- Pediatric Hepatobiliary Diseases and Treatments
- Liver physiology and pathology
- Liver Disease Diagnosis and Treatment
- Drug Transport and Resistance Mechanisms
- Liver Diseases and Immunity
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Mast cells and histamine
- MicroRNA in disease regulation
- Organ Transplantation Techniques and Outcomes
- Liver Disease and Transplantation
- Neuropeptides and Animal Physiology
- Circadian rhythm and melatonin
- Diet, Metabolism, and Disease
- Alcohol Consumption and Health Effects
- Gallbladder and Bile Duct Disorders
- Pancreatic function and diabetes
- Cancer-related molecular mechanisms research
- Digestive system and related health
- Polyamine Metabolism and Applications
- Peptidase Inhibition and Analysis
- Growth Hormone and Insulin-like Growth Factors
- Clinical Nutrition and Gastroenterology
- Eosinophilic Esophagitis
- Circular RNAs in diseases
- Pancreatitis Pathology and Treatment
Richard L. Roudebush VA Medical Center
2019-2024
Indiana University – Purdue University Indianapolis
2019-2024
Indiana University School of Medicine
2019-2024
Macquarie University
2023
Texas A&M University
2007-2022
Rotary International
2022
Sapienza University of Rome
2009-2022
University of Rome Tor Vergata
2022
Circle (United States)
2022
University Gastroenterology
2011-2021
Transmembrane protein 173 (TMEM173 or STING) signaling by macrophage activates the type I interferon-mediated innate immune response. The response contributes to hepatic steatosis and non-alcoholic fatty liver disease (NAFLD). We investigated whether STING regulates diet-induced in steatosis, inflammation, fibrosis mice.Mice with disruption of Tmem173 (STINGgt) on a C57BL/6J background, mice without this gene (controls), only myeloid cells were fed standard chow diet, high-fat diet (HFD; 60%...
Background and Aims Lipopolysaccharides (LPS) is increased in nonalcoholic fatty liver disease (NAFLD), but its relationship with inflammation not defined. Approach Results We studied Escherichia coli LPS patients biopsy‐proven NAFLD, 25 simple steatosis (nonalcoholic liver) steatohepatitis (NASH), mice diet‐induced NASH. NASH had higher serum hepatocytes localization than controls, which was correlated zonulin phosphorylated nuclear factor‐κB expression. Toll‐like receptor 4 positive (TLR4...
MicroRNAs are endogenous small non-coding RNAs that regulate gene expression and cancer development. A rare population of hepatocellular stem cells (HSCs) holds the extensive proliferative self-renewal potential necessary to form a liver tumour. We postulated specific transcriptional factors might microRNAs subsequently modulate products involved in phenotypic characteristics HSCs. evaluated microRNA human HSCs by microarray profiling, defined target genes functional effects two groups...
Background and Aims Indole is a microbiota metabolite that exerts anti‐inflammatory responses. However, the relevance of indole to human non‐alcoholic fatty liver disease (NAFLD) not clear. It also remains largely unknown whether how acts protect against NAFLD. The present study sought examine association between circulating levels fat content in subjects explore mechanisms underlying actions mice with diet‐induced Approach Results In cohort 137 subjects, were reversely correlated body mass...
Objective Conflicting microbiota data exist for primary sclerosing cholangitis (PSC) and experimental models. Goal: define the function of complex resident microbes their association relevant to PSC patients by studying germ-free (GF) antibiotic-treated specific pathogen-free (SPF) multidrug-resistant 2 deficient ( mdr2 −/− ) mice microbial profiles in patient cohorts. Design We measured weights, liver enzymes, RNA expression, histological, immunohistochemical fibrotic biochemical...
These studies characterized the secretion of GH-releasing factor (GRF) and somatostatin (SRIF) into hypophysial portal circulation in ewes after long term restricted feeding. In addition, we examined temporal relationship between concentrations these two hypothalamic peptides blood concentration GH jugular blood. Six sheep were fed 1000 g hay/day (normal feeding) 6 400-600 (restricted feeding). This resulted a wt loss 35% animals compared with 6% control 20 weeks. Fluctuations levels GRF...
Accumulating bile acids (BA) trigger cholangiocyte proliferation in chronic cholestasis. The aim of this study was to determine if ursodeoxycholate (UDCA) or tauroursodeoxycholate (TUDCA) feeding prevents the increased growth and secretion duct–ligated (BDL) rats, UDCA TUDCA effects are associated with apoptosis, inhibition is dependent on intracellular Ca2+ ([Ca2+]i) activation protein kinase C (PKC) alpha. Immediately after BDL, rats were fed (both 275 μmol/d) for 1 week. We determined...
Cholangiopathies are characterized by the heterogeneous proliferation of different-sized cholangiocytes. Large cholangiocytes proliferate a cAMP-dependent mechanism. The function small may depend on activation inositol trisphosphate (IP(3))/Ca(2+)-dependent signaling pathways; however, data supporting this speculation lacking. Four histamine receptors exist (HRH1, HRH2, HRH3, and HRH4). In several cells: 1) HRH1 increases intracellular Ca(2+) concentration levels; 2) increased [Ca(2+)](i)...
Biliary atresia (BA) is notable for marked ductular reaction and rapid development of fibrosis. Activation the Hedgehog (Hh) pathway promotes expansion populations immature epithelial cells that coexpress mesenchymal markers may be profibrogenic. We examined hypothesis in BA excessive Hh activation impedes morphogenesis enhances fibrogenesis by promoting accumulation with a phenotype. Livers remnant extrahepatic ducts from patients were evaluated quantitative reverse-transcription polymerase...
The mechanisms mediating hepatic accumulation of inflammatory cells in cholestatic liver disease remain enigmatic. Our thesis is that Hedgehog (Hh) pathway activation promotes immune interact with cholangiocytes. We believe myofibroblastic stellate (MF-HSCs) release soluble Hh ligands stimulate cholangiocytes to express chemokines recruit mononuclear cell types cognate receptors for these chemokines, thereby orchestrating a repair-related mechanism inflammation. To address this thesis, we...