A5073755467- Liver physiology and pathology
- Liver Disease Diagnosis and Treatment
- Pediatric Hepatobiliary Diseases and Treatments
- Liver Diseases and Immunity
- Liver Disease and Transplantation
- Pancreatitis Pathology and Treatment
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Organ Transplantation Techniques and Outcomes
- Alcohol Consumption and Health Effects
- Macrophage Migration Inhibitory Factor
- Retinoids in leukemia and cellular processes
- Microbial metabolism and enzyme function
- Cell Adhesion Molecules Research
- Phagocytosis and Immune Regulation
- Hepatitis C virus research
- Hepatitis B Virus Studies
- Drug Transport and Resistance Mechanisms
- Adenosine and Purinergic Signaling
- Hepatocellular Carcinoma Treatment and Prognosis
- Single-cell and spatial transcriptomics
- Mass Spectrometry Techniques and Applications
- Peptidase Inhibition and Analysis
- Pancreatic function and diabetes
- Estrogen and related hormone effects
- Hormonal Regulation and Hypertension
Beth Israel Deaconess Medical Center
2015-2025
Harvard University
2014-2024
Lomonosov Moscow State University
2023-2024
Joint Institute for Nuclear Research
2023-2024
Hadassah Medical Center
2013-2022
St.Petersburg V.M.Bekhterev Psychoneurological Research Institute
2016
Friedrich-Alexander-Universität Erlangen-Nürnberg
2004-2015
Centenary Institute
2013
The University of Sydney
2013
Harvard University Press
2009
Epithelial-mesenchymal transitions (EMTs) play an important role in tissue construction during embryogenesis, and evidence suggests that this process may also help to remodel some adult tissues after injury. Activation of the hedgehog (Hh) signaling pathway regulates EMT development. This is induced by chronic biliary injury, a condition which has been suggested have role. We evaluated hypothesis Hh promotes bile ductular cells (cholangiocytes). In liver sections from patients with injury...
<h3>Background/Aims</h3> We studied the role of lysyl oxidase-like 2 (LOXL2) in collagen crosslinking and hepatic progenitor cell (HPC) differentiation, therapeutic efficacy a LOXL2-blocking monoclonal antibody on liver fibrosis progression/reversal mice. <h3>Methods</h3> Anti-LOXL2 antibody, control antilysyl oxidase or placebo was administered during thioacetamide (TAA)-induced progression recovery. Therapeutic biliary tested BALB/c.<i>Mdr2−/−</i> 3,5-diethoxycarbonyl-1,4-dihydrocollidine...
Due to their bacterial ancestry, many components of mitochondria share structural similarities with bacteria. Release molecular danger signals from injured cell (mitochondria-derived damage-associated patterns, mito-DAMPs) triggers a potent inflammatory response, but role in fibrosis is unknown. Using liver resistant/susceptible mouse strain system, we demonstrate that mito-DAMPs released hepatocyte (with mtDNA as major active component) directly activate hepatic stellate cells, the...
Collagen stabilization through irreversible cross-linking is thought to promote hepatic fibrosis progression and limit its reversibility. However, the mechanism of this process remains poorly defined. We studied functional contribution lysyl oxidase (LOX) collagen progression/reversal in vivo using chronic administration LOX inhibitor β-aminopropionitrile (BAPN, or vehicle as control) C57Bl/6J mice with carbon tetrachloride (CCl4)-induced fibrosis. Fibrotic matrix stability was directly...
Abstract The vitronectin receptor integrin αvβ3 promotes angiogenesis by mediating migration and proliferation of endothelial cells, but also drives fibrogenic activation hepatic stellate cells (HSCs) in vitro. Expecting antifibrotic synergism, we studied the effect inhibition two vivo models liver fibrogenesis. Liver fibrosis was induced rats way bile duct ligation (BDL) for 6 weeks or thioacetamide (TAA) injections 12 weeks. A specific (αvβ5) inhibitor (Cilengitide) given intraperitoneally...
Studies have suggested the reversibility of liver fibrosis, but mechanisms fibrosis reversal are poorly understood. We investigated possible functional link between apoptosis, macrophages, and matrix turnover in rat during secondary to bile duct ligation (BDL). Biliary was induced by BDL for 4 wk. After Roux-en-Y (RY)-bilio-jejunal-anastomosis, resolution monitored up 12 wk hepatic collagen content, metalloproteinase (MMP) expression activities, fibrosis-related gene expression. MMP...
Fibrosis accompanies the wound‐healing response to chronic liver injury and is characterized by excessive hepatic collagen accumulation dominated type I. often progresses cirrhosis. Here we present in vivo evidence of an up 90% suppression procollagen α1(I) expression, a reduction septa formation, 40%‐60% decrease deposition mice with progressive advanced fibrosis that received cationic lipid nanoparticles loaded small interfering RNA gene. After intravenous injection, gene were retained...
Integrin αvβ6 is rapidly up‐regulated on cells of epithelial lineage during tissue injury, where one its primary functions activation latent transforming growth factor beta 1 (TGFβ1). In human liver cirrhosis, overexpressed by comprising the ductular reaction, and inhibition suppresses experimental biliary fibrosis in rodents. Here, we show that expressed actively proliferating subset hepatic progenitor required for their function vivo vitro through integrin αvβ6‐dependent TGFβ1 activation....
Failure of fibrotic liver to regenerate after resection limits therapeutic options and increases demand for transplantation, representing a significant clinical problem. The mechanism underlying regenerative failure in fibrosis is poorly understood. Seventy percent partial hepatectomy (PHx) was performed C57Bl/6 mice with or without carbon tetrachloride (CCl4)-induced fibrosis. Liver function regeneration monitored at 1 14 days thereafter by assessing mass, alanine aminotransferase (ALT),...
Congenital hepatic fibrosis (CHF) is a disease of the biliary epithelium characterized by bile duct changes resembling ductal plate malformations and progressive peribiliary fibrosis, in absence overt necroinflammation. Progressive liver leads to portal hypertension failure; however, mechanisms leading CHF remain elusive. caused mutations PKHD1 , gene encoding for fibrocystin, ciliary protein expressed cholangiocytes. Using fibrocystin‐defective ( Pkhd1 del4/del4 ) mouse, which orthologous...
Summary Background Recent animal studies have shown that platelets directly activate hepatic stellate cells to promote liver fibrosis, whereas anti‐platelet agents decrease fibrosis. It is unknown whether platelet inhibition by aspirin prevents fibrosis in humans. Aim To examine the association between use and among adults with suspected chronic disease. Methods We conducted a cross‐sectional analysis using data from National Health Nutrition Examination Survey III . identified 1856...
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...