Scholars@Duke
Steven Sok Choi

Steven Sok Choi

Associate Professor of Medicine
Medicine, Gastroenterology
Durham VA Medical Center, 508 Fulton Street, 111E, GI Clinic, Durham, NC 27705
Durham VA Medical Center, 508 Fulton Street, 111E, GI Clinic, Durham, NC 27705

Selected Publications

Proton pump inhibitor usage reduces sustained viral response rates for veterans with HIV/HCV coinfection on ledipasvir/sofosbuvir: a real-world study from a multicentre VA cohort.

Journal Article J Viral Hepat · April 2021 Previous studies have reported an association of proton pump inhibitor (PPI) use and decreased sustained viral response rate (SVR) in patients taking ledipasvir/sofosbuvir (LDV/SOF). The relationship between PPI usage and SVR is less clear in patients with ... Full text Link to item Cite

Relative Sarcopenia With Excess Adiposity Predicts Survival After Transjugular Intrahepatic Portosystemic Shunt Creation.

Journal Article AJR Am J Roentgenol · January 2020 OBJECTIVE. The purpose of this study was to assess the impact of relative sarcopenia with excess adiposity on mortality after transjugular intrahepatic portosystemic shunt (TIPS) creation. MATERIALS AND METHODS. In this single-institution retrospective stu ... Full text Link to item Cite

Unclear Statement.

Journal Article JAMA · July 23, 2019 Full text Link to item Cite

No Increased Mortality After TIPS Compared with Serial Large Volume Paracenteses in Patients with Higher Model for End-Stage Liver Disease Score and Refractory Ascites.

Journal Article Cardiovasc Intervent Radiol · May 2019 PURPOSE: To compare survival after transjugular intrahepatic portosystemic shunt (TIPS) creation versus serial large volume paracenteses (LVP) in patients with refractory ascites and higher Model for End-Stage Liver Disease (MELD) scores. MATERIALS AND MET ... Full text Link to item Cite

Proton Pump Inhibitor Use Is Associated with an Increased Frequency of New or Worsening Hepatic Encephalopathy after Transjugular Intrahepatic Portosystemic Shunt Creation.

Journal Article J Vasc Interv Radiol · February 2019 PURPOSE: To determine whether proton pump inhibitor (PPI) use increases the rate of new or worsening hepatic encephalopathy (HE) after transjugular intrahepatic portosystemic shunt (TIPS) creation. MATERIALS AND METHODS: In this retrospective study, 284 of ... Full text Link to item Cite

Correction to: Identifying Nonalcoholic Fatty Liver Disease Advanced Fibrosis in the Veterans Health Administration.

Journal Article Dig Dis Sci · October 2018 The original version of the article unfortunately contained errors in Table 3, Risk Factor column headings "Age > 50 (n = 115)," "Age > 50-64 (n = 154)," and "Age > 65 + (n = 60)." ... Full text Open Access Link to item Cite

Metastatic Hepatocellular Carcinoma Secreting Intact PTH: A Case Report

Conference AMERICAN JOURNAL OF GASTROENTEROLOGY · October 1, 2018 Link to item Cite

The role of external beam radiotherapy in the treatment of hepatocellular cancer.

Journal Article Cancer · September 1, 2018 Hepatocellular carcinoma (HCC) is increasing in incidence and mortality. Although the prognosis remains poor, long-term survival has improved from 3% in 1970 to an 18% 5-year survival rate today. This is likely because of the introduction of well tolerated ... Full text Link to item Cite

Identifying Nonalcoholic Fatty Liver Disease Advanced Fibrosis in the Veterans Health Administration.

Journal Article Dig Dis Sci · September 2018 BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease. Severe NAFLD with advanced fibrosis results in substantial morbidity and mortality. Associated with metabolic syndrome, NAFLD is often initially clinica ... Full text Link to item Cite

Markers of Tissue Repair and Cellular Aging Are Increased in the Liver Tissue of Patients With HIV Infection Regardless of Presence of HCV Coinfection.

Journal Article Open Forum Infect Dis · July 2018 Liver disease is a leading cause of HIV-related mortality. Hepatitis C virus (HCV)-related fibrogenesis is accelerated in the setting of HIV coinfection, yet the mechanisms underlying this aggressive pathogenesis are unclear. We identified formalin-fixed p ... Full text Open Access Link to item Cite

Hedgehog-YAP Signaling Pathway Regulates Glutaminolysis to Control Activation of Hepatic Stellate Cells.

Conference Gastroenterology · April 2018 BACKGROUND & AIMS: Cirrhosis results from accumulation of myofibroblasts derived from quiescent hepatic stellate cells (Q-HSCs); it regresses when myofibroblastic HSCs are depleted. Hedgehog signaling promotes transdifferentiation of HSCs by activating Yes ... Full text Link to item Cite

Albumin-bilirubin grade versus MELD score for predicting survival after transjugular intrahepatic portosystemic shunt (TIPS) creation.

Journal Article Diagn Interv Imaging · March 2018 OBJECTIVES: The purpose of this study was to compare the albumin-bilirubin (ALBI) grade and model for end-stage liver disease (MELD) scores for predicting survival after transjugular intrahepatic portosystemic shunt (TIPS) creation. MATERIALS AND METHODS: ... Full text Link to item Cite

Risk factors for biopsy-proven advanced non-alcoholic fatty liver disease in the Veterans Health Administration.

Journal Article Aliment Pharmacol Ther · January 2018 BACKGROUND: With its increasing incidence, nonalcoholic fatty liver disease (NAFLD) is of particular concern in the Veterans Health Administration (VHA). AIMS: To evaluate risk factors for advanced fibrosis in biopsy-proven NAFLD in the VHA, to identify pa ... Full text Link to item Cite

Alcoholic liver disease

Chapter · January 1, 2018 Consumption of alcohol is common in adults, and modest consumption has reported health benefits; however, chronic daily alcohol consumption above recommended limits is an important cause of chronic liver disease and cirrhosis. The amount and duration of al ... Full text Cite

Aging of the Liver: What This Means for Patients with HIV.

Journal Article Curr HIV/AIDS Rep · December 2016 As the HIV population continues to live longer as a result of antiretroviral therapy, liver-related mortality has become one of the leading causes of non-AIDS related death in this patient population. The liver possesses a remarkable regenerative capacity ... Full text Link to item Cite

Pleiotrophin regulates the ductular reaction by controlling the migration of cells in liver progenitor niches.

Journal Article Gut · April 2016 OBJECTIVE: The ductular reaction (DR) involves mobilisation of reactive-appearing duct-like cells (RDC) along canals of Hering, and myofibroblastic (MF) differentiation of hepatic stellate cells (HSC) in the space of Disse. Perivascular cells in stem cell ... Full text Open Access Link to item Cite

Osteopontin is a proximal effector of leptin-mediated non-alcoholic steatohepatitis (NASH) fibrosis.

Journal Article Biochim Biophys Acta · January 2016 INTRODUCTION: Liver fibrosis develops when hepatic stellate cells (HSC) are activated into collagen-producing myofibroblasts. In non-alcoholic steatohepatitis (NASH), the adipokine leptin is upregulated, and promotes liver fibrosis by directly activating H ... Full text Link to item Cite

Schistosome-induced cholangiocyte proliferation and osteopontin secretion correlate with fibrosis and portal hypertension in human and murine schistosomiasis mansoni.

Journal Article Clin Sci (Lond) · November 2015 Schistosomiasis is a major cause of portal hypertension worldwide. It associates with portal fibrosis that develops during chronic infection. The mechanisms by which the pathogen evokes these host responses remain unclear. We evaluated the hypothesis that ... Full text Open Access Link to item Cite

Statins activate the canonical hedgehog-signaling and aggravate non-cirrhotic portal hypertension, but inhibit the non-canonical hedgehog signaling and cirrhotic portal hypertension.

Journal Article Sci Rep · September 28, 2015 Liver cirrhosis but also portal vein obstruction cause portal hypertension (PHT) and angiogenesis. This study investigated the differences of angiogenesis in cirrhotic and non-cirrhotic PHT with special emphasis on the canonical (Shh/Gli) and non-canonical ... Full text Link to item Cite

Osteopontin neutralisation abrogates the liver progenitor cell response and fibrogenesis in mice.

Journal Article Gut · July 2015 BACKGROUND: Chronic liver injury triggers a progenitor cell repair response, and liver fibrosis occurs when repair becomes deregulated. Previously, we reported that reactivation of the hedgehog pathway promotes fibrogenic liver repair. Osteopontin (OPN) is ... Full text Link to item Cite

Role of Fn14 in acute alcoholic steatohepatitis in mice.

Journal Article Am J Physiol Gastrointest Liver Physiol · February 15, 2015 TNF-like weak inducer of apoptosis (TWEAK) is a growth factor for bipotent liver progenitors that express its receptor, fibroblast growth factor-inducible 14 (Fn14), a TNF receptor superfamily member. Accumulation of Fn14(+) progenitors occurs in severe ac ... Full text Link to item Cite

Hepatic stellate cells express thymosin Beta 4 in chronically damaged liver.

Journal Article PLoS One · 2015 Although the various biological roles of thymosin β4 (Tβ4) have been studied widely, the effect of Tβ4 and Tβ4-expressing cells in the liver remains unclear. Therefore, we investigated the expression and function of Tβ4 in chronically damaged livers. CCl4 ... Full text Open Access Link to item Cite

Abstract 4117: Utilizing RNA aptamers for biomarker discovery in a novel cell culture system for hepatocellular carcinoma

Conference Cancer Research · October 1, 2014 AbstractIntroduction: Current serum biomarkers for hepatocellular carcinoma (HCC) lack the sensitivity and specificity to be effective screening tools. Aptamers are single-stranded RNA oligonucleotides that ... Full text Cite

Myofibroblastic cells function as progenitors to regenerate murine livers after partial hepatectomy.

Journal Article Gut · August 2014 OBJECTIVE: Smoothened (SMO), a coreceptor of the Hedgehog (Hh) pathway, promotes fibrogenic repair of chronic liver injury. We investigated the roles of SMO+ myofibroblast (MF) in liver regeneration by conditional deletion of SMO in α smooth muscle actin ( ... Full text Link to item Cite

Osteopontin is up-regulated in chronic hepatitis C and is associated with cellular permissiveness for hepatitis C virus replication.

Journal Article Clin Sci (Lond) · June 2014 OPN (osteopontin)) is a Hh (Hedgehog)-regulated cytokine that is up-regulated during chronic liver injury and directly promotes fibrosis. We have reported that Hh signalling enhances viral permissiveness and replication in HCV (hepatitis C virus)-infected ... Full text Link to item Cite

Alcohol activates the hedgehog pathway and induces related procarcinogenic processes in the alcohol-preferring rat model of hepatocarcinogenesis.

Journal Article Alcohol Clin Exp Res · March 2014 BACKGROUND: Alcohol consumption promotes hepatocellular carcinoma (HCC). The responsible mechanisms are not well understood. Hepatocarcinogenesis increases with age and is enhanced by factors that impose a demand for liver regeneration. Because alcohol is ... Full text Link to item Cite

Hepatic gene expression profiles differentiate presymptomatic patients with mild versus severe nonalcoholic fatty liver disease.

Journal Article Hepatology · February 2014 UNLABELLED: Clinicians rely upon the severity of liver fibrosis to segregate patients with well-compensated nonalcoholic fatty liver disease (NAFLD) into subpopulations at high- versus low-risk for eventual liver-related morbidity and mortality. We compare ... Full text Link to item Cite

Potential role of Hedgehog signaling and microRNA-29 in liver fibrosis of IKKβ-deficient mouse.

Journal Article J Mol Histol · February 2014 Recent studies have reported that NF-κB mediated down-regulation of miRNA-29 and lower expression of miRNA-29 promoted the deposition of collagens in fibrotic liver. Our previous research demonstrated that the increased Hedgehog (Hh) signaling, a key regul ... Full text Link to item Cite

TWEAK/Fn14 signaling is required for liver regeneration after partial hepatectomy in mice.

Journal Article PLoS One · 2014 BACKGROUND & AIMS: Pro-inflammatory cytokines are important for liver regeneration after partial hepatectomy (PH). Expression of Fibroblast growth factor-inducible 14 (Fn14), the receptor for TNF-like weak inducer of apoptosis (TWEAK), is induced rapidly a ... Full text Open Access Link to item Cite

Cross-talk between Notch and Hedgehog regulates hepatic stellate cell fate in mice.

Journal Article Hepatology · November 2013 UNLABELLED: Liver repair involves phenotypic changes in hepatic stellate cells (HSCs) and reactivation of morphogenic signaling pathways that modulate epithelial-to-mesenchymal/mesenchymal-to-epithelial transitions, such as Notch and Hedgehog (Hh). Hh stim ... Full text Link to item Cite

Smoothened is a master regulator of adult liver repair.

Journal Article J Clin Invest · June 2013 When regenerative processes cannot keep pace with cell death, functional epithelia are replaced by scar. Scarring is characterized by both excessive accumulation of fibrous matrix and persistent outgrowth of cell types that accumulate transiently during su ... Full text Link to item Cite

Hedgehog signalling regulates liver sinusoidal endothelial cell capillarisation.

Journal Article Gut · February 2013 OBJECTIVE: Vascular remodelling during liver damage involves loss of healthy liver sinusoidal endothelial cell (LSEC) phenotype via capillarisation. Hedgehog (Hh) signalling regulates vascular development and increases during liver injury. This study there ... Full text Link to item Cite

Macrophage-derived Hedgehog ligands promotes fibrogenic and angiogenic responses in human schistosomiasis mansoni.

Journal Article Liver Int · January 2013 BACKGROUND: Schistosomiasis mansoni is a major cause of portal fibrosis and portal hypertension. The Hedgehog pathway regulates fibrogenic repair in some types of liver injury. AIMS: Determine if Hedgehog pathway activation occurs during fibrosis progressi ... Full text Link to item Cite

Paracrine Hedgehog signaling drives metabolic changes in hepatocellular carcinoma.

Journal Article Cancer Res · December 15, 2012 Hepatocellular carcinoma (HCC) typically develops in cirrhosis, a condition characterized by Hedgehog (Hh) pathway activation and accumulation of Hh-responsive myofibroblasts. Although Hh signaling generally regulates stromal-epithelial interactions that s ... Full text Link to item Cite

Hedgehog signaling blockade delays hepatocarcinogenesis induced by hepatitis B virus X protein.

Journal Article Cancer Res · November 15, 2012 The hepatitis B virus (HBV) encoded X protein (HBx) contributes centrally to the pathogenesis of hepatocellular carcinoma (HCC). Aberrant activation of the Hedgehog (Hh) pathway has been linked to many tumor types including HCC. Thus, experiments were desi ... Full text Link to item Cite

Hedgehog controls hepatic stellate cell fate by regulating metabolism.

Journal Article Gastroenterology · November 2012 BACKGROUND & AIMS: The pathogenesis of cirrhosis, a disabling outcome of defective liver repair, involves deregulated accumulation of myofibroblasts derived from quiescent hepatic stellate cells (HSCs), but the mechanisms that control transdifferentiation ... Full text Link to item Cite

NKT-associated hedgehog and osteopontin drive fibrogenesis in non-alcoholic fatty liver disease.

Journal Article Gut · September 2012 OBJECTIVE: Immune responses are important in dictating non-alcoholic steatohepatitis (NASH) outcome. We previously reported that upregulation of hedgehog (Hh) and osteopontin (OPN) occurs in NASH, that Hh-regulated accumulation of natural killer T (NKT) ce ... Full text Link to item Cite

Pancreatic secretory trypsin inhibitor I reduces the severity of chronic pancreatitis in mice overexpressing interleukin-1β in the pancreas.

Journal Article Am J Physiol Gastrointest Liver Physiol · March 1, 2012 IL-1β is believed to play a pathogenic role in the development of pancreatitis. Expression of human IL-1β in pancreatic acinar cells produces chronic pancreatitis, characterized by extensive intrapancreatic inflammation, atrophy, and fibrosis. To determine ... Full text Link to item Cite

Up-regulation of Hedgehog pathway is associated with cellular permissiveness for hepatitis C virus replication.

Journal Article Hepatology · November 2011 Featured Publication UNLABELLED: Studies of the hepatitis C virus (HCV) life-cycle rely heavily on Huh7.5 cells, but the reasons why these cells are exceptionally permissive for HCV replication are not clear. Based on recent clinical observations, we hypothesized that the Hedg ... Full text Link to item Cite

Hedgehog activity, epithelial-mesenchymal transitions, and biliary dysmorphogenesis in biliary atresia.

Journal Article Hepatology · April 2011 Featured Publication UNLABELLED: Biliary atresia (BA) is notable for marked ductular reaction and rapid development of fibrosis. Activation of the Hedgehog (Hh) pathway promotes the expansion of populations of immature epithelial cells that coexpress mesenchymal markers and ma ... Full text Link to item Cite

Hedgehog signaling in the liver.

Journal Article J Hepatol · February 2011 Featured Publication Reactivation of Hedgehog (Hh), a morphogenic signaling pathway that controls progenitor cell fate and tissue construction during embryogenesis occurs during many types of liver injury in adult. The net effects of activating the Hedgehog pathway include exp ... Full text Link to item Cite

Paracrine modulation of cholangiocyte serotonin synthesis orchestrates biliary remodeling in adults.

Journal Article Am J Physiol Gastrointest Liver Physiol · February 2011 Featured Publication Paracrine signaling between cholangiocytes and stromal cells regulates biliary remodeling. Cholangiocytes have neuroepithelial characteristics and serotonin receptor agonists inhibit their growth, but whether they are capable of serotonin biosynthesis is u ... Full text Link to item Cite

The role of Hedgehog signaling in fibrogenic liver repair.

Journal Article Int J Biochem Cell Biol · February 2011 Featured Publication Repair of adult liver, like many tissues, involves the coordinated response of a number of different cell types. In adult livers, fibroblastic cells, ductular cells, inflammatory cells, and progenitor cells contribute to this process. Our studies demonstra ... Full text Link to item Cite

Osteopontin is induced by hedgehog pathway activation and promotes fibrosis progression in nonalcoholic steatohepatitis.

Journal Article Hepatology · January 2011 Featured Publication UNLABELLED: Nonalcoholic steatohepatitis (NASH) is a leading cause of cirrhosis. Recently, we showed that NASH-related cirrhosis is associated with Hedgehog (Hh) pathway activation. The gene encoding osteopontin (OPN), a profibrogenic extracellular matrix ... Full text Link to item Cite

Hedgehog signaling antagonist promotes regression of both liver fibrosis and hepatocellular carcinoma in a murine model of primary liver cancer.

Journal Article PLoS One · 2011 Featured Publication OBJECTIVE: Chronic fibrosing liver injury is a major risk factor for hepatocarcinogenesis in humans. Mice with targeted deletion of Mdr2 (the murine ortholog of MDR3) develop chronic fibrosing liver injury. Hepatocellular carcinoma (HCC) emerges spontaneou ... Full text Open Access Link to item Cite

Viral factors induce Hedgehog pathway activation in humans with viral hepatitis, cirrhosis, and hepatocellular carcinoma.

Journal Article Lab Invest · December 2010 Featured Publication Hedgehog (Hh) pathway activation promotes many processes that occur during fibrogenic liver repair. Whether the Hh pathway modulates the outcomes of virally mediated liver injury has never been examined. Gene-profiling studies of human hepatocellular carci ... Full text Open Access Link to item Cite

Leptin promotes the myofibroblastic phenotype in hepatic stellate cells by activating the hedgehog pathway.

Journal Article J Biol Chem · November 19, 2010 Featured Publication 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 is ... Full text Link to item Cite

Activation of Rac1 promotes hedgehog-mediated acquisition of the myofibroblastic phenotype in rat and human hepatic stellate cells.

Journal Article Hepatology · July 2010 Featured Publication UNLABELLED: Hepatic accumulation of myofibroblastic hepatic stellate cells (MF-HSCs) is pivotal in the pathogenesis of cirrhosis. Two events are necessary for MF-HSCs to accumulate in damaged livers: transition of resident, quiescent hepatic stellate cells ... Full text Link to item Cite

Accumulation of natural killer T cells in progressive nonalcoholic fatty liver disease.

Journal Article Hepatology · June 2010 Featured Publication UNLABELLED: Liver inflammation is greater in nonalcoholic steatohepatitis (NASH) than steatosis, suggesting that immune responses contribute to nonalcoholic fatty liver disease (NAFLD) progression. Livers normally contain many natural killer T (NKT) cells ... Full text Link to item Cite

Hedgehog signaling is critical for normal liver regeneration after partial hepatectomy in mice.

Journal Article Hepatology · May 2010 Featured Publication UNLABELLED: Distinct mechanisms are believed to regulate growth of the liver during fetal development and after injury in adults, because the former relies on progenitors and the latter generally involves replication of mature hepatocytes. However, chronic ... Full text Link to item Cite

Signals from dying hepatocytes trigger growth of liver progenitors.

Journal Article Gut · May 2010 Featured Publication OBJECTIVE: The death rate of mature hepatocytes is chronically increased in various liver diseases, triggering responses that prevent liver atrophy, but often cause fibrosis. Mice with targeted disruption of inhibitor kappa B kinase (Ikk) in hepatocytes (H ... Full text Link to item Cite

Performance of the AST-to-platelet ratio index as a noninvasive marker of fibrosis in pediatric patients with chronic viral hepatitis.

Journal Article J Pediatr Gastroenterol Nutr · March 2010 Featured Publication We investigated the performance of aspartate aminotransferase to platelet ratio index (APRI) as a noninvasive marker of fibrosis and cirrhosis in children with chronic viral hepatitis. All of the patients 0 to 20 years old with chronic hepatitis B or C pre ... Full text Link to item Cite

Hedgehog pathway activation and epithelial-to-mesenchymal transitions during myofibroblastic transformation of rat hepatic cells in culture and cirrhosis.

Journal Article Am J Physiol Gastrointest Liver Physiol · December 2009 Featured Publication Myofibroblastic hepatic stellate cells (MF-HSC) are derived from quiescent hepatic stellate cells (Q-HSC). Q-HSC express certain epithelial cell markers and have been reported to form junctional complexes similar to epithelial cells. We have shown that Hed ... Full text Link to item Cite

Epithelial-to-mesenchymal transitions in the liver.

Journal Article Hepatology · December 2009 Featured Publication The outcome of liver injury is dictated by the effectiveness of repair. Successful repair (i.e., regeneration) results in replacement of dead epithelial cells with healthy epithelial cells, and reconstructs normal hepatic structure and function. Liver rege ... Full text Link to item Cite

Apoptosis and cytokines in non-alcoholic steatohepatitis.

Journal Article Clin Liver Dis · November 2009 Featured Publication Non-alcoholic fatty liver disease (NAFLD), one of the commonest causes of chronic liver disease in the United States, represents several overlapping clinicopathological states, ranging from simple steatosis to non-alcoholic steatohepatitis (NASH). Although ... Full text Link to item Cite

Pan-caspase inhibitor VX-166 reduces fibrosis in an animal model of nonalcoholic steatohepatitis.

Journal Article Hepatology · November 2009 Featured Publication UNLABELLED: Nonalcoholic fatty liver disease (NAFLD) is a potentially progressive liver disease that culminates in cirrhosis. Cirrhosis occurs more often in individuals with nonalcoholic steatohepatitis (NASH) than in those with steatosis (nonalcoholic fat ... Full text Link to item Cite

Hedgehog-mediated epithelial-to-mesenchymal transition and fibrogenic repair in nonalcoholic fatty liver disease.

Journal Article Gastroenterology · October 2009 Featured Publication BACKGROUND & AIMS: Repair responses define the ultimate outcomes of liver disease. This study evaluated the hypothesis that fibrogenic repair in nonalcoholic fatty liver disease (NAFLD) is mediated by Hedgehog (Hh) pathway activation and consequent inducti ... Full text Link to item Cite

Genetic differences in oxidative stress and inflammatory responses to diet-induced obesity do not alter liver fibrosis in mice.

Journal Article Liver Int · September 2009 Featured Publication OBJECTIVE: To determine how genetic factors might influence the progression of nonalcoholic fatty liver disease (NAFLD). DESIGN/INTERVENTION: Beginning in adolescence, male C57BL6 (BL6) and 129/SVJ mice were fed control (n=15/group) or high-fat (HF) diets ... Full text Link to item Cite

Repair-related activation of hedgehog signaling promotes cholangiocyte chemokine production.

Journal Article Hepatology · August 2009 Featured Publication UNLABELLED: The mechanisms mediating hepatic accumulation of inflammatory cells in cholestatic liver disease remain enigmatic. Our thesis is that Hedgehog (Hh) pathway activation promotes hepatic accumulation of immune cells that interact with cholangiocyt ... Full text Link to item Cite

Role for hedgehog pathway in regulating growth and function of invariant NKT cells.

Journal Article Eur J Immunol · July 2009 Featured Publication Lymphocyte accumulation is characteristic of chronic hepatitis, but the mechanisms regulating lymphocyte numbers and their roles in liver disease progression are poorly understood. The Hedgehog (Hh) pathway regulates thymic development and lymphopoeisis du ... Full text Link to item Cite

Similarities and differences in the pathogenesis of alcoholic and nonalcoholic steatohepatitis.

Journal Article Semin Liver Dis · May 2009 Featured Publication Subpopulations of individuals with alcohol-induced fatty livers and nonalcoholic steatosis develop steatohepatitis. Steatohepatitis is defined histologically: increased numbers of injured and dying hepatocytes distinguish this condition from simple steatos ... Full text Link to item Cite

Small-molecule inhibitors of integrin alpha2beta1 that prevent pathological thrombus formation via an allosteric mechanism.

Journal Article Proc Natl Acad Sci U S A · January 20, 2009 Featured Publication There is a grave need for safer antiplatelet therapeutics to prevent heart attack and stroke. Agents targeting the interaction of platelets with the diseased vessel wall could impact vascular disease with minimal effects on normal hemostasis. We targeted i ... Full text Link to item Cite

Liver cell-derived microparticles activate hedgehog signaling and alter gene expression in hepatic endothelial cells.

Journal Article Gastroenterology · January 2009 Featured Publication BACKGROUND & AIMS: Angiogenesis contributes to vascular remodeling during cirrhosis. In cirrhotic livers, cholangiocytes, and myofibroblastic hepatic stellate cells (MF-HSC) produce Hedgehog (Hh) ligands. During embryogenesis Hh ligands are released from l ... Full text Link to item Cite

Mechanisms of disease progression in nonalcoholic fatty liver disease.

Journal Article Semin Liver Dis · November 2008 Featured Publication Nonalcoholic fatty liver disease (NAFLD) encompasses a spectrum of hepatic pathology, ranging from simple steatosis (also called nonalcoholic fatty liver or NAFL) in its most benign form, to cirrhosis in its most advanced form. Nonalcoholic steatohepatitis ... Full text Link to item Cite

Hedgehog signaling regulates epithelial-mesenchymal transition during biliary fibrosis in rodents and humans.

Journal Article J Clin Invest · October 2008 Featured Publication 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 pathwa ... Full text Link to item Cite

The hedgehog pathway regulates remodelling responses to biliary obstruction in rats.

Journal Article Gut · September 2008 Featured Publication BACKGROUND: Chronic biliary obstruction provokes fibrosis and accumulation of immature ductular cells. This fibroductular reaction resolves following biliary decompression, suggesting that it may also be involved in the repair of biliary damage. The hedgeh ... Full text Link to item Cite

Fate-mapping evidence that hepatic stellate cells are epithelial progenitors in adult mouse livers.

Journal Article Stem Cells · August 2008 Featured Publication Liver injury activates quiescent hepatic stellate cells (Q-HSC) to proliferative myofibroblasts. Accumulation of myofibroblastic hepatic stellate cells (MF-HSC) sometimes causes cirrhosis and liver failure. However, MF-HSC also promote liver regeneration b ... Full text Link to item Cite

Hepatic triglyceride synthesis and nonalcoholic fatty liver disease.

Journal Article Curr Opin Lipidol · June 2008 Featured Publication PURPOSE OF REVIEW: Nonalcoholic fatty liver disease is a spectrum of diseases ranging from simple steatosis to cirrhosis. The hallmark of nonalcoholic fatty liver disease is hepatocyte accumulation of triglycerides. We will review the role of triglyceride ... Full text Link to item Cite

Hepatic accumulation of Hedgehog-reactive progenitors increases with severity of fatty liver damage in mice.

Journal Article Lab Invest · December 2007 Featured Publication Progenitors regenerate fatty livers but the mechanisms involved are uncertain. The Hedgehog pathway regulates mesendodermal progenitors and modulates mesenchymal-epithelial interactions during tissue remodeling. To determine if Hedgehog signaling increases ... Full text Link to item Cite

Hedgehog-mediated mesenchymal-epithelial interactions modulate hepatic response to bile duct ligation.

Journal Article Lab Invest · May 2007 Featured Publication In bile duct-ligated (BDL) rodents, as in humans with chronic cholangiopathies, biliary obstruction triggers proliferation of bile ductular cells that are surrounded by fibrosis produced by adjacent myofibroblastic cells in the hepatic mesenchyme. The prox ... Full text Link to item Cite

Sustained activation of Rac1 in hepatic stellate cells promotes liver injury and fibrosis in mice.

Journal Article Hepatology · November 2006 Featured Publication Rac, a small, GTP-binding protein in the Rho family, regulates several cellular functions, including the activation of NADPH oxidase, a major intracellular producer of reactive oxygen species (ROS). Hepatic stellate cells (HSCs) isolated from mice that are ... Full text Link to item Cite

Evidence for epithelial-mesenchymal transitions in adult liver cells.

Journal Article Am J Physiol Gastrointest Liver Physiol · October 2006 Featured Publication Both myofibroblastic hepatic stellate cells (HSC) and hepatic epithelial progenitors accumulate in damaged livers. In some injured organs, the ability to distinguish between fibroblastic and epithelial cells is sometimes difficult because cells undergo epi ... Full text Link to item Cite

Interleukin-15 increases hepatic regenerative activity.

Journal Article J Hepatol · September 2006 Featured Publication BACKGROUND/AIMS: Interleukin-15 (IL-15) is expressed in many organs. It generally inhibits apoptosis and increases cellular proliferation and differentiation. However, IL-15's roles in liver are unknown. We aimed to determine if IL-15 influences hepatic in ... Full text Link to item Cite

Role of inflammation in nonalcoholic steatohepatitis.

Journal Article Curr Opin Gastroenterol · November 2005 Featured Publication PURPOSE OF REVIEW: Products of hepatic macrophages and lymphocytes are acknowledged regulators of liver injury and repair. Recent studies have identified inflammatory modulators from sources within and outside the liver that are critical to the pathogenesi ... Full text Link to item Cite

Role for hedgehog signaling in hepatic stellate cell activation and viability.

Journal Article Lab Invest · November 2005 Featured Publication Hepatic stellate cells (HSC) have a complex phenotype that includes both neural and myofibroblastic features. The Hedgehog (Hh) pathway has been shown to direct the fate of neural and myofibroblastic cells during embryogenesis and during tissue remodeling ... Full text Link to item Cite

Epidermal denervation and its effects on keratinocytes and Langerhans cells.

Journal Article J Neurocytol · September 1996 Featured Publication Skin innervation has been considered to subserve sensory perception only, but several lines of evidence suggest that there are "effector' influences of skin innervation on the immune system and keratotinocytes. In this study, we transected the sciatic nerv ... Full text Link to item Cite

Inhibition of nitric oxide synthesis increases mortality in Sindbis virus encephalitis.

Journal Article J Virol · June 1996 Featured Publication Sindbis virus (SV) is an alphavirus that causes acute encephalomyelitis in mice. The outcome is determined by the strain of virus and by the age and genetic background of the host. The mortality rates after infection with NSV, a neurovirulent strain of SV, ... Full text Link to item Cite

Production and role of cytokines in the CNS of mice with acute viral encephalomyelitis.

Journal Article J Neuroimmunol · May 1996 Featured Publication Semliki Forest Virus (SFV) causes a more severe acute encephalomyelitis in B6 than in SJL mice despite similar T cell proliferation and antibody responses in these two strains. To determine the immunological mechanisms that may contribute to this differenc ... Full text Link to item Cite

A potential role for interferon-alpha in the pathogenesis of HIV-associated dementia.

Journal Article Brain Behav Immun · December 1995 Featured Publication Previous studies in patients receiving interferon-alpha (IFN-alpha) therapy and patients with systemic lupus erythematosus have demonstrated that elevated cerebrospinal fluid (CSF) levels of IFN-alpha are associated with cognitive dysfunction. We measured ... Full text Link to item Cite

Cytokine mRNA expression in postischemic/reperfused myocardium.

Journal Article Am J Pathol · February 1995 Featured Publication While the role of cytokines in mediating injury during hind limb skeletal muscle ischemia followed by reperfusion has recently been described, the role of cytokines in myocardial infarction and ischemia/reperfusion have remained relatively unexplored. We h ... Link to item Cite

Induction of nitric oxide synthase in demyelinating regions of multiple sclerosis brains.

Journal Article Ann Neurol · November 1994 Featured Publication The amount of messenger RNA encoding human inducible nitric oxide synthase and the presence and distribution of NADPH diaphorase were determined in tissue sections from multiple sclerosis (MS) and control brains. Levels of human nitric oxide synthase messe ... Full text Link to item Cite

Intracerebral cytokine mRNA expression during fatal and nonfatal alphavirus encephalitis suggests a predominant type 2 T cell response.

Journal Article J Immunol · February 1, 1994 Featured Publication Sindbis virus (SV) causes an acute encephalomyelitis in mice. A T cell-dependent inflammatory response is first detected 3 days after infection and includes T cells, B cells, and macrophages. The cytokines produced locally by intrinsic cells of the brain i ... Link to item Cite