Glycans are critically involved in a variety of physiological and pathological process, such as cell differentiation, host-pathogen interactions, and inflammation. This abundant class of biomolecules is found both inside and outside the cell where they meditate signaling cascades or modify the stability and function of other macromolecules such as proteins or lipids. Despite their abundance and biological importance, our understanding of structure-function relationships among glycans remains understudied and presents exciting opportunities for new discoveries.
In the Hsieh-Wilson lab, we combine chemical synthesis, biochemical assays, and cellular and in vivo studies to investigate the molecular functions of glycans and characterize their structure-function relationships.
In the Hsieh-Wilson lab, we combine chemical synthesis, biochemical assays, and cellular and in vivo studies to investigate the molecular functions of glycans and characterize their structure-function relationships.
Decoding heparan sulfate structure and function
Heparan sulfate (HS) and heparin are polysaccharides that undergo extensive post-glycosylational modification, giving rise to an immense diversity of sulfated structures. This diversity imbues HS with to the ability to bind a wide array of protein partners, mediating many processes such as cell differentiation, pathogen recognition and infection, and blood coagulation. However, the molecular recognition of HS and HS-binding proteins remains largely uncharacterized. To decode HS, we have developed automated synthetic methods to improve access across HS structure space, a suite of cell surface remodeling tools and glycomimetic polymers, and small molecule inhibitors to interrogate HS activity in vivo. Find out more...
Keywords: carbohydrate chemistry, synthetic methods, molecular recognition, microarrays, biomimetics, directed evolution, biophysical methods, structural biology, molecular modeling
Heparan sulfate (HS) and heparin are polysaccharides that undergo extensive post-glycosylational modification, giving rise to an immense diversity of sulfated structures. This diversity imbues HS with to the ability to bind a wide array of protein partners, mediating many processes such as cell differentiation, pathogen recognition and infection, and blood coagulation. However, the molecular recognition of HS and HS-binding proteins remains largely uncharacterized. To decode HS, we have developed automated synthetic methods to improve access across HS structure space, a suite of cell surface remodeling tools and glycomimetic polymers, and small molecule inhibitors to interrogate HS activity in vivo. Find out more...
Keywords: carbohydrate chemistry, synthetic methods, molecular recognition, microarrays, biomimetics, directed evolution, biophysical methods, structural biology, molecular modeling
Neuroplasticity and chondroitin sulfate
Chondroitin sulfate proteoglycans (CSPGs) are a key component of the extracellular matrix in the central nervous system, where they play a critical role in many important processes in development, neuroplasticity, inflammation, and more. The CS chains are decorated with sulfation groups, giving rise to specific sulfation motifs that serve as recognition elements for their interacting partners. We are working to develop chemical tools to understand the sulfation pattern-specific roles of CSPGs in the diseased and normal brain. Find out more...
Keywords: CNS disease, neuroregeneration, immunology, viral vectors, medicinal chemistry, enzyme inhibition, cellular assays, chemical probes
Chondroitin sulfate proteoglycans (CSPGs) are a key component of the extracellular matrix in the central nervous system, where they play a critical role in many important processes in development, neuroplasticity, inflammation, and more. The CS chains are decorated with sulfation groups, giving rise to specific sulfation motifs that serve as recognition elements for their interacting partners. We are working to develop chemical tools to understand the sulfation pattern-specific roles of CSPGs in the diseased and normal brain. Find out more...
Keywords: CNS disease, neuroregeneration, immunology, viral vectors, medicinal chemistry, enzyme inhibition, cellular assays, chemical probes
Glycan structure identification at the single-cell level
To study mechanisms of neuronal communication in the brain, our lab develops chemical tools to identify and characterize cell-surface glycans and their binding partners. Recently, we’ve been optimizing the resolution of our methods for use on single cells. These tools enable the study of the roles of glycans in development, memory formation, learning, and neurodegenerative diseases. Find out more...
Keywords: chemoenzymatic and metabolic labeling, cell surface engineering, single-cell technology, bioinformatics, systems biology
To study mechanisms of neuronal communication in the brain, our lab develops chemical tools to identify and characterize cell-surface glycans and their binding partners. Recently, we’ve been optimizing the resolution of our methods for use on single cells. These tools enable the study of the roles of glycans in development, memory formation, learning, and neurodegenerative diseases. Find out more...
Keywords: chemoenzymatic and metabolic labeling, cell surface engineering, single-cell technology, bioinformatics, systems biology
O-GlcNAc and other dynamic protein modifications
O-GlcNAc is a dynamic post-translational sugar modification on intracellular serine and threonine residues. This modification is ubiquitous and abundant, affecting processes like transcription, translation, metabolic flux, and signaling. Consequently, this modification is tied to a variety of diseases like diabetes, cancer and Alzheimer’s disease. Our lab has a variety of ongoing projects to study this elusive modification. Find out more...
Keywords: PTM interplay, proteomics, protein structure and function, enzyme regulation, neurodegenerative disease, chemoenzymatic labeling, bioorthogonal chemistry
O-GlcNAc is a dynamic post-translational sugar modification on intracellular serine and threonine residues. This modification is ubiquitous and abundant, affecting processes like transcription, translation, metabolic flux, and signaling. Consequently, this modification is tied to a variety of diseases like diabetes, cancer and Alzheimer’s disease. Our lab has a variety of ongoing projects to study this elusive modification. Find out more...
Keywords: PTM interplay, proteomics, protein structure and function, enzyme regulation, neurodegenerative disease, chemoenzymatic labeling, bioorthogonal chemistry
