A5031329695- Calcium signaling and nucleotide metabolism
- PARP inhibition in cancer therapy
- Adenosine and Purinergic Signaling
- Toxin Mechanisms and Immunotoxins
- Monoclonal and Polyclonal Antibodies Research
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- Glycosylation and Glycoproteins Research
- Diabetes and associated disorders
- SARS-CoV-2 and COVID-19 Research
- Liver Diseases and Immunity
- Adolescent and Pediatric Healthcare
- CAR-T cell therapy research
- COVID-19 Clinical Research Studies
- Multiple Myeloma Research and Treatments
- Cytomegalovirus and herpesvirus research
- RNA Research and Splicing
- Chronic Lymphocytic Leukemia Research
- Peptidase Inhibition and Analysis
- Pancreatic function and diabetes
- Hepatitis Viruses Studies and Epidemiology
- Neuroscience of respiration and sleep
- Long-Term Effects of COVID-19
- Neutropenia and Cancer Infections
University Medical Center Hamburg-Eppendorf
2015-2024
Universität Hamburg
2015-2024
Institute of Immunology
2002-2024
University Medical Center
2010-2015
Leibniz Institute of Virology (LIV)
2010
Massachusetts General Hospital
2008
MSH Medical School Hamburg – University of Applied Sciences and Medical University
2008
Harvard University
2008
Inserm
2007
Délégation Paris 7
2006
HIV targets CD4 T cells, which are required for the induction of high-affinity antibody responses and formation long-lived B cell memory. The depletion antigen-specific cells during infection is therefore believed to impede development protective immunity. Although several different HIV-related dysfunctions have been described, role follicular helper (TFH) in remains unknown. Here, we assessed HIV-specific TFH lymph nodes treatment-naive antiretroviral-treated HIV-infected individuals....
Abstract Background ADP-ribosylation is an enzyme-catalyzed posttranslational protein modification in which mono(ADP-ribosyl)transferases (mARTs) and poly(ADP-ribosyl)transferases (pARTs) transfer the ADP-ribose moiety from NAD onto specific amino acid side chains and/or units on target proteins. Results Using a combination of database search tools we identified genes encoding recognizable pART domains public genome databases. In humans, family encompasses 17 members. For 16 these genes,...
Abstract The P2X7 receptor (P2X7R) is an ATP-gated channel that mediates apoptosis of cells the immune system. capacity P2X7R to form large pores depends on its cytoplasmic tail, which harbors a putative TNFR-related death domain. Previous transfection studies indicated mouse forms much less efficiently than counterparts from humans and rats. In this study, we demonstrate allelic mutation (P451L) in predicted domain confers drastically reduced sensitivity ATP-induced pore formation some...
CD4+CD25+FoxP3+ regulatory T cells (T reg cells) play a major role in the control of immune responses but factors controlling their homeostasis and function remain poorly characterized. Nicotinamide adenine dinucleotide (NAD+) released during cell damage or inflammation results ART2.2–mediated ADP-ribosylation cytolytic P2X7 receptor on cells. We show that express ART2.2 enzyme high levels can be depleted by intravenous injection NAD+. Moreover, lower numbers are found mice deficient for...
Extracellular NAD and ATP exert multiple, partially overlapping effects on immune cells. Catabolism of both nucleotides by extracellular enzymes keeps concentrations low under steady-state conditions generates metabolites that are themselves signal transducers. its through purinergic P2 P1 receptors, whereas exerts serving as a substrate for ADP-ribosyltransferases (ARTs) glycohydrolases/ADPR cyclases like CD38 CD157. Both activate the P2X7 purinoceptor, although different mechanisms with...
In mammalian cells, DNA double-strand breaks (DSBs) are repaired by three pathways, nonhomologous end-joining (NHEJ), gene conversion (GC) and single-strand annealing (SSA). These pathways distinct with regard to repair efficiency mutagenic potential must be tightly controlled preserve viability genomic stability. Here, we employed chromosomal reporter constructs characterize the hierarchy of NHEJ, GC SSA at a single I-SceI-induced DSB in Chinese hamster ovary cells. We discovered that use...
Ion channels are desirable therapeutic targets, yet ion channel-directed drugs with high selectivity and few side effects still needed. Unlike small-molecule inhibitors, antibodies highly selective for target antigens but mostly fail to antagonize channel functions. Nanobodies-small, single-domain antibody fragments-may overcome these problems. P2X7 is a ligand-gated that, upon sensing adenosine 5'-triphosphate released by damaged cells, initiates proinflammatory signaling cascade, including...
Abstract Mono ADP-ribosyltransferase 2 (ART2) is an ectoenzyme expressed on mouse T lymphocytes, which catalyze the transfer of ADP-ribose groups from NAD+ onto several target proteins. In vitro, ADP-ribosylation by ART2 activates P2X7 ATP receptor and responsible for NAD+-induced cell death (NICD). Yet, origin extracellular role NICD in vivo remain elusive. a model acute inflammation induced polyacrylamide beads, we demonstrate release into exudates during early phase inflammatory response....
A limiting factor for the use of adeno-associated viruses (AAVs) as vectors in gene therapy is broad tropism AAV serotypes, i.e., parallel infection several cell types. Nanobodies are single immunoglobulin variable domains from heavy chain antibodies that naturally occur camelids. Their small size and high solubility allow easy reformatting into fusion proteins. Herein we show a membrane protein-specific nanobody can be inserted surface loop VP1 capsid protein AAV2. Using three structurally...
Background Leukemia-associated macrophages (LAMs) represent an important cell population within the tumor microenvironment, but little is known about phenotype, function, and plasticity of these cells. The present study provides extensive characterization in patients with acute myeloid leukemia (AML). Methods phenotype expression coregulatory markers were assessed on bone marrow (BM)-derived LAM populations, using multiparametric flow cytometry. BM blood aspirates obtained from newly...
Abstract ADP‐ribosyltransferases including toxins secreted by Vibrio cholera, Pseudomonas aerurginosa , and other pathogenic bacteria inactivate the function of human target proteins attaching ADP‐ribose onto a critical amino acid residue. Cross‐species polymerase chain reaction (PCR) database mining identified orthologs these ADP‐ribosylating in humans mouse. The genome contains four functional toxin‐related ADP‐ribosyltransferase genes ( ARTs ) two related intron‐containing pseudogenes;...
The double-stranded RNA (dsRNA)-dependent protein kinase (PKR) is induced as part of the IFN response in mammals and acts to shut down synthesis by phosphorylation eukaryotic initiation factor 2α (eIF2α). In fish, a PKR-like activity has been detected, but enzyme responsible eluded characterization. Here, we describe from zebrafish. Phylogenetic analysis shows that C-terminal domain more closely related PKR than any other three known eIF2α kinases. Surprisingly, instead two dsRNA binding...
Many sequences in eukaryotic genomes have the potential to adopt a left-handed Z-DNA conformation. We used previously described assay based on binding of mAb inquire whether is formed rat nucleolin (Ncl) gene metabolically active, permeabilized nuclei. Using real-time PCR measure formation, sequence element Z1 [(CA)(10)(CG)(8)] promoter region was found be enriched 571- 4,040-fold different cell lines, whereas Z2 [AC(GC)(5)CCGT(CG)(2)] first intron 12- 34-fold. Ncl activity 1.5- 16-fold...
Mono ADP-ribosylation is a posttranslational protein modification that has been implicated in the regulation of key biological functions bacteria as well animals. Recently, first cDNAs for eucaryotic mono(ADPribosyl)transferases were cloned and found to exhibit significant sequence similarity only one other known protein, T cell differentiation antigen Rt6. In this paper we describe secondary structure analyses Rt6 related proteins show conserved motifs amino acid residues consistent with...
Abstract Extracellular NAD+ and ATP trigger the shedding of CD62L externalization phosphatidylserine on murine T cells. These events depend P2X7 ion channel. Although acts as a soluble ligand to activate P2X7, gating by requires ecto-ADP-ribosyltransferase ART2.2-catalyzed transfer ADP-ribose moiety from onto Arg125 P2X7. Steady-state concentrations in extracellular compartments are highly regulated usually well below threshold required for activating The goal this study was identify...
Cryptorchidism is a common reproductive abnormality, possibly resulting from abnormal hormone production/action by the fetal testis. Insulin-like factor 3 (Insl3) thought to be involved in gubernaculum development and transabdominal testicular descent, but its importance unclear, due partly lack of suitable Insl3 antibodies. We generated (by genetic immunization) validated novel antirat antibody, which we used characterize immunoexpression rat Leydig cells (LCs) life until adulthood...
ADP-ribosylation is a post-translational modification regulating protein function in which amino acid-specific ADP-ribosyltransferases (ARTs) transfer ADP-ribose from NAD onto specific target proteins. Attachment of the bulky usually inactivates by sterically blocking its interaction with other P2X7, an ATP-gated ion channel important roles inflammation and cell death, contrast, activated ADP-ribosylation. Here, we report structural basis for this gating present first molecular model...
The purpose of our study was to develop a tool for blocking the function specific leukocyte ecto-enzyme in vivo. ART2.2 is toxin-related that transfers ADP-ribose moiety from NAD onto other cell surface proteins. induces T death by activating cytolytic P2x7 purinoceptor via ADP-ribosylation. Here, we report generation ART2.2-blocking single domain antibodies an immunized llama. variable heavy-chain (VHH domain) represents smallest known antigen-binding unit generated adaptive immune...
The chemokine receptor CXCR3 is highly expressed on Th1 polarized T cells and has been predicted to play an important role in cell recruitment immune response a number of inflammatory autoimmune diseases. For testing whether plays renal inflammation, CXCR3-deficient mice were generated nephrotoxic nephritis was induced C57BL/6 CXCR3−/− wild-type mice. Induction the leads increased mRNA expression IP-10/CXCL10 (8.6-fold), Mig/CXCL9 (2.3-fold), I-TAC/CXCL11 (4.9-fold) during autologous phase...