A5043723880- Signaling Pathways in Disease
- Drug Transport and Resistance Mechanisms
- Pediatric Hepatobiliary Diseases and Treatments
- Nuclear Receptors and Signaling
- Aldose Reductase and Taurine
- Cancer-related gene regulation
- Liver Disease and Transplantation
- Peptidase Inhibition and Analysis
- Liver Diseases and Immunity
- Hepatitis B Virus Studies
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Liver Disease Diagnosis and Treatment
- Gallbladder and Bile Duct Disorders
- Wnt/β-catenin signaling in development and cancer
- Calpain Protease Function and Regulation
- Liver physiology and pathology
- Cancer Mechanisms and Therapy
- Macrophage Migration Inhibitory Factor
- Galectins and Cancer Biology
- Metabolism and Genetic Disorders
- Diabetes Treatment and Management
- Hemoglobinopathies and Related Disorders
- Complement system in diseases
- RNA and protein synthesis mechanisms
- RNA modifications and cancer
Heidelberg University
2024-2025
University Hospital Heidelberg
2025
Heidelberg University
2025
Children's Healthcare of Atlanta
2022-2024
Emory University
2022-2024
Heinrich Heine University Düsseldorf
2014-2023
Düsseldorf University Hospital
2017-2023
E Ink (South Korea)
2023
Klinik und Poliklinik für Urologie, Kinderurologie und Andrologie
2021
Philipps University of Marburg
2012-2016
<h3>Objective</h3> Cholestatic liver diseases in humans as well bile acid (BA)-feeding and common duct ligation (CBDL) rodents trigger hyperplasia of cholangiocytes within the portal fields. Furthermore, elevation BA levels enhances proliferation invasiveness cholangiocarcinoma (CCA) cells animal models, thus promoting tumour progression. TGR5 is a G-protein coupled receptor, which highly expressed postulated to mediate proliferative effects BA. <h3>Design</h3> BA-dependent cholangiocyte was...
Hepatic failure is commonly associated with anemia, which may result from gastrointestinal bleeding, vitamin deficiency, or liver‐damaging diseases, such as infection and alcohol intoxication. At least in theory, anemia during hepatic accelerated clearance of circulating erythrocytes. Here we show that bile duct ligation (BDL) mice leads to severe despite increased reticulocyte numbers. Bilirubin stimulated suicidal death human Mechanistically, bilirubin triggered rapid Ca 2+ influx,...
•TGR5 is downregulated in cholangiocytes PSC and Abcb4-/- livers a cell type-specific manner.•Interleukin-8 reduces TGR5 levels biliary epithelial cells organoids.•Biliary damage aggravated Tgr5-deficient mice attenuated overexpressing Tgr5.•ScRNA-seq shows that overexpression of Tgr5 ameliorates the activated, inflammatory phenotype.•norUDCA treatment restores Tgr5-expression mice. Background & AimsPrimary sclerosing cholangitis (PSC) characterized by chronic inflammation progressive...
Background and Aims: A recent multicenter genetic exploration of the biliary atresia splenic malformation syndrome identified mutations in ciliary gene PKD1L1 as candidate etiologic contributors. We hypothesized that deletion Pkd1l1 developing hepatoblasts would lead to cholangiopathy mice. Approach Results: CRISPR-based genome editing inserted loxP sites flanking exon 8 murine gene. Fl/Fl cross-bred with alpha-fetoprotein-Cre expressing mice generate a liver-specific intrahepatic -deficient...
TGR5 (Gpbar1) is a G protein-coupled receptor responsive to bile acids (BAs), which expressed in different non-parenchymal cells of the liver, including biliary epithelial cells, liver-resident macrophages, sinusoidal endothelial (LSECs), and activated hepatic stellate (HSCs). Mice with targeted deletion are more susceptible towards cholestatic liver injury induced by cholic acid-feeding duct ligation, resulting reduced proliferative response increased injury. Conjugated lithocholic acid...
We aimed to investigate the mechanistic, functional, and therapeutic role of glycogen synthase kinase 3β (GSK-3β) in regulation activation proinflammatory oncogenic transcription factor nuclear activated T cells (NFATc2) pancreatic cancer. IHC, qPCR, immunoblotting, immunofluorescence microscopy, proliferation assays were used analyze mouse human tissues cell lines. Protein-protein interactions promoter analyzed by coimmunoprecipitation, DNA pulldown, reporter, ChIP assays. Preclinical...
Cyp2c70 is the liver enzyme in rodents responsible for synthesis of primary 6-hydroxylated muricholate bile acid (BA) species. KO mice are devoid protective, hydrophilic muricholic acids, leading to a more human-like BA composition and subsequent cholestatic injury. Pharmacological inhibition ileal transporter (IBAT) has been shown be therapeutic models. Here, we aimed determine if IBAT with SC-435 protective mice. As compared WT mice, found male female exhibited increased levels serum...
Antibody-induced bile salt export pump deficiency (AIBD) is an acquired form of intrahepatic cholestasis, which may develop following orthotopic liver transplantation (OLT) for progressive familial cholestasis type 2 (PFIC-2). Approximately 8-33% patients with PFIC-2 who underwent a transplant (BSEP) antibodies, trans-inhibit this transporter from the extracellular, biliary side. AIBD diagnosed by demonstration BSEP-reactive and BSEP-inhibitory antibodies in patient serum. We developed...
Cyp2c70 knockout (KO) mice lack the liver enzyme responsible for synthesis of 6-hydroxylated muricholate bile acid species and possess a more hydrophobic human-like composition. KO develop cholestatic injury that can be prevented by administration an ileal transporter (IBAT) inhibitor. In this study, we investigated potential inhibitor (SC-435) steroidal FXR agonist (cilofexor) to modulate established hepatobiliary consequent relationship intrahepatic content hydrophobicity phenotype. Oral...
Introduction The Ileal Bile Acid Transporter (Asbt, Slc10a2) is the major bile acid (BA) uptake mechanism in ileum and kidney tubules. ASBT inhibitors have been developed as a treatment of cholestasis. Cholestatic liver disease often characterized by obstruction flow into duodenum, so that benefit ileal inhibition limited here. aim our study was to determine if specific hepatoprotective cholestatic injury whether these mice are prone or protected against development cholemic nephropathy.
TGR5 (Gpbar-1) is a G-Protein-coupled bile acid (BA) receptor (Kawamata et al. 2003) expressed on nonparenchymal liver cells such as hepatic stellate (HSCs) and sinusoidal endothelial (LSECs) (Keitel 2006, 2008). Lithocholic (LCA) hydrophobic acid. Feeding mice with diet containing 1%LCA leads to the development of severe toxic injury (Fickert 2006). The most relevant complication damage portal hypertension (PH). It has been demonstrated previously that activated HSCs contribute PH by...
TGR5 (Gpbar-1) is a G-Protein-coupled membrane-bound cell surface-receptor for bile acids associated not only with the regulation of acid homeostasis, but also suppression macrophage activity (1,2). It expressed in several different organs and types, e.g. nonparenchymal liver cells monocytes/macrophages. Thereby, can function as mediator modulating pathologies distinguished by inflammatory processes Lithocholic (LCA) hydrophobic toxic properties produced intestinal bacteria. Feeding diet...
Introduction: TGR5 (Gpbar-1) is a membrane bound G-Protein-coupled bile acid receptor (Kawamata et al. 2003), which expressed in several different cell types such as hepatic stellate cells (HSCs) and liver sinusoidal endothelial (LSECs). Lithocholic (LCA) hydrophobic secondary acid. Mice being fed diet containing 1% LCA are destined to suffer from toxic damage (Woolbright 2014, Fickert 2006). Liver often accompanied by an elevation of portal pressure. It assumed that HSCs able cause...
<p>Supplementary Figure Legends</p>
<p>Stat3 expression and proliferation studies upon genetic pharmacological modification of NFATc2 GSK-3β</p>
<p>Expression luciferase activity upon genetic an pharmacolgical modification of NFATc2 and GSK-3β</p>