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...
THIS STUDY UTILIZES THE DHF BIOREPOSITORY Principal Investigator: Xiaoying Liu, PhD, Research Assistant Professor of Medicine (Gastroenterology and Hepatology), Northwestern Medicine, Northwestern Feinberg School of Medicine A rare liver disorder, primary sclerosing cholangitis (PSC) occurs when thickening of bile ducts block the normal, necessary flow of bile within the digestive system. Buildup of toxic bile acids can lead to irreversible liver cirrhosis, cancer, and the need for a risky, life-altering liver transplant. For unknown reasons, up to 70% of patients with PSC also have inflammatory bowel disease (IBD), especially ulcerative colitis. Today, effective treatments don’t yet exist to prevent this progressive and potentially fatal liver disease. Dr. Xiaoying Liu’s team is using this year’s DHF grant award to better understand the disease process of PSC in order to stop it from damaging the liver. The researchers are studying a molecular pathway called “unfolded protein response (UPR)” that springs into action to protect cells from toxicity in the liver. This exciting study stands on the shoulders of previously successful DHF funded research proving increased UPR pathway gene expression in post-liver transplant patients. Dr. Liu hopes to further delineate the protective role of UPR to create a first-in-the-world liver cell atlas in PSC to map cell signaling and cellular interactions. These studies offer important promise for identifying molecular targets to develop much needed new drug therapies for PSC...
