A5004797092- Biotin and Related Studies
- Mitochondrial Function and Pathology
- Alzheimer's disease research and treatments
- S100 Proteins and Annexins
- Cellular transport and secretion
- Trace Elements in Health
- Click Chemistry and Applications
- Metabolism and Genetic Disorders
- ATP Synthase and ATPases Research
- Molecular Sensors and Ion Detection
- Genetic Neurodegenerative Diseases
- Electrochemical Analysis and Applications
- Metabolism, Diabetes, and Cancer
- RNA modifications and cancer
- Botulinum Toxin and Related Neurological Disorders
- Metal complexes synthesis and properties
- Tryptophan and brain disorders
- X-ray Diffraction in Crystallography
- Receptor Mechanisms and Signaling
- Crystallization and Solubility Studies
- Parkinson's Disease Mechanisms and Treatments
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Amyotrophic Lateral Sclerosis Research
- RNA Research and Splicing
- Research Data Management Practices
Emory University
2018-2025
Emory and Henry College
2025
Institute for Neurodegenerative Disorders
2021-2024
Analytical Services
2021-2023
Icahn School of Medicine at Mount Sinai
2023
National Center for Environmental Health
2018
Centers for Disease Control and Prevention
2018
Georgia Institute of Technology
2004-2015
The Wallace H. Coulter Department of Biomedical Engineering
2015
Phosphorylation of α-synuclein at the serine-129 site (α-syn Ser129P) is an established pathologic hallmark synucleinopathies and a therapeutic target. In physiologic states, only fraction α-syn phosphorylated this site, most studies have focused on roles post-translational modification. We found that unlike wild-type (WT) α-syn, which widely expressed throughout brain, overall pattern Ser129P restricted, suggesting intrinsic regulation. Surprisingly, preventing blocked activity-dependent...
Abstract Proteomic profiling of brain cell types using isolation-based strategies pose limitations in resolving cellular phenotypes representative their native state. We describe a mouse line for type-specific expression biotin ligase TurboID, vivo biotinylation proteins. Using adenoviral and transgenic approaches to label neurons, we show robust protein neuronal soma axons throughout the brain, allowing quantitation over 2000 neuron-derived proteins spanning synaptic proteins, transporters,...
Due to the lipophilicity of metal-ion receptor, previously reported Cu(I)-selective fluorescent probes form colloidal aggregates, as revealed by dynamic light scattering. To address this problem, we have developed a hydrophilic triarylpyrazoline-based probe, CTAP-2, that dissolves directly in water and shows rapid, reversible, highly selective 65-fold fluorescence turn-on response Cu(I) aqueous solution. CTAP-2 proved be sufficiently sensitive for direct in-gel detection bound...
The measurement of reliable Cu(I) protein binding affinities requires competing reference ligands with similar strengths; however, the literature on such is not only sparse but often conflicting. To address this deficiency, we have created and characterized a series water-soluble monovalent copper ligands, MCL-1, MCL-2, MCL-3, that form well-defined, air-stable, colorless complexes in aqueous solution. X-ray structural data, electrochemical measurements, an extensive network equilibrium...
Atherosclerosis preferentially occurs in arterial regions exposed to disturbed blood flow ( d-flow ), while stable s-flow ) are protected. The proatherogenic and atheroprotective effects of mediated part by the global changes endothelial cell (EC) gene expression, which regulates dysfunction, inflammation, atherosclerosis. Previously, we identified kallikrein-related peptidase 10 Klk10 , a secreted serine protease) as flow-sensitive mouse ECs, but its role biology atherosclerosis was...
•Cytosolic TurboID biotinylates >50% of the proteome in microglia and neuronal cells.•TurboID-NES has minimal impacts on cellular proteomic composition function.•About 1340 proteins labeled by differentiate from neurons vitro.•TurboID profiling captures microglial activation lipopolysaccharide. Different brain cell types play distinct roles development disease. Molecular characterization cell-specific mechanisms using type–specific approaches at protein (proteomic) level can provide...
Spore formation is required for environmental survival and transmission of the human enteropathogenic Clostridioides difficile . In all bacterial spore formers, sporulation regulated through activation master response regulator, Spo0A. However, factors mechanisms that directly regulate C Spo0A activity are not defined. well-studied Bacillus species, inactivated by Spo0E, a small phosphatase. To understand Spo0E function in , we created null mutation spo0E ortholog assessed physiology. The...
Abstract Methionine plays a critical role in various biological and cell regulatory processes, making its chemoproteomic profiling indispensable for exploring functions potential protein therapeutics. Building on the principle of rapid oxidation methionine, we report Copper(I)-Nitrene Platform robust, selective labeling methionine to generate stable sulfonyl sulfimide conjugates under physiological conditions. We demonstrate versatility this platform label bioactive peptides, intact proteins...
In Alzheimer's disease (AD) and other tauopathies, tau dissociates from microtubules forms toxic aggregates that contribute to neurodegeneration. Although some of the pathological interactions have been identified postmortem brain tissue, these studies are limited by their inability capture transient interactions. To investigate interactome aggregate-prone fragments tau, we applied an in vitro proximity labeling technique using split TurboID biotin ligase (sTurbo) fused with microtubule...
Abstract Deep molecular phenotyping of cells at transcriptomic and proteomic levels is an essential first step to understanding cellular contributions development, aging, injury, disease. Since proteome transcriptome level abundances only modestly correlate with each other, complementary profiling both needed. We report a novel method called simultaneous protein RNA –omics (SPARO) capture the cell type-specific simultaneously from in vitro vivo experimental model systems. This leverages...
Dynamic protein post-translational methylation is essential for cellular function, highlighted by the role of in transcriptional regulation and its aberrant dysregulation diseases, including cancer. This underscores importance cataloging methylproteome. However, comprehensive analysis methylproteome remains elusive due to limitations current enrichment pipelines. Here, we employ an l-methionine analogue, ProSeMet, that chemoenzymatically converted SAM analogue ProSeAM cells vivo tag proteins...
Chromatin remodeling complexes, such as the SWItch/Sucrose Non-Fermentable (SWI/SNF) complex, play key roles in regulating gene expression by modulating nucleosome positioning. The core subunit SMARCB1 is essential for these functions, it anchors complex to acidic patch, enabling effective chromatin remodeling. While biallelic inactivation of a hallmark several aggressive pediatric malignancies, functional implication missense mutations not fully understood. Current diagnostic approaches...
Fluorescent proteins (FPs) have revolutionized molecular and cellular biology; yet, discrimination over autofluorescence, spectral deconvolution, or detection at low concentrations remain challenging problems in many biological applications. By optically depopulating a photoinduced dark state with orange secondary laser co-excitation, the higher-energy green AcGFP fluorescence is dynamically increased. Modulating this then modulates higher-energy, collected fluorescence; enabling its...
G-protein-coupled receptors (GPCRs) are a target for over 34% of current drugs. The calcium-sensing receptor (CaSR), family C GPCR, regulates systemic calcium (Ca2+) homeostasis that is critical many physiological, calciotropical, and noncalciotropical outcomes in multiple organs. However, the mechanisms by which extracellular Ca2+ (Ca2+ex) CaSR mediate networks intracellular Ca2+-signaling players involved throughout life cycle largely unknown. Here we report first protein-protein...
TIMM50, an essential TIM23 complex subunit, is suggested to facilitate the import of ~60% mitochondrial proteome. In this study, we characterized a TIMM50 disease-causing mutation in human fibroblasts and noted significant decreases core protein levels (TIMM50, TIMM17A/B, TIMM23). Strikingly, deficiency had no impact on steady-state most its putative substrates, suggesting that even low functional are sufficient maintain majority complex-dependent As mutations have been linked severe...
Congenital heart defects can lead to right ventricular (RV) pressure-overload and failure. Cell-based therapies, including mesenchymal stromal cells (MSCs) c-kit positive (CPCs) have been studied clinically as options restore function in disease states. Many studies indicated these act through paracrine mechanisms prevent apoptosis, promote cellular function, regulate gene/protein expression. We aimed determine the proteomic response of diseased hearts cell therapy.
The obesity pandemic currently affects more than 70 million Americans and 650 individuals worldwide. In addition to increasing susceptibility pathogenic infections (eg, SARS-CoV-2), promotes the development of many cancer subtypes increases mortality rates in most cases. We others have demonstrated that, context B-cell acute lymphoblastic leukemia (B-ALL), adipocytes promote multidrug chemoresistance. Furthermore, that B-ALL cells exposed adipocyte secretome alter their metabolic states...
Cu(I)-responsive fluorescent probes based on a photoinduced electron transfer (PET) mechanism generally show incomplete fluorescence recovery relative to the intrinsic quantum yield of reporter. Previous studies with an N-aryl thiazacrown Cu(I)-receptor revealed that is compromised by Cu(I)-N coordination and resultant ternary complex formation solvent molecules. Building upon strategy successfully increased contrast Cu(I) in methanol, we integrated arylamine PET donor into backbone...
Quantifying the magnitude and dynamics of protein oxidation during cell signaling is technically challenging. Computational modeling provides tractable, quantitative methods to test hypotheses redox mechanisms that may be simultaneously operative signal transduction. The interleukin-4 (IL-4) pathway, which has previously been reported induce reactive oxygen species PTP1B, controlled by several other putative regulation; widespread proteomic thiol observed via 2D differential gel...
Protein phosphatase 2A (PP2A) is a heterotrimer composed of single catalytic and scaffolding subunits one several possible regulatory subunits. We identified PPTR-2, subunit PP2A, as binding partner for the giant muscle protein UNC-89 (obscurin) in Caenorhabditis elegans. PPTR-2 required sarcomere organization when its paralogue, PPTR-1, deficient. localizes to at dense bodies M-lines, colocalizing with M-lines. PP2A components C. elegans include LET-92, (PAA-1), five (SUR-6, RSA-1, CASH-1)....