Another is the exploration of a new kind of carbohydrate chain that may regulate leukocyte extravasation through the endothelium. In addition, we have also used artificial glycosides to study the biosynthesis of glycans containing glucuronic acids. Some cases of congenital hepatic fibrosis and hypoglycemia are now known to be caused by PMI deficiency. Simple dietary supplements of mannose correct faulty glycosylation and clinical pathology in PMI-deficient patients. Other CDGS patients with these and other glycosylation deficiencies are now enrolled in Phase I mannose trials.
Preliminary results are encouraging.
We also found a novel type of carboxylated oligosaccharide in endothelial cells that binds to proteins implicated in the control of leukocyte extravasation. Detailed structural analysis of the carbohydrate and how it interacts with the leukocyte proteins are now an important focus in the lab. We continue to study the biosynthesis of oligosaccharides capped by terminal GalNAca-1,4GlcA residues, and to use artificial glycosides to probe the organization of glycosyltransferases in the Golgi.