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Szabo, Gyongyi

One or more keywords matched the following properties of Szabo, Gyongyi

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overview	Background Education: MD, University Medical School Debrecen, Hungary PhD, Hungarian Academy of Sciences (Immunology/Medicine) Post-Graduate Training: Internal Medicine Residency, University of Massachusetts Medical Center Worcester, MA Gastroenterology and Hepatology Fellowship, Division of Gastroenterology, University of Massachusetts Medical Center, Worcester, MA Current Research Activities Bench Research: Immune alterations induced by acute alcohol consumption: My laboratory is one of the few focusing on immunomodulation by moderate alcohol use in humans. In addition to understanding mechanisms for the increased susceptibility to infections after alcohol use, results from our investigations have relevance to decreased cardiovascular morbidity after moderate alcohol use as well as to accelerated liver disease in chronic hepatitis C virus infection. My laboratory studies changes in the interaction between accessory cells (monocytes and dendritic cells) and T lymphocytes after moderate alcohol use. The overall aim of our studies is to delineate the effect of alcohol on antigen presenting cell function and determine role of cytokine and co-stimulatory molecules leading to decreased antigen-specific T cell proliferation and impaired antimicrobial defense after alcohol use. Intracellular signaling pathways in leukocytes mediating altered cytokine production after alcohol use. We are studying intracellular signaling mechanisms leading to decreased NF- B activation in monocytic and immune cells after acute alcohol treatment in relation to signals mediated by toll-like receptors. Recent interest is to define the NF-kB-mediated intracellular mechanisms that lead to the opposite effects of acute and chronic alcohol use on pro-inflammatory cytokine production. Immune mechanisms leading to increased liver injury in HCV plus alcohol. The hypothesis is that impaired dendritic cell costimulatory activity is a pivotal defect of host response to hepatitis C infection and alcohol further reduces immunity by inhibiting maturation and functions of myeloid dendritic cells in HCV. Immunopathogenesis of liver injury in obese mice: This is a developing project to investigate the hypothesis that leptin deficient, ob/ob mice have increased susceptibility to immune-mediated liver injury in a model of Concanavalin-A or LPS-induced hepatitis. We found that in contrast to lean mice, ob/ob mice have over-activation of the NF- B signaling pathway in the liver, a mechanisms likely to contribute to increased susceptibility to liver injury. Results from these experiments have direct clinical relevance to mechanisms of liver injury in non-alcoholic steatohepatitis in human. Clinical Research: Immune mechanisms of increased liver injury in HCV plus alcohol: overlap with bench research project #3. Therapeutic studies in chronic hepatitis C: I am an investigator at the UMass Memorial site of the national HALT-C trial supported by NIH. Therapeutic approaches in non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). A clinical trial to investigate the potential therapeutic benefit of an insulin sensitizing agent in NASH is being initiated. Additional therapeutic approaches in patients with NAFLD are under development. NAFLD /NASH have recently been recognized as one of the most prevalent liver diseases in the USA, and the most common cause of cryptogenic cirrhosis. Research Figure

Property

Value

overview

Background

Education:

MD, University Medical School Debrecen, Hungary
PhD, Hungarian Academy of Sciences (Immunology/Medicine)

Post-Graduate Training:

Internal Medicine Residency, University of Massachusetts Medical Center Worcester, MA

Gastroenterology and Hepatology Fellowship, Division of Gastroenterology, University of Massachusetts Medical Center, Worcester, MA

Current Research Activities

Bench Research:

Immune alterations induced by acute alcohol consumption: My laboratory is one of the few focusing on immunomodulation by moderate alcohol use in humans. In addition to understanding mechanisms for the increased susceptibility to infections after alcohol use, results from our investigations have relevance to decreased cardiovascular morbidity after moderate alcohol use as well as to accelerated liver disease in chronic hepatitis C virus infection. My laboratory studies changes in the interaction between accessory cells (monocytes and dendritic cells) and T lymphocytes after moderate alcohol use. The overall aim of our studies is to delineate the effect of alcohol on antigen presenting cell function and determine role of cytokine and co-stimulatory molecules leading to decreased antigen-specific T cell proliferation and impaired antimicrobial defense after alcohol use.
Intracellular signaling pathways in leukocytes mediating altered cytokine production after alcohol use. We are studying intracellular signaling mechanisms leading to decreased NF- B activation in monocytic and immune cells after acute alcohol treatment in relation to signals mediated by toll-like receptors. Recent interest is to define the NF-kB-mediated intracellular mechanisms that lead to the opposite effects of acute and chronic alcohol use on pro-inflammatory cytokine production.
Immune mechanisms leading to increased liver injury in HCV plus alcohol. The hypothesis is that impaired dendritic cell costimulatory activity is a pivotal defect of host response to hepatitis C infection and alcohol further reduces immunity by inhibiting maturation and functions of myeloid dendritic cells in HCV.
Immunopathogenesis of liver injury in obese mice: This is a developing project to investigate the hypothesis that leptin deficient, ob/ob mice have increased susceptibility to immune-mediated liver injury in a model of Concanavalin-A or LPS-induced hepatitis. We found that in contrast to lean mice, ob/ob mice have over-activation of the NF- B signaling pathway in the liver, a mechanisms likely to contribute to increased susceptibility to liver injury. Results from these experiments have direct clinical relevance to mechanisms of liver injury in non-alcoholic steatohepatitis in human.

Clinical Research:

Immune mechanisms of increased liver injury in HCV plus alcohol: overlap with bench research project #3.
Therapeutic studies in chronic hepatitis C: I am an investigator at the UMass Memorial site of the national HALT-C trial supported by NIH.
Therapeutic approaches in non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). A clinical trial to investigate the potential therapeutic benefit of an insulin sensitizing agent in NASH is being initiated. Additional therapeutic approaches in patients with NAFLD are under development. NAFLD /NASH have recently been recognized as one of the most prevalent liver diseases in the USA, and the most common cause of cryptogenic cirrhosis.

Research Figure

One or more keywords matched the following items that are connected to Szabo, Gyongyi

Item Type	Name
Academic Article	Diverse regulation of NF-kappaB and peroxisome proliferator-activated receptors in murine nonalcoholic fatty liver.
Academic Article	Hepatitis C core and nonstructural 3 proteins trigger toll-like receptor 2-mediated pathways and inflammatory activation.
Academic Article	Subversion of plasmacytoid and myeloid dendritic cell functions in chronic HCV infection.
Academic Article	Toll-like receptor 2 mediates inflammatory cytokine induction but not sensitization for liver injury by Propioni- bacterium acnes.
Academic Article	Critical role of toll-like receptors and the common TLR adaptor, MyD88, in induction of granulomas and liver injury.
Academic Article	The critical role of toll-like receptor (TLR) 4 in alcoholic liver disease is independent of the common TLR adapter MyD88.
Academic Article	MicroRNA expression profile in Lieber-DeCarli diet-induced alcoholic and methionine choline deficient diet-induced nonalcoholic steatohepatitis models in mice.
Academic Article	Identification and characterization of broadly neutralizing human monoclonal antibodies directed against the E2 envelope glycoprotein of hepatitis C virus.
Academic Article	Type I interferons protect from Toll-like receptor 9-associated liver injury and regulate IL-1 receptor antagonist in mice.
Academic Article	Up-regulation of microRNA-155 in macrophages contributes to increased tumor necrosis factor {alpha} (TNF{alpha}) production via increased mRNA half-life in alcoholic liver disease.
Academic Article	Deficiency in myeloid differentiation factor-2 and toll-like receptor 4 expression attenuates nonalcoholic steatohepatitis and fibrosis in mice.
Academic Article	Fatty acid and endotoxin activate inflammasomes in mouse hepatocytes that release danger signals to stimulate immune cells.
Academic Article	Hepatocyte-specific hypoxia-inducible factor-1a is a determinant of lipid accumulation and liver injury in alcohol-induced steatosis in mice.
Academic Article	The presence of p47phox in liver parenchymal cells is a key mediator in the pathogenesis of alcoholic liver steatosis.
Academic Article	Circulating microRNAs in exosomes indicate hepatocyte injury and inflammation in alcoholic, drug-induced, and inflammatory liver diseases.
Academic Article	Plasma microRNA profiles distinguish lethal injury in acetaminophen toxicity: a research study.
Academic Article	IL-1 receptor antagonist ameliorates inflammasome-dependent alcoholic steatohepatitis in mice.
Academic Article	Chronic alcohol-induced microRNA-155 contributes to neuroinflammation in a TLR4-dependent manner in mice.
Academic Article	Selective priming to Toll-like receptor 4 (TLR4), not TLR2, ligands by P. acnes involves up-regulation of MD-2 in mice.
Academic Article	Increased lipopolysaccharide sensitivity in alcoholic fatty livers is independent of leptin deficiency and toll-like receptor 4 (TLR4) or TLR2 mRNA expression.
Academic Article	Modulation of non-alcoholic steatohepatitis by pattern recognition receptors in mice: the role of toll-like receptors 2 and 4.
Academic Article	Heme oxygenase-1 mediates the anti-inflammatory effects of acute alcohol on IL-10 induction involving p38 MAPK activation in monocytes.
Academic Article	Toll-like receptors 1 and 6 are involved in TLR2-mediated macrophage activation by hepatitis C virus core and NS3 proteins.
Academic Article	Bone marrow-derived immune cells mediate sensitization to liver injury in a myeloid differentiation factor 88-dependent fashion.
Academic Article	VSL#3 probiotic treatment attenuates fibrosis without changes in steatohepatitis in a diet-induced nonalcoholic steatohepatitis model in mice.
Academic Article	Interferon regulatory factor 3 and type I interferons are protective in alcoholic liver injury in mice by way of crosstalk of parenchymal and myeloid cells.
Academic Article	Dendritic cells in hepatitis C infection: can they (help) win the battle?
Academic Article	Mitochondrial antiviral signaling protein defect links impaired antiviral response and liver injury in steatohepatitis in mice.
Academic Article	An essential role for monocyte chemoattractant protein-1 in alcoholic liver injury: regulation of proinflammatory cytokines and hepatic steatosis in mice.
Academic Article	Lipopolysaccharide induces and activates the Nalp3 inflammasome in the liver.
Academic Article	Induction of Bcl-3 by acute binge alcohol results in toll-like receptor 4/LPS tolerance.
Academic Article	Alcohol-induced IL-1? in the brain is mediated by NLRP3/ASC inflammasome activation that amplifies neuroinflammation.
Concept	Mice, Obese
Concept	Mice, Knockout
Concept	Mice
Concept	Mice, Inbred C57BL
Concept	Mice, Transgenic
Concept	Mice, Mutant Strains
Academic Article	STING-IRF3 pathway links endoplasmic reticulum stress with hepatocyte apoptosis in early alcoholic liver disease.
Academic Article	High fat diet feeding results in gender specific steatohepatitis and inflammasome activation.
Academic Article	Micro-RNA-155 deficiency prevents alcohol-induced serum endotoxin increase and small bowel inflammation in mice.
Academic Article	Both bone marrow-derived and non-bone marrow-derived cells contribute to AIM2 and NLRP3 inflammasome activation in a MyD88-dependent manner in dietary steatohepatitis.
Academic Article	Exosome-mediated delivery of functionally active miRNA-155 inhibitor to macrophages.
Academic Article	microRNA-122 regulates hypoxia-inducible factor-1 and vimentin in hepatocytes and correlates with fibrosis in diet-induced steatohepatitis.
Academic Article	Exosomes derived from alcohol-treated hepatocytes horizontally transfer liver specific miRNA-122 and sensitize monocytes to LPS.
Academic Article	Biodistribution and function of extracellular miRNA-155 in mice.
Academic Article	MicroRNA-155 Deficiency Attenuates Liver Steatosis and Fibrosis without Reducing Inflammation in a Mouse Model of Steatohepatitis.
Academic Article	Progression of non-alcoholic steatosis to steatohepatitis and fibrosis parallels cumulative accumulation of danger signals that promote inflammation and liver tumors in a high fat-cholesterol-sugar diet model in mice.
Academic Article	Inflammasome activation and function in liver disease.
Academic Article	Metabolic danger signals, uric acid and ATP, mediate inflammatory cross-talk between hepatocytes and immune cells in alcoholic liver disease.
Academic Article	Increased number of circulating exosomes and their microRNA cargos are potential novel biomarkers in alcoholic hepatitis.
Academic Article	Inhibition of sterile danger signals, uric acid and ATP, prevents inflammasome activation and protects from alcoholic steatohepatitis in mice.
Academic Article	Alcoholic hepatitis accelerates early hepatobiliary cancer by increasing stemness and miR-122-mediated HIF-1a activation.
Academic Article	Adult mouse model of early hepatocellular carcinoma promoted by alcoholic liver disease.
Academic Article	The pro-inflammatory effects of miR-155 promote liver fibrosis and alcohol-induced steatohepatitis.
Academic Article	Therapeutic Benefits of Spleen Tyrosine Kinase Inhibitor Administration on Binge Drinking-Induced Alcoholic Liver Injury, Steatosis, and Inflammation in Mice.
Academic Article	Inhibition of spleen tyrosine kinase activation ameliorates inflammation, cell death, and steatosis in alcoholic liver disease.
Academic Article	Endoplasmic Reticulum Stress-induced Hepatocellular Death Pathways Mediate Liver Injury and Fibrosis via Stimulator of Interferon Genes.
Academic Article	Interleukin-1 inhibition facilitates recovery from liver injury and promotes regeneration of hepatocytes in alcoholic hepatitis in mice.
Academic Article	Alcohol-related changes in the intestinal microbiome influence neutrophil infiltration, inflammation and steatosis in early alcoholic hepatitis in mice.
Academic Article	Recovery of ethanol-induced Akkermansia muciniphila depletion ameliorates alcoholic liver disease.
Academic Article	Alcohol-induced miR-155 and HDAC11 inhibit negative regulators of the TLR4 pathway and lead to increased LPS responsiveness of Kupffer cells in alcoholic liver disease.
Academic Article	Extracellular vesicles from mice with alcoholic liver disease carry a distinct protein cargo and induce macrophage activation through heat shock protein 90.
Academic Article	MicroRNA 122, Regulated by GRLH2, Protects Livers of Mice and?Patients From Ethanol-Induced Liver Disease.
Academic Article	IL-1a in acetaminophen toxicity: a sterile danger signal.
Academic Article	Hypoxia downregulates protein S expression.
Academic Article	FXR and TGR5 Agonists Ameliorate Liver Injury, Steatosis, and Inflammation After Binge or Prolonged Alcohol Feeding in Mice.
Academic Article	Abnormal neutrophil traps and impaired efferocytosis contribute to liver injury and sepsis severity after binge alcohol use.
Academic Article	Pharmacological Inhibition of CCR2/5 Signaling Prevents and Reverses Alcohol-Induced Liver Damage, Steatosis, and Inflammation in Mice.
Academic Article	Macrophage-Specific Hypoxia-Inducible Factor-1a Contributes to Impaired Autophagic Flux in Nonalcoholic Steatohepatitis.
Academic Article	Alcoholic Liver Disease Accelerates Early Hepatocellular Cancer in a?Mouse Model.
Academic Article	Reduced gut microbiome protects from alcohol-induced neuroinflammation and alters intestinal and brain inflammasome expression.
Academic Article	Inhibition of Triggering Receptor Expressed on Myeloid Cells 1 Ameliorates Inflammation and Macrophage and Neutrophil Activation in Alcoholic Liver Disease in Mice.
Academic Article	Dysregulated Autophagy and Lysosome Function Are Linked to Exosome Production by Micro-RNA 155 in Alcoholic Liver Disease.
Academic Article	Inhibition of the Inflammasome Signaling Cascade Reduces Alcohol Consumption in Female But Not Male Mice.
Academic Article	Chronic alcohol-induced neuroinflammation involves CCR2/5-dependent peripheral macrophage infiltration and microglia alterations.
Academic Article	Deficiency of miR-208a Exacerbates CCl4-Induced Acute Liver Injury in Mice by Activating Cell Death Pathways.
Academic Article	Steatosis, inflammasome upregulation, and fibrosis are attenuated in miR-155 deficient mice in a high fat-cholesterol-sugar diet-induced model of NASH.
Academic Article	Protective effect of LNA-anti-miR-132 therapy on liver fibrosis in mice.
Academic Article	Differential role of MLKL in alcohol-associated and non-alcohol-associated fatty liver diseases in mice and humans.
Academic Article	Gut microbial trimethylamine is elevated in alcohol-associated hepatitis and contributes to ethanol-induced liver injury in mice.
Academic Article	Altered ethanol metabolism and increased oxidative stress enhance alcohol-associated liver injury in farnesoid X receptor-deficient mice.
Academic Article	Granulocyte colony-stimulating factor attenuates liver damage by M2 macrophage polarization and hepatocyte proliferation in alcoholic hepatitis in mice.
Academic Article	Transcriptional regulation of Acsl1 by CHREBP and NF-kappa B in macrophages during hyperglycemia and inflammation.
Academic Article	Neutrophil extracellular traps contribute to liver damage and increase defective low-density neutrophils in alcohol-associated hepatitis.
Academic Article	Alcohol-induced extracellular ASC specks perpetuate liver inflammation and damage in alcohol-associated hepatitis even after alcohol cessation.
Academic Article	Protective role of cGAS in NASH is related to the maintenance of intestinal homeostasis.
Academic Article	Bile acid-induced IRF3 phosphorylation mediates cell death, inflammatory responses, and fibrosis in cholestasis-induced liver and kidney injury via regulation of ZBP1.
Academic Article	Combined Insults of a MASH Diet and Alcohol Binges Activate Intercellular Communication and Neutrophil Recruitment via the NLRP3-IL-1? Axis in the Liver.
Academic Article	A novel experimental model of MetALD in male mice recapitulates key features of severe alcohol-associated hepatitis.
Academic Article	Neutrophil extracellular traps activate hepatic stellate cells and monocytes via NLRP3 sensing in alcohol-induced acceleration of MASH fibrosis.
Academic Article	In vivo Bruton's tyrosine kinase inhibition attenuates alcohol-associated liver disease by regulating CD84-mediated granulopoiesis.
Academic Article	IRF3 regulates neuroinflammatory responses and the expression of genes associated with Alzheimer's disease.
Academic Article	miR-21: A therapeutic target for delaying severe liver disease and hepatocellular carcinoma in high-fat-diet-fed mice.

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