A5047932077- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Heat shock proteins research
- Immunotherapy and Immune Responses
- Immune Response and Inflammation
- Chronic Kidney Disease and Diabetes
- Endoplasmic Reticulum Stress and Disease
- Glycosylation and Glycoproteins Research
- Mitochondrial Function and Pathology
- Renal and related cancers
- Reproductive System and Pregnancy
- Renal Diseases and Glomerulopathies
- RNA Research and Splicing
- Gene Regulatory Network Analysis
- Receptor Mechanisms and Signaling
- Computational Drug Discovery Methods
- Protein purification and stability
- S100 Proteins and Annexins
- Enzyme Structure and Function
- Multiple Sclerosis Research Studies
- Dialysis and Renal Disease Management
- Ubiquitin and proteasome pathways
- Metabolism and Genetic Disorders
- IL-33, ST2, and ILC Pathways
- Signaling Pathways in Disease
Otto-von-Guericke University Magdeburg
2015-2024
University Clinic for Nephrology and Hypertension, Diabetology and Endocrinology
2022
Diabetes Australia
2015-2016
University Hospital Magdeburg
2006-2009
Klinikum Magdeburg
2009
Institute of Immunology
2006
University of Cambridge
2000
Heidelberg University
1998
German Cancer Research Center
1998
Oregon State University
1994-1996
Abstract Background Structural analysis of cellular interaction networks contributes to a deeper understanding network-wide interdependencies, causal relationships, and basic functional capabilities. While the structural metabolic is well-established field, similar methodologies have been scarcely developed applied signaling regulatory networks. Results We propose formalisms methods, relying on adapted partially newly introduced approaches, which facilitate with focus aspects. use two...
Cellular decisions are determined by complex molecular interaction networks. Large-scale signaling networks currently being reconstructed, but the kinetic parameters and quantitative data that would allow for dynamic modeling still scarce. Therefore, computational studies based upon structure of these great interest. Here, a methodology relying on logical formalism is applied to functional analysis network governing activation T cells via cell receptor, CD4/CD8 co-receptors, accessory...
Opioids are widely used for the treatment of severe pain. However, it is also known that opioids, in particular morphine, cause immunosuppression. Therefore, their use may complicate persons with an already impaired immune system, e.g., patients suffering from cancer or AIDS. We investigated mechanisms opioid-induced immunosuppression primary human T lymphocytes and cell line Jurkat. demonstrated morphine endogenous opioid beta-endorphin inhibited transcription IL-2 activated as well...
Ischemia-reperfusion injury (IRI) is the leading cause of ARF. A pathophysiologic role coagulation system in renal IRI has been established, but functional relevance thrombomodulin (TM)-dependent activated protein C (aPC) generation and intracellular targets aPC remain undefined. Here, we investigated TM-dependent therapeutic application a murine model an vitro hypoxia reoxygenation (HR) using proximal tubular cells. In IRI, endogenous levels were reduced. Genetic or reconstitution...
T cell activation involves the conformational of tyrosine kinase Lck.
Established therapies for diabetic nephropathy (dNP) delay but do not prevent its progression. The shortage of established may reflect the inability to target tubular compartment. chemical chaperone tauroursodeoxycholic acid (TUDCA) ameliorates maladaptive endoplasmic reticulum (ER) stress signaling and experimental dNP. Additionally, TUDCA activates farnesoid X receptor (FXR), which is highly expressed in cells. We hypothesized that ER via FXR agonism specifically Indeed, induced expression...
Transmembrane adapter proteins are a class of molecules that mediate signals from an extracellular receptor to the cytoplasm cell. We have cloned novel transmembrane protein called KAP10, approximately 10-kDa is encoded within 100 bp DAP12 locus on human chromosome 19. KAP10 predominantly expressed in immune cells, including NK T and monocytes. show unlike other proteins, binds phosphatidylinositol-3 kinase following phosphorylation cytoplasmic YINM motif, which results activation Akt. In...
Abstract In naive T cells, engagement of the TCR with agonist peptide:MHC molecules leads to phosphorylation key intracellular signaling intermediates within seconds and this peaks minutes. However, cell does not commit proliferation IL-2 cytokine production unless receptor contact is sustained for several hours. The biochemical basis transition full activation may underlie how cells receive survival signals while maintaining tolerance, currently well understood. We show here that CD8...
Abstract Brain inflammation is accompanied by transection of axons and death neurons in the acute lesions multiple sclerosis. We explored mechanisms inflammatory damage to vitro using cocultures rat embryonal cortical with microglia activated interferon‐gamma (IFNγ) lipopolysaccharide (LPS). Previously, we have demonstrated that are highly toxic nitric oxide (NO) derived from inducible synthase (iNOS) necessary sufficient mediate this toxicity. Here, show addition dexamethasone (1 µM)...
SPECIFIC AIMSIn this study, we investigated the role of ER60 (ERp57/GRP58) in formation disulfide bonds within major histocompatibility (MHC) class I heavy chain. We also examined calnexin recruiting into early folding complexes with nascent chain (HC).PRINCIPAL FINDINGS1. ER60/ERp57 forms disulfide-bonded intermediates chainMouse EL4 cells were metabolically labeled for 15 min [35S] cysteine/methionine. After labeling, washed PBS containing N-ethyl-maleimide (NEM), a membrane-permeable...
Abstract Background The Y-box protein-1 (YB-1) fulfills pleiotropic functions relating to gene transcription, mRNA processing, and translation. It remains elusive how YB-1 shuttling into the nuclear cytoplasmic compartments is regulated whether limited proteolysis by 20S proteasome releases fragments with distinct function(s) subcellular distribution(s). Results To address these questions, mapping of domains responsible for targeting was performed. Three localization signals (NLS) were...
Antigenic stimulation of the T cell receptor (TCR) initiates a change from resting state into an activated one, which ultimately results in proliferation and acquisition effector functions. To accomplish this task, cells require dramatic changes metabolism. Therefore, we investigated metabolic intermediates indicating for crucial pathways reflecting status cells. Moreover analyzed possible regulatory molecules required initiation changes. We found that inducing conditions result increase key...
TAPASIN, a V-C1 (variable-constant) immunoglobulin superfamily (IgSF) molecule that links MHC class I molecules to the transporter associated with antigen processing (TAP) in endoplasmic reticulum (ER) is encoded by TAPBP gene, located near at 6p21.3. A related gene was identified chromosome position 12p13.3 between CD27 and VAMP1 genes group of MHC-paralogous loci. The which we have called TAPBP-R (R for related), also encodes member IgSF, TAPASIN-R. Its putative product contains similar...
Background: In multiple sclerosis inflammation is primarily injurious to the central nervous system, but its therapeutic suppression might inhibit repair-promoting factors. Objectives: We aimed at better describing complexity of biological effects during an acute relapse and analysed intervention with high-dose i.v. glucocorticoids immunomodulatory treatment interferon-beta (IFNβ). Methods: studied intracellular expression levels pro-inflammatory mediators tumour necrosis factor alpha (TNFα)...
CD95 is a multifunctional receptor that induces cell death or proliferation depending on the signal, type, and cellular context. Here, we describe thus far unknown function of as silencer T activation. Naive human cells triggered by antigen-presenting expressing membrane-bound form ligand (CD95L) stimulated anti-CD3 -CD28 antibodies in presence recombinant CD95L had reduced activation proliferation, whereas preactivated, CD95-sensitive underwent apoptosis. Triggering during priming...
Abstract Background Signaling through the TCR is crucial for generation of different cellular responses including proliferation, differentiation, and apoptosis. A growing body evidence indicates that differences in magnitude duration signal are critical determinants eliciting responses. Results Here, we have analyzed signaling dynamics correlating with either unresponsiveness or proliferation induced upon TCR/CD28 ligation primary human T cells. We used two widely employed methods to...
Abstract Background Expression of the cold shock protein Y-box 1 (YB-1) is associated with deleterious outcome in various malignant diseases. Our group recently showed that detection an 18 kDa YB-1 fragment (YB-1/p18) human plasma identifies patients We now tested prevalence, clinical, and diagnostic value YB-1/p18 common tumors. Methods A newly established monoclonal antibody was used to detect by immunoblotting samples from 151 unselected tumor patients, alongside markers measures, during...