Nadine Samara, Ph.D.

The overall aim of our group is to characterize the O-glycosyltransferases that synthesize O-glycans or polysaccharides that influence host-microbe interactions. In higher eukaryotes, the mucus that coats the epithelium and protects underlying tissue from damage and infection while providing an optimal environment for commensal microbes obtains its protective properties from densely O-glycosylated mucin proteins. The large family of isoenzymes that initiate mucin-type O-glycosylation by transferring O-GalNAc to Thr/Ser residues are the polypeptide N-acetylgalactosaminyltransferases (GalNAc-Ts). These enzymes are critical for normal development, and their dysfunction is associated with developmental diseases, neurological disorders, and cancer. However, we are only beginning to understand how GalNAc-Ts recognize and modify their substrates. Similarly, microbes synthesize protective polysaccharide, glycoprotein, and glycolipid structures such as capsular polysaccharide (CPS) that are virulence factors, and the machinery responsible for the synthesis of these structures are potential anti-microbial targets. We primarily use biochemical and structural methods, including X-ray crystallography and cryo-electron microscopy, to obtain atomic level details on how O-glycosyltransferases recognize, bind to, and modify their substrates.