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Gyongyi Szabo, M.D., Ph.D.

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Overview

Mentoring
Available: 01/09/23, Expires: 12/31/25

Alcoholic hepatitis (AH) is a severe form of alcoholic liver disease (ALD) with a >30% mortality within 180 days after diagnosis. There is no effective therapy or reliable biomarkers to monitor disease progression and outcome. In this NIH supported study, we will assess the small and large RNA composition of circulating extracellular vesicles(EV) from patients with alcoholic hepatitis, heavy alcohol use and normal controls. Large data sets from RNA sequencing will be evaluated and correlated with clinical outcomes such as mortality, organ failure, infections. In addition, our translational research lab studies non-alcoholic steatohepatitis and fibrosis. We use mouse models to dissect the mechanistic roles of key signaling molecules identified in patient samples and test novel therapeutic interventions in preclinical models.

Available: 02/01/23, Expires: 12/31/24

Alcoholic and non-alcoholic steatohepatitis (NASH) represent over 50% of liver diseases worldwide and activation of the inflammatory cascade contributes to disease progression. There is also emerging evidence about alcohol use accelerating NASH that is the liver manifestation of the metabolic syndrome, obesity and insulin resistance/Type 2 diabetes. This project will aim to answer critical questions related to key determinants of disease progression and clinical outcomes using bedside to bench approaches. We will utilize human biospecimens prospectively collected in the AlcHepNet clinical trial to evaluate the functional, phenotypic and metabolomic characteristics of major circulating immune cell populations in the well-defined patient populations including: severe alcoholic hepatitis (AH), heavy drinkers and healthy controls. We will particularly focus on circulating immune cells as “liquid biopsy” tools for biomarker discovery in assessing immunosuppression, parameters associated with infections and response to therapy in AH patients. Using preclinical models, we will test immunometabolic profiles in a mouse model of NASH and the combination of NASH and alcohol binge drinking. These experiments will likely reveal new mechanisms and potential therapeutic targets related to metabolic reprogramming of immune cells my metabolic insults that promote long-term inflammation and fibrosis progression.


Research
The research activities and funding listed below are automatically derived from NIH ExPORTER and other sources, which might result in incorrect or missing items. Faculty can login to make corrections and additions.
  1. R01AA017729 (SZABO, GYONGYI) Sep 23, 2019 - Jan 31, 2022
    NIH/NIAAA
    Innate Immune Signaling in Alcoholic Liver Disease
    Role Description: This application further investigates if the absence of TLR4, but not of the MyD88 adaptor, protects mice from alcoholic liver disease.
    Role: Principal Investigator
  2. U01AA026933 (SZABO, GYONGYI) Sep 19, 2019 - Jun 30, 2023
    NIH
    Biomarkers of Disease in Alcoholic Hepatitis
    Role: Principal Investigator
  3. R01AA011576 (SZABO, GYONGYI) Sep 19, 2019 - Mar 31, 2021
    NIH/NIAAA
    Alcohol and Monocyte Signaling
    Role Description: The overall goal of this research is to define molecular mechanisms that regulate the switch from the acute, anti-inflammatory to the chronic, pro-inflammatory effects of alcohol.
    Role: Principal Investigator
  4. UH2AA026970 (SZABO, GYONGYI) Sep 22, 2018 - Jun 30, 2020
    NIH
    Extracellular Vesicles in Alcoholic Liver Disease: Basic and Pre-Clinical Discovery
    Role: Principal Investigator
  5. U01AA026977 (SZABO, GYONGYI) Aug 1, 2018 - Jun 30, 2023
    NIH
    Alcoholic Hepatitis Clinical and Translational Network Late Phase Clinical Trials and Observational Studies 4/9
    Role: Principal Investigator

Bibliographic
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Funded by the NIH National Center for Advancing Translational Sciences through its Clinical and Translational Science Awards Program, grant number UL1TR002541.