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.
Dr. Nadine Samara was born in New York City and has lived in Lebanon, Saudi Arabia, and the United States. Upon graduating from the American University of Beirut with a BS in Chemistry, she returned to the United States and obtained a PhD in Molecular Biophysics from The Johns Hopkins University School of Medicine. She then started her postdoctoral research as an NIGMS-PRAT Fellow at NIDDK/NIH. In 2015, Dr. Samara transitioned to a Staff Scientist Position at NIDCR/NIH, where she is now an Earl Stadtman Investigator and Chief of the Structural Biochemistry Unit. As a Distinguished Scholar at NIH, Dr. Samara will focus on building an inclusive and diverse environment within the lab and institute.
- Zhang L, Mann M, Syed Z, Reynolds HM, Tian E, Samara NL, Zeldin DC, Tabak LA, Ten Hagen KG. (2021). Furin cleavage of the SARS-CoV-2 spike is modulated by O-glycosylation. PNAS, vol. 118, No. 47 e2109905118.
- May C, Ji S, Zulfeqhar S, Revoredo L, Daniel EJP, Gerken TA, Tabak LA, Samara NL, Ten Hagen KG (2020). Differential splicing of the lectin domain of an O-glycosyltransferase modulates both peptide and glycopeptide preferences. JBC, July 15, 2020.
- Fernandez AJ, Daniel EJP, Mahajan SP, Gray JJ, Gerken TA, Tabak LA, Samara NL (2019). The structure of the colorectal cancer-associated enzyme GalNAc-T12 reveals how non-conserved residues dictate its function. PNAS, vol. 116, pp. 20404-20410.
- Wu J, Samara NL, Kuraoka I, Yang W (2019). Evolution of Inosine-Specific Endonuclease V from Bacterial DNase to Eukaryotic RNase. Molecular Cell, vol. 76, pp. 1-13.
- Ji S, Samara NL, Revoredo L, Zhang L, Tran DT, Muirhead K, Tabak LA, Ten Hagen KG (2018). A molecular switch orchestrates enzyme specificity and secretory granule morphology. Nature Communications, 9, 3508.
- Samara NL, Yang W (2018). Cation trafficking propels RNA hydrolysis. Nature Structural & Molecular Biology, 25(8), 715–721.
- Samara NL, Gao Y, Wu J, Yang W (2017). Detection of Reaction Intermediates in Mg2+-Dependent DNA Synthesis and RNA Degradation by Time-Resolved X-Ray Crystallography.Methods Enzymol., 592, pp.283-327.
- Li CL, Golebiowski FM, Onishi Y, Samara NL, Sugasawa K, Yang W (2015). Tripartite DNA Lesion Recognition and Verification by XPC, TFIIH, and XPA in Nucleotide Excision Repair. Molecular Cell, vol. 59, issue 6, pp. 1025-34.
- Samara NL, Ringel AE, Wolberger C (2012). A Role for Inter-subunit Interactions in Maintaining SAGA Deubiquitinating Module Structure and Activity. Structure, vol. 20, issue 8, pp.1414-24.
- Samara NL, Wolberger C (2011). A New Chapter in the Transcription SAGA. Current Opinions in Structural Biology, vol. 21, issue 6, pp. 767-74.
- Samara NL, Datta AB, Berndsen CE, Zhang X, Yao T, Cohen RE, Wolberger C (2010). Structural Insights into the Assembly and Function of the SAGA Deubiquitinating Module. Science, vol. 328, pp.1025-29.