Principal Investigator: Ryan Shaw, PhD, Post-doctoral Scholar, Transplant Surgery Scientist Training Program, Northwestern Medicine, Northwestern University Feinberg School of Medicine

Co-Principal Investigator: Richard M. Green, MD, Professor of Medicine (Gastroenterology and Hepatology), Northwestern Medicine, Northwestern University Feinberg School of Medicine

Liver diseases such as primary sclerosing cholangitis (PSC) inflame and scar and block bile ducts, leading to back-up of bile in the liver and blood (jaundice) and prevent the normal secretion of bile into the intestines to aid digestion. Too much bile in the liver can lead to end-stage cirrhosis of this vital organ. Up to 85% of PSC patient also have ulcerative colitis or Crohn’s disease. With few effective treatments and no cure, adults and children with PSC and other cholestatic liver diseases face cirrhosis of the liver, liver failure and death without a liver transplant.

Decades of work in the Green lab have shown in mouse models the protective influence of a gene in the liver called X-box Binding Protein 1 (XBP1). Because humans have different bile acids than mice, these species-specific differences limit the direct translation of mouse XBP1 cholestasis studies to corresponding human liver diseases. Granted the DHF award this year, the investigators plan to use two recently developed strains of “humanized” mice to investigate the role of XBP1 in a more human-like system. One producing humanized bile and the other, possessing humanized livers, these unique animal models will greatly aid in the development of novel drug or genetic therapies for PSC and other liver diseases that cause back-up of bile flow through the liver.