Postdoctoral Position Available

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

Academic Role: Professor

Faculty Appointment(s) In:
   Gastroenterology
   Medicine

Other Affiliation(s):
   Center for AIDS Research
   Program in Immunology and Virology

Current Research Activities

Bench Research:

1. 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.
2. 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.
3. 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.
4. 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:

1. Immune mechanisms of increased liver injury in HCV plus alcohol: overlap with bench research project #3.
2. Therapeutic studies in chronic hepatitis C: I am an investigator at the UMass Memorial site of the national HALT-C trial supported by NIH.
3. 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.

Representative Publications:

1. Szabo G, Chavan S, Mandrekar P, Catalano D: 1999. Acute alcohol consumption attenuates IL-8 and MCP-1 induction in response to ex vivo stimulation. J. Clin. Immunol. 19:67-76.
2. Mandrekar P, Catalano D, Szabo G: 1999. Inhibition of LPS-mediated NF- B activation by ethanol in human monocytes. International Immunology. 11:1781-90.
3. Szabo G: 2000. New insights into the molecular mechanisms of alcoholic hepatitis: The role of NF- B activation? J. Lab. Clin. Med. 135:367-369
4. Fang WC, Saltzman J, Rososhandsky S, Szabo G, Heard S, Banner B, Katz E: 2000. Acceptance of an ABO-incomplete mismatched liver allograft with the use of Daclizumab and Mycophenolate mofetil Liver Transplantation 6:497-500
5. Szabo G, Katz E, Bonkovsky H: 2000. Management of recurrent hepatitis C after liver transplantation: a concise review Am. J. Gastroenterology 9:2164-2170.
6. Szabo G, Catalano D, Bellerose G, Mandrekar P: 2001. Interferon-alpha and alcohol augment nuclear regulatory factor- B activation in HepG2 cells and IFN increases pro-inflammatory cytokine production. Alcoholism: Clin. & Exp. Res. 25:1188-1197.
7. Szabo G, Gavala C, Mandrekar P: 2001. Tacrolimus and cyclosporine A inhibit allostimulatory capacity and cytokine production of human myeloid dendritic cells. J. Investigative Medicine. 49:442-449.
8. Szabo G, Mandrekar P, Dolganiuc A, Catalano D, Kodys K: 2001. Reduced alloreactive T cell activation after alcohol intake is due to impaired monocyte accessory cell function and correlates with elevated IL-10 and decreased IFN? levels. Alcoholism: Clin. & Exp. Res. 25(12):1766-1772.
9. Szabo G, Dolganiuc A: 2002. Immunologic marker analysis of cells in the various stages of hematopoietic differentiation. In: Clinical Applications of Immunophenotypic Analysis. Editor: K. Paloczi, R.G. Landes Co., Publisher (in press).
10. Szabo G, Romics L, Frendl G: 2002. Liver in sepsis and systemic inflammatory response syndrome. In Hepatic Manifestations of Systemic Diseases, Ed. H.L. Bonkovsky Clinics in Liver Disease Publisher: W.B. Saunders, Philadelphia (in press).
11. Drechsler Y, Mandrekar P, Chavan S, Szabo G: 2002. Fc-gamma receptor crosslinking mediates NF B activation, reduced antigen presentation capacity and IL-12 production in monocytes without inhibition of myeloid dendritic cell development. J. Leuk. Biol. (in press).
12. Szabo G & Mandrekar P: May 1, 2002. Ethanol-mediated regulation of transcription factors in immunocompetent cells. Frontiers in Bioscience 7, a80-89. (in press)

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

Office: Research 215
Phone: 508-856-5275
E-mail: Gyongyi.Szabo@umassmed.edu

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Postdoctoral Position Available Immediate opening! Two postdoctoral positions are available immediately to study cellular and molecular mechanisms resulting in immunosuppression after alcohol use. The focus of this research is the role of monocytes and dendritic cells in decreased antigen-specific T cell activation after alcohol use. Intracellular signalling mechanisms resulting in decreased NF-kB activation and inflammatory cytokine induction after acute alcohol consumption are being investigated. Please contact Dr. Szabo for details.