A5053603176- Redox biology and oxidative stress
- Cancer, Lipids, and Metabolism
- Cancer, Hypoxia, and Metabolism
- Peroxisome Proliferator-Activated Receptors
- Ferroptosis and cancer prognosis
- Sulfur Compounds in Biology
- Extracellular vesicles in disease
- Immune cells in cancer
- Mitochondrial Function and Pathology
- RNA modifications and cancer
- Head and Neck Cancer Studies
- Adipose Tissue and Metabolism
- Enzyme Structure and Function
- Metabolomics and Mass Spectrometry Studies
- Epigenetics and DNA Methylation
- Diet and metabolism studies
- Click Chemistry and Applications
- Nitric Oxide and Endothelin Effects
- Osteoarthritis Treatment and Mechanisms
- Muscle Physiology and Disorders
- Computational Drug Discovery Methods
- Alzheimer's disease research and treatments
- Nanoplatforms for cancer theranostics
- Biochemical and Molecular Research
- Sirtuins and Resveratrol in Medicine
Institute of Molecular Medicine
2009-2025
Wake Forest University
2016-2025
Atrium Health Wake Forest Baptist
2015-2024
Wake Forest Baptist Comprehensive Cancer Center
2018-2024
Winston-Salem/Forsyth County Schools
2018-2023
ETH Zurich
2020
Scripps Research Institute
2020
Dongfang Electric Corporation (China)
2018
Winston-Salem State University
2011-2015
Yale University
2004-2014
Objective Ample evidence exists for the role of abnormal gut microbiota composition and increased permeability (‘leaky gut’) in chronic inflammation that commonly co-occurs both obesity diabetes, yet detailed mechanisms involved this process have remained elusive. Design In study, we substantiate causal by use faecal conditioned media along with transplantation. Using untargeted comprehensive approaches, discovered mechanism which obese instigates permeability, abnormalities glucose...
Cysteine sulfenic acid formation in proteins results from the oxidative modification of susceptible cysteine residues by hydrogen peroxide, alkyl hydroperoxides, and peroxynitrite. This species represents a biologically significant occurring during oxidant signaling or stress, it can modulate protein function. Most methods to identify such oxidatively modified rely on monitoring loss one more thiol group(s) selective labeling nascent groups following reduction oxidized proteins. Our previous...
The order of FGFR1 tyrosine autophosphorylation is kinetically controlled and determined by primary tertiary structures.
Isoform-specific signaling of Akt, a major hub and prominent therapeutic target, remained poorly defined until recently. Subcellular distribution, tissue-specific expression, substrate specificity, posttranslational modifications are believed to underlie isoform-specific Akt. The studies reported here show inhibition Akt2 activity under physiologically relevant conditions oxidation created by PDGF-induced reactive oxygen species. Combined MS functional assays identified Cys124 located in the...
Objectives: Our study aims at producing acellular extracellular matrix scaffolds from the human pancreas (hpaECMs) as a first critical step toward production of new-generation, fully human-derived bioartificial endocrine pancreas. In this pancreas, hardware will be represented by hpaECMs, whereas software consist in cellular compartment generated patient's own cells. Background: Extracellular (ECM)-based obtained through decellularization native organs have become favored platform field...
Abstract: Identification of differential sensitivity cancer cells as compared to normal has the potential reveal a therapeutic window for use silver nanoparticles (AgNPs) agent therapy. Exposure AgNPs is known cause dose-dependent toxicities, including induction oxidative stress and DNA damage, which can lead cell death. Triple-negative breast (TNBC) subtypes are more vulnerable agents that damage than other subtypes. We hypothesized TNBC may be susceptible AgNP cytotoxicity, vulnerability...
Protein sulfenic acids are formed by the reaction of biologically relevant reactive oxygen species with protein thiols. Sulfenic acid formation modulates function enzymes and transcription factors either directly or through subsequent disulfide bonds. Identifying site, timing, conditions remains crucial to understanding cellular redox regulation. Current methods for trapping analyzing involve use dimedone other nucleophilic 1,3-dicarbonyl probes that form covalent adducts cysteine-derived...
Cellular exposure to reactive oxygen species induces rapid oxidation of DNA, proteins, lipids and other biomolecules. At the proteome level, cysteine thiol is a prominent post-translational process that implicated in normal physiology numerous pathologies. Methods for investigating protein include direct labeling with selective chemical probes indirect tag-switch techniques. Common both approaches blocking free thiols using electrophiles prevent post-lysis or thiol-mediated cross-reactions....
Abstract Background Precisely how silver nanoparticles (AgNPs) kill mammalian cells still is not fully understood. It clear if AgNP-induced damage differs from cation (Ag + ), nor it known AgNP transmitted cell membranes, including endosomes, to other organelles. Cells can differ in relative sensitivity AgNPs or Ag , which adds another layer of complexity identifying specific mechanisms action. Therefore, we determined there were effects that differed with high low either toxicant. Methods...
While radiation therapy is commonly used for treating cancer, resistance can limit long-term control of the disease. In this study, we investigated reprogramming energy metabolism in radiosensitive and radioresistant head neck squamous cell carcinomas (HNSCC) using a preclinical matched model resistance. Our investigation found that rSCC-61 cells: 1. They display increased glucose uptake decreased fatty acid uptake; 2. deviate from classical Warburg effect by diverting glycolytic flux into...
Silver nanoparticles (AgNPs) show promise for treatment of aggressive cancers including triple-negative breast cancer (TNBC) in preclinical models. For clinical development AgNP-based therapeutics, it will be necessary to clearly define the specific physicochemical features that used, and tie these properties biological outcomes. To fill this knowledge gap, we performed thorough structure/function, mechanistic, safety, efficacy studies assess potential AgNPs treat TNBC. We establish AgNPs,...
Metabolic reprogramming between resistance and tolerance occurs within the immune system in response to sepsis. While metabolic tissues such as liver are subjected damage during sepsis, how their energy ensures survival is unclear. Employing comprehensive metabolomic, lipidomic, transcriptional profiling a mouse model of we show that hepatocyte lipid metabolism, mitochondrial tricarboxylic acid (TCA) energetics, redox balance significantly reprogrammed after cecal ligation puncture (CLP). We...
Activating the macrophage NLRP3 inflammasome can promote excessive inflammation with severe cell and tissue damage organ dysfunction. Here, we show that pharmacological or genetic inhibition of pyruvate dehydrogenase kinase (PDHK) significantly attenuates activation in murine human macrophages septic mice by lowering caspase-1 cleavage interleukin-1β (IL-1β) secretion. Inhibiting PDHK reverses inflammasome-induced metabolic reprogramming, enhances autophagy, promotes mitochondrial fusion...
Abstract Brain‐derived extracellular vesicles (EVs) play an active role in Alzheimer's disease (AD), relaying important physiological information about their host tissues. The internal cargo of EVs is protected from degradation, making attractive AD biomarkers. However, it unclear how circulating relate to isolated disease‐vulnerable brain regions. We developed a novel method for collecting the hippocampal interstitial fluid (ISF) live mice. (EV ISF ) were via ultracentrifugation and...
Chromatin structure is regulated through posttranslational modifications of histone variants that modulate transcription. Although highly homologous, display unique amino acid sequences associated with specific functions. Abnormal incorporation contributes to cancer initiation, therapy resistance, and metastasis. This study reports that, among its biologic functions, H3.1 serves as a chromatin redox sensor engaged by mitochondrial H2O2. In breast cells, the oxidation H3.1Cys96 promotes...
Pyruvate:ferredoxin oxidoreductase (PFOR) catalyzes the oxidative decarboxylation of pyruvate to acetyl-CoA and CO2. The catalytic proficiency this enzyme for reverse reaction, synthase, is poorly understood. Conversion links Wood-Ljungdahl pathway autotrophic CO2 fixation reductive tricarboxylic acid cycle, which in these anaerobes stage biosynthesis all cellular macromolecules. results described here demonstrate that Clostridium thermoaceticum PFOR a highly efficient synthase....
Symptoms of autonomic failure are frequently the presentation advanced age and neurodegenerative diseases that impair adaptation to common physiologic stressors. The aim this work was examine interaction between sympathetic motor nervous system, involvement system (SNS) in neuromuscular junction (NMJ) presynaptic function, stability postsynaptic molecular organization, skeletal muscle composition function.