A5012480874- Hedgehog Signaling Pathway Studies
- Inflammasome and immune disorders
- Liver physiology and pathology
- Pediatric Hepatobiliary Diseases and Treatments
- Genetic and Kidney Cyst Diseases
- Liver Disease Diagnosis and Treatment
- Epigenetics and DNA Methylation
- Autoimmune and Inflammatory Disorders Research
- Immunodeficiency and Autoimmune Disorders
- IL-33, ST2, and ILC Pathways
- Immune Response and Inflammation
- Immune Cell Function and Interaction
- Adenosine and Purinergic Signaling
- Genetics and Neurodevelopmental Disorders
- Diabetes and associated disorders
- Peptidase Inhibition and Analysis
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Drug-Induced Hepatotoxicity and Protection
- Endoplasmic Reticulum Stress and Disease
- Pediatric health and respiratory diseases
- Autoimmune and Inflammatory Disorders
- Psoriasis: Treatment and Pathogenesis
- Digestive system and related health
- S100 Proteins and Annexins
- Neonatal Respiratory Health Research
Istituto Giannina Gaslini
2011-2019
Istituti di Ricovero e Cura a Carattere Scientifico
2012-2019
University of Genoa
2011-2017
Duke University
2007-2013
Ospedale Policlinico San Martino
2013
Duke Medical Center
2007-2011
Zero to Three
2011
National Cancer Research Institute
2011
Duke University Hospital
2007-2010
University Gastroenterology
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...
Liver inflammation is greater in nonalcoholic steatohepatitis (NASH) than steatosis, suggesting that immune responses contribute to fatty liver disease (NAFLD) progression. Livers normally contain many natural killer T (NKT) cells produce factors modulate inflammatory and fibrogenic responses. Such are relatively depleted but their status more advanced NAFLD uncertain. We hypothesized NKT accumulate promote fibrosis progression NASH. aimed determine if livers become enriched with during...
Nonalcoholic steatohepatitis (NASH) is a leading cause of cirrhosis. Recently, we showed that NASH-related cirrhosis associated with Hedgehog (Hh) pathway activation. The gene encoding osteopontin (OPN), profibrogenic extracellular matrix protein and cytokine, direct transcriptional target the Hh pathway. Thus, hypothesize signaling induces OPN to promote liver fibrosis in NASH. Hepatic expression were analyzed wild-type (WT) mice, Patched-deficient (Ptc+/−) (overly active signaling)...
<h3>Objectives</h3> To analyse the prevalence of <i>CECR1</i> mutations in patients diagnosed with early onset livedo reticularis and/or haemorrhagic/ischaemic strokes context inflammation or polyarteritis nodosa (PAN). Forty-eight from 43 families were included study. <h3>Methods</h3> Direct sequencing was performed by Sanger analysis. Adenosine deaminase 2 (ADA2) enzymatic activity analysed monocyte isolated and healthy controls incubated adenosine without an ADA1 inhibitor....
Abstract Nonalcoholic fatty liver disease (NAFLD) is a potentially progressive that culminates in cirrhosis. Cirrhosis occurs more often individuals with nonalcoholic steatohepatitis (NASH) than those steatosis (nonalcoholic [NAFL]). The difference between NAFL and NASH the extent of hepatocyte apoptosis, which extensive NASH. Because phagocytosis apoptotic cells activates hepatic stellate (HSCs), we examined hypothesis pan-caspase inhibitor, VX-166, would reduce progression fibrosis mouse...
Myofibroblastic hepatic stellate cells (MF-HSC) are derived from quiescent (Q-HSC). Q-HSC express certain epithelial cell markers and have been reported to form junctional complexes similar cells. We shown that Hedgehog (Hh) signaling plays a key role in HSC growth. Because Hh ligands regulate epithelial-to-mesenchymal transition (EMT), we determined whether EMT then assessed these change as into MF-HSC the process is modulated by signaling. were isolated healthy livers cultured promote...
Abstract Liver injury activates quiescent hepatic stellate cells (Q-HSC) to proliferative myofibroblasts. Accumulation of myofibroblastic (MF-HSC) sometimes causes cirrhosis and liver failure. However, MF-HSC also promote regeneration by producing growth factors for oval cells, bipotent progenitors hepatocytes cholangiocytes. Genes that are expressed primary cell (HSC) isolates overlap those hepatocytic ductular emerge when HSC cultured under certain conditions. We evaluated the hypothesis a...
Distinct mechanisms are believed to regulate growth of the liver during fetal development and after injury in adults, because former relies on progenitors latter generally involves replication mature hepatocytes. However, chronic adults increases production Hedgehog (Hh) ligands, developmental morphogens that control progenitor cell fate orchestrate various aspects tissue construction embryogenesis. This raises possibility similar Hh-dependent also might adult regeneration. The current...
Trans-differentiation of quiescent hepatic stellate cells (Q-HSCs), which exhibit epithelial and adipocytic features, into myofibroblastic-HSC (MF-HSCs) is a key event in liver fibrosis. Culture models demonstrated that Hedgehog (Hh) pathway activation required for transition epithelioid/adipocytic Q-HSCs MF-HSCs. Hh signaling inhibits adiposity promotes epithelial-to-mesenchymal transitions (EMTs). Leptin (anti-adipogenic, pro-EMT factor) HSC trans-differentiation fibrosis, suggesting the...
Depression and anxiety are common in patients with nonalcoholic fatty liver disease (NAFLD). However, their associations histological severity of NAFLD unknown.This study examined the association(s) depression, antidepressant pharmacotherapy features NAFLD.We analysed 567 biopsy-proven enrolled Duke Clinical Database. Depressive symptoms were assessed using Hospital Anxiety & Scale (HADS). The depression multiple logistic (or ordinal logistic) regression models without adjusting for...
The death rate of mature hepatocytes is chronically increased in various liver diseases, triggering responses that prevent atrophy, but often cause fibrosis. Mice with targeted disruption inhibitor kappa B kinase (Ikk) (HEP mice) provide a model to investigate this process because inhibiting Ikk-nuclear factor-kappaB (NF-kappaB) signalling increases their apoptosis.Cell proliferation, apoptosis, progenitors, fibrosis and production Hedgehog (Hh) ligands (progenitor myofibroblast growth...
<h3>Objectives</h3> To define in patients affected by familial Mediterranean fever (FMF) whether or not interleukin (IL)-1β secretion (1) is enhanced, (2) correlates with the type of <i>MEFV</i> mutation and (3) mediated NLRP3. <h3>Methods</h3> Freshly isolated monocytes from 21 FMF (12 homozygous 9 heterozygous), 14 healthy carriers 30 donors (HDs), unstimulated after lipopolysaccharide (LPS)-induced activation, were analysed for redox state (production reactive oxygen species (ROS)...
<h3>Background:</h3> Chronic biliary obstruction provokes fibrosis and accumulation of immature ductular cells. This fibroductular reaction resolves following decompression, suggesting that it may also be involved in the repair damage. The hedgehog (Hh) pathway becomes activated liver after bile duct ligation (BDL), might modulate hepatic remodelling because Hh ligands are potent morphogens. <h3>Objective:</h3> To study induction during progression resolution fibrosis, to clarify whether...
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...