A5051493149- Advanced Proteomics Techniques and Applications
- Mass Spectrometry Techniques and Applications
- Advanced Biosensing Techniques and Applications
- HIV Research and Treatment
- Metabolomics and Mass Spectrometry Studies
- Advanced biosensing and bioanalysis techniques
- HIV/AIDS drug development and treatment
- Single-cell and spatial transcriptomics
- Glycosylation and Glycoproteins Research
- Biosensors and Analytical Detection
- Cannabis and Cannabinoid Research
- Bacterial Genetics and Biotechnology
- Pharmacological Effects and Toxicity Studies
- Biochemical Analysis and Sensing Techniques
- Bioinformatics and Genomic Networks
- Genomics and Phylogenetic Studies
- vaccines and immunoinformatics approaches
- Bacteriophages and microbial interactions
- Ubiquitin and proteasome pathways
- Clostridium difficile and Clostridium perfringens research
- Transgenic Plants and Applications
- Pesticide Residue Analysis and Safety
- Gene expression and cancer classification
- HIV-related health complications and treatments
- Microbial Inactivation Methods
University of Pittsburgh
2019-2025
Johns Hopkins Medicine
2021-2024
Johns Hopkins University
2009-2024
University of Baltimore
2021-2024
Laboratory of Molecular Genetics
2023-2024
Genomic Health (United States)
2019-2020
Center for Genomic Science
2020
University of Virginia
2019-2020
University Surgical Associates
2020
Coral Reef Alliance
2020
Single cell proteomics is a powerful tool with potential for markedly enhancing understanding of cellular processes. Here we report the development and application multiplexed single using trapped ion mobility time-of-flight mass spectrometry. When employing carrier channel to improve peptide signal, this method allows over 40,000 tandem spectra be acquired in 30 min. Using KRAS
Abstract Epigenetic programming has been shown to play a role in nearly every human system and disease where anyone thought look. However, the levels of heterogeneity at which epigenetic or epiproteomic modifications occur single cell resolution across population remains elusive. While recent advances sequencing technology have allowed between 1 3 histone post-translational be analyzed each cell, over twenty separate chemical PTMs are known exist, allowing thousands possible combinations....
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...
Reproducible quantification of large biological cohorts is critical for clinical/pharmaceutical proteomics yet remains challenging because most prevalent methods suffer from drastically declined commonly quantified proteins and substantially deteriorated quantitative quality as cohort size expands. MS2-based data-independent acquisition approaches represent tremendous advancements in reproducible protein measurement, but often with limited depth. We developed IonStar, an MS1-based approach...
In-depth and reproducible protein measurement in many biological samples is often critical for pharmaceutical/biomedical proteomics but remains challenging. MS1-based quantification using quadrupole/ultrahigh-field Orbitrap (Q/UHF-Orbitrap) holds great promise, the critically important experimental approaches enabling reliable large-cohort analysis have long been overlooked. Here we described an IonStar strategy achieving excellent quantitative quality of MS1 quantification. Key features...
Alzheimer's disease (AD) is characterized by accumulation of misfolded proteins. Genetic studies implicate microglia, brain-resident phagocytic immune cells, in AD pathogenesis. As positive effectors, microglia clear toxic proteins, whereas as negative they release proinflammatory mediators. An imbalance these functions contributes to progression. Polymorphisms human CD33, an inhibitory microglial receptor, are linked susceptibility; higher CD33 expression correlates with increased risk....
Appropriate interactions between antiretroviral therapies (ART) and drug transporters metabolizing enzymes at the blood brain barrier (BBB) are critical to ensure adequate dosing of achieve HIV suppression. These proteins modulated by demographic lifestyle factors, including substance use. While understudied, illicit substances share transport metabolism pathways with ART, increasing potential for adverse drug:drug interactions. This is particularly important when considering as it...
The green peach aphid, Myzus persicae, is a vector of the Potato leafroll virus (PLRV, Luteoviridae), transmitted exclusively by aphids in circulative manner. PLRV transmission efficiency was significantly reduced when clonal lineage M. persicae reared on turnip as compared with weed physalis, and this transient effect caused host-switch response. A trend higher titer physalis-reared turnip-reared observed at 24 h 72 after acquisition. major difference proteomes these up-regulation predicted...
The mechanisms leading to schizophrenia are likely be diverse. However, there may common pathophysiological pathways for subtypes of the disease. authors tested hypothesis that increased protein insolubility and ubiquitination underlie pathophysiology a subtype schizophrenia.Prefrontal cortex superior temporal gyrus from postmortem brains individuals with without were subjected cold sarkosyl fractionation, separating proteins into soluble insoluble fractions. Protein ubiquitin levels...
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...
The endospores formed by strains of type A Clostridium perfringens that produce the C. enterotoxin (CPE) are known to be more resistant heat and cold than do not this toxin. high resistance these spores allows them survive cooking process, leading a large number food-poisoning cases each year. relative importance factors contributing establishment in species is currently unknown. present study examines both CPE(+) CPE(-) for affect other species. We have found concentrations DPA metal ions,...
Recent work detailed the unique characteristics of fragmentation spectra derived from peptides single human cells. This valuable report utilized an ultrahigh-field Orbitrap and directly compared obtained high-concentration bulk cell HeLa lysates to those nanogram dilutions same nanowell-processed The analysis demonstrated marked differences between generated at high single-cell loads, most strikingly, loss high-mass y-series fragment ions. As significant exist in physics time-of-flight mass...
Mutations in KRAS are common drivers of human cancers and often those with the poorest overall prognosis for patients. A recently developed compound, MRTX1133, has shown promise inhibiting activity KRASG12D mutant proteins, which is one main pancreatic cancer. To better understand mechanism action this I performed both proteomics metabolomics on four cancer cell lines. obtain increased granularity proteomic observations, single-cell was successfully two these Following quality filtering, a...
The structural characteristics of a spore enable it to withstand stresses that typically kill vegetative cell. Spores remain dormant until small molecule signals induce them germinate into bacilli. Germination requires degradation the thick cortical peptidoglycan by germination-specific lytic enzymes (GSLEs). Bacillus anthracis has four putative GSLEs, based upon sequence similarities with in other species: SleB, CwlJ1, CwlJ2, and SleL. In this study, roles CwlJ2 were examined. expression...
Development of cancer therapeutics partially depends upon selection appropriate animal models. Therefore, improvements to model are beneficial. Forty-nine human tumor xenografts at in vivo passages 1, 4 and 10 were subjected cDNA microarray analysis yielding a dataset 823 Affymetrix HG-U133 Plus 2.0 arrays. To illustrate mining strategies supporting therapeutic studies, transcript expression was determined: 1) relative other models, 2) with successive passage, 3) during the vitro transition....
Abstract Human sialic acid-binding immunoglobulin-like lectins (Siglecs) are expressed on subsets of immune cells. Siglec-8 is an inhibitory Siglec eosinophils and mast cells, which effectors in allergic disorders including eosinophilic esophagitis. Inhibition occurs when crosslinked by multivalent ligands target tissues. Previously we discovered a high-affinity sialoglycan ligand human airways composed terminally sialylated keratan sulfate chains carried single protein, DMBT1. Here extend...
// Xiaoying Ye 1 , King C. Chan Andrew M. Waters Matthew Bess Adam Harned Bih-Rong Wei 2 Jadranka Loncarek 3 Brian T. Luke 4 Benjamin Orsburn 5 Bradley D. Hollinger Robert Stephens Rachel Bagni Alex Martinko 6 James A. Wells Dwight V. Nissley Frank McCormick 7 Gordon Whiteley Josip Blonder Cancer Research Technology Program, Frederick National Laboratory for Research, Leidos Biomedical Inc., Frederick, MD 21702, USA of Biology and Genetics, Center Institute, Bethesda, 20892, Protein Dynamics...
Dipicolinic acid (DPA) is a major component of bacterial endospores, comprising 5–15% the spore dry weight, and important for stability resistance properties. The biosynthetic precursor to DPA, dihydro-dipicolinic (DHDPA), produced by DHDPA synthase within lysine biosynthesis pathway. In Bacillus subtilis, most other bacilli clostridia, oxidized DPA products spoVF operon. Analysis genomes clostridia in Cluster I, including pathogens Clostridium perfringens, botulinum tetani, has shown that...
Recent increases in mass spectrometry speed, sensitivity, and resolution now permit comprehensive proteomics coverage. However, the results are often hindered by sub-optimal data processing pipelines. In almost all MS/MS peptide search engines, users must limit their space to a canonical database due time constraints q value considerations, but this typically does not reflect individual genetic variations of organism being studied. addition, engines will nearly always assume presence only...
Recent advances in the sensitivity and speed of mass spectrometers coupled with improved sample preparation methods have enabled field single cell proteomics to proliferate. While heavy development is occurring label free space, dramatic improvements throughput are provided by multiplexing tandem tags. Hundreds or thousands cells can be analyzed this method, yielding large data sets which may contain poor arising from loss material during sorting digestion, labeling, lysis. To date, no tools...
Tenofovir (TFV) is a nucleotide reverse transcriptase inhibitor prescribed for the treatment and prevention of human immunodeficiency virus infection chronic hepatitis B infection. Here, we demonstrate that creatine kinase brain-type (CKB) can form tenofovir-diphosphate (TFV-DP), pharmacologically active metabolite, in vitro identify nine missense mutations (C74S, R96P, S128R, R132H, R172P, R236Q, C283S, R292Q, H296R) diminish this activity. Additional characterization these reveals five...