Publications by authors named "Austen L Michalak"

The cellular glycocalyx, composed of membrane associated glycoproteins and glycolipids, is a complex and dynamic interface that facilitates interactions between cells and their environment. The glycocalyx composition is continuously changing through biosynthesis of new glycoconjugates and membrane turnover. Various glycocalyx components, such as mucins, can also be rapidly shed from the cell surface in response to acute events, such as pathogenic threat.

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Extracellular glycans, such as glycosaminoglycans (GAGs), provide an essential regulatory component during the development and maintenance of tissues. GAGs, which harbor binding sites for a range of growth factors (GFs) and other morphogens, help establish gradients of these molecules in the extracellular matrix (ECM) and promote the formation of active signaling complexes when presented at the cell surface. As such, GAGs have been pursued as biologically active components for the development of biomaterials for cell-based regenerative therapies.

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Glycosylation is a ubiquitous post-translational modification that decorates proteins and lipids with glycans. These glycans can play critical roles in regulating biological events, and therefore, the discovery of strategies that target these molecules represent an important advancement toward understanding and controlling glycan-mediated cellular phenotypes. We describe the use of a small molecule, surfen, to temporarily silence the functions mediated by heparan sulfate glycosaminoglycans in mouse embryonic stem cells.

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Recently, the field of stem cell-based regeneration has turned its attention toward chemical approaches for controlling the pluripotency and differentiation of embryonic stem cells (ESCs) using drug-like small molecule modulators. Growth factor receptors or their associated downstream kinases that regulate intracellular signaling pathways during differentiation are typically the targets for these molecules. The glycocalyx, which plays an essential role in actuating responses to growth factors at the cellular boundary, offers an underexplored opportunity for intervention using small molecules to influence differentiation.

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