A5036369388- Inflammasome and immune disorders
- interferon and immune responses
- Immune Response and Inflammation
- Cell death mechanisms and regulation
- Immune cells in cancer
- Cytokine Signaling Pathways and Interactions
- Phagocytosis and Immune Regulation
- Heme Oxygenase-1 and Carbon Monoxide
- RNA and protein synthesis mechanisms
- Endoplasmic Reticulum Stress and Disease
- Erythrocyte Function and Pathophysiology
- CRISPR and Genetic Engineering
- Herpesvirus Infections and Treatments
- Plant Virus Research Studies
- Immune Cell Function and Interaction
- Gout, Hyperuricemia, Uric Acid
- RNA regulation and disease
- Immunodeficiency and Autoimmune Disorders
- Plant-Microbe Interactions and Immunity
- NF-κB Signaling Pathways
- Transgenic Plants and Applications
- Sphingolipid Metabolism and Signaling
- ATP Synthase and ATPases Research
- Vibrio bacteria research studies
- RNA Research and Splicing
Research Institute of Molecular Pathology
2022-2024
Ludwig-Maximilians-Universität München
2016-2022
University of California, Berkeley
2019-2021
Howard Hughes Medical Institute
2020
LMU Klinikum
2018
University Hospital Bonn
2014-2016
University of Bonn
2012-2015
Inflammasome activation culminates in of caspase‐1, which leads to the maturation and subsequent release cytokines interleukin 1 (IL‐1) family results a particular form cell death known as pyroptosis. In addition, murine system, so‐called non‐canonical inflammasome involving caspase‐11 has been described that directly responds cytosolic LPS. Here, we show human monocytic line THP1 activates response LPS TLR4‐independent fashion. This is mediated by caspase‐4 accompanied caspase‐1 activation,...
TLR8 is among the highest-expressed pattern-recognition receptors in human myeloid compartment, yet its mode of action poorly understood. engages two distinct ligand binding sites to sense RNA degradation products, although it remains unclear how these ligands are formed cellulo context complex molecule sensing. Here, we identified lysosomal endoribonuclease RNase T2 as a non-redundant upstream component TLR8-dependent recognition. activity required for rendering single-stranded, exogenous...
Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) is a critical regulator of cell death and inflammation, but its relevance for human disease pathogenesis remains elusive. Studies monogenic disorders might provide insights into mechanisms therapeutic targeting RIPK1 common diseases. Here, we report on eight patients from six unrelated pedigrees with biallelic loss-of-function mutations in presenting primary immunodeficiency and/or intestinal inflammation. Mutations were...
The application of designer nucleases allows the induction DNA double-strand breaks (DSBs) at user-defined genomic loci. Due to imperfect repair mechanisms, DSBs can lead alterations in architecture, such as disruption reading frame a critical exon. This be exploited generate somatic knockout cell lines. While high genome editing activities achieved various cellular systems, obtaining clones that contain all-allelic frameshift mutations target locus interest remains laborious task. To this...
IL-1β is a cytokine of pivotal importance to the orchestration inflammatory responses. Synthesized as an inactive pro-cytokine, requires proteolytic maturation gain biological activity. Here, we identify intrinsic apoptosis non-canonical trigger maturation. Guided by discovery immunomodulatory activity vioprolides, cyclic peptides isolated from myxobacteria, observe independent canonical inflammasome pathways, yet dependent on apoptosis. Mechanistically, vioprolides inhibit MCL-1 and BCL2,...
Type I interferons (IFNs) are essential for anti-viral immunity, but often impair protective immune responses during bacterial infections. An important question is how type IFNs strongly induced viral infections, and yet appropriately restrained The Super susceptibility to tuberculosis 1 (Sst1) locus in mice confers resistance diverse Here we provide evidence that Sp140 a gene encoded within the Sst1 represses IFN transcription We generated Sp140-/- found they susceptible infection by...
Effector-triggered immunity (ETI) is a form of pathogen sensing that involves detection pathogen-encoded virulence factors or 'effectors'. To discover novel ETI pathways in mammals, we developed screening approach which individual are expressed human monocytes and transcriptional responses assessed by RNA-seq. Using this approach, identify poxvirus effector, myxoma virus M3.1, elicits an anti-viral NF-κB response. We find unleashed pathway senses M3.1 attack two complexes: ZAP TBK1....
Necroptosis is a form of regulated cell death that can occur downstream several immune pathways. While previous studies have shown dysregulated necroptosis lead to strong inflammatory responses, little known about the identity endogenous molecules trigger these responses. Using reductionist in vitro model, we found soluble TNF strongly released context necroptosis. On one hand, promotes translation by inhibiting negative regulatory mechanisms acting at post-transcriptional level. other...
ABSTRACT The NLRP3 inflammasome plays a central role in antimicrobial defense, as well sterile inflammatory conditions. activity is governed by two independent signals. first signal primes NLRP3, allowing it to respond its activation signal. In the murine system, mitotic spindle kinase NEK7 has been identified crucial factor relaying NLRP3. Here we show that requirement for can be bypassed TAK1-dependent post-translational priming. Under pro-inflammatory conditions activate TAK1, was...
The peroxisomal proliferator-activated receptor γ (PPARγ) is a nuclear that controls inflammation and immunity. Innate immune defense against bacterial infection appears to be compromised by PPARγ. relevance of PPARγ in myeloid cells, organize anti-bacterial immunity, for the outcome responses intracellular bacteria such as Listeria monocytogenes vivo unknown. We found macrophages rapidly led increased expression This prompted us investigate whether cells influences innate immunity using...
TNF is a highly pro-inflammatory cytokine that contributes not only to the regulation of immune responses but also development severe inflammatory diseases. synthesized as transmembrane protein, which further matured via proteolytic cleavage by metalloproteases such ADAM17, process known shedding. At present, mainly detected measuring precursor or mature bulk cell populations techniques ELISA immunoblotting. However, these methods do provide information on exact timing and extent at...
Abstract Type I interferons (IFN-Is) are essential for antiviral immunity but must be tightly regulated 1–3 . The conserved transcriptional repressor SP140 inhibits interferon beta ( Ifnb1 ) expression via an unknown mechanism 4,5 Here we report that does not directly repress transcription. Instead, negatively regulates mRNA stability by repressing the of a previously uncharacterized regulator call RESIST (REgulated Stimulator Interferon Stabilization Transcript, annotated as Annexin-2...