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American Liver Foundation
39 Broadway, Suite 2700
New York, New York 10006
PSC Seed Grant Award
University of Calgary, Alberta, Canada
“Role of Glypican-6 in Primary Sclerosing Cholangitis”
Primary sclerosing cholangitis (PSC) is strongly associated with inflammatory bowel disease (IBD). Dr Eksteen proposed that this association occurs as a result of inappropriate recruitment of mucosal lymphocytes from the gut into the liver. I have shown that mucosal T cells are recruited to the liver in PSC due to aberrant expression of gut adhesion molecules but it remains unknown why some individuals with IBD develop PSC whilst others don’t. Glyplican-6 has been identified a major genetic risk factor for PSC. Glypicans act as extra-cellular scaffolds to which adhesion molecules and cytokines bind.
Genetic alterations in Glypican-6 increase its affinity to bind gut adhesion molecules and recruit mucosal T cells to the liver to perpetuate biliary inflammation.
Aims and Design:
He expects to find that genetic mutations in glypican-6 leads to an altered extracellular milieu in the liver that is permissive for gut T cells to enter the liver and cause biliary inflammation. This work would clarify if glypican-6 is a valid target for future therapeutic development.