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. 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. Using our glycomic analysis platform, lectin microarrays, on the NCI-60, a set of human tumor lines, my laboratory has identified new glycan regulation mechanisms and the role of glycosylation in epigenetic loops controlling cell fate. Specifically, we have shown that miRNA are a major regulator of the human glycome. By integrating our glycomic dataset with miRNA expression data using a multidimensional analysis, we discovered unique associations of miRNA and glycan structures that map onto the miRNA regulation of genes involved in glycan biosynthetic pathways. We have validated these pathways and begun to interrogate further the relationship between miRNA and the glycome. We have discovered a series of glycosylation related genes, in miRNA controlled networks, that directly impact cell fate through regulation of epithelial to mesenchymal transition. Our work opens up cell regulatory loops to include glycosylation, which can impact multiple signaling pathways of the cell. This argues both that the miRNA networks can map specific cell glycosylation into known regulatory networks, and that glycans are both outcomes and inputs into these networks, providing a new point of control to target.
Prof. Christine Payne (404-385-3125)