Co-Principal Investigators:

Xiaoying Liu, PhD, Research Assistant Professor of Medicine (Gastroenterology and Hepatology), Northwestern Medicine, Northwestern Feinberg School of Medicine

Richard M. Green, MD, Professor of Medicine (Gastroenterology and Hepatology), Northwestern Medicine, Northwestern Feinberg School of Medicine

A chronic disease of the liver that currently doesn’t have any treatment, primary sclerosing cholangitis (PSC) causes destructive scarring of the ducts that carry bile to the small intestine to help digest fats. Affecting some 50,000 Americans, PSC can occur alone, but is associated with ulcerative colitis or Crohn’s disease in 80% of PSC cases (Only about 6% of IBD patients have PSC). While the exact reason for this overlap still eludes scientists, thankfully, the inevitable progression of PSC toward cirrhosis is not worsened by IBD or treatment for IBD. Limited understanding of PSC has meant that, currently, there aren’t any effective medical therapies to stop dangerous disease progression. Ultimately, PSC patients develop liver cirrhosis, need a liver transplant, or die from their disease.

X-box binding protein 1 (XBP1) is a protein that protects cells from injury. In previous studies, the Liu/Green team found in an animal model that when mice lacked XBP1 in their liver, they were more prone to develop liver damage. Granted the DHF award this year, the investigators plan to explore their hypothesis that progressive PSC results when the XBP1 signaling pathway fails to adequately activate to protect the liver. toThis study will be the first of its kind to use liver biopsies from patients with PSC to measure the XBP1 pathway in several different liver cell types injured by the disease. By identifying the role of XBP1 in PSC, the researchers hope to identify novel targets that can be used to develop new and life-saving therapies, such as an XBP1 activator.