A5064985797- Parkinson's Disease Mechanisms and Treatments
- Alzheimer's disease research and treatments
- Advanced Proteomics Techniques and Applications
- Amyotrophic Lateral Sclerosis Research
- Connexins and lens biology
- RNA Research and Splicing
- Ubiquitin and proteasome pathways
- Rheumatoid Arthritis Research and Therapies
- Cell Adhesion Molecules Research
- RNA and protein synthesis mechanisms
- S100 Proteins and Annexins
- Biotin and Related Studies
- Neurological diseases and metabolism
- Cholinesterase and Neurodegenerative Diseases
- Metabolomics and Mass Spectrometry Studies
- Extracellular vesicles in disease
- Mass Spectrometry Techniques and Applications
- Glycosylation and Glycoproteins Research
- RNA modifications and cancer
- Neurological Disease Mechanisms and Treatments
- Monoclonal and Polyclonal Antibodies Research
- Autophagy in Disease and Therapy
- Genetic Neurodegenerative Diseases
- Neurological disorders and treatments
- Neurogenetic and Muscular Disorders Research
Johns Hopkins Medicine
2016-2025
Johns Hopkins University
2016-2025
Liechtenstein Institute
2023
Hudson Institute
2023
John Wiley & Sons (United States)
2023
National Institute of Mental Health
2020
Mayo Clinic in Florida
2020
WinnMed
2020
Institute of Natural Science
2015
Kyung Hee University
2015
Significance The majority of cellular proteins undergo rapid degradation and synthesis to minimize the toxic effect cells tissues guarantee normal functions. It has been appreciated that with longer half-lives exist in certain tissues. Here we identify synaptic long-lived by high-resolution mass spectrometry. In general, exhibit slower turnover than cytosolic proteins, protein from mouse brain is enhanced enriched environment exposure. Moreover, are dynamically regulated during changes...
Protein ubiquitination is an essential post-translational modification regulating neurodevelopment, synaptic plasticity, learning, and memory, its dysregulation contributes to the pathogenesis of neurological diseases. Here we report a systematic analysis ubiquitinated proteome (ubiquitome) in rat brain using newly developed monoclonal antibody that recognizes diglycine tag on lysine residues trypsinized peptides (K-GG peptides). Initial specificity showed can distinguish K-GG from linear GG...
The aim of this study is to identify the potential cerebrospinal fluid (CSF) biomarkers for Alzheimer's disease and evaluate these markers on independent CSF samples using parallel reaction monitoring (PRM) assays.
Translation initiation generally occurs at AUG codons in eukaryotes, although it has been shown that non-AUG or noncanonical translation can also occur. However, the evidence for sites (TISs) is largely indirect and based on ribosome profiling (Ribo-seq) studies. Here, using a strategy specifically designed to enrich N termini of proteins, we demonstrate many human proteins are translated TISs. The large majority TISs mapped 5′ untranslated regions were led N-terminal extension annotated...
Biotin-based labeling strategies are widely employed to study protein-protein interactions, subcellular proteomes and post-translational modifications, as well as, used in drug discovery. While the high affinity of streptavidin for biotin greatly facilitates capture biotinylated proteins, it still presents a challenge, currently employed, recovery peptides. Here we describe strategy designated Biotinylation Site Identification Technology (BioSITe) peptides LC-MS/MS analyses. We demonstrate...
Abstract Cryptic peptides, hidden from the immune system under physiologic conditions, are revealed by changes to MHC class II processing and hypothesized drive loss of tolerance self-antigens in autoimmunity. Rheumatoid arthritis (RA) is an autoimmune disease characterized responses citrullinated self-antigens, which arginine residues converted citrullines. Here, we investigate hypothesis that citrullination exposes cryptic peptides modifying protein structure proteolytic cleavage. We show...
Diabetes mellitus is the leading cause of cardiovascular and renal disease in United -States. Despite beneficial interventions available for patients with diabetes, there remains a need additional therapeutic targets therapies diabetic kidney (DKD). Inflammation oxidative stress are increasingly recognized as important causes diseases. closely associated mitochondrial damage. The molecular connection between inflammation metabolism to be elucidated. Recently, nicotinamide adenine nucleotide...
This study examined whether cerebrospinal fluid (CSF) baseline levels of the synaptic protein NPTX2 predict time to onset symptoms mild cognitive impairment (MCI), both alone and when accounting for traditional CSF Alzheimer's disease (AD) biomarker levels. Longitudinal were also examined.
Complementing genome sequence with deep transcriptome and proteome data could enable more accurate assembly annotation of newly sequenced genomes. Here, we provide a proof-of-concept an integrated approach for analysis the Anopheles stephensi, which is one most important vectors malaria parasite. To achieve broad coverage genes, carried out sequencing profiling multiple anatomically distinct sites. Based on transcriptomic alone, identified corrected 535 events incomplete involving 1196...
Neurons and oligodendrocytes communicate to regulate oligodendrocyte development ensure appropriate axonal myelination. Here, we show that Glycerophosphodiester phosphodiesterase 2 (GDE2) signaling underlies a neuronal pathway promotes maturation through the release of soluble neuronally derived factors. Mice lacking global or GDE2 expression have reduced mature myelin proteins but retain normal numbers precursor cells (OPCs). Wild-type (WT) OPCs cultured in conditioned medium (CM) from...
Farnesol enhances the amounts of farnesylated PARIS and PGC-1α, preventing dopaminergic neuronal loss in Parkinson’s disease models.
Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder characterized by loss of dopaminergic neurons in substantia nigra (SN) brain. Despite decades studies, precise pathogenic mechanism PD still elusive. An unbiased proteomic analysis patient's brain allows identification critical proteins and molecular pathways that lead to dopamine cell death α-synuclein deposition resulting devastating clinical symptoms. In this study, we conducted an in-depth proteome human SN...
Abstract Energy metabolism and membraneless organelles have been implicated in human diseases including neurodegeneration. How energy deficiency regulates ribonucleoprotein particles such as stress granules (SGs) is still unclear. Here we identified a unique type of induced by under physiological conditions uncovered the mechanisms which dynamics diverse stress-induced are regulated. Severe rapid formation deficiency-induced (eSGs) independently eIF2α phosphorylation, whereas moderate...
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by the loss of upper and lower motor neurons, which eventually may lead to death. Critical mission developing effective therapies for ALS discovery biomarkers that can illuminate mechanisms neurodegeneration have diagnostic, prognostic, or pharmacodynamic value. Here, we merged unbiased discovery-based approaches targeted quantitative comparative analyses identify proteins are altered in...
Pathologic α-synuclein plays an important role in the pathogenesis of α-synucleinopathies such as Parkinson’s disease (PD). Disruption proteostasis is thought to be central pathologic toxicity; however, molecular mechanism this deregulation poorly understood. Complementary proteomic approaches cellular and animal models PD were used identify characterize interactome. We report that highest biological processes interacted with mice included RNA processing translation initiation. Regulation...
Parkinson's disease (PD) is the second most common neurodegenerative disorder that results in motor dysfunction and, eventually, cognitive impairment. α-Synuclein protein known as a central to pathophysiology of PD, but underlying pathological mechanism still remains be elucidated. In an effort understand how α-synuclein underlies pathology various PD mouse models with overexpression have been developed. However, systemic analysis brain proteome those lacking. this study, we established two...
Plasma extracellular vesicles (EVs) are cell-derived lipid particles and reportedly play a role in sepsis pathogenesis. This study aimed to identify EV cargo proteins septic patients explore their association with key pathophysiology. EVs were subjected Tandem Mass Tag (TMT)-based quantitative proteomic analysis. We identified 522 differentially expressed (DE) (n=15) compared the healthy controls (n=10). The KEGG analysis of DE revealed multiple functional pathways linked sepsis, e.g.,...
ADP-ribosylation, characterized by the addition of adenosine diphosphate ribose, can occur in both monomeric (MARylation) and polymeric (PARylation) forms. Little is known about specific contributions MARylation PARylation to cellular processes due a lack tools for jointly investigating these individual We present novel mass spectrometry (MS)-based proteomics approach that preserves information native ADP-ribosylation form associated with modification site within single experiment. Our...
FYCO1 (FYVE and coiled-coil domain containing 1) is an adaptor protein, expressed ubiquitously required for microtubule-dependent, plus-end-directed transport of macroautophagic/autophagic vesicles. We have previously shown that loss-of-function mutations in cause cataracts with no other ocular and/or extra-ocular phenotype. Here, we show fyco1 homozygous knockout (fyco1−/−) mice recapitulate the cataract phenotype consistent a critical role autophagy lens morphogenesis. Transcriptome...