A5076938696- Redox biology and oxidative stress
- Ubiquitin and proteasome pathways
- Click Chemistry and Applications
- Sulfur Compounds in Biology
- Genomics, phytochemicals, and oxidative stress
- Peptidase Inhibition and Analysis
- Carbohydrate Chemistry and Synthesis
- Molecular Sensors and Ion Detection
- Chemical Synthesis and Analysis
- Histone Deacetylase Inhibitors Research
- Fluorine in Organic Chemistry
- Advanced biosensing and bioanalysis techniques
- Heat shock proteins research
- Muscle Physiology and Disorders
- Diet, Metabolism, and Disease
- Autophagy in Disease and Therapy
- Amino Acid Enzymes and Metabolism
- Adenosine and Purinergic Signaling
- Protein Kinase Regulation and GTPase Signaling
- Biotin and Related Studies
- Cancer, Hypoxia, and Metabolism
- Protein Degradation and Inhibitors
- Endoplasmic Reticulum Stress and Disease
- Glutathione Transferases and Polymorphisms
- Enzyme Structure and Function
Drexel University
2022-2025
Wayne State University
2014-2024
Division of Chemistry
2016
Johns Hopkins University
2010-2015
Johns Hopkins Medicine
2010-2015
New York University
2004-2010
Singapore Bioimaging Consortium
2008-2009
National University of Singapore
2008-2009
Agency for Science, Technology and Research
2008-2009
Pohang University of Science and Technology
2000-2003
Sulforaphane [1-isothiocyanato-4-(methylsulfinyl)butane], a naturally occurring isothiocyanate derived from cruciferous vegetables, is highly potent inducer of phase 2 cytoprotective enzymes and can protect against electrophiles including carcinogens, oxidative stress, inflammation. The mechanism action sulforaphane believed to involve modifications critical cysteine residues Keap1, which lead stabilization Nrf2 activate the antioxidant response element enzymes. However, dithiocarbamate...
Parkinson's disease (PD) is a progressive neurodegenerative movement disorder characterized by the loss of nigrostriatal dopaminergic neurons. Mounting evidence suggests that Nrf2 promising target for neuroprotective interventions in PD. However, electrophilic chemical properties canonical Nrf2-based drugs cause irreversible alkylation cysteine residues on cellular proteins resulting side effects. Bach1 known transcriptional repressor pathway. We report levels are up-regulated PD postmortem...
A group of styryl-based neutral compounds has been synthesized in this study for potential use as vivo imaging agents beta-amyloid plaques. Of 56 candidates, 14 were found to label plaques well on Alzheimer's disease (AD) human brain sections vitro. The binding affinity fibrils was then determined by measuring the change fluorescence intensity. Interestingly, we that a class quinaldine-styryl scaffold displays specific fibrils. representative compound, STB-8, used ex and experiments an AD...
The cell-by date: fluorescent compound CDy1 selectively stains embryonic stem cells (see scheme). was used to identify fibroblasts undergoing reprogramming induced pluripotent prior the expression of green protein under control Oct4 promoter. Detailed facts importance specialist readers are published as "Supporting Information". Such documents peer-reviewed, but not copy-edited or typeset. They made available submitted by authors. Please note: publisher is responsible for content...
Reversible lysine acetylation is one of the most important protein posttranslational modifications that plays essential roles in both prokaryotes and eukaryotes. However, only a few deacetylases (KDACs) have been identified prokaryotes, perhaps part due to their limited sequence homology. Herein, we developed ‘clip-chip’ strategy enable unbiased, activity-based discovery novel KDACs Escherichia coli proteome. In-depth biochemical characterization confirmed YcgC serine hydrolase involving...
The combinatorial fluorescent dapoxyl dye library was prepared by both solution- and solid-phase synthesis, generating 80 unique derivatives. A fluorescence-based screening toward human serum albumin (HSA) found one highly sensitive HSA binder (A41-S) with over 55-fold intensity change. Displacement assay showed the selective binding of A41-S to site I HSA, addressing its potential be a probe.
During muscle differentiation, mitochondria undergo dramatic changes in their morphology and distribution to prepare for the higher rate of energy consumption. By applying a mitochondria-targeted rosamine library C2C12 myogenesis, we discovered one compound that controls differentiation. When treated undifferentiated myoblasts, our selected compound, B25, inhibited myotube formation, when fully differentiated myotubes, it induced fission multinucleated myotubes into mononucleated fragments....
A bodipy probe was developed for site-specific labeling of tagged proteins inside live cells which displays a large spectral change upon covalent coupling to the designed peptide that contains two pairs Arg-Cys.
The tissue microenvironment plays a critical role in regulating inflammation. Chronic inflammation leads to an influx of inflammatory cells and mediators, extracellular matrix turnover, increased adenosine. Low molecular weight (LMW) fragments hyaluronan (HA), component, play lung fibrosis by inducing gene expression at the injury site. Adenosine, crucial negative regulator inflammation, protects tissues from immune destruction via adenosine A2a receptor (A2aR). Therefore, these two products...
Histone acetyltransferase enzymes (HATs) are important therapeutic targets, but there few cell-based assays available for evaluating the pharmacodynamics of HAT inhibitors. Here we present application a FRET-based reporter, Histac, in live-cell studies p300/CBP inhibition, by both genetic and pharmacologic disruption. shRNA knockdown led to increased Histac FRET, thus suggesting role acetylation histone H4 tail. Additionally, describe new inhibitor, C107, show that it can also increase...
Glutathionylation involves reversible protein cysteine modification that regulates the function of numerous proteins in response to redox stimuli, thereby altering cellular processes. Herein we developed a selective and versatile approach identifying glutathionylation by using mutant glutathione synthetase (GS). GS wild-type catalyzes coupling γGlu-Cys Gly form glutathione. We generated azido-Ala place with high catalytic efficiency selectivity. Transfection this (F152A/S151G) incubation...
A fluorescent dye library approach for the development of a bioanalyte sensor was sought. The screening rosamine against diverse macromolecules led to discovery highly sensitive human serum albumin binder, G13, with ∼36-fold fluorescence intensity change. G13 showed selective response HSA over other including albumins from species. potential use detection in biofluids is described.
A small molecule capable of distinguishing the distinct states resulting from cellular differentiation would be enormous value, for example, in efforts aimed at regenerative medicine. We screened a collection fluorescent molecules ability to distinguish differentiated state mouse skeletal muscle cell line. High-throughput fluorescence-based screening C2C12 myoblasts and myotubes resulted identification six compounds with desired selectivity, which was confirmed by high-content same states....
Lighten up! To investigate intracellular binders of myotube-specific probes, a thiol-reactive derivative, CDy2, was prepared. In live cells, the derivative selectively localizes in mitochondria and covalently labels its binding partners. Detailed facts importance to specialist readers are published as ”Supporting Information”. Such documents peer-reviewed, but not copy-edited or typeset. They made available submitted by authors. Please note: The publisher is responsible for content...
The isothiocyanate sulforaphane (SFN) has multiple protein targets in mammalian cells, affecting processes of fundamental importance for the maintenance cellular homeostasis, among which are those regulated by stress response transcription factor nuclear erythroid 2 p45-related (NRF2) and serine/threonine kinase mechanistic target rapamycin (mTOR). Whereas way SFN activates NRF2 is well established, molecular mechanism(s) how inhibits mTOR not understood. aim this study was to investigate We...
Protein cysteine is susceptible to diverse oxidations, including disulfide, S-sulfenylation, S-nitrosylation, and S-glutathionylation, that regulate many biological processes in physiology diseases. Despite evidence supporting distinct outcomes of individual oxoforms, the approach for examining functional effects resulting from a specific oxoform, such as remains limited. In this report, we devised dehydroglutathione (dhG)-mediated strategy, named G-PROV, introduces non-reducible...