Marc Ringelhan
- Liver Disease Diagnosis and Treatment
- Hepatitis B Virus Studies
- Liver physiology and pathology
- Hepatitis C virus research
- Endoplasmic Reticulum Stress and Disease
- Cancer Mechanisms and Therapy
- Immune Response and Inflammation
- Immune Cell Function and Interaction
- Immune cells in cancer
- Pediatric Hepatobiliary Diseases and Treatments
- Pancreatic function and diabetes
- Lipid metabolism and biosynthesis
- Immunotherapy and Immune Responses
- HIV Research and Treatment
- Liver Diseases and Immunity
- NF-κB Signaling Pathways
- interferon and immune responses
- Microtubule and mitosis dynamics
- Gallbladder and Bile Duct Disorders
- Hepatitis Viruses Studies and Epidemiology
- Cancer Immunotherapy and Biomarkers
- PI3K/AKT/mTOR signaling in cancer
- Cancer Cells and Metastasis
- Drug-Induced Hepatotoxicity and Protection
- Organ Transplantation Techniques and Outcomes
Technical University of Munich
2015-2025
Klinikum rechts der Isar
2015-2024
German Center for Infection Research
2014-2024
Helmholtz Zentrum München
2013-2023
Karolinska Institutet
2022
German Cancer Research Center
2016-2020
Heidelberg University
2016-2020
DKFZ-ZMBH Alliance
2020
LMU Klinikum
2017-2018
München Klinik
2018
Abstract Hepatocellular carcinoma (HCC) can have viral or non-viral causes 1–5 . Non-alcoholic steatohepatitis (NASH) is an important driver of HCC. Immunotherapy has been approved for treating HCC, but biomarker-based stratification patients optimal response to therapy unmet need 6,7 Here we report the progressive accumulation exhausted, unconventionally activated CD8 + PD1 T cells in NASH-affected livers. In preclinical models NASH-induced therapeutic immunotherapy targeted at programmed...
X-linked inhibitor of apoptosis protein (XIAP) has been identified as a potent regulator innate immune responses, and loss-of-function mutations in XIAP cause the development lymphoproliferative syndrome type 2 (XLP-2) humans. Using gene-targeted mice, we show that loss or deletion its RING domain lead to excessive cell death IL-1β secretion from dendritic cells triggered by diverse Toll-like receptor stimuli. Aberrant is TNF dependent requires RIP3 but independent cIAP1/cIAP2. The observed...
Mouse transgenesis has provided fundamental insights into pancreatic cancer, but is limited by the long duration of allele/model generation. Here we show transfection-based multiplexed delivery CRISPR/Cas9 to pancreas adult mice, allowing simultaneous editing multiple gene sets in individual cells. We use method induce cancer and exploit mutational signatures for phylogenetic tracking metastatic disease. Our results demonstrate that CRISPR/Cas9-multiplexing enables key applications, such as...
Alternatively polarized macrophages (Mϕ) shape the microenvironment of hepatocellular carcinoma (HCC) and temper anticancer immune responses. We investigated if sorafenib alters HCC by restoring classical macrophage polarization triggering tumor-directed natural killer (NK) cell In vivo experiments were conducted with (25 mg/kg)-treated C57BL/6 wildtype as well hepatitis B virus (HBV) lymphotoxin transgenic mice without HCC. Monocyte-derived Mϕ or tumor-associated (TAM) isolated from tissue...
Ductular reactions (DRs) are observed in virtually all forms of human liver disease; however, the histogenesis and function DRs injury not entirely understood. It is widely believed that contain bipotential progenitor cells (LPCs) serve as an emergency cell pool to regenerate both cholangiocytes hepatocytes may eventually give rise hepatocellular carcinoma (HCC). Here, we used a murine model allows highly efficient specific lineage labeling biliary compartment analyze their potential...
Abstract Hepatitis B virus (HBV) is a major global health concern, and the development of curative therapeutics urgently needed. Such efforts are impeded by lack physiologically relevant, pre-clinical animal model HBV infection. Here, we report that expression entry receptor, human sodium-taurocholate cotransporting polypeptide (hNTCP), on macaque primary hepatocytes facilitates infection in vitro, where all replicative intermediates including covalently closed circular DNA (cccDNA) present....
Article9 May 2021Open Access Source Data Interferon-induced degradation of the persistent hepatitis B virus cccDNA form depends on ISG20 Daniela Stadler orcid.org/0000-0002-7342-9751 Institute Virology, School Medicine, Technical University Munich / Helmholtz Zentrum München, Munich, Germany Search for more papers by this author Martin Kächele GermanyThese authors contributed equally to work Alisha N Jones Structural Biology, Neuherberg, Center Integrated Protein Science and Bavarian NMR at...
Chronic hepatitis B virus (HBV) infection remains the most common risk factor for hepatocellular carcinoma (HCC). Efficient suppression of HBV viremia and necroinflammation as a result nucleos(t)ide analogue treatment is able to reduce HCC incidence; nevertheless, hepatocarcinogenesis can occur in absence active hepatitis, correlating with high surface antigen (HBsAg) levels. Nuclear κB (NF‐κB) central player chronic inflammation development. However, severe inflammation, role NF‐κB...
Abstract Dynamic polarisation of tumour cells is essential for metastasis. While the role during dedifferentiation and migration well established, metastasising phases detachment has not been investigated. Here we identify characterise a type maintained by single in liquid phase termed single-cell (sc) polarity investigate its We demonstrate that sc an inherent feature from different entities observed circulating patients. Functionally, propose pole directly involved early attachment,...
Hepatic steatosis is characterized by intrahepatic lipid accumulation and may lead to irreversible liver damage if untreated. Here, we investigate whether multispectral optoacoustic tomography (MSOT) can offer label-free detection of content enable non-invasive characterization hepatic analyzing the spectral region around 930 nm, where lipids characteristically absorb. In a pilot study, apply MSOT measure surrounding tissues in five patients with healthy volunteers, revealing significantly...
The human hepatitis B virus (HBV) is a major cause of chronic and hepatocellular carcinoma, but molecular mechanisms driving liver disease carcinogenesis are largely unknown. We therefore studied cellular pathways altered by HBV infection.We performed gene expression profiling primary hepatocytes infected with proved the results in HBV-replicating cell lines tissue using real-time polymerase chain reaction Western blotting. Activation signal transducer activator transcription (STAT3) was...
Although most hepatocellular carcinoma (HCC) cases are driven by hepatitis and cirrhosis, a subset of patients with chronic B develop HCC in the absence advanced liver disease, indicating oncogenic potential virus (HBV). We investigated role HBV transcripts proteins on development inflammation HBV-transgenic mice.
Tumor immune escape is a critical problem which frequently accounts for the failure of therapeutic tumor vaccines. Among most potent suppressors immunity are myeloid derived suppressor cells (MDSCs). MDSCs can be targeted by all-trans-retinoic-acid (atRA), reduced their numbers and increased response rates in several vaccination studies. However, not much known about optimal administration interval between atRA vaccine as well its mode action.Here we demonstrate 2 different murine models...
•LCMV infection activates NF-κB signaling in hepatocytes.•Macrophages, TNFR1 do not induce LCMV-driven hepatocyte NF-κB-activation.•IkkβΔHep mice display increased viral infection/replication and lower ISG induction.•IfnarΔHep recapitulate aberrant virus replication as observed IkkβΔHep mice.•NF-κB is required for efficient induction HBV-/HDV-infected HepaRG. Background & AimsHepatic innate immune control of infections has largely been attributed to Kupffer cells, the liver-resident...