Jorge A. Bezerra

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BACKGROUND & AIMS A genome-level understanding of the molecular basis of segmental gene expression along the anterior-posterior (A-P) axis of the mammalian gastrointestinal (GI) tract is lacking. We hypothesized that functional patterning along the A-P axis of the GI tract could be defined at the molecular level by analyzing expression profiles of large(More)
BACKGROUND Biliary atresia is the commonest cause of pathological jaundice in infants and the leading indication for liver transplantation in children worldwide. The cause and pathogenesis remain largely unknown. Because of clinical heterogeneity and experimental difficulties in addressing molecular mechanisms underlying multifactorial disorders in human(More)
The urokinase-type plasminogen activator (uPA) plays a central role in liver repair. Nevertheless, the hepatic overexpression of uPA results in panlobular injury and neonatal mortality. Here, we define the molecular mechanisms of liver injury and explore whether uPA can regulate liver repair independently of plasminogen. To address the hypothesis that the(More)
Using a small scale ENU mutagenesis approach we identified a recessive germline mutant, designated Lampe1 that exhibited growth retardation and spontaneous hepatosteatosis. Low resolution mapping based on 20 intercrossed Lampe1 mice revealed linkage to a ∼14 Mb interval on the distal site of chromosome 11 containing a total of 285 genes. Exons and 50 bp(More)
BACKGROUND The urokinase-type (uPA) and tissue-type (tPA) plasminogen activators regulate liver matrix remodelling through the conversion of plasminogen (Plg) to the active protease plasmin. Based on the efficient activation of plasminogen when uPA is bound to its receptor (uPAR) and on the role of uPA in plasmin-mediated liver repair, we hypothesized that(More)
Biliary atresia is a fibroinflammatory obstruction of extrahepatic bile duct that leads to end-stage liver disease in children. Despite advances in understanding the pathogenesis of biliary atresia, very little is known about the role of microRNAs (miRNAs) in onset and progression of the disease. In this study, we aimed to investigate the entire biliary(More)
BACKGROUND Livers of infants with biliary atresia and of neonatal mice infected with rotavirus (RRV) have increased expression of interferon-gamma (IFNgamma) and interleukin (IL)-12. While the expression of IFNgamma regulates the obstruction of extrahepatic bile ducts by lymphocytes, the role of IL-12 in the pathogenesis of biliary obstruction is unknown.(More)
In the United States, biliary atresia (BA) is the most frequent indication for liver transplantation in pediatric patients. BA is a complex disease, with suspected environmental and genetic risk factors. A genome-wide association study in Chinese patients identified association to the 10q24.2 (hg18) genomic region. This signal was upstream of two genes,(More)
BACKGROUND Young age at portoenterostomy has been linked to improved outcome in biliary atresia, but pre-existing biological factors may influence the rate of disease progression. In this study, we aimed to determine whether molecular profiling of the liver identifies stages of disease at diagnosis. METHODS We examined liver biopsies from 47 infants with(More)
UNLABELLED Biliary atresia is a rapidly progressive obstructive cholangiopathy of infants. Mechanistic studies in the mouse model of Rhesus rotavirus (RRV)-induced biliary atresia have linked the importance of effector lymphocytes to the pathogenesis of extrahepatic bile duct (EHBD) injury and obstruction in experimental biliary atresia; however, studies of(More)
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