John C. Samuelson, MD, PhD

Biography

Our lab studies the glycobiology of protozoan parasites that cause diarrhea (Cryptosporidium and Giardia), dysentery (Entamoeba), birth defects (Toxoplasma), and blindness (Acanthamoeba). In particular, we use mass spectrometric, biochemical, and genetic methods to characterize sugars added to glycoproteins, as well as the enzymes that make or remove these sugars (glycosyltransferases and glycosyl hydrolases, respectively). For example, we showed that asparagine-linked glycans (N-glycans) of Cryptosporidium have a single mannose arm that is hardly modified and so is distinct from complex, highly modified N-glycans of the host. In contrast, Cryptosporidium vaccine candidates have mucin-like domains densely modified with O-GalNAc that resemble host intestinal mucins. We discovered a large set of nuclear proteins of Toxoplasma that are decorated with O-linked fucose and showed that O-fucosyltransferase is a homolog of plant Spindly. The host is lacking Spindly but has an O-GlcNAc transferase with a similar structure to Spindly that modifies an even larger set of nucleocytosolic proteins. We also identified a second Toxoplasma O-fucosyltransferase that modifies a secreted protein MIC2, which is essential for parasite adherence to and invasion into host cells.

The Samuelson lab also studies sugar polymers and glycoproteins present in cyst and oocyst walls of these parasites, which are critical for their transmission from person to person. The simple model we have developed is that these walls contain sugar polymers similar to those in fungal and plant walls: chitin (Entamoeba), glucan (Toxoplasma), and cellulose, chitin, and xylan (Acanthamoeba). In contrast to fungi and plants, glycoproteins in the parasite walls are few and are for the most part lectins (proteins that bind sugars), which bind the sugar polymers. These wall lectins are unique to each parasite and may be targets for diagnostic reagents. Finally, we have explored the potential use of alcohol-based hand sanitizers to prevent transmission of Giardia, Entamoeba, and Acanthamoeba.