A5090987806- Neuroscience and Neuropharmacology Research
- Genetics, Aging, and Longevity in Model Organisms
- RNA and protein synthesis mechanisms
- Genomics, phytochemicals, and oxidative stress
- Ion channel regulation and function
- Pharmacological Receptor Mechanisms and Effects
- Genetics and Neurodevelopmental Disorders
- Pain Mechanisms and Treatments
- Insect Resistance and Genetics
- Genomics and Rare Diseases
- Receptor Mechanisms and Signaling
- Biochemical Acid Research Studies
University of Georgia
2021-2024
Emory University
2023-2024
Abstract N-methyl- d -aspartate receptors (NMDARs) are members of the glutamate receptor family and participate in excitatory postsynaptic transmission throughout central nervous system. Genetic variants GRIN genes encoding NMDAR subunits associated with a spectrum neurological disorders. The M3 transmembrane helices couple directly to agonist-binding domains form helical bundle crossing closed that occludes pore. functions as transduction element whose conformational change couples ligand...
Advances in sequencing technology have generated a large amount of genetic data from patients with neurological conditions. These provided diagnosis many rare diseases, including number pathogenic de novo missense variants GRIN genes encoding N-methyl-d-aspartate receptors (NMDARs). To understand the ramifications for neurons and brain circuits affected by patient variants, functional analysis variant receptor is necessary model systems. For NMDARs, this needs to assess multiple properties...
Caenorhabditis elegans is a useful model organism to study the xenobiotic detoxification pathways of various natural and synthetic toxins, but mechanisms phase II are understudied. 1-Hydroxyphenazine (1-HP), toxin produced by bacterium Pseudomonas aeruginosa, kills C. elegans. We previously showed that detoxifies 1-HP adding one, two, or three glucose molecules in N2 worms. Our current evaluates roles some UDP-glycosyltransferase (ugt) genes play detoxification. show ugt-23 ugt-49 knockout...
Many cases of accidental death associated with drug overdose are due to chronic opioid use, tolerance, and addiction. Analgesic tolerance is characterized by a decreased response the analgesic effects opioids, requiring increasingly higher doses maintain desired level pain relief. Overactivation GluN2B-containing N-methyl-d-Aspartate receptors thought play key role in mechanisms underlying cellular adaptation that takes place development tolerance. Herein, we describe novel GluN2B-selective...
Subunit-selective inhibition of N-methyl-d-aspartate receptors (NMDARs) is a promising therapeutic strategy for several neurological disorders, including epilepsy, Alzheimer's and Parkinson's disease, depression, acute brain injury. We previously described the dihydroquinoline–pyrazoline (DQP) analogue 2a (DQP-26) as potent NMDAR negative allosteric modulator with selectivity GluN2C/D over GluN2A/B. However, moderate (<100-fold) subunit selectivity, inadequate cell-membrane permeability,...
Caenorhabditis elegans is an ideal model organism for studying the xenobiotic detoxification pathways of various natural and synthetic toxins. We developed a new workflow to study effects 1-hydroxyphenazine (1-HP), toxin produced by bacterium Pseudomonas aeruginosa, on survival C. elegans. Prior research has demonstrated that can detoxify 1-HP through general mechanism O-glycosylation. As part Vertically Integrated Projects (VIP) undergraduate team, we have plate-based toxicity assay...
ABSTRACT Caenorhabditis elegans is an ideal model organism to study the xenobiotic detoxification pathways of various natural and synthetic toxins. One toxin shown cause death in C. 1-hydroxyphenazine (1-HP), a molecule produced by bacterium Pseudomonas aeruginosa. We previously showed that median lethal dose (LD50) for 1-HP C 179 μM PD1074 between 150-200 N2 ( lab strain). also detoxifies glycosylation adding one, two, or three glucose molecules worms. This tested whether...