B, Nelson-Maney N, Blaustein RB, Monach PA, Nigrovic PA; Immunological Genome Project Consortium
Nature Communications 2021
JAK inhibition prevents the induction of pro-inflammatory HLA-DR+ CD90+ RA synovial fibroblasts by IFNɣ
Zhao S, Grieshaber-Bouyer R, Rao DA, Kolb P, Chen H, Andreeva I, Tretter T, Lorenz HM, Watzl C, Wabnitz G, Tykocinski LO, Merkt W
Arthritis Rheumatol 2021
Arthritis flares mediated by tissue-resident memory T cells in the joint
Chang MH*, Levescot A*, Nelson-Maney N, Blaustein RB, Winden KD, Morris A, Wactor A, Balu S, Grieshaber-Bouyer R, Wei K, Henderson LA, Iwakura Y, Clark RA, Rao DA, Fuhlbrigge RC#, Nigrovic PA#
Cell Reports 2021
IL-1β-driven osteoclastogenic Tregs accelerate bone erosion in arthritis
Levescot A, Chang MH, Schnell J, Nelson-Maney N, Yan J, Martínez-Bonet M, Grieshaber-Bouyer R, Lee PY, Wei K, Blaustein RB, Morris A, Wactor A, Iwakura Y, Lederer JA, Rao DA, Charles JF, Nigrovic PA
J Clin Invest 2021
Gut CD4+ T cell phenotypes are a continuum molded by microbes, not by TH archetypes
Kiner E, Willie E, Vijaykumar B, Chowdhary K, Schmutz H, Chandler J, Schnell A, Thakore PI, LeGros G, Mostafavi S, Mathis D, Benoist C; Immunological Genome Project Consortium [consortium including Grieshaber-Bouyer R]
Nature Immunology 2021
A microRNA expression and regulatory element activity atlas of the mouse immune system
Rose SA, Wroblewska A, Dhainaut M, Yoshida H, Shaffer JM, Bektesevic A, Ben-Zvi B, Rhoads A, Kim EY, Yu B, Lavin Y, Merad M, Buenrostro JD, Brown BD; Immunological Genome Consortium. [consortium including Grieshaber-Bouyer R]
Nature Immunology 2021
2020
ImmGen at 15
Immunological Genome Project Consortium [consortium including Grieshaber-Bouyer R]
Nature Immunology 2020
Biosimilars – Opportunities and Risks
Grieshaber-Bouyer R#, Lorenz HM
Internist (Berl) 2020
2019
Divergent mononuclear cell participation and cytokine release profiles define hip and knee osteoarthritis
Grieshaber-Bouyer R*, Kämmerer T*, Rosshirt N, Nees T, Koniezke P, Hagmann S, Tripel E, Schiltenwolf M, Kirsch J, Moradi B
J Clin Med 2019
Neutrophil heterogeneity as therapeutic opportunity in immune-mediated disease
Grieshaber-Bouyer R, Nigrovic PA
Front Immunol 2019
2018
Maestro endothelium conducts the neutrophils
Grieshaber-Bouyer R, Nigrovic PA
Blood 2018
2017
CD177 modulates human neutrophil migration through activation-mediated integrin and chemoreceptor regulation
Bai M*, Grieshaber-Bouyer R*, Wang JX, Schmider AB, Wilson ZS, Zeng L, Halyabar O, Godin MD, Nguyen HN, Levescot A, Cunin P, Lefort CT, Soberman RJ, Nigrovic PA
Blood 2017
Arthroscopic Repair of Recurrent Posterior Shoulder Subluxation after Total Shoulder Arthroplasty
Grieshaber-Bouyer R#, Gerber C
JBJS Case Connect 2017
In The News
Ein Rheumawirkstoff aus der Krebsmedizin
FAZ, May 16, 2024
Mit T-Zell-Engagern gegen Rheuma
Tagesschau, May 13, 2024
How a “date” between immune cells makes rheumatism disappear
Bionity, May 06, 2024
Artrite reumatoide, l’impiego di anticorpi monoclonali rivoluziona la terapia dei casi gravi
insalute news, May 02, 2024
FAU team develops new approach for treating autoimmune diseases
Friedrich-Alexander-Universität Erlangen-Nürnberg, May 02, 2024
Clinical report: Academic trials signal autoimmune opportunities for T cell engagers
BioCentury, May 01, 2024
Rheuma: T- trifft B-Zelle
MT im Dialog, April 30, 2024
Wie ein „Date“ von Immunzellen Rheuma verschwinden lässt
Informationsdienst Wissenschaft e.V., April 26, 2024
Rheuma schon vor dem Ausbruch verhindern?
Tagesschau, March 12, 2024
Studie: Rheuma kann schon vor dem Ausbruch verhindert werden
Bayerischer Rundfunk, March 05, 2024
Central inflammation system discovered
MSN news, January 31, 2024
Super code cracked: Central inflammation system discovered
Friedrich-Alexander-Universität Erlangen-Nürnberg, January 31, 2024
Neu an der Uni: Prof. Dr. med. Ricardo Grieshaber-Bouyer
Friedrich-Alexander-Universität Erlangen-Nürnberg, October 01, 2023
Personalized Treatment Recommendations for Spondyloarthropathies
Centers for Personalized Medicine (ZPM), 2022
Tracking neutrophil development along a continuous spectrum with single cell analysis
10X Genomics, July 23, 2021
INNATE IMMUNITY IN THE FOCUS OF HEIDELBERG’s RHEUMATOLOGY
Research Award by the German Society for Rheumatology (DGRh)
Heidelberg University Hospital, October 19, 2020
Research Support
We are deeply grateful to all our funders for enabling our research, in particular the Deutsche Forschungsgemeinschaft, the Else Kröner-Fresenius Stiftung and the Interdisciplinary Center for Clinical Research (IZKF) Erlangen.
Teaching
We are integrated in the Medical curriculum, IZKF scientist training programs and the iImmune Integrated Immunology M.Sc. programme @FAU Erlangen-Nürnberg.
Directions
Erlangen:
Professorship for Clinical Systems Immunology
Glückstraße 4A
91054 Erlangen
Heidelberg:
Institute for Immunology
Im Neuenheimer Feld 305
69120 Heidelberg
Data processing policy (Datenschutzerklärung)
Imprint (Impressum)