Our laboratory has been focusing on liver fibrogenesis and elucidating the mechanistic links between activation of redox pathways, hepatocyte cell death and stellate cell activation. We have particularly been interested in the role of NADPH oxidases and their cell-specific roles in liver injury and repair. Previously we demonstrated that the non-phagocytic NADPH oxidase (NOX4) dysregulates insulin responses in the liver and precipitates stress signaling in non-alcoholic steatohepatitis (NASH) leading to fibrosis.
As NASH is becoming the most common liver disease in the US and worldwide our ultimate goal is to translate our findings and develop novel therapeutic approaches that reverse fibrosis in NASH and improve patient outcomes.
Patients with type II diabetes mellitus develop more progressive NASH often leading to liver failure and complications such as hepatocellular carcinoma. We are studying how advanced glycation end products (AGEs) are involved in inflammation and fibrosis focusing on NADPH oxidase-mediated redox stress, and how this is involved activation of stellate cells and matrix turnover.
Aging-related pathways affect the wound healing process. We explore the age-related modulation of hepatocyte stress signals, myofibroblast transdifferentiation and innate immune responses in the aging liver.
Alcoholic hepatitis clinically carries a dismal prognosis, with no effective treatment available. In this translational project we investigate novel pathways that can be targeted for development of rational therapy.
We are working on developing novel small molecule inhibitors for treatment of fibrosis in NASH.