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.

Ongoing projects:

  1. 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.

  2. Liver fibrosis and aging-  The incidence of advanced liver disease in the aging population is increasing and often these patients are not candidates for liver transplant.

  3. Alcoholic liver disease and danger signals – Excessive alcohol intake induces liver inflammation and cell death

  4. PSC is a fibrosing liver disease that has no approved treatment, and is often associated with ulcerative colitis. The affected extra- intrahepatic bile ducts often show an onion-skin appearance where the duct is surrounded by dense fibrous tissue