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:

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.