A5026288648- Extracellular vesicles in disease
- Advanced Proteomics Techniques and Applications
- Platelet Disorders and Treatments
- Protease and Inhibitor Mechanisms
- Sepsis Diagnosis and Treatment
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Blood Coagulation and Thrombosis Mechanisms
- Trauma, Hemostasis, Coagulopathy, Resuscitation
- Nitric Oxide and Endothelin Effects
- Cell Adhesion Molecules Research
- Amino Acid Enzymes and Metabolism
- Chronic Myeloid Leukemia Treatments
- Metabolomics and Mass Spectrometry Studies
- Immune Response and Inflammation
- Chronic Lymphocytic Leukemia Research
- Atherosclerosis and Cardiovascular Diseases
- ATP Synthase and ATPases Research
- Sirtuins and Resveratrol in Medicine
- Protein Kinase Regulation and GTPase Signaling
- Advanced biosensing and bioanalysis techniques
- Biochemical and Structural Characterization
- Student Assessment and Feedback
- Vitamin K Research Studies
- Computational Drug Discovery Methods
- Melanoma and MAPK Pathways
Georgia Institute of Technology
2016-2023
AID Atlanta
2020
Parker Hannifin (United States)
2020
University of North Carolina at Chapel Hill
2010-2014
UNC Lineberger Comprehensive Cancer Center
2012
Indiana University School of Medicine
2012
University of Virginia
2005-2011
University of Kansas
1998-2003
University of Kansas Medical Center
1998-2000
United States Congress
2000
Abstract To examine mechanisms by which native low-density lipoprotein (n-LDL) perturbs endothelial cell (EC) release of superoxide anion (O 2 − ) and nitric oxide (NO), ECs were incubated with n-LDL at 240 mg cholesterol per deciliter for 4 days media changes every 24 hours. increases EC O more than fourfold nitrite production 57%. In the conditioned from day-4 incubations, total nitrogen oxides 20 times control (C-EC) levels. However, did not alter NO synthase (eNOS) enzyme activity as...
Platelet-derived microparticles are the most abundant type of microparticle in human blood and contribute to many biologically significant processes. Here, we report first proteomic analysis generated from activated platelets. Using 1D SDS-PAGE liquid chromatography coupled a linear ion trap mass spectrometer, identification 578 proteins was accomplished using minimum 5 MS/MS detections at least two different peptides for each protein. These displayed intrinsic well-characterized on For...
Bladder cancer leads to approximately 13 000 deaths annually in the United States. Early disease is often treated with minimal morbidity and has good prognosis, while opposite true for advanced disease. Currently, no tools exist early detection of this cancer. Microparticles are small, subcellular particles released by essentially all cells upon activation known be produced constitutively cells. Since most bladder cancers originate urothelial lining lumen organ, we hypothesize that these...
The three EglN prolyl hydroxylases (EglN1, EglN2, and EglN3) regulate the stability of HIF transcription factor. We recently showed that loss however, also leads to down-regulation Cyclin D1 decreased cell proliferation in a HIF-independent manner. Here we report EglN2 can hydroxylate FOXO3a on two specific residues vitro vivo. Hydroxylation these sites prevents binding USP9x deubiquitinase, thereby promoting proteasomal degradation FOXO3a. FOXO factors repress transcription. Failure...
Abstract Native LDL (n-LDL) increases human umbilical vein endothelial cell (EC) adherence of mononuclear cells. Such phenotypic changes suggest that n-LDL alters the usual expression adhesion molecules to enhance adhesive properties endothelium. To investigate mechanisms governing adherence, ECs were exposed in concentrations up 240 mg/dL for 2 and 4 days. n-LDL–treated bound nearly threefold more phorbol myristate acetate (PMA)–stimulated U937 cells than control but did not bind...
Summary Microparticles (MPs) are small membrane vesicles generated by essentially all cell types. In the plasma, most MPs derived from platelets, but those other sources, particularly leukocytes (macrophages, lymphocytes, and neutrophils), endothelial cells, even smooth muscle cells can be detected appear to play an important role in normal physiology various diseases. previous work we analyzed proteome of isolated platelets (platelet MPs). Here, report on a comparative analysis...
Protein kinases play key roles in oncogenic signaling and are a major focus the development of targeted cancer therapies. Imatinib, BCR-Abl tyrosine kinase inhibitor, is successful front-line treatment for chronic myelogenous leukemia (CML). However, resistance to imatinib may be acquired by mutations or hyperactivation Src family such as Lyn. We have used multiplexed inhibitor beads (MIBs) quantitative mass spectrometry (MS) compare expression activity an imatinib-resistant (MYL-R)...
Rolling neutrophils form tethers with submicron diameters. Here, we report that these detach, forming elongated neutrophil-derived structures (ENDS) in the vessel lumen. We studied ENDS formation mice and humans vitro vivo. do not contain mitochondria, endoplasmic reticulum, or DNA, but are enriched for S100A8, S100A9, 57 other proteins. Within hours of formation, round up, some them begin to present phosphatidylserine on their surface (detected by annexin-5 binding) release S100A8–S100A9...
The generation of oxygen radicals during leukocyte-endothelial cell interaction is considered to represent one the fundamental steps microvascular injury following ischemia and reperfusion. Indirect evidence also suggests that this relationship may be important hemorrhagic shock. purpose study was characterize temporal changes reactive species (ROS) in mesenteric endothelium, vivo, as a consequence shock reperfusion, correlate ROS production leukocyte adherence. Following control period,...
Hemorrhage induced by snake venom metalloproteinases (SVMPs) is a complex phenomenon resulting in capillary disruption and blood extravasation. The mechanism of action SVMPs has been investigated using various methodologies however the precise molecular events associated with microvessel remains not fully understood. To gain insight into hemorrhagic process, we analyzed global effects HF3, an extremely SVMP from Bothrops jararaca, mouse skin plasma. We report that HF3-treated there was...
Abstract DNA-dependent protein kinase (DNA-PK) plays a critical role in non-homologous end joining (NHEJ), the predominant pathway that repairs DNA double-strand breaks (DSB) response to ionizing radiation (IR) govern genome integrity. The interaction of catalytic subunit DNA-PK (DNA-PKcs) with Ku70/Ku80 heterodimer on DSBs leads activation; however, it is not known if upstream signaling events this activation. Here, we reveal regulatory step governing activation by SIRT2 deacetylation,...
Post-translational modifications of proteins regulate diverse cellular functions, with mounting evidence suggesting that hierarchical cross-talk between distinct may fine-tune responses. For example, in apoptosis, caspases promote cell death via cleavage key structural and enzymatic some instances is inhibited by phosphorylation near the scissile bond. In this study, we systematically investigated how protein affects susceptibility to caspase using an N-terminomic strategy, namely, a...
The zebrafish (Danio rerio) was used to investigate protein expression in the liver following arsenic exposure. Several disorders have been linked exposure, including cancer, diabetes, and cardiovascular disease. mechanisms of toxicity are poorly understood. Prior studies described altered gene expression, inflammation, mitogenic signaling acute or chronic exposure models. A proteomic approach employed arsenic-induced alteration proteome a 7-day 50 ppb sodium arsenite. Over 740 unique...
The chemical and enzymatic pathways of vitamin K1 epoxide quinone reduction have been investigated. the by thiols is known to involve a thiol-adduct hydroxy K enolate intermediate which eliminates water yield quinone. Sodium borohydride treatment resulted in carbonyl generating relatively stable compounds that did not proceed presence base. NAD(P)H:quinone oxidoreductase (DT-diaphorase. E.C. I.6.99.2) hydroquinone was significant process intact microsomes. but 1/5th rate dithiothreitol...
Abstract LC‐MS/MS with certain labeling techniques such as isotope‐coded affinity tag (ICAT) enables quantitative analysis of paired protein samples. However, current identification and quantification differentially expressed peptides (and proteins) are not reliable for large proteomics screening complex biological The number replicates is often limited because the high cost experiments supply Traditionally, a simple fold change cutoff used, which results in rate false positives. Standard...
The pathogenesis of generalized microvascular injury following hemorrhagic shock and total ischemia appears to be dependent on leukocytes interacting with the venular endothelium. purpose this study was compare leukocyte adherence sequestration that in small bowel mesentery rats. Leukocyte measured by direct visualization vivo using intravital microscopy. In addition, also quantitated measuring tissue levels myeloperoxidase, a marker infiltration. Mean arterial blood pressure decreased 40 mm...