This application is in the area of Chemical Biology (Area 2). Glycosylation,? which creates a diverse array of carbohydrate epitopes attached to cell surface? proteins and lipids, is an inherently complex system that is poorly understood.? Carbohydrates play crucial roles in a diverse array of medically relevant? biological processes from viral pathogenesis to tumor cell metastasis and stem? cell differentiation. However, due to the biosynthetic and molecular complexity of? these biopolymers, we have little comprehension of how glycan synthesis is? controlled. Systems-based approaches to biology, in which large datasets are? analyzed using bioinformatic algorithms, provide an important avenue for? exploring the mechanics of complex systems that cannot be predicted a-priori.? Application of such approaches to glycosylation however has been limited due to? the lack of methodology for high-throughput analysis of carbohydrates? (glycomics). Recent work in my laboratory on lectin microarray technology has? begun to address the analytical problems inherent in glycomics and thus pave? the way for systematic analysis of the glycome. I propose to use the NCI-60 cell? panel as a model system to integrate glycomic information with proteomic,? genomic and metabolic pertubation data to create a predictive model of how cell? surface glycosylation is encoded. To achieve this objective, we will reinvent? bioinformatics technology for glycomics including analytical and databasing? methods, integration of information and predictive modeling, providing useful? tools for the study of glycomics in a wide variety of contexts. Detailed knowledge? of how the genome and other factors control glycosylation will have a strong? impact on a diverse swath of fields where carbohydrates play important roles? including immunology, cancer research and developmental biology and may? impact their use as potential biomarkers for disease.
| Agrawal, Praveen; Kurcon, Tomasz; Pilobello, Kanoelani T et al. (2014) Mapping posttranscriptional regulation of the human glycome uncovers microRNA defining the glycocode. Proc Natl Acad Sci U S A 111:4338-43 |
| Liang, Yaxuan; Eng, William S; Colquhoun, David R et al. (2014) Complex N-linked glycans serve as a determinant for exosome/microvesicle cargo recruitment. J Biol Chem 289:32526-37 |
| Kasper, Brian T; Koppolu, Sujeethraj; Mahal, Lara K (2014) Insights into miRNA regulation of the human glycome. Biochem Biophys Res Commun 445:774-9 |
| Ribeiro, Joao P; Mahal, Lara K (2013) Dot by dot: analyzing the glycome using lectin microarrays. Curr Opin Chem Biol 17:827-31 |
| Pilobello, Kanoelani T; Agrawal, Praveen; Rouse, Richard et al. (2013) Advances in lectin microarray technology: optimized protocols for piezoelectric print conditions. Curr Protoc Chem Biol 5:1-23 |
| Rakus, John F; Mahal, Lara K (2011) New technologies for glycomic analysis: toward a systematic understanding of the glycome. Annu Rev Anal Chem (Palo Alto Calif) 4:367-92 |
| Batista, Bianca S; Eng, William S; Pilobello, Kanoelani T et al. (2011) Identification of a conserved glycan signature for microvesicles. J Proteome Res 10:4624-33 |
| Gaziel-Sovran, Avital; Segura, Miguel F; Di Micco, Raffaella et al. (2011) miR-30b/30d regulation of GalNAc transferases enhances invasion and immunosuppression during metastasis. Cancer Cell 20:104-18 |
| Krishnamoorthy, Lakshmi; Mahal, Lara K (2009) Glycomic analysis: an array of technologies. ACS Chem Biol 4:715-32 |
