- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- IL-33, ST2, and ILC Pathways
- CAR-T cell therapy research
- Myasthenia Gravis and Thymoma
- Computational Drug Discovery Methods
- Bioinformatics and Genomic Networks
- Eosinophilic Disorders and Syndromes
- Congenital heart defects research
- Sphingolipid Metabolism and Signaling
- Cancer, Hypoxia, and Metabolism
- Microbial Metabolic Engineering and Bioproduction
- Ubiquitin and proteasome pathways
- Balance, Gait, and Falls Prevention
- Autoimmune and Inflammatory Disorders Research
- interferon and immune responses
- Peripheral Neuropathies and Disorders
- Cytomegalovirus and herpesvirus research
- Cytokine Signaling Pathways and Interactions
- Polyomavirus and related diseases
- Liver physiology and pathology
- Gene expression and cancer classification
- Cancer Research and Treatments
- Radiopharmaceutical Chemistry and Applications
- Multiple Myeloma Research and Treatments
Reaction Biology (Germany)
2024-2025
Institute of Medical Microbiology and Hygiene
2017-2024
University of Freiburg
2019-2024
University of Konstanz
2024
University Medical Center Freiburg
2017
University of Würzburg
2015
Maastricht University
2010-2014
Bortezomib is a potent inhibitor of proteasomes currently used to eliminate malignant plasma cells in multiple myeloma patients. It also effective depleting both alloreactive acute Ab-mediated transplant rejection and their autoreactive counterparts animal models lupus myasthenia gravis (MG). In this study, we demonstrate that bortezomib at 10 nM or higher concentrations killed long-lived cultured thymus from nine early-onset MG patients consistently halted spontaneous production not only...
The T-box transcription factors T-bet and Eomesodermin regulate type 1 immune responses in innate adaptive lymphocytes. is widely expressed the system but was initially identified as lineage-specifying factor of Th1 CD4 + T cells, where it governs expression signature cytokine IFN- γ represses alternative cell fates like Th2 Th17. T-bet’s paralog Eomes less abundantly cells are mostly found context persistent antigen exposure, bone marrow transplantation, chronic infection or inflammation...
Abstract Mitochondria react to infection with sub-lethal signals in the apoptosis pathway. Mitochondrial can be inflammatory but mechanisms are only partially understood. We show that activation of caspase-activated DNase (CAD) mediates mitochondrial pro-inflammatory functions and substantially contributes host defense against viral infection. In cells lacking CAD, activity was reduced. Experimental CAD caused transient DNA-damage a pronounced DNA damage response, involving major kinase...
Though mostly defective, human endogenous retroviruses (HERV) can retain open reading frames, which are especially expressed in the placenta. There, envelope (env) proteins of HERV-W (Syncytin-1), HERV-FRD (Syncytin-2), and HERV-K (HML-2) were implicated tolerance against semi-allogenic fetus. Here, we show that known HERV env-binding receptors ASCT-1 -2 MFSD2 by DCs T-cells. When used as effectors coculture systems, CHO cells transfected to express Syncytin-1, -2, or HML-2 did not affect...
Abstract The clinical potential of therapies on tumor metastases can be specifically tested that have naturally developed through the migration cells from primary tumor. Removing allows for a clearer assessment substance’s efficacy in targeting metastatic sites alone, free influence If is still present during treatment, it difficult to determine whether reduction spread due anti-metastatic effect treatment or merely reduced growth tumor, which could indirectly limit progression metastases....
Abstract Immune-mediated nephritis is a leading cause of acute kidney injury and chronic disease. While the role B cells antibodies has been extensively investigated in past, advent immune-checkpoint inhibitors led to reappraisal T renal immunology. However, it remains elusive how with specificity for autoantigens are activated participate immune-mediated nephritis. Here, we followed fate function pathogen-activated autoreactive CD8 that specific autoantigen. We demonstrate recently splenic...
Natural intraepithelial lymphocytes (IELs) are thymus-derived adaptive immune cells, which important contributors to intestinal homeostasis. Similar other innate-like T they induced in the thymus through high-avidity interaction that would otherwise lead clonal deletion conventional CD4 and CD8 cells. By applying single-cell RNA-sequencing (scRNA-seq) on a heterogeneous population of thymic CD4-CD8αβ-TCRαβ+NK1.1- IEL precursors (NK1.1- IELPs), we define developmental trajectory can be...
The two T-box transcription factors T-bet and Eomesodermin (Eomes) are important regulators of cytotoxic lymphocytes (CTLs), such as activated CD8 T cells, which essential in the fight against intracellular pathogens tumors. Both share a great degree homology based on sequence analysis result exert partial functional redundancy during viral infection. However, actual between Eomes remains matter debate is further confounded by their distinct spatiotemporal expression pattern cells. To...
The T-box transcription factor Eomes (also known as Tbr2) shows short-lived expression in various localized domains of the embryo, including epiblast cells during gastrulation and intermediate progenitor cerebral cortex. In these tissues fulfills crucial roles for lineage specification progenitors. To directly observe Eomes-dependent cell lineages living we generated a novel dual-fluorescence reporter allele that expresses membrane-bound tdTomato protein investigation morphology nuclear GFP...
Development of T cells is controlled by the signal strength TCR. The scaffold protein kinase D-interacting substrate 220 kilodalton (Kidins220) binds to TCR; however, its role in cell development was unknown. Here, we show that cell-specific Kidins220 knockout (T-KO) mice have strongly reduced invariant natural killer (iNKT) numbers and modest decreases conventional cells. Enhanced apoptosis due increased TCR signaling T-KO iNKT thymocytes developmental stages 2 3 shows down-regulates at...
Abstract The recent advances in cellular immunotherapies have revolutionized the treatment options for hematological malignancies. Among others, genetically engineered T cells to express chimeric antigen receptors targeting CD19 shown clinical success patients with B cell However, depending on study design only one two thirds of experience a complete response upon CAR treatment. Antigen escape, immune suppressive microenvironment, dysfunction as well lack persistence been discussed be...
Abstract Within the last decade, major technological advances in flow cytometry and (single cell) RNA-sequencing have deepened our understanding of complex anti-tumoral immune responses. This allows a comprehensive monitoring novel therapies pre-clinical models. Conventional is reaching its technical limitation. The emitted fluorescence signal target population stained with antibodies evaluated simple bandpass filters, which leads to spectral overlap thus number parameters that can be...
Abstract Background BK polyoma virus (BKPyV) associated nephropathy (BKPyVAN) is a major cause of kidney graft loss in renal transplant patients. Interferons (IFNs) are an important innate immune response against viral infections and genetic polymorphisms the IFN‐pathways can affect susceptibility mortality during infection. Here, we investigated whether dinucleotide polymorphism rs368234815 (ΔG/TT) IFNL4 gene contributed to BKPyV reactivation or BKPyVAN after living‐donor transplantation....
Abstract In the autoimmune disease myasthenia gravis (MG), autoantibodies against muscle AChR are mainly produced by both short- and long-lived plasma cells, which resistant to standard immunosuppressive drugs (i.e. glucocorticoids). A novel therapy eliminate cells is proteasome inhibitor bortezomib, used treat patients with multiple myeloma (MM, a cell malignancy). Previously, we demonstrated that bortezomib also reduced autoantibody titers in an animal model of MG (Gomez, A. M. J. Immunol....
Abstract Current high-throughput technology in genomics creates a large amount of biological data. Bioinformatics approaches are directed towards understanding such data on systems biology level. Advanced mathematical methods like principal component analysis, clustering, neural networks, support vector machine (SVM) and networks can help to find patterns the However, really understand must be combined with existing knowledge. One do so is associate these functional classifications as found...
Current high-throughput technology in genomics creates a large amount of biological data. Bioinformatics approaches are directed towards understanding such data on systems biology level. Advanced mathematical methods like principal component analysis, clustering, neural networks, support vector machine (SVM) and networks can help to find patterns the However, really understand must be combined with existing knowledge. One do so is associate these functional classifications as found Gene...
Abstract The stepwise development of thymic invariant natural killer T (iNKT) cells is controlled by the TCR signal strength. scaffold protein Kinase D interacting substrate 220 kDa (Kidins220) binds to regulating signaling. cell-specific Kidins220 knock-out (T-KO) mice contain severely decreased iNKT numbers. Very early in signals are reduced T-KO. In later steps, signaling increased T-KO leading enhanced apoptosis cells. Kidins220’s absence affects iNKT1 subset most as it requires weakest...
The stepwise development of thymic invariant natural killer T (iNKT) cells is controlled by the TCR signal strength. scaffold protein Kinase D interacting substrate 220 kDa (Kidins220) binds to regulating signaling. cell-specific Kidins220 knock-out (T-KO) mice contain severely decreased iNKT numbers. Very early in signals are reduced T-KO. In later steps, signaling increased T-KO leading enhanced apoptosis cells. Kidins220’s absence affects iNKT1 subset most as it requires weakest for...