A5033386717- Glycosylation and Glycoproteins Research
- Carbohydrate Chemistry and Synthesis
- Galectins and Cancer Biology
- RNA modifications and cancer
- Microtubule and mitosis dynamics
- Protein Tyrosine Phosphatases
- Autophagy in Disease and Therapy
- Genomics and Phylogenetic Studies
- Drug Transport and Resistance Mechanisms
- Regulation of Appetite and Obesity
- Biochemical Analysis and Sensing Techniques
- Chromosomal and Genetic Variations
- Mitochondrial Function and Pathology
- Drug-Induced Hepatotoxicity and Protection
- Endoplasmic Reticulum Stress and Disease
- Ubiquitin and proteasome pathways
- Diet and metabolism studies
- Adipose Tissue and Metabolism
- Olfactory and Sensory Function Studies
- Immunodeficiency and Autoimmune Disorders
- Cellular transport and secretion
- Alzheimer's disease research and treatments
- Epigenetics and DNA Methylation
- Genetics, Aging, and Longevity in Model Organisms
- Lysosomal Storage Disorders Research
University of Kansas Medical Center
2012-2024
Scripps Research Institute
2022-2024
Discovery Institute
2019-2021
Sanford Burnham Prebys Medical Discovery Institute
2018-2021
University of Tasmania
2021
University of Pennsylvania
2018
University of Kansas
2014
O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification involving an attachment of single β-N-acetylglucosamine moiety to serine or threonine residues in nuclear and cytoplasmic proteins. Cellular O-GlcNAc levels are regulated by two enzymes: transferase (OGT) O-GlcNAcase (OGA), which add remove the modification, respectively. The can rapidly change response fluctuations extracellular environment; however, O-GlcNAcylation returns baseline level quickly after stimulus...
Autophagy can degrade cargos with the help of selective autophagy receptors such as p62/SQSTM1, which facilitates degradation ubiquitinated cargo. While process has been linked to aging, impact in lifespan regulation remains unclear. We have recently shown Caenorhabditis elegans that transcript levels sqst-1/p62 increase upon a hormetic heat shock, suggesting role SQST-1/p62 stress response and aging. Here, we find is required for benefits including longevity, improved neuronal proteostasis,...
Chronic, low-grade inflammation increases the risk for atherosclerosis, cancer, and autoimmunity in diseases such as obesity diabetes. Levels of CD4+ T helper 17 (Th17) cells, which secrete interleukin 17A (IL-17A), are increased contribute to inflammatory milieu; however, relationship between signaling events triggered by excess nutrient levels IL-17A–mediated is unclear. Here, using cytokine, quantitative real-time PCR, immunoprecipitation, ChIP assays, along with lipidomics MS-based...
Any defects in the correct formation of mitotic spindle will lead to chromosomal segregation errors, arrest, or aneuploidy. We demonstrate that O-linked N-acetylglucosamine (O-GlcNAc), a post-translational modification serine and threonine residues nuclear cytoplasmic proteins, regulates function. In O-GlcNAc transferase O-GlcNAcase gain function cells, is incorrectly assembled. Chromosome condensation centrosome assembly impaired these cells. The disruption architecture due reduction...
Overdose of acetaminophen (APAP) results in acute liver failure. We have investigated the role a posttranslational modification proteins called O-GlcNAcylation, where O-GlcNAc transferase (OGT) adds and O-GlcNAcase (OGA) removes single β-D-N-acetylglucosamine (O-GlcNAc) moiety, pathogenesis APAP-induced injury. Hepatocyte-specific OGT knockout mice (OGT KO), which reduced wild-type (WT) controls were treated with 300 mg/kg APAP development injury was studied over time course from 0 to 24 h....
Alterations in O-GlcNAc cycling, the addition and removal of O-GlcNAc, lead to mitotic defects increased aneuploidy. Herein, we generated stable O-GlcNAcase (OGA, enzyme that removes O-GlcNAc) knockdown HeLa cell lines characterized effect reduction OGA activity on cycle progression. After release from G1/S, cells progressed normally through S phase but demonstrated exit defects. Cyclin A was while B D expression reduced. Retinoblastoma protein (RB) phosphorylation also compared control. At...
The condition of having a healthy, functional proteome is known as protein homeostasis, or proteostasis. Establishing and maintaining proteostasis the province network, approximately 2,700 components that regulate synthesis, folding, localization, degradation. network fundamental entity in biology essential for cellular health has direct relevance to many diseases conformation. However, it not well defined annotated, which hinders its characterization disease. In this series manuscripts, we...
Ketogenic diets induce hepatocyte fatty acid oxidation and ketone body production. To further evaluate how ketogenic affect bioenergetic infrastructure, we analyzed livers from C57Bl/6J male mice maintained for 1 month on a or standard chow diet. Compared with the diet, diet increased cytosolic mitochondrial protein acetylation also altered succinylation patterns. SIRT3 decreased while SIRT5 increased, gluconeogenesis, oxidative phosphorylation, biogenesis pathway proteins were variably...
Asperuloside is an iridoid glycoside found in many medicinal plants that has produced promising anti-obesity results animal models. In previous studies, three months of asperuloside administration reduced food intake, body weight, and adipose masses rats consuming a high fat diet (HFD). However, the mechanisms by which exerts its properties were not clarified. Here, we investigated homeostatic nutrient-sensing regulating intake mice HFD. We confirmed and, importantly, identified some could...
Summary Autophagy-lysosomal impairment is an early and prominent feature of neurodegeneration. Autophagy activation reduces protein aggregates lipid level abnormalities. We performed a high-content imaging-based screen assessing 940,000 small molecules to identify those that reduce droplet numbers. Of 77 validated, structurally diverse hits, 24 increased autophagy flux reporter activity, consistent with accelerated clearance by lipophagy. these, we show CCT020312 activates independently...
Caloric need has long been thought a major driver of appetite. However, it is unclear whether caloric regulates appetite in environments offered by many societies today where there no shortage food. Here we observed that wildtype mice with free access to food did not match calorie intake expenditure. While the size meal affected subsequent intake, was compensation for earlier under- or over-consumption. To test how spontaneous eating subject control, manipulated O-linked...
Abstract Pharmacologic or genetic manipulation of O-GlcNAcylation, an intracellular, single sugar post-translational modification, are difficult to interpret due the pleotropic nature O-GlcNAc and vast signaling pathways it regulates. To address this issue, we employed either OGT (O-GlcNAc transferase), OGA (O-GlcNAcase) liver knockouts, pharmacological inhibition coupled with multi-Omics analysis bioinformatics. We identified numerous genes, proteins, phospho-proteins, metabolites that were...
SUMMARY Chronic, low-grade inflammation increases the risk of atherosclerosis, cancer, and autoimmunity in diseases like obesity diabetes. Here, we show that increased levels nutrient-responsive, post-translational protein modification, O-GlcNAc (O-linked β-N-acetylglucosamine) are present naïve CD4+ T cells from a diet-induced murine model, elevation leads to pro-inflammatory IL-17A production. Importantly, helper 17 (Th17) cells, which secrete IL-17A, contribute inflammatory milieu. We...
O‐linked N‐Acetylglucosamine, more commonly referred to as O‐GlcNAc, is a single glycosidic post‐translational modification. OGT (O‐GlcNAc Transferase) and OGA (O‐GlcNAcase) are the sole enzymes responsible for addition (O‐GlcNAcylation) removal of respectively. OGA, present in all multicellular organisms organ tissues. Importantly, knockouts embryonically lethal, demonstrating requirement O‐GlcNAcylation early organismal development. Like most intracellular modifications, O‐GlcNAc regulates...
O‐linked N‐acetylglucosamine (O‐GlcNAc) is a post‐translational modification involving an attachment of single residue to serine or threonine residues in nuclear and cytoplasmic proteins. The O‐GlcNAc processed by transferase (OGT), which adds the protein O‐GlcNAcase (OGA), removes it. Recent evident links regulation mitochondrial function O‐GlcNAcylation. For example, we used quantitative proteomics screen determine that OGT OGA gain altered expression including proteins involved...
O‐GlcNAc is a post‐translational modification (PTM) consisting of single N‐acetylglucosamine moiety attached to serine and threonine residues in nuclear cytoplasmic proteins. levels can cycle dynamically response hormones, nutrients, or stress order regulate multitude cellular processes. For instance cycling an important regulator mitosis. Recently, we demonstrated that cells with gain function either transferase (OGT) O‐GlcNAcase (OGA) have disrupted mitotic spindles exit defects. OGT/OGA...
O‐linked N ‐acetylglucosamine (O‐GlcNAc) is a highly dynamic post‐translational modification that involves an addition of single N‐ acetylglucosamine to serine and threonine residue in mitochondria, nuclear cytoplasmic proteins. O‐GlcNAc cycling the removal by transferase (OGT) O‐GlcNAcase (OGA) respectively. Disruptions contribute diseases such as diabetes, cancer, neurodegeneration. Accumulative dysfunctional mitochondria can also lead development neurodegenerative diseases, importantly,...
Regulated mitotic progression coupled with high‐fidelity chromosome segregation is crucial for normal cellular division. Phosphorylation. Although, phosphorylation plays a critical role regulating mitosis, it alone cannot account all the complexities of mitosis. We have demonstrated that O‐GlcNAcylation proper regulation and disruptions in O‐GlcNAc signaling lead to aberrant cell (b‐N‐acetylglucosamine) an ubiquitous protein modification consisting single N‐acetylglucosamine residue attached...
Sickle Cell Disease (SCD), caused by a point mutation in the adult β‐globin gene, leads to chronic damage multiple organs and stroke, as well cardiovascular abnormalities dysfunction. However, SCD patients are phenotypically normal if they carry compensatory mutations that result continued expression of fetal γ‐globin. Thus, logical clinical goal for treatment is up‐regulate γ‐globin synthesis. One mode silencing occurs at GATA binding sites located −566 or −567 relative A G transcription...