A5038199352- Photoacoustic and Ultrasonic Imaging
- Autophagy in Disease and Therapy
- Neurotransmitter Receptor Influence on Behavior
- Optical Imaging and Spectroscopy Techniques
- MicroRNA in disease regulation
- Cannabis and Cannabinoid Research
- Nanoplatforms for cancer theranostics
- Neuroscience and Neuropharmacology Research
- Parkinson's Disease Mechanisms and Treatments
- Redox biology and oxidative stress
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Epigenetics and DNA Methylation
- Mitochondrial Function and Pathology
- Receptor Mechanisms and Signaling
- Amino Acid Enzymes and Metabolism
- Spectroscopy Techniques in Biomedical and Chemical Research
- Amyotrophic Lateral Sclerosis Research
- Cell death mechanisms and regulation
- Tryptophan and brain disorders
- Photoreceptor and optogenetics research
- Ion channel regulation and function
- Immune Response and Inflammation
- Developmental Biology and Gene Regulation
- Neurogenesis and neuroplasticity mechanisms
- Nuclear Receptors and Signaling
University of Maryland, Baltimore
2019-2023
Johns Hopkins Medicine
2012-2022
Johns Hopkins University
2012-2022
H. L. Snyder Medical Foundation
2013-2021
Suez Canal University
1999-2014
Institute of Pathology Celle
2011
University of Iowa
2001-2008
Neurodegeneration in familial amyotrophic lateral sclerosis (ALS) is associated with enhanced redox stress caused by dominant mutations superoxide dismutase–1 (SOD1). SOD1 a cytosolic enzyme that facilitates the conversion of (O2•–) to H2O2. Here we demonstrate not just catabolic enzyme, but can also directly regulate NADPH oxidase–dependent (Nox-dependent) O2•– production binding Rac1 and inhibiting its GTPase activity. Oxidation H2O2 uncoupled reversible fashion, producing self-regulating...
DNA damage-activated nuclease identified Cells that experience stresses and accumulate excessive damage to undergo cell death mediated by a nuclear enzyme known as PARP-1. During this process, apoptosis-inducing factor (AIF) translocates the nucleus activates one or more nucleases cleave DNA. Wang et al. found macrophage migration inhibitory (MIF) is an AIF-associated endonuclease contributes PARP-1-induced fragmentation (see Perspective Jonas). In mouse neurons in culture, loss of MIF...
Stroke is a major cause of mortality and morbidity worldwide. Extracellular glutamate accumulation leading to overstimulation the ionotropic receptors mediates neuronal injury in stroke neurodegenerative disorders. Here we show that miR-223 controls response by regulating functional expression receptor subunits GluR2 NR2B brain. Overexpression lowers levels targeting 3′-UTR target sites (TSs) NR2B, inhibits NMDA-induced calcium influx hippocampal neurons, protects brain from cell death...
A subset of adult peripheral blood leukocytes functions as endothelial cell progenitors called angioblasts. They can incorporate into the vasculature in animal models neovascularization and accelerate restoration flow to mouse ischemic limbs. Earlier reports suggested that CD34-expressing (CD34+) but not CD34+ cell-depleted (CD34−) differentiate cells (EC) vitro vivo. Recent findings suggest CD14+ cells, which are typically CD34−, also have angioblast-like properties vitro. To determine...
Reactive oxygen species (ROS) generated by NADPH oxidases (Nox) have been implicated in the regulation of signal transduction. However, cellular mechanisms that link Nox activation with plasma membrane receptor signaling remain poorly defined. We found Nox2-derived ROS influence formation an active interleukin-1 (IL-1) complex endosomal compartment directing H2O2-dependent binding TRAF6 to IL-1R1/MyD88 complex. Clearance both superoxide and H2O2 from within significantly abrogated...
Amyotrophic lateral sclerosis (ALS), one of the most common adult-onset neurodegenerative diseases, has no known cure. Enhanced redox stress and inflammation have been associated with pathoprogression ALS through a poorly defined mechanism. Here we determined that dysregulated in mice caused by NADPH oxidases Nox1 Nox2 significantly influenced progression motor neuron disease mutant SOD1(G93A) expression. Deletion either Nox gene slowed improved survival. However, 50% survival rates were...
Significance d -amino acids are increasingly recognized as important signaling molecules in the mammalian central nervous system. Cysteine is amino acid with fastest vitro spontaneous racemization rate, but its -stereoisomer has not been examined. Here, we establish presence of endogenous -cysteine brain. Using sensitive and specific assays, delineate actions a negative regulator growth factor during cortical development identify putative binding partner mediating these effects. By...
Cocaine exerts its behavioral stimulant effects by facilitating synaptic actions of neurotransmitters such as dopamine and serotonin. It is also neurotoxic broadly cytotoxic, leading to overdose deaths. We demonstrate that the cytotoxic cocaine reflect selective enhancement autophagy, a process physiologically degrades metabolites cellular organelles, uncontrolled autophagy can lead cell death. In brain cultures, markedly increases levels LC3-II depletes p62, both characteristic autophagy....
Significance Inositol hexakisphosphate kinase 1 (IP6K1) regulates numerous physiological functions. We describe a role of IP6K1 in neural development, because its deletion results defects neuronal migration and brain malformation. physiologically interacts with α-actinin localizes to focal adhesions. phosphorylation both adhesion through product 5-diphosphoinositol pentakisphosphate (5-IP7).
The plant hormone salicylic acid (SA) controls several physiological processes and is a key regulator of multiple levels immunity. To decipher the mechanisms through which SA's effects are mediated, particularly in immunity, two high-throughput screens were developed to identify SA-binding proteins (SABPs). Glyceraldehyde 3-Phosphate Dehydrogenase (GAPDH) from plants (Arabidopsis thaliana) was identified these screens. Similar subsequent analyses using SA analogs, conjunction with either...
Minimally-invasive monitoring of electrophysiological neural activities in real-time—that enables quantification functions without a need for invasive craniotomy and the longer time constants fMRI PET—presents very challenging yet significant task neuroimaging. In this paper, we present vivo functional PA (fPA) imaging chemoconvulsant rat seizure model with intact scalp using fluorescence quenching-based cyanine voltage-sensitive dye (VSD) characterized by lipid vesicle mimicking different...
Significance Huntington’s disease (HD) is a progressive neurodegenerative disorder affecting the striatum. The striatal-enriched transcription factor COUP-TF-interacting protein 2 (Ctip2) depleted in HD and has been identified as putative for enzyme inositol polyphosphate multikinase (IPMK). IPMK displays soluble phosphate kinase activity, lipid several noncatalytic activities including its role transcriptional coactivator. We describe severe depletion patients animal cell models of disease....
Significance Histone H2AX elicits proper DNA repair through its phosphorylation by ataxia-telangiectasia mutated (ATM) kinase. While ATM senses reactive oxygen species, the role of in maintenance redox homeostasis remains unknown. Here we establish that deletion leads to impairment mitochondrial function and repression biogenesis gene PGC-1α. Restoring PGC-1α abrogates deficits mitigates cell death. This study unveils a for associated with neuroprotection.
We report the transcranial functional photoacoustic (fPA) neuroimaging of N-methyl-D-aspartate (NMDA) evoked neural activity in rat hippocampus. Concurrent quantitative electroencephalography (qEEG) and microdialysis were used to record real-time circuit dynamics excitatory neurotransmitter concentrations, respectively.We hypothesized that location-specific fPA voltage-sensitive dye (VSD) contrast would identify changes hippocampus which correlate with NMDA-evoked...
Significance The induction of immediate early genes (IEGs) by neural stimuli underlies much the plasticity brain function, but regulatory mechanisms have been obscure. Inositol polyphosphate multikinase (IPMK) is a notably pleiotropic enzyme that displays inositol phosphate kinase activity and phosphatidylinositol exhibits physiologically noncatalytic actions such as stabilizing mammalian target rapamycin complex 1 complex. We report IPMK required for IEG activation neurotrophic stimuli....
Botch promotes embryonic neurogenesis by inhibiting the initial S1 furin-like cleavage step of Notch maturation. The biochemical process which inhibits maturation is not known. Here, we show that has γ-glutamyl cyclotransferase (GGCT) activity deglycinates Notch, prevents cleavage. Moreover, monoglycinated on carbon glutamate 1,669. deglycinase required for inhibition signaling both in vitro and vivo. When γ-glutamyl-glycine at position 1,669 degylcinated, it replaced 5-oxy-proline. These...
The coronavirus disease 2019 (COVID-19) pandemic has devastated global health and the economy, underscoring urgent need for extensive research into mechanisms of severe acute respiratory syndrome 2 (SARS-CoV-2) viral entry development effective therapeutic interventions. We established a cell line expressing human angiotensin-converting enzyme (ACE2). used it as model pseudotyped using murine leukemia virus (MLV) SARS-CoV-2 spike (S) protein on its surface firefly luciferase reporter....
Coordinated and specific regulation of tumor necrosis factor (TNF) interleukin (IL)-1 signaling pathways how whether they are modified by different agents key events for proper immune responses. The IkappaB kinase complex (IKK)/NF-kappaB JNK/AP-1 central mediators TNF IL-1 during inflammatory Here we show that l-mimosine, a toxic non-protein amino acid has been shown to reduce serum TNFalpha levels affect responses, specifically inhibits TNF-induced IKK but not JNK in cell type-specific...