Don't sugarcoat it: understanding and targeting glycosylation changes in pancreatic and liver cancers

Pancreatic ductal adenocarcinoma (PDAC) and hepatocellular carcinoma (HCC), the most common forms of pancreatic and liver cancer, are among the deadliest cancer types. Although we know which mutations cause PDAC/HCC, we have no effective therapies. In addition to mutations, cancer cells exhibit changes in their protein modifications. Glycosylation, the addition of sugars, is one such modification. Doctors measure glycosylated proteins in PDAC/HCC patients, but we do not understand how these glycosylation changes contribute to the aggressiveness of PDAC/HCC. First, I will build new models of PDAC/HCC in mice. Second, working with glycobiology experts, I will use mass spectrometry-based glycomics and lectin microarrays to document glycosylation changes in PDAC/HCC cells compared to healthy cells. Third, by removing them in mice or human cells, I will investigate how proteins responsible for glycosylation changes contribute to PDAC/HCC. This project will provide detailed knowledge of glycosylation changes and possibly new therapeutic targets in PDAC/HCC.