- Mass Spectrometry Techniques and Applications
- Metabolomics and Mass Spectrometry Studies
- Advanced Proteomics Techniques and Applications
- Analytical Chemistry and Chromatography
- Microfluidic and Capillary Electrophoresis Applications
- Antifungal resistance and susceptibility
- Diet and metabolism studies
- Peptidase Inhibition and Analysis
- Nitric Oxide and Endothelin Effects
- Fungal and yeast genetics research
- Redox biology and oxidative stress
- Ubiquitin and proteasome pathways
- Osteoarthritis Treatment and Mechanisms
- Signaling Pathways in Disease
- Asthma and respiratory diseases
- Mitochondrial Function and Pathology
- Gut microbiota and health
- Molecular Biology Techniques and Applications
- Microbial Natural Products and Biosynthesis
- Analytical chemistry methods development
- Alzheimer's disease research and treatments
- Hepatitis C virus research
- Machine Learning in Bioinformatics
- Respiratory viral infections research
- Monoclonal and Polyclonal Antibodies Research
Duke University
2015-2024
North Carolina Biotechnology Center
2021
Duke University Hospital
2009-2020
Duke Medical Center
2009-2020
Airbus (Germany)
2019-2020
University of Alaska Fairbanks
2016
Center for Genomic Science
2015
Fifth Tianjin Central Hospital
2014
Xiamen University
2010
Research Triangle Park Foundation
1982-2003
Abstract Introduction Increasing evidence suggests a role for the gut microbiome in central nervous system disorders and specific gut‐brain axis neurodegeneration. Bile acids (BAs), products of cholesterol metabolism clearance, are produced liver further metabolized by bacteria. They have major regulatory signaling functions seem dysregulated Alzheimer's disease (AD). Methods Serum levels 15 primary secondary BAs their conjugated forms were measured 1464 subjects including 370 cognitively...
Song-learning birds and humans share independently evolved similarities in brain pathways for vocal learning that are essential song speech not found most other species. Comparisons of transcriptomes song-learning relative to nonlearners identified convergent gene expression specializations specific regions avian learners humans. The strongest shared profiles relate bird motor striatal nuclei, respectively, with human laryngeal cortex parts the striatum control production learning. Most...
A molecular signature, derived from integrated analysis of clinical data, the metabolome, and proteome in prospective human studies, improved prediction death patients with sepsis, potentially identifying a subset who merit intensive treatment.
Abstract Introduction The Alzheimer's Disease Research Summits of 2012 and 2015 incorporated experts from academia, industry, nonprofit organizations to develop new research directions transform our understanding disease (AD) propel the development critically needed therapies. In response their recommendations, big data at multiple levels are being generated integrated study network failures in disease. We used metabolomics as a global biochemical approach identify peripheral metabolic...
Vendor-independent software tools for quantification of small molecules and metabolites are lacking, especially targeted analysis workflows. Skyline is a freely available, open-source tool quantitative mass spectrometry method development data processing with 10 year history supporting six major instrument vendors. Designed initially proteomics analysis, we describe the expansion to molecule including selected reaction monitoring, high-resolution spectrometry, calibrated quantification. This...
As the lipidomics field continues to advance, self-evaluation within community is critical. Here, we performed an interlaboratory comparison exercise for using Standard Reference Material (SRM) 1950-Metabolites in Frozen Human Plasma, a commercially available reference material. The study comprised 31 diverse laboratories, with each laboratory different workflow. A total of 1,527 unique lipids were measured across all laboratories and consensus location estimates associated uncertainties...
Protein S-acylation is a major posttranslational modification whereby cysteine thiol converted to thioester. A prototype S-palmitoylation (fatty acylation), in which protein undergoes acylation with hydrophobic 16 carbon lipid chain. Although this well-recognized determinant of function and localization, current techniques study cellular are cumbersome and/or technically demanding. We recently described simple robust methodology rapidly identify S-nitrosylation sites proteins via...
Late-onset Alzheimer's disease (AD) can, in part, be considered a metabolic disease. Besides age, female sex and APOE ε4 genotype represent strong risk factors for AD that also give rise to large differences. We systematically investigated group-specific alterations by conducting stratified association analyses of 139 serum metabolites 1,517 individuals from the Neuroimaging Initiative with biomarkers. observed substantial differences effects 15 partially overlapping status groups. Several...
The goal of this work was to evaluate the improvement in proteome coverage complex protein mixtures gained by analyzing samples using both LC/ESI/MS/MS and LC/MALDI/MS/MS. Parallel analyses a single sample were accomplished interfacing Probot fractionation system with nanoscale LC system. configured perform post-column split such that fraction (20%) column effluent sent for on-line data acquisition, majority (80%) mixed matrix solution deposited onto MALDI target plate. split-flow approach...
Chlamydia trachomatis is an obligate intracellular pathogen responsible for ocular and genital infections of significant public health importance. C. undergoes a biphasic developmental cycle alternating between two distinct forms: the infectious elementary body (EB), replicative but non-infectious reticulate (RB). The molecular basis these transitions metabolic properties EB RB forms are poorly understood as bacteria have traditionally been difficult to manipulate through classical genetic...
Because proteins are the major functional components of cells, knowledge their cellular localization is crucial to gaining an understanding biology multicellular organisms. We have generated a protein expression map Arabidopsis root providing identity and cell type-specific nearly 2,000 proteins. Grouping into categories revealed unique functions identified biomarkers. Cellular colocalization provided support for numerous protein-protein interactions. With binary comparison, we found that...
The proteomic analysis of bronchoalveolar lavage fluid (BALF) can give insight into pulmonary disease pathology and response to therapy. Here, we describe the first gel-free quantitative BALF in idiopathic fibrosis (IPF), a chronic fatal scarring lung disease. We utilized two-dimensional reversed-phase liquid chromatography ion-mobility-assisted data-independent acquisition (HDMSE) for quantitation >1000 proteins immunodepleted from right middle lower lobes normal controls patients with IPF....
Transcription errors occur in all living cells; however, it is unknown how these affect cellular health. To answer this question, we monitor yeast cells that are genetically engineered to display error-prone transcription. We discover suffer from a profound loss proteostasis, which sensitizes them the expression of genes associated with protein-folding diseases humans; thus, transcription represent new molecular mechanism by can acquire disease phenotypes. further find error rate increases...
A challenge facing metabolomics in the analysis of large human cohorts is cross-laboratory comparability quantitative measurements. In this study, 14 laboratories analyzed various blood specimens using a common experimental protocol provided with Biocrates AbsoluteIDQ p400HR kit, to quantify up 408 metabolites. The included plasma and serum from male female donors, mouse rat plasma, as well NIST SRM 1950 reference plasma. metabolite classes covered range polar (e.g., amino acids biogenic...
Abstract Selective serotonin reuptake inhibitors (SSRIs) are the first-line treatment for major depressive disorder (MDD), yet their mechanisms of action not fully understood and therapeutic benefit varies among individuals. We used a targeted metabolomics approach utilizing panel 180 metabolites to gain insights into response citalopram/escitalopram. Plasma samples from 136 participants with MDD enrolled Mayo Pharmacogenomics Research Network Antidepressant Medication Pharmacogenomic Study...
Branched-chain amino acids (BCAA) and their cognate α-ketoacids (BCKA) are elevated in an array of cardiometabolic diseases. Here we demonstrate that the major metabolic fate uniformly-13C-labeled α-ketoisovalerate ([U-13C]KIV) heart is reamination to valine. Activation cardiac branched-chain α-ketoacid dehydrogenase (BCKDH) by treatment with BCKDH kinase inhibitor, BT2, does not impede strong flux [U-13C]KIV Sequestration BCAA BCKA away from mitochondrial oxidation likely due low levels...
We aimed to identify markers in blood (serum) predict clinically relevant knee osteoarthritis (OA) progression defined as the combination of both joint structure and pain worsening over 48 months. A set 15 serum proteomic corresponding 13 total proteins reached an area under receiver operating characteristic curve (AUC) 73% for distinguishing progressors from nonprogressors a cohort 596 individuals with OA. Prediction based on these was far better than traditional prediction baseline...
Transport of cyclosporin A (CsA) across Caco-2 cells is modulated by its directional efflux, mediated a p-glycoprotein-like pump (Augustijns et al., Biochem. Biophys. Res. Comm. 197:360-365, 1994). In addition to this unidirectional flux, oxidative metabolism CsA cytochrome P450 likely influence the absorption cyclic peptide intestinal mucosa. Thus, in vitro cell culture system was investigated. Formation several metabolites observed during course transport monolayers. Results from LC/MS/MS...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDetermination of bioactive peptides using capillary zone electrophoresis/mass spectrometryM. A. Moseley, L. J. Deterding, K. B. Tomer, and W. JorgensonCite this: Anal. Chem. 1991, 63, 2, 109–114Publication Date (Print):January 15, 1991Publication History Published online1 May 2002Published inissue 15 January 1991https://pubs.acs.org/doi/10.1021/ac00002a005https://doi.org/10.1021/ac00002a005research-articleACS PublicationsRequest reuse...
The solution chemistry conditions necessary for optimum analysis of peptides by capillary zone electrophoresis (CZE)/electrospray ionization mass spectrometry and CZE electrospray tandem have been studied. To maximize the signal-to-noise ratio spectra it was found to use acidic buffers low ionic strength. This not only increases total ion current, but also serves fully protonate peptides, minimizing distribution current across ensemble possible charge states.The protonates which is...
Reversible protein cysteine nitrosylation (S-nitrosylation) is a common mechanism utilized in signal transduction and other diverse cellular processes. Protein denitrosylation largely mediated by denitrosylases, but the functional scope significance of these enzymes are incompletely defined, part due to limited information on their cognate substrates. Here, using Jurkat cells, we employed stable isotope labeling amino acids cell culture (SILAC), coupled biotin switch technique mass...