A5012554206- Glycosylation and Glycoproteins Research
- Carbohydrate Chemistry and Synthesis
- Proteoglycans and glycosaminoglycans research
- Monoclonal and Polyclonal Antibodies Research
- Ubiquitin and proteasome pathways
- Galectins and Cancer Biology
- Platelet Disorders and Treatments
- Chemical Synthesis and Analysis
- Peptidase Inhibition and Analysis
- Ion channel regulation and function
- Nerve injury and regeneration
- Cell Adhesion Molecules Research
- RNA and protein synthesis mechanisms
- Neuroscience and Neuropharmacology Research
- Connective tissue disorders research
- Click Chemistry and Applications
- Silk-based biomaterials and applications
- Cancer, Hypoxia, and Metabolism
- Cellular transport and secretion
- Signaling Pathways in Disease
- Neuroinflammation and Neurodegeneration Mechanisms
- Angiogenesis and VEGF in Cancer
- Biochemical Analysis and Sensing Techniques
- Alzheimer's disease research and treatments
- Nicotinic Acetylcholine Receptors Study
California Institute of Technology
2015-2025
Howard Hughes Medical Institute
2006-2017
Pasadena City College
2016
Genomics Institute of the Novartis Research Foundation
2004-2008
Science Applications International Corporation (United States)
2007
Center for Cancer Research
2007
Rockefeller University
1999-2005
Nathan Kline Institute for Psychiatric Research
2005
National Chung Cheng University
2001
Duke Medical Center
2001
Metabolic Sensor The enzyme O-GlcNAc transferase (OGT) catalyzes the transfer of N -acetylglucosamine from uridine diphospho- (UDP-GlcNAc) to serine or threonine residues intracellular proteins and responds metabolic status cell. Yi et al. (p. 975 ; see Perspective by Mattaini Vander Heiden ) show that O-GlcNAcylation phosphofructokinase 1 (PFK1) reduces its activity, thus influencing rates glycolysis within cells. PFK1 was increased in cells exposed hypoxia, several cell lines derived human...
The misfolding and accumulation of tau protein into intracellular aggregates known as neurofibrillary tangles is a pathological hallmark neurodegenerative diseases such Alzheimer's disease. However, while propagation marker for disease progression, exactly how propagates from one cell to another what mechanisms govern this spread are still unclear. Here, we report that cellular internalization regulated by quaternary structure have developed assay screen genetic modulators uptake. Using...
Significance O -GlcNAcylation is an abundant posttranslational modification suggested to have both neuroprotective and neurodegenerative functions. Although previous studies on -GlcNAc illustrated its potential modulate preexisting phenotypes in animal models, the importance of induction neuropathology functioning healthy adult neurons remained unclear. We generated a forebrain-specific transferase conditional knockout mouse found that diminution signaling induced progressive...
Transcellular propagation of protein aggregate "seeds" has been proposed to mediate the progression neurodegenerative diseases in tauopathies and α-synucleinopathies. We previously reported that tau α-synuclein aggregates bind heparan sulfate proteoglycans (HSPGs) on cell surface, promoting cellular uptake intracellular seeding. However, specificity binding mode these HSPGs remain unknown. Here, we measured direct interaction with modified heparins determine size sulfation requirements for...
The covalent modification of intracellular proteins by O -linked β- N -acetylglucosamine ( -GlcNAc) is emerging as a crucial regulatory posttranslational akin to phosphorylation. Numerous studies point the significance -GlcNAc in cellular processes such nutrient sensing, protein degradation, and gene expression. Despite its importance, breadth functional roles are only beginning be elucidated. Advances our understanding will require development new strategies for detection study...
We report a new chemoenzymatic strategy for the rapid and sensitive detection of O-GlcNAc posttranslational modifications. The approach exploits ability an engineered mutant β-1,4-galactosyltransferase to selectively transfer unnatural ketone functionality onto glycosylated proteins. Once transferred, moiety serves as versatile handle attachment biotin, thereby enabling chemiluminescent modified protein. Importantly, this permits visualization proteins that are at limits using traditional...
We report an advanced chemoenzymatic strategy for the direct fluorescence detection, proteomic analysis, and cellular imaging of O-GlcNAc-modified proteins. O-GlcNAc residues are selectively labeled with fluorescent or biotin tags using engineered galactosyltransferase enzyme [3 + 2] azide-alkyne cycloaddition chemistry. demonstrate that this approach can be used in-gel detection mass spectrometric identification proteins, identifying 146 novel glycoproteins from mammalian brain....
We report a carbohydrate microarray-based approach for the rapid, facile analysis of glycosaminoglycan-protein interactions. The key structural determinants responsible protein binding, such as sulfate groups that participate in interactions, were elucidated. Specificities also readily compared across families or functional classes, and comparisons among glycosaminoglycan subclasses provided more comprehensive understanding specificity. To validate approach, we showed fibroblast growth...
Production of proinflammatory cytokines in response to T cell receptor activation requires glycosylation an NF-κB subunit.
Chondroitin sulfate proteoglycans (CSPGs) represent a major barrier to regenerating axons in the central nervous system (CNS), but structural diversity of their polysaccharides has hampered efforts dissect structure-activity relationships underlying physiological activity. By taking advantage our ability chemically synthesize specific oligosaccharides, we demonstrate that sugar epitope on CSPGs, chondroitin sulfate-E (CS-E), potently inhibits axon growth. Removal CS-E motif significantly...
We report the generation of chondroitin sulfate (CS) glycomimetics with tunable chemical and biological properties. Our approach greatly simplifies synthesis complex glycosaminoglycans, providing synthetically accessible, bioactive structures programmable sulfation sequence. Using these glycopolymers, we demonstrate that multivalent interactions are critical for modulating CS activity discover an unexpected tolerance unnatural polymeric architectures. envision will facilitate further...
OBJECTIVE— O-linked N-acetylglucosamine (O-GlcNAc) is upregulated in diabetic tissues and plays a role insulin resistance glucose toxicity. Here, we investigated the extent of GlcNAcylation on human erythrocyte proteins compared site-specific from normal individuals. RESEARCH DESIGN AND METHODS—GlcNAcylated or GlcNAcylated peptides were tagged selectively enriched by chemoenzymatic approach identified mass spectrometry. The enrichment was combined with solid-phase chemical derivatization...
Heparan sulfate (HS) glycosaminoglycans participate in critical biological processes by modulating the activity of a diverse set protein binding partners. Such proteins include all known members chemokine superfamily, which are thought to guide migration immune cells through their interactions with HS. Here, we describe an expedient, divergent synthesis prepare defined HS glycomimetics that recapitulate overall structure and glycosaminoglycans. Our approach uses core disaccharide precursor...
Chondroitin sulfate glycosaminoglycans are sulfated polysaccharides involved in cell division, neuronal development, and spinal cord injury. Here, we report the synthesis identification of a chondroitin tetrasaccharide that stimulates growth differentiation neurons. These studies represent first, direct investigations into structure-activity relationships using homogeneous synthetic molecules define as minimal motif required for activity.