A5054443109- Mass Spectrometry Techniques and Applications
- Cellular transport and secretion
- Advanced Proteomics Techniques and Applications
- Osteoarthritis Treatment and Mechanisms
- Neuroscience and Neuropharmacology Research
- Antifungal resistance and susceptibility
- Fungal and yeast genetics research
- RNA modifications and cancer
- Retinal Development and Disorders
- Glycosylation and Glycoproteins Research
- Extracellular vesicles in disease
- Metabolomics and Mass Spectrometry Studies
- Ubiquitin and proteasome pathways
- RNA and protein synthesis mechanisms
- Microbial Natural Products and Biosynthesis
- Peptidase Inhibition and Analysis
- Biotin and Related Studies
- Genetics and Neurodevelopmental Disorders
- Signaling Pathways in Disease
- Bacteriophages and microbial interactions
- RNA Research and Splicing
- Erythrocyte Function and Pathophysiology
- Galectins and Cancer Biology
- Lipid Membrane Structure and Behavior
- Inflammatory mediators and NSAID effects
Duke University
2016-2025
Oregon Health & Science University
2024
University College London
2024
National Academy of Sciences of Ukraine
2024
University of Veterinary Medicine
2024
Duke Medical Center
2012-2023
Duke University Hospital
2010-2023
North Carolina Biotechnology Center
2020-2021
Louisiana State University
2021
Joint Center for Structural Genomics
2020
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...
Brassinosteroids (BRs) regulate multiple aspects of plant growth and development require an active BRASSINOSTEROID-INSENSITIVE1 (BRI1) BRI1-ASSOCIATED RECEPTOR KINASE1 (BAK1) for hormone perception signal transduction. Many animal receptor kinases exhibit ligand-dependent oligomerization followed by autophosphorylation activation the intracellular kinase domain. To determine if early events in BR signaling share this mechanism, we used coimmunoprecipitation epitope-tagged proteins to show...
Inhibitory synapses dampen neuronal activity through postsynaptic hyperpolarization. The composition of the inhibitory postsynapse and mechanistic basis its regulation, however, remain poorly understood. We used an in vivo chemico-genetic proximity-labeling approach to discover proteins. Quantitative mass spectrometry not only recapitulated known proteins but also revealed a large network new proteins, many which are either implicated neurodevelopmental disorders or unknown function....
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...
Abstract The pace of repair declines with age and, while exposure to a young circulation can rejuvenate fracture repair, the cell types and factors responsible for rejuvenation are unknown. Here we report that macrophage cells produce promote osteoblast differentiation old bone marrow stromal cells. Heterochronic parabiosis exploiting mice in which macrophages be depleted fractionated transplantation experiments show slow healing mice. Proteomic analysis secretomes identify differential...
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....
Abstract Excitatory synapse formation during development involves the complex orchestration of both structural and functional alterations at postsynapse. However, molecular mechanisms that underlie excitatory synaptogenesis are only partially resolved, in part because internal machinery developing synapses is largely unknown. To address this, we apply a chemicogenetic approach, vivo biotin identification (iBioID), to discover aspects proteome nascent synapses. This approach uncovered sixty...
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...
Calcineurin governs stress survival, sexual differentiation, and virulence of the human fungal pathogen Cryptococcus neoformans. is activated by increased Ca2+ levels caused stress, transduces signals dephosphorylating protein substrates. Herein, we identified characterized calcineurin substrates in C. neoformans employing phosphoproteomic TiO2 enrichment quantitative mass spectrometry. The targets include transactivator Crz1 as well novel whose functions are linked to P-bodies/stress...
ABSTRACT Dengue virus is the most prevalent cause of arthropod-borne infection worldwide. Due to limited coding capacity viral genome and complexity life cycle, host cell proteins play essential roles throughout course infection. Host RNA-binding mediate various aspects replication through their physical interactions with RNA. Here we describe a technique designed identify such in context infected cells using UV cross-linking followed by antisense-mediated affinity purification mass...
A novel data-independent acquisition (DIA) method incorporating a scanning quadrupole in front of collision cell and orthogonal acceleration time-of-flight mass analyzer is described. The has been characterized for the qualitative quantitative label-free proteomic analysis complex biological samples. principle DIA discussed, analytical instrument characteristics, such as transmission width, scan/integration time, chromatographic separation, have optimized relation to sample complexity number...
Heat shock protein 90 (Hsp90) is an essential chaperone involved in the fungal stress response that can be harnessed as a novel antifungal target for treatment of invasive aspergillosis. We previously showed genetic repression Hsp90 reduced Aspergillus fumigatus virulence and potentiated effect echinocandin caspofungin. In this study, we sought to identify sites posttranslational modifications (phosphorylation or acetylation) are important function A. fumigatus. Phosphopeptide enrichment...
Significance O-GlcNAc is an abundant, reversible posttranslational modification (PTM) of nuclear and cytoplasmic proteins in animals plants. regulates a wide range biological processes, aberrant O-GlcNAcylation implicated numerous human diseases. However, key aspects signaling remain poorly understood. For example, it not known whether “reader” exist to recognize bind O-GlcNAc, as true for many other PTMs. We used biochemical method identify candidate reader proteins, then characterized them...
In contrast to their postsynaptic counterparts, the contributions of activity-dependent cytoskeletal signaling presynaptic plasticity remain controversial and poorly understood. To identify evaluate these pathways, we conducted a proteomic analysis cytomatrix using in vivo biotin identification (iBioID). The resultant proteome was heavily enriched for actin cytoskeleton regulators, including Rac1, Rho GTPase that activates Arp2/3 complex nucleate branched filaments. Strikingly, find Rac1 are...
Mutation of the Wiskott-Aldrich syndrome protein and SCAR homology (WASH) complex subunit, SWIP, is implicated in human intellectual disability, but cellular etiology this association unknown. We identify neuronal WASH proteome, revealing a network endosomal proteins. To uncover how dysfunction SWIP leads to disease, we generate mouse model WASHC4c.3056C>G mutation. Quantitative spatial proteomics analysis SWIPP1019R brain reveals that mutation destabilizes uncovers significant perturbations...
Ten-eleven translocation (TET) proteins are DNA dioxygenases that mediate active demethylation. TET3 is the most highly expressed TET protein in thymic developing T cells. TET3, either independently or cooperation with TET1 TET2, has been implicated cell lineage specification by regulating However, TET-deficient mice exhibit complex phenotypes, suggesting exerts multifaceted roles, potentially interacting other proteins. We performed liquid chromatography tandem mass spectrometry primary...
We aimed to identify serum biomarkers that predict knee osteoarthritis (OA) before the appearance of radiographic abnormalities in a cohort 200 women. As few as six peptides, corresponding proteins, reached AUC 77% probability distinguish those who developed OA from age-matched individuals did not develop up 8 years later. Prediction based on these blood was superior traditional prediction age and BMI (AUC 51%) or pain 57%). These results prolonged molecular derangement joint tissue onset...
Chemical cross-linking combined with mass spectrometry is a viable approach to study the low-resolution structure of protein and complexes. However, unambiguous identification residues involved in cross-link remains analytically challenging. To enable more effective analysis across various MS platforms, we have developed novel set collision-induced dissociative reagents methodology for chemical experiments using tandem (CID-CXL-MS/MS). These incorporate single gas-phase cleavable bond within...
The fungus Aspergillus fumigatus is a leading infectious killer in immunocompromised patients. Calcineurin, calmodulin (CaM)-dependent protein phosphatase comprised of calcineurin A (CnaA) and B (CnaB) subunits, localizes at the hyphal tips septa to direct A. invasion virulence. Here we identified novel serine-proline rich region (SPRR) located between two conserved CnaA domains, CnaB-binding helix CaM-binding domain, that evolutionarily unique filamentous fungi also completely absent human...