A5073644538- Glycosylation and Glycoproteins Research
- Mitochondrial Function and Pathology
- Genetic Neurodegenerative Diseases
- Monoclonal and Polyclonal Antibodies Research
- Galectins and Cancer Biology
- Carbohydrate Chemistry and Synthesis
- Epigenetics and DNA Methylation
- Cancer-related gene regulation
- Air Quality and Health Impacts
- Advanced Proteomics Techniques and Applications
- Ubiquitin and proteasome pathways
- Health, Environment, Cognitive Aging
- Peptidase Inhibition and Analysis
- RNA Research and Splicing
- vaccines and immunoinformatics approaches
- Metabolomics and Mass Spectrometry Studies
- Muscle Physiology and Disorders
- Viral Infectious Diseases and Gene Expression in Insects
- Redox biology and oxidative stress
- Latin American and Latino Studies
- Immunotherapy and Immune Responses
- Genetics and Neurodevelopmental Disorders
- Fungal Infections and Studies
- Adipose Tissue and Metabolism
- Genetic Syndromes and Imprinting
Johns Hopkins Medicine
2015-2024
Johns Hopkins University
2015-2024
University of Arkansas for Medical Sciences
2022
Walter Reed Army Institute of Research
2022
University of Baltimore
2012-2019
Article8 August 2017Open Access Transparent process Phosphorylation of the FUS low-complexity domain disrupts phase separation, aggregation, and toxicity Zachary Monahan Department Pharmacology Molecular Therapeutics, Uniformed Services University, Bethesda, MD, USA Search for more papers by this author Veronica H Ryan Neuroscience Graduate Program, Brown Providence, RI, Abigail M Janke Pharmacology, Physiology, Biotechnology, Kathleen A Burke Shannon N Rhoads Gül Zerze Chemical Biomolecular...
"History and Memory in African-American Culture." History: Reviews of New Books, 24(1), pp. 10–11
The study of the human urinary proteome has potential to offer significant insights into normal physiology as well disease pathology. information obtained from such studies could be applied diagnosis various diseases. high sensitivity, resolution, and mass accuracy latest generation spectrometers provides an opportunity accurately catalog proteins present in urine, including those at low levels. To this end, we carried out a comprehensive analysis healthy individuals using high-resolution...
Redox-switches are critical cysteine thiols that modified in response to changes the cell's environment conferring a functional effect. S-nitrosylation (SNO) is emerging as an important modulator of these regulatory switches; however, much remains unknown about nature specific residues and how oxidative signals interpreted. Because their labile nature, SNO-modifications routinely detected using biotin switch assay. Here, new isotope coded thiol-reactive multiplex reagent, cysTMT(6), used...
To complement the recent genomic sequencing of Chinese hamster ovary (CHO) cells, proteomic analysis was performed on CHO cells including cellular proteome, secretome, and glycoproteome using tandem mass spectrometry (MS/MS) multiple fractions obtained from gel electrophoresis, multidimensional liquid chromatography, solid phase extraction glycopeptides (SPEG). From 120 different analyses generating 682 097 MS/MS spectra, 93 548 unique peptide sequences were identified with at most 0.02...
Isobaric tags for relative and absolute quantitation (iTRAQ) is a prominent mass spectrometry technology protein identification quantification that capable of analyzing multiple samples in single experiment. Frequently, iTRAQ experiments are carried out using an aliquot from pool all samples, or "masterpool", one the channels as reference sample standard to estimate abundances biological combine abundance estimates experiments. In this manuscript, we show masterpool counterproductive. We...
Melanins are synthesized macromolecules that found in all biological kingdoms. These pigments have a myriad of roles range from microbial virulence to key components the innate immune response invertebrates. also exhibit unique properties with potential applications physics and material sciences, ranging electrical batteries novel therapeutics. In fungi, melanins, such as eumelanins, cell wall provide protection against biotic abiotic elements. Elucidation smallest fungal wall-associated...
Gangliosides, sialic acid bearing glycosphingolipids, are components of the outer leaflet plasma membranes all vertebrate cells. They contribute to cell regulation by interacting with proteins in their own (cis) or extracellular milieu (trans). As amphipathic membrane constituents, gangliosides present challenges for identifying ganglioside protein interactome. To meet these challenges, we synthesized bifunctional clickable photoaffinity gangliosides, delivered them cultured cells, then...
As Nathan Huggins once stated, altering American history to account fully for the nation's black voices would change tone and meaning-the frame substance-of entire story. Rather than a sort of Pilgrim's Progress tale bold ascent triumph, with parts told in full be transmuted into an existential tragedy, closer, said, Sartre's No Exit vision life Bunyan. The relation between memory has received increasing attention both from historians literary critics. In this volume, group leading scholars...
In the heart, lysine acetylation has been implicated in processes ranging from transcriptional control of pathological remodeling, to cardioprotection arising caloric restriction. Given emerging importance this post-translational modification, we used a proteomic approach investigate broader role heart using guinea pig model. Briefly, hearts were fractionated into myofilament-, mitochondrial- and cytosol-enriched fractions prior proteolysis affinity-enrichment acetylated peptides. LC-MS/MS...
The modification of intracellular proteins by monosaccharides O ‐linked β‐ N ‐acetylglucosamine ( O‐ GlcNAc) is an essential and dynamic PTM metazoans. addition removal ‐GlcNAc catalyzed the transferase (OGT) ‐GlcNAcase, respectively. One mechanism which thought to mediate regulating phosphorylation. To provide insight into pathways regulated ‐GlcNAc, we have utilized SILAC‐based quantitative proteomics carry out comparisons site‐specific phosphorylation in OGT wild‐type Null cells....
Post-translational modifications (PTMs) of proteins regulate various cellular processes. PTMs polyglutamine-expanded huntingtin (Htt) protein, which causes Huntington's disease (HD), are likely modulators HD pathogenesis. Previous studies have identified and characterized several on exogenously expressed Htt fragments, but none them were designed to systematically characterize the endogenous full-length protein. We found that Htt, was immunoprecipitated from knock-in mouse human post-mortem...
O-Linked N-acetyl-β-d-glucosamine (O-GlcNAc) is a dynamic post-translational modification that modifies and regulates over 3000 nuclear, cytoplasmic, mitochondrial proteins. Upon exposure to stress injury, cells tissues increase the O-GlcNAc modification, or O-GlcNAcylation, of numerous proteins promoting cellular response thus survival. The aim this study was identify are differentially O-GlcNAcylated upon acute oxidative (H2O2) provide insight into mechanisms by which promotes We achieved...
Phosphoinositide 3-kinases (PI3Ks) are ubiquitous lipid kinases that activate signaling cascades controlling cell survival, proliferation, protein synthesis, and vesicle trafficking. PI3Ks have dual kinase specificity: a activity phosphorylates the 3′-hydroxyl of phosphoinositides protein-kinase includes autophosphorylation. Despite wealth biochemical structural information on PI3Kα, little is known about identity roles individual active-site residues in catalysis. To close this gap, we...
FUS (fused in sarcoma) is an abundant, predominantly nuclear protein involved RNA processing. Under various conditions, functionally associates with and other macromolecules to form distinct, reversible phase-separated liquid structures. Persistence of the state increased cytoplasmic localization are both hypothesized predispose irreversible aggregation, which a pathological hallmark subtypes amyotrophic lateral sclerosis frontotemporal dementia. We previously showed that phosphorylation...
The dynamic modification of specific serine and threonine residues intracellular proteins by O-linked N-acetyl-β-D-glucosamine (O-GlcNAc) mitigates injury promotes cytoprotection in a variety stress models. O-GlcNAc transferase (OGT) the O-GlcNAcase are sole enzymes that add remove O-GlcNAc, respectively, from thousands substrates. It remains unclear how just two can be specifically controlled to affect glycosylation target signaling pathways both basally response stress. Several lines...
Thymic stromal lymphopoietin (TSLP) is a cytokine that plays diverse roles in the regulation of immune responses. TSLP requires heterodimeric receptor complex consisting IL-7 α subunit and its unique (gene symbol CRLF2) to transmit signals cells. Abnormal signaling (e.g. overexpression or TSLPR) contributes development number diseases including asthma leukemia. However, detailed understanding pathways activated by remains elusive. In this study, we performed global quantitative...
Phosphorylation has been shown to have a significant impact on expanded huntingtin-mediated cellular toxicity. Several phosphorylation sites identified the huntingtin (Htt) protein. To find new potential therapeutic targets for Huntington's Disease (HD), we used mass spectrometry identify novel N-terminal Htt, expressed in HEK293 cells. Using site-directed mutagenesis introduced alterations of N586 Htt construct containing 82 polyglutamine repeats. The effects these toxicity were evaluated...
Here, we examine key regulatory pathways underlying the transition from compensated hypertrophy (HYP) to decompensated heart failure (HF) and sudden cardiac death (SCD) in a guinea pig pressure-overload model by integrated multiome analysis. Relative protein abundances sham-operated HYP HF hearts were assessed iTRAQ LC-MS/MS. Metabolites quantified LC-MS/MS or GC-MS. Transcriptome profiles obtained using mRNA microarrays. The proteome exhibited classic biosignatures of HYP, left ventricular...
Huntington's disease (HD) is an incurable neurodegenerative disorder caused by a CAG expansion in the huntingtin gene (HTT). Post-translational modifications of protein (HTT), such as phosphorylation, acetylation and ubiquitination, have been implicated HD pathogenesis. Arginine methylation/dimethylation important modification with emerging role neurodegeneration; however, arginine methylation HTT remains largely unexplored. Here we report nearly two dozen novel sites on endogenous from...
Intracellular protein aggregation is the hallmark of several neurodegenerative diseases. Aggregates formed by polyglutamine (polyQ)-expanded proteins, such as Huntingtin, adopt amyloid-like structures that are resistant to denaturation. We used a novel purification strategy isolate aggregates human Huntingtin N-terminal fragments with expanded polyQ tracts from both yeast and mammalian (PC-12) cells. Using mass spectrometry we identified species trapped within these aggregates. found...
Assessing personal exposure to environmental toxicants is a critical challenge for predicting disease risk. Previously, using human serum albumin (HSA)-based biomonitoring, we reported dosimetric relationships between adducts at HSA Cys34 and ambient air pollutant levels (Smith et al., Chem. Res. Toxicol. 2021, 34, 1183). These results provided the foundation explore modifications other sites in reveal novel of complex exposures. Thus, Pan-Protein Adductomics (PPA) technology here next step...